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History Isaac Newton

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Isaac Newton

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Sir Isaac Newton PRS MP (25 December 1642 – 20 March 1727) was an English physicist and mathematician who is widely regarded as one of the most influential scientists of all time and as a key figure in the scientific revolution. His book Philosophiæ Naturalis Principia Mathematica ("Mathematical Principles of Natural Philosophy"), first published in 1687, laid the foundations for most of classical mechanics. Newton also made seminal contributions to optics and shares credit with Gottfried Leibniz for the invention of the infinitesimal calculus.

Newton's Principia formulated the laws of motion and universal gravitation that dominated scientists' view of the physical universe for the next three centuries. It also demonstrated that the motion of objects on the Earth and that of celestial bodies could be described by the same principles. By deriving Kepler's laws of planetary motion from his mathematical description of gravity, Newton removed the last doubts about the validity of the heliocentric model of the cosmos.

Newton built the first practical reflecting telescope and developed a theory of colour based on the observation that a prism decomposes white light into the many colours of the visible spectrum. He also formulated an empirical law of cooling and studied the speed of sound. In addition to his work on the calculus, as a mathematician Newton contributed to the study of power series, generalised the binomial theorem to non-integer exponents, and developed Newton's method for approximating the roots of a function.

Newton was a fellow of Trinity College and the second Lucasian Professor of Mathematics at the University of Cambridge. He was a devout but unorthodox Christian and, unusually for a member of the Cambridge faculty, he refused to take holy orders in the Church of England, perhaps because he privately rejected the doctrine of trinitarianism. In addition to his work on the mathematical sciences, Newton also dedicated much of his time to the study of alchemy and biblical chronology, but most of his work in those areas remained unpublished until long after his death. In his later life, Newton became president of the Royal Society. He also served the British government as Warden and Master of the Royal Mint.

Life

Early life

Main article: Early life of Isaac Newton

Isaac Newton was born (according to the Julian calendar in use in England at the time) on Christmas Day, 25 December 1642, (NS 4 January 1643.[1]) at Woolsthorpe Manor in Woolsthorpe-by-Colsterworth, a hamlet in the county of Lincolnshire. He was born three months after the death of his father, a prosperous farmer also named Isaac Newton. Born prematurely, he was a small child; his mother Hannah Ayscough reportedly said that he could have fit inside a quart mug (≈ 1.1 litres). When Newton was three, his mother remarried and went to live with her new husband, the Reverend Barnabus Smith, leaving her son in the care of his maternal grandmother, Margery Ayscough. The young Isaac disliked his stepfather and maintained some enmity towards his mother for marrying him, as revealed by this entry in a list of sins committed up to the age of 19: "Threatening my father and mother Smith to burn them and the house over them."[8] Although it was claimed that he was once engaged,[9] Newton never married.

From the age of about twelve until he was seventeen, Newton was educated at The King's School, Grantham. He was removed from school, and by October 1659, he was to be found at Woolsthorpe-by-Colsterworth, where his mother, widowed by now for a second time, attempted to make a farmer of him. He hated farming.[10] Henry Stokes, master at the King's School, persuaded his mother to send him back to school so that he might complete his education. Motivated partly by a desire for revenge against a schoolyard bully, he became the top-ranked student.[11] The Cambridge psychologist Simon Baron-Cohen considers it "fairly certain" that Newton had Asperger syndrome.[12]

In June 1661, he was admitted to Trinity College, Cambridge as a sizar – a sort of work-study role.[13] At that time, the college's teachings were based on those of Aristotle, whom Newton supplemented with modern philosophers, such as Descartes, and astronomers such as Copernicus, Galileo, and Kepler. In 1665, he discovered the generalised binomial theorem and began to develop a mathematical theory that later became infinitesimal calculus. Soon after Newton had obtained his degree in August 1665, the university temporarily closed as a precaution against the Great Plague. Although he had been undistinguished as a Cambridge student,[14] Newton's private studies at his home in Woolsthorpe over the subsequent two years saw the development of his theories on calculus,[15] optics and the law of gravitation. In 1667, he returned to Cambridge as a fellow of Trinity.[16] Fellows were required to become ordained priests, something Newton desired to avoid due to his unorthodox views. Luckily for Newton, there was no specific deadline for ordination, and it could be postponed indefinitely. The problem became more severe later when Newton was elected for the prestigious Lucasian Chair. For such a significant appointment, ordaining normally could not be dodged. Nevertheless, Newton managed to avoid it by means of a special permission from Charles II (see "Middle years" section below).

Middle years

Mathematics

Newton's work has been said "to distinctly advance every branch of mathematics then studied".[17] His work on the subject usually referred to as fluxions or calculus, seen in a manuscript of October 1666, is now published among Newton's mathematical papers.[18] The author of the manuscript De analysi per aequationes numero terminorum infinitas, sent by Isaac Barrow to John Collins in June 1669, was identified by Barrow in a letter sent to Collins in August of that year as:[19]

Mr Newton, a fellow of our College, and very young ... but of an extraordinary genius and proficiency in these things.

Newton later became involved in a dispute with Leibniz over priority in the development of infinitesimal calculus (the Leibniz–Newton calculus controversy). Most modern historians believe that Newton and Leibniz developed infinitesimal calculus independently, although with very different notations. Occasionally it has been suggested that Newton published almost nothing about it until 1693, and did not give a full account until 1704, while Leibniz began publishing a full account of his methods in 1684. (Leibniz's notation and "differential Method", nowadays recognised as much more convenient notations, were adopted by continental European mathematicians, and after 1820 or so, also by British mathematicians.) Such a suggestion, however, fails to notice the content of calculus which critics of Newton's time and modern times have pointed out in Book 1 of Newton's Principia itself (published 1687) and in its forerunner manuscripts, such as De motu corporum in gyrum ("On the motion of bodies in orbit"), of 1684. The Principia is not written in the language of calculus either as we know it or as Newton's (later) 'dot' notation would write it. But his work extensively uses an infinitesimal calculus in geometric form, based on limiting values of the ratios of vanishing small quantities: in the Principia itself Newton gave demonstration of this under the name of 'the method of first and last ratios'[20] and explained why he put his expositions in this form,[21] remarking also that 'hereby the same thing is performed as by the method of indivisibles'.

Because of this, the Principia has been called "a book dense with the theory and application of the infinitesimal calculus" in modern times[22] and "lequel est presque tout de ce calcul" ('nearly all of it is of this calculus') in Newton's time.[23] His use of methods involving "one or more orders of the infinitesimally small" is present in his De motu corporum in gyrum of 1684[24] and in his papers on motion "during the two decades preceding 1684".[25]

Newton had been reluctant to publish his calculus because he feared controversy and criticism.[26] He was close to the Swiss mathematician Nicolas Fatio de Duillier. In 1691, Duillier started to write a new version of Newton's Principia, and corresponded with Leibniz.[27] In 1693 the relationship between Duillier and Newton deteriorated, and the book was never completed.

Starting in 1699, other members of the Royal Society (of which Newton was a member) accused Leibniz of plagiarism, and the dispute broke out in full force in 1711. The Royal Society proclaimed in a study that it was Newton who was the true discoverer and labelled Leibniz a fraud. This study was cast into doubt when it was later found that Newton himself wrote the study's concluding remarks on Leibniz. Thus began the bitter controversy which marred the lives of both Newton and Leibniz until the latter's death in 1716.[28]

Newton is generally credited with the generalised binomial theorem, valid for any exponent. He discovered Newton's identities, Newton's method, classified cubic plane curves (polynomials of degree three in two variables), made substantial contributions to the theory of finite differences, and was the first to use fractional indices and to employ coordinate geometry to derive solutions to Diophantine equations. He approximated partial sums of the harmonic series by logarithms (a precursor to Euler's summation formula), and was the first to use power series with confidence and to revert power series. Newton's work on infinite series was inspired by Simon Stevin's decimals.[29]

He was appointed Lucasian Professor of Mathematics in 1669 on Barrow's recommendation. In that day, any fellow of Cambridge or Oxford was required to become an ordained Anglican priest. However, the terms of the Lucasian professorship required that the holder not be active in the church (presumably so as to have more time for science). Newton argued that this should exempt him from the ordination requirement, and Charles II, whose permission was needed, accepted this argument. Thus a conflict between Newton's religious views and Anglican orthodoxy was averted.[30]

Optics

From 1670 to 1672, Newton lectured on optics.[32] During this period he investigated the refraction of light, demonstrating that a prism could decompose white light into a spectrum of colours, and that a lens and a second prism could recompose the multicoloured spectrum into white light.[33] Modern scholarship has revealed that Newton's analysis and resynthesis of white light owes a debt to corpuscular alchemy.[34]

He also showed that the coloured light does not change its properties by separating out a coloured beam and shining it on various objects. Newton noted that regardless of whether it was reflected or scattered or transmitted, it stayed the same colour. Thus, he observed that colour is the result of objects interacting with already-coloured light rather than objects generating the colour themselves. This is known as Newton's theory of colour.[35]

From this work, he concluded that the lens of any refracting telescope would suffer from the dispersion of light into colours (chromatic aberration). As a proof of the concept, he constructed a telescope using a mirror as the objective to bypass that problem.[36][37] Building the design, the first known functional reflecting telescope, today known as a Newtonian telescope,[37] involved solving the problem of a suitable mirror material and shaping technique. Newton ground his own mirrors out of a custom composition of highly reflective speculum metal, using Newton's rings to judge the quality of the optics for his telescopes. In late 1668[38] he was able to produce this first reflecting telescope. In 1671, the Royal Society asked for a demonstration of his reflecting telescope.[39] Their interest encouraged him to publish his notes On Colour, which he later expanded into his Opticks. When Robert Hooke criticised some of Newton's ideas, Newton was so offended that he withdrew from public debate. Newton and Hooke had brief exchanges in 1679–80, when Hooke, appointed to manage the Royal Society's correspondence, opened up a correspondence intended to elicit contributions from Newton to Royal Society transactions,[40] which had the effect of stimulating Newton to work out a proof that the elliptical form of planetary orbits would result from a centripetal force inversely proportional to the square of the radius vector (see Newton's law of universal gravitation – History and De motu corporum in gyrum). But the two men remained generally on poor terms until Hooke's death.[41]

Newton argued that light is composed of particles or corpuscles, which were refracted by accelerating into a denser medium. He verged on soundlike waves to explain the repeated pattern of reflection and transmission by thin films (Opticks Bk.II, Props. 12), but still retained his theory of 'fits' that disposed corpuscles to be reflected or transmitted (Props.13). Later physicists instead favoured a purely wavelike explanation of light to account for the interference patterns, and the general phenomenon of diffraction. Today's quantum mechanics, photons and the idea of wave–particle duality bear only a minor resemblance to Newton's understanding of light.

In his Hypothesis of Light of 1675, Newton posited the existence of the ether to transmit forces between particles. The contact with the theosophist Henry More, revived his interest in alchemy. He replaced the ether with occult forces based on Hermetic ideas of attraction and repulsion between particles. John Maynard Keynes, who acquired many of Newton's writings on alchemy, stated that "Newton was not the first of the age of reason: He was the last of the magicians."[42] Newton's interest in alchemy cannot be isolated from his contributions to science.[5] This was at a time when there was no clear distinction between alchemy and science. Had he not relied on the occult idea of action at a distance, across a vacuum, he might not have developed his theory of gravity. (See also Isaac Newton's occult studies.)

In 1704, Newton published Opticks, in which he expounded his corpuscular theory of light. He considered light to be made up of extremely subtle corpuscles, that ordinary matter was made of grosser corpuscles and speculated that through a kind of alchemical transmutation "Are not gross Bodies and Light convertible into one another, ...and may not Bodies receive much of their Activity from the Particles of Light which enter their Composition?"[43] Newton also constructed a primitive form of a frictional electrostatic generator, using a glass globe (Optics, 8th Query).

In an article entitled "Newton, prisms, and the 'opticks' of tunable lasers[44] it is indicated that Newton in his book Opticks was the first to show a diagram using a prism as a beam expander. In the same book he describes, via diagrams, the use of multiple-prism arrays. Some 278 years after Newton's discussion, multiple-prism beam expanders became central to the development of narrow-linewidth tunable lasers. Also, the use of these prismatic beam expanders led to the multiple-prism dispersion theory.[44]

Mechanics and gravitation

In 1679, Newton returned to his work on (celestial) mechanics, i.e., gravitation and its effect on the orbits of planets, with reference to Kepler's laws of planetary motion. This followed stimulation by a brief exchange of letters in 1679–80 with Hooke, who had been appointed to manage the Royal Society's correspondence, and who opened a correspondence intended to elicit contributions from Newton to Royal Society transactions.[40] Newton's reawakening interest in astronomical matters received further stimulus by the appearance of a comet in the winter of 1680–1681, on which he corresponded with John Flamsteed.[45] After the exchanges with Hooke, Newton worked out a proof that the elliptical form of planetary orbits would result from a centripetal force inversely proportional to the square of the radius vector (see Newton's law of universal gravitation – History and De motu corporum in gyrum). Newton communicated his results to Edmond Halley and to the Royal Society in De motu corporum in gyrum, a tract written on about 9 sheets which was copied into the Royal Society's Register Book in December 1684.[46] This tract contained the nucleus that Newton developed and expanded to form the Principia.

The Principia was published on 5 July 1687 with encouragement and financial help from Edmond Halley. In this work, Newton stated the three universal laws of motion that enabled many of the advances of the Industrial Revolution which soon followed and were not to be improved upon for more than 200 years, and are still the underpinnings of the non-relativistic technologies of the modern world. He used the Latin word gravitas (weight) for the effect that would become known as gravity, and defined the law of universal gravitation.

In the same work, Newton presented a calculus-like method of geometrical analysis by 'first and last ratios', gave the first analytical determination (based on Boyle's law) of the speed of sound in air, inferred the oblateness of the spheroidal figure of the Earth, accounted for the precession of the equinoxes as a result of the Moon's gravitational attraction on the Earth's oblateness, initiated the gravitational study of the irregularities in the motion of the moon, provided a theory for the determination of the orbits of comets, and much more.

Newton made clear his heliocentric view of the solar system – developed in a somewhat modern way, because already in the mid-1680s he recognised the "deviation of the Sun" from the centre of gravity of the solar system.[47] For Newton, it was not precisely the centre of the Sun or any other body that could be considered at rest, but rather "the common centre of gravity of the Earth, the Sun and all the Planets is to be esteem'd the Centre of the World", and this centre of gravity "either is at rest or moves uniformly forward in a right line" (Newton adopted the "at rest" alternative in view of common consent that the centre, wherever it was, was at rest).[48]

Newton's postulate of an invisible force able to act over vast distances led to him being criticised for introducing "occult agencies" into science.[49] Later, in the second edition of the Principia (1713), Newton firmly rejected such criticisms in a concluding General Scholium, writing that it was enough that the phenomena implied a gravitational attraction, as they did; but they did not so far indicate its cause, and it was both unnecessary and improper to frame hypotheses of things that were not implied by the phenomena. (Here Newton used what became his famous expression "hypotheses non fingo"[50]).

With the Principia, Newton became internationally recognised.[51] He acquired a circle of admirers, including the Swiss-born mathematician Nicolas Fatio de Duillier, with whom he formed an intense relationship. This abruptly ended in 1693, and at the same time Newton suffered a nervous breakdown.[52]

Classification of cubics

Besides the work of Newton and others on calculus, the first important demonstration of the power of analytic geometry was Newton's classification of cubic curves in the Euclidean plane in the late 1600s. He divided them into four types, satisfying different equations, and in 1717 Stirling, probably with Newton's help, proved that every cubic was one of these four. Newton also claimed that the four types could be obtained by plane projection from one of them, and this was proved in 1731.[53]

In the 1690s, Newton wrote a number of religious tracts dealing with the literal interpretation of the Bible. Henry More's belief in the Universe and rejection of Cartesian dualism may have influenced Newton's religious ideas. A manuscript he sent to John Locke in which he disputed the existence of the Trinity remained unpublished until 1785, more than half a century after his death.[54][55] Later works – The Chronology of Ancient Kingdoms Amended (1728) and Observations Upon the Prophecies of Daniel and the Apocalypse of St. John (1733) – were published after his death. He also devoted a great deal of time to alchemy (see above).

Newton was also a member of the Parliament of England for Cambridge University in 1689–90 and 1701–2, but according to some accounts his only comments were to complain about a cold draught in the chamber and request that the window be closed.[56][57][58]

Newton moved to London to take up the post of warden of the Royal Mint in 1696, a position that he had obtained through the patronage of Charles Montagu, 1st Earl of Halifax, then Chancellor of the Exchequer. He took charge of England's great recoining, somewhat treading on the toes of Lord Lucas, Governor of the Tower (and securing the job of deputy comptroller of the temporary Chester branch for Edmond Halley). Newton became perhaps the best-known Master of the Mint upon the death of Thomas Neale in 1699, a position Newton held for the last 30 years of his life.[59][60] These appointments were intended as sinecures, but Newton took them seriously, retiring from his Cambridge duties in 1701, and exercising his power to reform the currency and punish clippers and counterfeiters. As Master of the Mint in 1717 in the "Law of Queen Anne" Newton moved the Pound Sterling de facto from the silver standard to the gold standard by setting the bimetallic relationship between gold coins and the silver penny in favour of gold. This caused silver sterling coin to be melted and shipped out of Britain. Newton was made President of the Royal Society in 1703 and an associate of the French Académie des Sciences. In his position at the Royal Society, Newton made an enemy of John Flamsteed, the Astronomer Royal, by prematurely publishing Flamsteed's Historia Coelestis Britannica, which Newton had used in his studies.[61]

In April 1705, Queen Anne knighted Newton during a royal visit to Trinity College, Cambridge. The knighthood is likely to have been motivated by political considerations connected with the Parliamentary election in May 1705, rather than any recognition of Newton's scientific work or services as Master of the Mint.[63] Newton was the second scientist to be knighted, after Sir Francis Bacon.

Towards the end of his life, Newton took up residence at Cranbury Park, near Winchester with his niece and her husband, until his death in 1727.[64] His half-niece, Catherine Barton Conduitt,[65] served as his hostess in social affairs at his house on Jermyn Street in London; he was her "very loving Uncle,"[66] according to his letter to her when she was recovering from smallpox.

Newton died in his sleep in London on 20 March 1727 (OS 20 March 1726; NS 31 March 1727)[1] and was buried in Westminster Abbey. A bachelor, he had divested much of his estate to relatives during his last years, and died intestate. After his death, Newton's hair was examined and found to contain mercury, probably resulting from his alchemical pursuits. Mercury poisoning could explain Newton's eccentricity in late life.[67]

After death

Fame

The mathematician Joseph-Louis Lagrange often said that Newton was the greatest genius who ever lived, and once added that Newton was also "the most fortunate, for we cannot find more than once a system of the world to establish."[68] English poet Alexander Pope was moved by Newton's accomplishments to write the famous epitaph:

Nature and nature's laws lay hid in night;

God said "Let Newton be" and all was light.

Newton himself had been rather more modest of his own achievements, famously writing in a letter to Robert Hooke in February 1676:

If I have seen further it is by standing on the shoulders of giants.[69]

Two writers think that the above quote, written at a time when Newton and Hooke were in dispute over optical discoveries, was an oblique attack on Hooke (said to have been short and hunchbacked), rather than – or in addition to – a statement of modesty.[70][71] On the other hand, the widely known proverb about standing on the shoulders of giants published among others by 17th-century poet George Herbert (a former orator of the University of Cambridge and fellow of Trinity College) in his Jacula Prudentum (1651), had as its main point that "a dwarf on a giant's shoulders sees farther of the two", and so its effect as an analogy would place Newton himself rather than Hooke as the 'dwarf'.

In a later memoir, Newton wrote:

I do not know what I may appear to the world, but to myself I seem to have been only like a boy playing on the sea-shore, and diverting myself in now and then finding a smoother pebble or a prettier shell than ordinary, whilst the great ocean of truth lay all undiscovered before me.[72]

Albert Einstein kept a picture of Newton on his study wall alongside ones of Michael Faraday and James Clerk Maxwell.[73] Newton remains influential to today's scientists, as demonstrated by a 2005 survey of members of Britain's Royal Society (formerly headed by Newton) asking who had the greater effect on the history of science, Newton or Einstein. Royal Society scientists deemed Newton to have made the greater overall contribution.[74] In 1999, an opinion poll of 100 of today's leading physicists voted Einstein the "greatest physicist ever;" with Newton the runner-up, while a parallel survey of rank-and-file physicists by the site PhysicsWeb gave the top spot to Newton.[75]

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v t e

Main article: Newton's laws of motion

In the Principia, Newton gives the famous three laws of motion, stated here in modern form.

Newton's First Law (also known as the Law of Inertia) states that an object at rest tends to stay at rest and that an object in uniform motion tends to stay in uniform motion unless acted upon by a net external force. The meaning of this law is the existence of reference frames (called inertial frames) where objects not acted upon by forces move in uniform motion (in particular, they may be at rest).

Newton's Second Law states that an applied force, , on an object equals the rate of change of its momentum, , with time. Mathematically, this is expressed as

Since the law applies only to systems of constant mass,[124] m can be brought out of the derivative operator. By substitution using the definition of acceleration, the equation can be written in the iconic form

The first and second laws represent a break with the physics of Aristotle, in which it was believed that a force was necessary in order to maintain motion. They state that a force is only needed in order to change an object's state of motion. The SI unit of force is the newton, named in Newton's honour.

Newton's Third Law states that for every action there is an equal and opposite reaction. This means that any force exerted onto an object has a counterpart force that is exerted in the opposite direction back onto the first object. A common example is of two ice skaters pushing against each other and sliding apart in opposite directions. Another example is the recoil of a firearm, in which the force propelling the bullet is exerted equally back onto the gun and is felt by the shooter. Since the objects in question do not necessarily have the same mass, the resulting acceleration of the two objects can be different (as in the case of firearm recoil).

Unlike Aristotle's, Newton's physics is meant to be universal. For example, the second law applies both to a planet and to a falling stone.

The vector nature of the second law addresses the geometrical relationship between the direction of the force and the manner in which the object's momentum changes. Before Newton, it had typically been assumed that a planet orbiting the Sun would need a forward force to keep it moving. Newton showed instead that all that was needed was an inward attraction from the Sun. Even many decades after the publication of the Principia, this counterintuitive idea was not universally accepted, and many scientists preferred Descartes' theory of vortices.[125]

News Dortmund 4-1 Real Madrid - as it happened

noreply@blogger.com (Rep Oi Tj) — Thu, 25 Apr 2013 15:38:00 +0000

Champions League semi-final

first leg

Borussia Dortmund 4-1 Real Madrid - as it happened

Robert Lewandowski scored four as Borussia Dortmund walloped Real Madrid in the first leg of their semi-final

Champions League

Dortmund 4	Robert Lewandowski 8, Robert Lewandowski 50, Robert Lewandowski 55, Robert Lewandowski 67 Pen
Real Madrid 1	Cristiano Ronaldo 43

Chemical Compound

noreply@blogger.com (Rep Oi Tj) — Wed, 30 Jan 2013 21:14:00 +0000

Chemical compound

From Wikipedia, the free encyclopedia

A water molecule is an example of a chemical compound, consisting of two partshydrogen and one part oxygen.

A chemical compound is a pure chemical substance consisting of two or more different chemical elements^[1]^[2]^[3] that can be separated into simpler substances by chemical reactions.^[4] Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms^[3] that are held together in a defined spatial arrangement by chemical bonds. Chemical compounds can be molecular compounds held together by covalent bonds, salts held together by ionic bonds, intermetallic compounds held together by metallic bonds, or complexes held together by coordinate covalent bonds. Pure chemical elements are not considered chemical compounds, even if they consist of molecules that contain only multiple atoms of a single element (such as H₂, S₈, etc.),^[5] which are called diatomic molecules or polyatomic molecules.

Wider definitions

There are exceptions to the definition above, and many solid chemical materials familiar on Earth (for example many silicate minerals) do not have simple formulas in which various elements that are chemically bonded to each other stand in exact and fixed ratios. These crystalline compounds are called "non-stoichiometric compounds". They vary in composition due to either the presence of foreign elements trapped within the crystal structure or a deficit or excess of the constituent elements. Such non-stoichiometric chemical compounds form most of the crust and mantle of the Earth.

Other compounds regarded as chemically identical may have varying amounts of heavy or light isotopes of the constituent elements, which changes the ratio of elements by mass slightly.

Elementary concepts

Characteristic properties of compounds:

Elements in a compound are present in a definite proportion

Example- 2 atoms of hydrogen + 1 atom of oxygen becomes 1 molecule of compound-water.

Compounds have a definite set of properties

Elements that comprise a compound do not retain their original properties.
For example, hydrogen (combustible and non-supportive of combustion) + oxygen (non-combustible and supportive of combustion) becomes water (non-combustible and non-supportive of combustion)

Valency is the number of hydrogen atoms that can combine with one atom of the element to form a compound.

Compounds compared to mixtures

The physical and chemical properties of compounds differ from those of their constituent elements. This is one of the main criteria that distinguish a compound from a mixture of elements or other substances—a mixture's properties are generally closely related to, and depend on, the properties of its constituents. Another criterion that distinguishes a compound from a mixture is that constituents of a mixture can usually be separated by simple mechanical means, such as filtering, evaporation, or magnetic force, but components of a compound can only be separated by a chemical reaction. Conversely, mixtures can be created by mechanical means alone, but a compound can only be created (either from elements or from other compounds, or a combination of the two) by a chemical reaction.

Some mixtures are so intimately combined that they have some properties similar to compounds and may easily be mistaken for compounds. One example is alloys. Alloys are made mechanically, most commonly by heating the constituent metals to a liquid state, mixing them thoroughly, and then cooling the mixture quickly so that the constituents are trapped in the base metal. Other examples of compound-like mixtures include intermetallic compounds and solutions of alkali metals in a liquid form of ammonia.

Formula

Main article: Chemical formula

Chemists describe compounds using formulas in various formats. For compounds that exist as molecules, the formula for the molecular unit is shown. For polymeric materials, such as mineralsand many metal oxides, the empirical formula is normally given, e.g. NaCl for table salt.

The elements in a chemical formula are normally listed in a specific order, called the Hill system. In this system, the carbon atoms (if there are any) are usually listed first, any hydrogen atoms are listed next, and all other elements follow in alphabetical order. If the formula contains no carbon, then all of the elements, including hydrogen, are listed alphabetically. There are, however, several important exceptions to the normal rules. For ionic compounds, the positive ion is almost always listed first and the negative ion is listed second. For oxides, oxygen is usually listed last.

Organic acids generally follow the normal rules with C and H coming first in the formula. For example, the formula for trifluoroacetic acid is usually written as C₂HF₃O₂. More descriptive formulas can convey structural information, such as writing the formula for trifluoroacetic acid as CF₃CO₂H. On the other hand, the chemical formulas for most inorganic acids and bases are exceptions to the normal rules. They are written according to the rules for ionic compounds (positive first, negative second), but they also follow rules that emphasize their Arrhenius definitions. Specifically, the formula for most inorganic acids begins with hydrogen and the formula for most bases ends with the hydroxide ion (OH^-). Formulas for inorganic compounds do not often convey structural information, as illustrated by the common use of the formula H₂SO₄ for a molecule (sulfuric acid) that contains no H-S bonds. A more descriptive presentation would be O₂S(OH)₂, but it is almost never written this way.

Phases and thermal properties

Compounds may have several possible phases. All compounds can exist as solids, at least at low enough temperatures. Molecular compounds may also exist as liquids, gases, and, in some cases, even plasmas. All compounds decompose upon applying heat. The temperature at which such fragmentation occurs is often called the decomposition temperature. Decomposition temperatures are not sharp and depend on the rate of heating.

CAS number

Every chemical substance, including chemical compounds, that has been described in the literature carries a unique numerical identifier, its CAS number.

References

^ Brown, Theodore L.; LeMay, H. Eugene; Bursten, Bruce E.; Murphy, Catherine J.; Woodward, Patrick (2009), Chemistry: The Central Science, AP Edition (11th ed.), Upper Saddle River, NJ: Pearson/Prentice Hall, pp. 5–6, ISBN 0-13-236489-1
^ Hill, John W.; Petrucci, Ralph H.; McCreary, Terry W.; Perry, Scott S. (2005), General Chemistry (4th ed.), Upper Saddle River, NJ: Pearson/Prentice Hall, p. 6, ISBN 978-0-13-140283-6
^ ^a ^b Whitten, Kenneth W.; Davis, Raymond E.; Peck, M. Larry (2000), General Chemistry (6th ed.), Fort Worth, TX: Saunders College Publishing/Harcourt College Publishers, p. 15, ISBN 978-0-03-072373-5
^ Wilbraham, Antony; Matta, Michael; Staley, Dennis; Waterman, Edward (2002), Chemistry (1st ed.), Upper Saddle River, NJ: Pearson/Prentice Hall, p. 36, ISBN 0-13-251210-6
^ Halal, John (2008), "Chapter 8: General Chemistry", Milady's Hair Structure and Chemistry Simplified (5 ed.), Milady Publishing, pp. 96–98, ISBN 1-4283-3558-7

PEDIATRIC CLINIC DONATION AND ANNOUNCEMENT FOR NEW CHARITY CAMPAIGN 'BE MY FRIEND'

noreply@blogger.com (Rep Oi Tj) — Wed, 30 Jan 2013 21:10:00 +0000

Alkaloid brand is as distinguishable and recognized as is its motto –Health above all – a slogan which acts as a motive for accomplishing the company’s mission for a healthier world and superior quality of its products and services. Alkaloid’s firm commitment is the care for the health of each individual, the quality of every person’s life, the healthcare system and the environment.

Among the numerous events organized as part of the celebration of the company’s 75^thJubilee was the humanitarian happening which took place on 3 September 2011 for the company employees and the members of their families. The funds raised by the employees, who donated a sum of MKD 200 to “Trajce Mukaetov’ Foundation, were used for purchasing equipment for the Pediatric Oncology ward of the Pediatric Clinic within the Clinical Centre in Skopje.

The equipment purchased is worth nearly EUR 7,000, raised for only a day and a half, and it consists of apparatuses aimed for treatment of children with cancer, such as infusion pumps for cytostatic therapy application, inhalation apparatuses, transportable monitors for gauging various parameters and a transportable ECG apparatus with 12 outlets.

As part of its commitment to social responsibility and the care for people’s health, Alkaloid has decided to continue its charity activities and to help the most fragile category of patients, the children with carcinogenic diseases. Alkaloid will carry out the charity campaign named ‘Be my friend’ in cooperation with ‘Borka- For Each New Day’, the association which has worked on raising awareness of malign diseases among the citizens for five years now.

The project activities will last 9 months and primarily they will be focused on monthly supplies of certain apparatuses and materials for the clinic, aimed to alleviate the stay and the treatment of the patients hospitalized at the Pediatric Oncology ward, as well as their families during the treatment. The parents of the children with malignant diseases will be able to make use of the psycho-social aid in cooperation with the support groups organized by ‘Borka’.

For the purpose of this project, as part of Alkaloid’s contribution to the enhancement and development of the community in which it operates, the company will allocate at least MKD 1.2 million from the sales of ‘Becutan’ brand products.

The campaign starts on 15 February, the International Childhood Cancer Day. It is the first time that this day has been officially marked in the Republic of Macedonia, thus making our country part of the global struggle for raising awareness of early detection and diagnostics of malignant diseases in children, resulting in 70% curability of all diagnosed cases by application of an appropriate treatment, which is organized by the International Confederation of Childhood Cancer and the Union for International Cancer Control.

Sumber : www.alkaloid.com

The Immunopathogenesis of Human Immunodeficiency Virus Infection

noreply@blogger.com (Rep Oi Tj) — Wed, 30 Jan 2013 21:01:00 +0000

The human immunodeficiency virus (HIV) is probably the most intensively studied virus in the history of biomedical research. A large number of distinct isolates have been cloned and sequenced, and the genes of the virus and several of the protein products of these genes have been characterized1. Furthermore, many of the pathogenic mechanisms associated with HIV infection that lead to clinical disease have been established, such as the functional abnormalities and quantitative depletion of CD4 T lymphocytes that cause the profound immunosuppression characteristic of advanced HIV infection2. It is generally agreed that HIV itself has the primary role in the initiation and propagation of the pathogenic process3. Nonetheless, a number of important issues concerning the pathogenesis of HIV infection and disease from both a virologic and an immunologic standpoint remain unresolved. Foremost among them is the observation that the viral burden in peripheral-blood mononuclear cells is low at the same time that CD4 T lymphocytes are progressively depleted and immune function deteriorates in most patients2. Although a recent study demonstrated that in patients with HIV a substantial percentage of peripheral-blood mononuclear cells are infected with the virus,4 the body of evidence favors an extremely low viral burden in peripheral-blood mononuclear cells. The recent findings of a much greater viral burden and greater viral propagation in lymphoid tissue than in peripheral blood (see below) may help resolve this issue. The question has nonetheless stimulated investigation into additional mechanisms of immune dysregulation associated with HIV infection, and a series of immunologic and nonimmunologic mechanisms of immune-cell dysfunction and destruction have been proposed. In this article, we shall outline the available knowledge concerning the pathogenesis of HIV infection and discuss information that has recently emerged in this area.

THE COURSE OF HIV INFECTION

Although the course of HIV infection may vary somewhat among individual patients, a common pattern of development has been recognized (Figure 1FIGURE 1Typical Course of HIV Infection.)5. Primary infection with HIV is followed by the development of detectable humoral and cellular immune responses to the virus and a prolonged period (median, 10 years) of clinical latency, during which the patient is usually asymptomatic, followed by the appearance of constitutional signs and symptoms5. Clinically apparent disease then develops, and even with treatment,6-8 death usually ensues within two years9. The contributions of the different pathogenic mechanisms of HIV infection probably vary considerably during each stage of this infection.

Acute HIV Syndrome

In 50 to 70 percent of patients with primary HIV infection an acute mononucleosis-like syndrome develops approximately three to six weeks after initial infection (Figure 2FIGURE 2The Progression of HIV Infection from Primary Infection through the Acute HIV Syndrome to the Stage of Clinical Latency.)10. This period is associated with high levels of viremia, and within one week to three months there is an immune response to HIV11,12. HIV is widely disseminated during this early stage of infection,10 strongly suggesting that the subsequent course of HIV infection may be influenced by the seeding of virus, particularly in the lymphoid organs, during this short period. Furthermore, the HIV-specific immunity initiated during this stage is associated with a dramatic decline in viremia11,12. However, this immunity is apparently inadequate to suppress viral replication completely, since HIV expression persists in lymph nodes even when plasma viremia is difficult to detect13 and HIV messenger RNA (mRNA) is virtually undetectable in peripheral-blood mononuclear cells13,14.

Detectable viremia declines markedly or disappears weeks to months after the acute syndrome subsides, and the change is temporally associated with the emergence of an HIV-specific immune response11,12. It is highly likely, however, that viral replication is never completely curtailed, since it is detectable in lymph nodes during apparently quiescent stages of infection13. Although a substantial percentage of patients with HIV infection do not have a clinically recognizable acute syndrome after primary infection, the events described above probably occur even in the absence of symptoms.

Clinical Latency

After primary infection, viral dissemination, the appearance of HIV-specific immunity, and the apparent curtailment of viral replication, most patients have a period of “clinical latency” that lasts for years5. The term clinical latency is misleading, however, since during this period virtually all patients have a gradual deterioration of the immune system, manifested particularly by the depletion of CD4 T cells2,5. Furthermore, although a patient always has many more infected cells that are not expressing detectable HIV mRNA or protein than cells in which viral expression is readily detected,15,16 there is probably never a true state of complete microbiologic latency (i.e., no viral expression) during the course of HIV infection.

The most obvious and quantifiable aspect of the deterioration that occurs during the clinically latent stage is the depletion of peripheral-blood CD4 T cells. Although this depletion may occur even without large increases in plasma concentrations of virus (as manifested by p24 antigenemia or culturable virus), viral replication in lymphoid organs, together with the spectrum of immunologic events that are directly or indirectly triggered by the virus, may contribute to it. Thus, HIV disease is clearly progressive during the so-called latent period.

Clinically Apparent Disease

The inevitable outcome of the progressive deterioration of the immune system that occurs in most patients with HIV infection is clinically apparent disease or an acquired immunodeficiency syndrome (AIDS)-defining illness, either severe and persistent constitutional signs and symptoms or an opportunistic infection or neoplasm5,17. Exceptions to the direct correlation between deteriorating immune function and clinically apparent disease are the progressive generalized lymphadenopathy that some patients have early in the course of infection and that may be caused by a vigorous immune response against HIV in the lymph nodes18; Kaposi's sarcoma, which can occur before the onset of severe immunosuppression19 and which may be influenced by a complex interplay of growth factors20-22; and neurologic disease that may reflect direct or indirect effects of the virus or its products on neurons and other cells of the nervous system23. The profound immunosuppression that occurs during this phase of HIV infection is the end stage of the immunopathogenic events that began at the time of primary infection, when the virus disseminated and seeded the lymphoid organs, and continued for years through the clinically latent but microbiologically active stages of infection.

IMMUNOPATHOGENIC MECHANISMS OF HIV INFECTION

Mechanisms of CD4 T-Lymphocyte Dysfunction

In patients with HIV infection, immunosuppression is due to quantitative as well as functional defects in CD4 T cells. The potential mechanisms of CD4 T-cell dysfunction are listed in Table 1TABLE 1Potential Mechanisms of the Functional and Quantitative Depletion of CD4 T Lymphocytes.. Several of these have been reviewed previously2 and will be discussed only briefly here. Other, more recently proposed mechanisms will be discussed in greater detail.

Single-Cell Killing and Syncytia Formation

In vitro single-cell killing and syncytia formation occur through direct HIV-mediated cytopathic effects24-26. Single-cell killing may result from the accumulation of unintegrated viral DNA or from the inhibition of cellular protein synthesis after HIV infection24. The formation of syncytia involves fusion of the cell membrane of an infected cell with the cell membranes of uninfected CD4 cells, which results in giant multinucleated cells. A direct relation between the presence of syncytia and the degree of the cytopathic effect of the virus in individual cells has been demonstrated in vitro,27 and HIV isolated during the accelerated phase of infection in vivo has a greater capacity to induce syncytia in vitro28. Syncytia have rarely been seen in vivo, however. In vitro, their formation may be regulated by the leukocyte adhesion molecule LFA-1 (lymphocyte-function-associated antigen 1) produced by human CD4 T lymphocytes inoculated with HIV27,29.

HIV-Specific Immune Responses

Both humoral and cellular immune responses contribute to antiviral immunity5. The major antiviral effects of antibodies are attributed to their neutralizing properties30. However, antibodies directed against some regions of the envelope of HIV may have an additional protective function related to their ability to mediate antibody-dependent cellular cytotoxicity after binding to natural killer cells,5leading to the killing of HIV-infected cells that express viral-envelope proteins on their surfaces. HIV-specific cytotoxic T lymphocytes may play an important part in the immune response against HIV, and they have been found in a substantial percentage of patients with HIV infection5,31-33. These mechanisms of immunity and the effector cells involved may have a dual role, however. The first is a protective role in the initial immune response to HIV infection, at which time these mechanisms may help to control or even clear the infection. The second is a pathogenic role during the chronic phase of infection, when the same mechanisms may be involved in the elimination of HIV-infected cells (i.e., CD4 T cells, follicular dendritic cells, and macrophages) and may thus contribute to the progressive deterioration of the immune system.

Autoimmune Mechanisms

Nonpolymorphic determinants of major-histocompatibility-complex (MHC) class II molecules, particularly HLA-DR and HLA-DQ, share some degree of structural homology with the gp120 and gp41 proteins of HIV type 1,34 and antibodies to these HIV proteins could therefore cross-react with HLA class II molecules. In fact, antibodies that react with class II molecules have been found in the serum of patients with HIV infection. These antibodies could prevent interaction between CD4 and class II molecules expressed on the antigen-presenting cells, thus impairing the cellular interaction required for efficient antigen presentation and inhibiting antigen-specific functions mediated by helper CD4 T cells34,35.

The hypothesis that gp120 functions as an “alloepitope”36,37 is also based on the homology between HLA-DR and HLA-DQ molecules and this HIV-envelope glycoprotein. It has been suggested that gp120 bound to the CD4 molecules of T cells may trigger a long-term allogeneic immune response. Both of these possibilities, however, need to be substantiated with more convincing experimental evidence before their role in the pathogenesis of HIV infection can be determined.

Anergy

Complexes of gp120 antigen and antibody bind to CD4 molecules, and the CD4 cells become refractory to further in vitro stimulation through the activation of their CD3 molecules38. Similarly, in vitro peripheral-blood mononuclear cells inoculated with HIV no longer respond to stimulation with anti-CD3 antibodies39. These findings led to the hypothesis that a negative signal is delivered to CD4 cells after their component CD4 molecules react with gp120 or gp120-anti-gp120 complexes. In this regard, anti-gp120 antibodies have recently been detected on CD4 T lymphocytes in patients with AIDS40.

Superantigens

Considerable attention has been given to the possibility that a superantigen, either retrovirally encoded or unrelated to HIV, may play an important part in the immunopathogenesis of HIV infection41. Superantigens are microbial or viral antigens that are capable of binding to nearly all T cells that have a specific variable region of the β chain of the T-cell antigen receptor (Figure 3FIGURE 3Recognition of Conventional Antigens and Superantigens by CD4 T Cells.). Unlike conventional antigenic peptides that bind in the groove of the MHC class II molecules, require interaction with specific variable components (variable α, joining α, variable β, diversity β, and joining β) of the α and β chains of the T-cell antigen receptor, and thus result in the stimulation of only a tiny fraction of T cells, superantigens bind only to the variable-β region of the T-cell antigen receptor. These superantigens therefore induce massive stimulation and expansion of T cells bearing the specific variable-β regions, followed by deletion or anergy42. The superantigen hypothesis regarding HIV infection stems from the observations that endogenous or exogenous retroviral-encoded superantigens stimulate murine CD4 T cells in vivo, leading to the anergy or deletion of a substantial percentage of CD4 T cells that have the specific variable-β regions43-57. In line with this hypothesis, there have been reports that patients with HIV infection have perturbations of T-cell subgroups bearing certain specific variable-β regions58,59. However, rather than cause deletions of specific subgroups of T cells, it is more likely that superantigens, if present in HIV infection, serve as potent activators of T cells, rendering them more susceptible to infection with the virus.

Apoptosis

Programmed cell death, or apoptosis, is a normal mechanism of cell death that was originally described in the context of the response of immature thymocytes to cellular activation60-62. It is a mechanism whereby the body eliminates autoreactive clones of T cells60-63. It has recently been suggested that both qualitative and quantitative defects in CD4 T cells in patients with HIV infection may be the result of activation-induced cell death or apoptosis64-67. Since apoptosis can be induced in mature murine CD4 T cells after cross-linking CD4 molecules to one another and triggering the T-cell antigen receptor,68 there has been speculation that cross-linking of the CD4 molecule by HIV gp120 or gp120-anti-gp120 immune complexes prepares the cell for the programmed death that occurs when an MHC class II molecule in complex with an antigen binds to the T-cell antigen receptor (Figure 4FIGURE 4Apoptosis (Programmed Cell Death) in HIV Infection.)66,67. Thus, the mere activation of a prepared cell by a specific antigen or superantigen could lead to the death of the cell, without direct infection by HIV. However, programmed cell death occurs spontaneously in vitro in the absence of an antigenic stimulus and occurs in CD8 cells69,70. If confirmed, the apoptosis hypothesis, like the superantigen hypothesis, would help explain the depletion of CD4 T cells without requiring that each depleted cell be infected with HIV.

INDUCTION OF HIV EXPRESSION

Although HIV in vitro can infect both resting and activated CD4 T cells equally well,71 its ability to replicate in T cells is strictly dependent on the state of activation of the cells71-73. Furthermore, efficient viral replication in monocytes or macrophages depends on both the activation and the differentiation states of these cells5. The role of these cells as reservoirs of HIV and as effectors of tissue damage in organs such as the brain has been reviewed elsewhere2,5,74.

Models of coinfection or simultaneous cotransfection of cells with HIV and other viruses have demonstrated that certain viruses, such as cytomegalovirus, herpes simplex virus, hepatitis B virus, human herpesvirus 6, and human T-cell lymphotropic virus type I can up-regulate the expression of HIV75. For the purpose of this discussion, viral expression refers to the production of viral mRNA or protein and may not reflect complete viral replication. In addition, the presence of other microbes, such as mycoplasma, may induce the expression of HIV76. Of particular relevance was the demonstration that a group of cytokines is capable of regulating the induction of HIV expression from the state of latent or chronic infection to active viral expression77. Many of the cytokines involved in the homeostatic regulation of the human immune response, such as interleukin-1, interleukin-3, interleukin-6, tumor necrosis factor (TNF)-α and TNF-β, interferon γ, granulocyte-macrophage colony-stimulating factor, and macrophage colony-stimulating factor, stimulate HIV replication in cell lines of monocyte-macrophage lineage with chronic infection and in primary cultures of cells of the same lineage75,77-80. In addition, TNF-α and TNF-β may induce the expression of HIV in T-cell lines with chronic infection75. In contrast, interferon alfa and interferon β exert a suppressive effect on HIV infection,81-85 as may interleukin-4 and transforming growth factor-β75,86-88. Since cytokines may be produced and may act locally in tissues, without entering the circulation, their plasma concentrations need not be elevated for them to have an important role in the modulation of HIV expression at the tissue level. The complex immunoregulatory network of cytokines that maintains immune homeostasis,75,77-79 even during states of apparent immunologic quiescence, may serve to sustain a constant level of viral expression, particularly in the lymph nodes (see below), throughout the prolonged course of infection.

ROLE OF THE LYMPHOID ORGANS IN HIV INFECTION

A number of recent studies have focused on the role of the lymphoid organs in the pathogenesis of HIV infection13,89-95. These organs may represent the major anatomical sites for the establishment as well as the short- and long-term propagation of HIV infection13,93. Although most studies necessarily focus on HIV infection of peripheral-blood mononuclear cells, the lymphocytes that are in the peripheral blood at any given time represent only about 2 percent of the total lymphocyte pool, most of which is in the lymphoid organs96. Hence, in certain pathologic processes involving lymphoid cells, the peripheral blood may not accurately reflect the status of disease. Furthermore, specific immune responses are generated predominantly in the lymphoid organs97 rather than in the peripheral blood.

The presence of HIV has been demonstrated in lymphoid organs by in situ hybridization95,98 and the polymerase chain reaction (PCR),93,94 but that does not mean that lymphoid organs are the preferential anatomical sites of HIV infection. A study using standard PCR to detect HIV DNA and reverse transcriptase PCR to detect HIV RNA found 5 to 10 times more HIV-infected cells93 and higher concentrations of both regulatory and structural mRNAs13 in the lymphoid organs (lymph nodes, adenoids, and tonsils) of a group of patients than in their peripheral blood. This viral burden in lymphoid organs is greater throughout the period of clinical latency13. In this regard, the assumptions that the body burden of HIV is very low and that HIV is latent during the long period of clinical latency, which are based on studies of peripheral blood, may not be correct.

The role of lymphoid organs as reservoirs of HIV infection has been confirmed by in situ hybridization95,98 and electron microscopy89,99. In early and intermediate disease, HIV particles in complex with antibodies and complement accumulate in lymph nodes, where they are trapped within the network of follicular dendritic cells in the germinal centers89,95,98-101. Follicular dendritic cells function during the normal immune response to trap antigens in the environment of the germinal center and to allow the presentation of antigen to competent immune cells102,103. This is an efficient natural means of initiating and propagating an appropriate immune response to antigenic challenge, be it microbial or environmental. At the early stage of HIV infection, only a few isolated cells in the lymph nodes have been found to be infected with HIV, predominantly CD4 T lymphocytes and rarely follicular dendritic cells, either in or outside the germinal centers95,98. In the advanced stages of infection, free viral particles are no longer detected in the lymphoid organs; HIV is detectable only in cells95 (and Pantaleo G: unpublished data). The progression of disease is temporally associated with the degeneration of the network of follicular dendritic cells and the loss of the ability of lymphoid organs to trap HIV particles, thus contributing to increased viremia (see below).

These observations have allowed the development of a hypothesis describing the role of lymphoid organs in the immunopathogenic mechanisms that propagate HIV infection (Figure 5FIGURE 5The Complex, Multifaceted Roles of the Lymphoid Organs in the Pathogenesis of HIV Disease.). After HIV enters through the circulation or mucosa, it is carried, like other invading microbes, to the regional lymph nodes. Primary infection results in an intense viremia that leads to the seeding of multiple lymph nodes, which causes detectable or subclinical lymphadenopathy,10-12 and the initiation of an HIV-specific immune response. Associated with this process is the nodal accumulation of CD4 T cells, either by in situ proliferation or migration to the lymph nodes. These cells are activated104 and can provide help for HIV-specific B-cell responses in the germinal centers105. This antigen-driven migration and concentration of CD4 T cells in the lymph nodes may contribute to the abrupt decline in the level of circulating CD4 T cells characteristic of the acute HIV syndrome10-12,106. Furthermore, the activated state of these cells facilitates their infection by the virus trapped in the lymph node, as well as the subsequent replication of virus within the cells. In this regard, a substantial proportion of CD4 T cells (25 to 50 percent) are activated in the lymph nodes of patients with HIV infection, as compared with a small percentage (5 to 10 percent) in the blood (Pantaleo G: unpublished data). Cytokines such as TNF-α that are released by activated germinal-center B cells may contribute to the induction of viral replication107. Thus, the microenvironment of the lymphoid organs is ideal for the initial establishment and propagation of HIV infection.

Down-regulation of viral replication in peripheral-blood mononuclear cells (Graziosi C: unpublished data) and a decrease in plasma viremia and p24 antigenemia11,12 generally signal the transition from the acute to the latent phase of HIV infection. However, HIV is concentrated in lymphoid organs and actively replicates during clinical latency13,93. The dichotomy between the absence of HIV in the peripheral blood and its presence in lymphoid organs is probably related to histopathologic alterations such as follicular hyperplasia and the expansion of the network of follicular dendritic cells,91,92,95,98,99,101 which may alter the circulatory kinetics of CD4 T cells, including those infected with HIV. Furthermore, HIV-infected cells may be unable to enter the circulation. The trapping of virus in lymph nodes (whether extracellularly or in T cells that cannot recirculate), the emergence of HIV-specific immunity, and the death of the initial pool of infected cells may explain the clearance of HIV particles and HIV-infected cells in the circulation during the prolonged period of clinical latency.

As the late stages of HIV disease evolve, the architecture of the lymph nodes is disrupted and the network of follicular dendritic cells dissolves, removing the trapping mechanisms for HIV virions, although HIV-infected CD4 T cells can still be identified95 (and Pantaleo G: unpublished data). HIV is thus free to recirculate, a finding that has been interpreted as a reflection of a massive increase in the total viral burden in late-stage disease. However, rather than a true increase in viral burden, these high levels of viremia in late-stage disease may reflect at least in part the recirculation of HIV particles removed from the constraints of lymph-node entrapment.

CONCLUSIONS

The immunopathogenic mechanisms of HIV infection are complex and not well understood. Although the clinical course is characterized by a prolonged period of latency after primary infection, HIV replication continues at high levels in the lymphoid organs during this period. Initial seeding of the lymphoid organs probably occurs during the period of viremia soon after primary infection and is often accompanied by an acute HIV syndrome. These early events probably play a critical part in determining the subsequent course of HIV disease. Peripheral-blood measurements do not accurately reflect the total-body burden of HIV infection; the lymphoid organs are the major reservoirs of virus and sites of viral replication. The mechanisms whereby individual CD4 cells are depleted are not entirely clear, and although HIV itself has a direct or indirect role in the cytopathic process, other mechanisms, such as apoptosis, inappropriate cell signaling, immune-mediated mechanisms, and superantigen stimulation, are being actively studied. Recognition of the critical nature of the events early in the course of infection as well as the role of the lymphoid organs in the evolution of HIV disease has important implications not only for a better understanding of the immunopathogenic mechanisms of HIV infection, but also in the design of therapy.

Sumber : http://www.nejm.org

HIV-AIDS

noreply@blogger.com (Rep Oi Tj) — Wed, 30 Jan 2013 20:56:00 +0000

HIV/AIDS

From Wikipedia, the free encyclopedia

This article is about the disease. For the virus, see HIV. For other uses, see AIDS (disambiguation).

HIV/AIDS
Classification and external resources
The red ribbon is a symbol for solidarity with HIV-positive people and those living with AIDS.
ICD-10	B 20 – B 24
ICD-9	042-044
OMIM	609423
DiseasesDB	5938
MedlinePlus	000594
eMedicine	emerg/253
MeSH	D000163

Human immunodeficiency virus infection / acquired immunodeficiency syndrome (HIV/AIDS) is

a disease of the human immune systemcaused by the human immunodeficiency virus (HIV).^[1] During the

initial infection a person may experience a brief period of influenza-like illness. This is typically followed by

a prolonged period without symptoms. As the illness progresses it interferes more and more with the immune

system, making the person much more likely to get infections, including opportunistic infections, and tumors

that do not usually affect people who have working immune systems.

HIV is transmitted primarily via unprotected sexual intercourse, (including anal and even oral sex),

contaminated blood transfusions, hypodermic needles, and from mother to child during pregnancy,

delivery, or breastfeeding.^[2] Some bodily fluids, such as saliva and tears, do not transmit HIV.^[3]

Prevention of HIV infection, primarily through safe sex and needle-exchange programs, is a key

strategy to control the spread of the disease.There is no cure or vaccine; however, antiretroviral treatment can slow

the course of the disease and may lead to a near-normal life expectancy. While antiretroviral treatment reduces the

risk of death and complications from the disease, these medications are expensive and may be associated with side effects.

Genetic research indicates that HIV originated in west-central Africa during the early twentieth

century.^[4] AIDS was first recognized by the Centers for Disease Control and Prevention (CDC)

in 1981 and its cause—HIV infection—was identified in the early part of the decade.^[5] Since its

discovery, AIDS has caused nearly 30 million deaths (as of 2009).^[6] As of 2010, approximately

34 million people have contracted HIV globally.^[7] AIDS is considered a pandemic—a disease

outbreak which is present over a large area and is actively spreading.^[8]

HIV/AIDS has had a great impact on society, both as an illness and as a source of discrimination.

The disease also has significant economic impacts. There are many misconceptions about HIV/AIDS
such as the belief that it can be transmitted by casual non-sexual contact. The disease has also become
subject to many controversies involving religion.

There are three main stages of HIV infection: acute infection, clinical latency and AIDS.^[9]^[10]

Acute infection

Main symptoms of acute HIV infection

The initial period following the contraction of HIV is called acute HIV, primary HIV or acute retroviral
syndrome.^[9]^[11] Many individuals develop an influenza-like illness or a mononucleosis-like illness 2–4
weeks post exposure while others have no significant symptoms.^[12]^[13]Symptoms occur in 40–90% of the cases and most commonly include fever, large tender lymph nodes, throat inflammation, a rash, headache, and/or sores of the mouth and genitals.^[11]^[13] The rash, which occurs in 20–50% of cases, presents itself on the trunk and is classicallymaculopapular.^[14] Some people also develop opportunistic infections at this stage.^[11] Gastrointestinal symptoms such as nausea, vomiting ordiarrhea may occur, as may neurological symptoms of peripheral neuropathy or Guillain-Barre syndrome.^[13] The duration of the symptoms varies, but is usually one or two weeks.^[13]

Due to their nonspecific character, these symptoms are not often recognized as signs of HIV infection. Even cases that do get seen by a family doctor or a hospital are often misdiagnosed as one of the many common infectious diseases with overlapping symptoms. Thus, it is recommended that HIV be considered in patients presenting an unexplained fever who may have risk factors for the infection.^[13]

Clinical latency

The initial symptoms are followed by a stage called clinical latency, asymptomatic HIV, or chronic HIV.^[10] Without treatment, this second stage of the natural history of HIV infection can last from about three years^[15] to over 20 years^[16] (on average, about eight years).^[17] While typically there are few or no symptoms at first, near the end of this stage many people experience fever, weight loss, gastrointestinal problems and muscle pains.^[10] Between 50 and 70% of people also develop persistent generalized lymphadenopathy, characterized by unexplained, non-painful enlargement of more than one group of lymph nodes (other than in the groin) for over three to six months.^[9]

Although most HIV-1 infected individuals have a detectable viral load and in the absence of treatment will eventually progress to AIDS, a small proportion (about 5%) retain high levels of CD4⁺ T cells (T helper cells) without antiretroviral therapy for more than 5 years.^[13]^[18] These individuals are classified as HIV controllers or long-term nonprogressors (LTNP), and those who also maintain a low or undetectable viral load without anti-retroviral treatment are known as "elite controllers" or "elite suppressors".^[18]

Acquired immunodeficiency syndrome

Main symptoms of AIDS.

Acquired immunodeficiency syndrome (AIDS) is defined in terms of either a CD4⁺ T cell count below 200 cells per µL or the occurrence of specific diseases in association with an HIV infection.^[13] In the absence of specific treatment, around half the people infected with HIV develop AIDS within ten years.^[13] The most common initial conditions that alert to the presence of AIDS are pneumocystis pneumonia (40%),cachexia in the form of HIV wasting syndrome (20%) and esophageal candidiasis.^[13] Other common signs include recurring respiratory tractinfections.^[13]

Opportunistic infections may be caused by bacteria, viruses, fungi and parasites that are normally controlled by the immune system.^[19]Which infections occur partly depends on what organisms are common in the person's environment.^[13] These infections may affect nearly every organ system.^[20]

People with AIDS have an increased risk of developing various viral induced cancers including: Kaposi's sarcoma, Burkitt's lymphoma, primary central nervous system lymphoma, and cervical cancer.^[14] Kaposi's sarcoma is the most common cancer occurring in 10 to 20% of people with HIV.^[21] The second most common cancer is lymphoma which is the cause of death of nearly 16% of people with AIDS and is the initial sign of AIDS in 3 to 4%.^[21] Both these cancers are associated with human herpesvirus 8.^[21] Cervical cancer occurs more frequently in those with AIDS due to its association with human papillomavirus (HPV).^[21]

Additionally, they frequently have systemic symptoms such as prolonged fevers, sweats (particularly at night), swollen lymph nodes, chills, weakness, and weight loss.^[22] Diarrhea is another common symptom present in about 90% of people with AIDS.^[23]

Transmission

Average per act risk of getting HIV
by exposure route to an infected source
Exposure Route	Chance of infection
Blood Transfusion	90% ^[24]
Childbirth (to child)	25%^[25]
Needle-sharing injection drug use	0.67%^[24]
Percutaneous needle stick	0.30%^[26]
Receptive anal intercourse^*	0.04–3.0%^[27]
Insertive anal intercourse^*	0.03%^[28]
Receptive penile-vaginal intercourse^*	0.05–0.30%^[27]^[29]
Insertive penile-vaginal intercourse^*	0.01–0.38% ^[27]^[29]
Receptive oral intercourse^*§	0–0.04% ^[27]
Insertive oral intercourse^*§	0–0.005%^[30]
^* assuming no condom use ^§ source refers to oral intercourse performed on a man

HIV is transmitted by three main routes: sexual contact, exposure to infected body fluids or tissues, and from mother to child during pregnancy, delivery, or breastfeeding (known as vertical transmission).^[2] There is no risk of acquiring HIV if exposed to feces, nasal secretions, saliva, sputum, sweat, tears, urine, or vomit unless these are contaminated with blood.^[26] It is possible to be co-infectedby more than one strain of HIV—a condition known as HIV superinfection.^[31]

Sexual

The most frequent mode of transmission of HIV is through sexual contact with an infected person.^[2] Worldwide, the majority of cases of transmission occur through heterosexual contacts (i.e. sexual contacts between people of the opposite sex).^[2] However, the pattern of transmission varies significantly between countries. In the United States, as of 2009, most sexual transmission occurred in men who have sex with men,^[2] with this population accounting for 64% of all new cases.^[32]

As regards unprotected heterosexual contacts, estimates of the risk of HIV transmission per sexual act appear to be four to ten times higher in low-income countries than in high-income countries.^[33] In low-income countries, the risk of female-to-male transmission is estimated as 0.38% per act, and of male-to-female transmission as 0.30% per act; the equivalent estimates for high-income countries are 0.04% per act for female-to-male transmission, and 0.08% per act for male-to-female transmission.^[33] The risk of transmission from anal intercourse is especially high, estimated as 1.4–1.7% per act in heterosexual as well as homosexual contacts.^[33]^[34] While the risk of transmission from oral sex is relatively low, it is still present.^[35] The risk from receiving oral sex has been described as "nearly nil"^[36] however a few cases have been reported.^[37] The per act risk is estimated at 0–0.04% for receptive oral intercourse.^[38] In settings involving commercial sex worldwide, risk of female-to-male transmission has been estimated as 2.4% per act and male-to-female transmission as 0.08% per act.^[33]

Risk of transmission increases in the presence of many sexually transmitted infections^[39] and genital ulcers.^[33] Genital ulcers appear to increase the risk approximately fivefold.^[33] Other sexually transmitted infections, such as gonorrhea, chlamydia,trichomoniasis, and bacterial vaginosis, are associated with somewhat smaller increases in risk of transmission.^[38]

The viral load of an infected person is an important risk factor in sexual as well as mother-to-child transmission.^[40] During the first 2.5 months of an HIV infection a person's infectiousness is twelve times higher due to this high viral load.^[38] If the person is in the late stages of infection, rates of transmission are approximately eightfold greater.^[33]

Rough sex can be a factor associated with an increased risk of transmission.^[41] Sexual assault is also believed to carry an increased risk of HIV transmission as condoms are rarely worn, physical trauma to the vagina or rectum is likely, and there may be a greater risk of concurrent sexually transmitted infections.^[42]

Body fluids

CDC poster from 1989 highlighting the threat of AIDS associated with drug use

The second most frequent mode of HIV transmission is via blood and blood products.^[2] Blood-borne transmission can be through needle-sharing during intravenous drug use, needle stick injury, transfusion of contaminated blood or blood product, or medical injections with unsterilised equipment. The risk from sharing a needle during drug injection is between 0.63 and 2.4% per act, with an average of 0.8%.^[43] The risk of acquiring HIV from a needle stick from an HIV-infected person is estimated as 0.3% (about 1 in 333) per act and the risk following mucus membrane exposure to infected blood as 0.09% (about 1 in 1000) per act.^[26] In the United States intravenous drug users made up 12% of all new cases of HIV in 2009,^[32] and in some areas more than 80% of people who inject drugs are HIV positive.^[2]

Blood transfusions with infected blood result in transmission of infection in about 93% of cases.^[43] In developed countries the risk of acquiring HIV from a blood transfusion is extremely low (less than one in half a million) where improved donor selection and HIV screening is performed.^[2] In the UK the risk is reported at one in five million.^[44] However, in low income countries only half of the blood used for transfusions may be appropriately screened (as of 2008).^[45] It is estimated that up to 15% of HIV infections in these areas come from transfusion of infected blood and blood products, representing between 5% and 10% of global infections.^[2]^[46]

Unsafe medical injections play a significant role in HIV spread in sub-Saharan Africa. In 2007, between 12 and 17% of infections in this region were attributed to medical syringe use.^[47] The World Health Organisation estimates the risk of transmission as a result of a medical injection in Africa at 1.2%.^[47] Significant risks are also associated with invasive procedures, assisted delivery, and dental care in this area of the world.^[47]

People giving or receiving tattoos, piercings, and scarification are theoretically at risk of infection but no confirmed cases have been documented.^[48] It is not possible for mosquitoes or other insects to transmit HIV.^[49]

Mother-to-child

HIV can be transmitted from mother to child during pregnancy, during delivery, or through breast milk.^[50]^[51] This is the third most common way way in which HIV is transmitted globally.^[2] In the absence of treatment, the risk of transmission before or during birth is around 20% and in those who also breastfeed 35%.^[50] As of 2008, vertical transmission accounted for about 90% of cases of HIV in children.^[50] With appropriate treatment the risk of mother-to-child infection can be reduced to about 1%.^[50] Preventive treatment involves the mother taking antiretroviral during pregnancy and delivery, an elective caesarean section, avoiding breastfeeding, and administering antiretroviral drugs to the newborn.^[52] Many of these measures are however not available in the developing world.^[52] If blood contaminates food during pre-chewing it may pose a risk of transmission.^[48]

Virology

Main article: HIV

A diagram showing the structure of HIV virus

HIV is the cause of the spectrum of disease known as HIV/AIDS. HIV is a retrovirus that primarily infects components of the human immune systemsuch as CD4⁺ T cells, macrophages and dendritic cells. It directly and indirectly destroys CD4⁺ T cells.^[53]

HIV is a member of the genus Lentivirus,^[54] part of the family of Retroviridae.^[55] Lentiviruses share many morphological and biological characteristics. Many species of mammals are infected by lentiviruses, which are characteristically responsible for long-duration illnesses with a long incubation period.^[56] Lentiviruses are transmitted as single-stranded, positive-sense, enveloped RNA viruses. Upon entry into the target cell, the viral RNA genomeis converted (reverse transcribed) into double-stranded DNA by a virally encoded reverse transcriptase that is transported along with the viral genome in the virus particle. The resulting viral DNA is then imported into the cell nucleus and integrated into the cellular DNA by a virally encoded integrase and host co-factors.^[57] Once integrated, the virus may become latent, allowing the virus and its host cell to avoid detection by the immune system.^[58]Alternatively, the virus may be transcribed, producing new RNA genomes and viral proteins that are packaged and released from the cell as new virus particles that begin the replication cycle anew.^[59]

Two types of HIV have been characterized: HIV-1 and HIV-2. HIV-1 is the virus that was originally discovered (and initially referred to also as LAV or HTLV-III). It is more virulent, more infective,^[60] and is the cause of the majority of HIV infections globally. The lower infectivity of HIV-2 as compared with HIV-1 implies that fewer people exposed to HIV-2 will be infected per exposure. Because of its relatively poor capacity for transmission, HIV-2 is largely confined to West Africa.^[61]

Pathophysiology

Main article: Pathophysiology of HIV/AIDS

Scanning electron micrograph of HIV-1, colored green, budding from a culturedlymphocyte.

After the virus enters the body there is a period of rapid viral replication, leading to an abundance of virus in the peripheral blood. During primary infection, the level of HIV may reach several million virus particles per milliliter of blood.^[62] This response is accompanied by a marked drop in the number of circulating CD4⁺ T cells. The acute viremia is almost invariably associated with activation of CD8⁺ T cells, which kill HIV-infected cells, and subsequently with antibody production, or seroconversion. The CD8⁺ T cell response is thought to be important in controlling virus levels, which peak and then decline, as the CD4⁺ T cell counts recover. A good CD8⁺ T cell response has been linked to slower disease progression and a better prognosis, though it does not eliminate the virus.^[63]

The pathophysiology of AIDS is complex.^[64] Ultimately, HIV causes AIDS by depleting CD4⁺ T cells. This weakens the immune system and allowsopportunistic infections. T cells are essential to the immune response and without them, the body cannot fight infections or kill cancerous cells. The mechanism of CD4⁺ T cell depletion differs in the acute and chronic phases.^[65] During the acute phase, HIV-induced cell lysis and killing of infected cells by cytotoxic T cells accounts for CD4⁺ T cell depletion, although apoptosis may also be a factor. During the chronic phase, the consequences of generalized immune activation coupled with the gradual loss of the ability of the immune system to generate new T cells appear to account for the slow decline in CD4⁺ T cell numbers.^[66]

Although the symptoms of immune deficiency characteristic of AIDS do not appear for years after a person is infected, the bulk of CD4⁺ T cell loss occurs during the first weeks of infection, especially in the intestinal mucosa, which harbors the majority of the lymphocytes found in the body.^[67] The reason for the preferential loss of mucosal CD4⁺ T cells is that the majority of mucosal CD4⁺ T cells express the CCR5 protein which HIV uses as a co-receptor to gain access to the cells, whereas only a small fraction of CD4⁺ T cells in the bloodstream do so.^[68]

HIV seeks out and destroys CCR5 expressing CD4⁺ T cells during acute infection.^[69] A vigorous immune response eventually controls the infection and initiates the clinically latent phase. CD4⁺ T cells in mucosal tissues remain particularly affected.^[69] Continuous HIV replication results in a state of generalized immune activation persisting throughout the chronic phase.^[70] Immune activation, which is reflected by the increased activation state of immune cells and release of pro-inflammatory cytokines, results from the activity of several HIV gene products and the immune response to ongoing HIV replication. It is also linked to the breakdown of the immune surveillance system of the gastrointestinal mucosal barrier caused by the depletion of mucosal CD4⁺ T cells during the acute phase of disease.^[71]

Diagnosis

Main article: Diagnosis of HIV/AIDS

A generalized graph of the relationship between HIV copies (viral load) and CD4⁺ T cell counts over the average course of untreated HIV infection.

CD4⁺ T Lymphocyte count (cells/mm³) HIV RNA copies per mL of plasma

HIV/AIDS is diagnosed via laboratory testing and then staged based on the presence of certain signs or symptoms.^[11] HIV testing is recommended for all those at high risk, which includes anyone diagnosed with a sexually transmitted illness.^[14] In many areas of the world a third of HIV carriers only discover they are infected at an advanced stage of the disease when AIDS or severe immunodeficiency has become apparent.^[14]

HIV testing

Most people infected with HIV develop specific antibodies (i.e. seroconvert) within three to twelve weeks of the initial infection.^[13]Diagnosis of primary HIV before seroconversion is done by measuring HIV-RNA or p24 antigen.^[13] Positive results obtained by antibody orPCR testing are confirmed either by a different antibody or by PCR.^[11]

Antibody tests in children younger than 18 months are typically inaccurate due to the continued presence of maternal antibodies.^[72] Thus HIV infection can only be diagnosed by PCR testing for HIV RNA or DNA, or via testing for the p24 antigen.^[11] Much of the world lacks access to reliable PCR testing and many places simply wait until either symptoms develop or the child is old enough for accurate antibody testing.^[72] In sub-Saharan Africa as of 2007–2009 between 30–70% of the population was aware of their HIV status.^[73] In 2009 between four and 42% of the population was tested.^[73] These figures represent substantial increases from ten years previous.^[73]

Classifications of HIV infection

Two main clinical staging systems are used to classify HIV and HIV-related disease for surveillance purposes: the WHO disease staging system for HIV infection and disease,^[11] and the CDC classification system for HIV infection.^[74] The CDC's classification system is more frequently adopted in developed countries. Since the WHO's staging system does not require laboratory tests, it is suited to the resource-restricted conditions encountered in developing countries, where it can also be used to help guide clinical management. Despite their differences, the two systems allow comparison for statistical purposes.^[9]^[11]^[74]

The World Health Organization first proposed a definition for AIDS in 1986.^[11] Since then, the WHO classification has been updated and expanded several times, with the most recent version being published in 2007.^[11] The WHO system uses the following categories:

Primary HIV infection: May be either asymptomatic or associated with acute retroviral syndrome.^[11]
Stage I: HIV infection is asymptomatic with a CD4⁺ T cell count (also known as CD4 count) greater than 500/uL.^[11] May include generalized lymph node enlargement.^[11]
Stage II: Mild symptoms which may include minor mucocutaneous manifestations and recurrent upper respiratory tract infections. A CD4 count of less than 500/uL.^[11]
Stage III: Advanced symptoms which may include unexplained chronic diarrhea for longer than a month, severe bacterial infections including tuberculosis of the lung as well as a CD4 count of less than 350/uL.^[11]
Stage IV or AIDS: severe symptoms which includes toxoplasmosis of the brain, candidiasis of the esophagus, trachea, bronchi or lungs and Kaposi's sarcoma. A CD4 count of less than 200/uL.^[11]

The United States Center for Disease Control and Prevention also created a classification system for HIV, and updated it in 2008.^[74] In this system HIV infections are classified based on CD4 count and clinical symptoms,^[74] and describes the infection in three stages:

Stage 1: CD4 count ≥ 500 cells/uL and no AIDS defining conditions
Stage 2: CD4 count 200 to 500 cells/uL and no AIDS defining conditions
Stage 3: CD4 count ≤ 200 cells/uL or AIDS defining conditions
Unknown: if insufficient information is available to make any of the above classifications

For surveillance purposes, the AIDS diagnosis still stands even if, after treatment, the CD4⁺ T cell count rises to above 200 per µL of blood or other AIDS-defining illnesses are cured.^[9]

Prevention

Main article: Prevention of HIV/AIDS

AIDS Clinic, McLeod Ganj, Himachal Pradesh, India, 2010

Sexual contact

Consistent condom use reduces the risk of HIV transmission by approximately 80% over the long term.^[75] When one partner of a couple is infected, consistent condom use results in rates of HIV infection for the uninfected person of below 1% per year.^[76] There is some evidence to suggest thatfemale condoms may provide an equivalent level of protection.^[77] Application of a vaginal gel containing tenofovir (a reverse transcriptase inhibitor) immediately before sex seems to reduce infection rates by approximately 40% among African women.^[78] By contrast, use of the spermicide nonoxynol-9 may increase the risk of transmission due to its tendency to cause vaginal and rectal irritation.^[79] Circumcision in Sub-Saharan Africa "reduces the acquisition of HIV by heterosexual men by between 38% and 66% over 24 months".^[80] Based on these studies, the World Health Organization and UNAIDS both recommended male circumcision as a method of preventing female-to-male HIV transmission in 2007.^[81] Whether it protects against male-to-female transmission is disputed^[82]^[83] and whether it is of benefit in developed countries and among men who have sex with men is undetermined.^[84]^[85]^[86] Some experts fear that a lower perception of vulnerability among circumcised men may result in more sexual risk-taking behavior, thus negating its preventive effects.^[87] Women who have undergone female genital cutting have an increased risk of HIV.^[88]

Programs encouraging sexual abstinence do not appear to affect subsequent HIV risk.^[89] Evidence for a benefit from peer education is equally poor.^[90]Comprehensive sexual education provided at school may decrease high risk behavior.^[91] A substantial minority of young people continues to engage in high-risk practices despite knowing about HIV/AIDS, underestimating their own risk of becoming infected with HIV.^[92] It is not known if treating other sexually transmitted infections is effective in preventing HIV.^[39]

Pre-exposure

Treating people with HIV whose CD4 count ≥ 350cells/µL with antiretrovirals protects 96% of their partners from infection.^[93] Pre-exposure prophylaxis with a daily dose of the medicationstenofovir, with or without emtricitabine, is effective in a number of groups including: men who have sex with men, couples where one is HIV positive, and young heterosexuals in Africa.^[78]

Universal precautions within the health care environment are believed to be effective in decreasing the risk of HIV.^[94] Intravenous drug use is an important risk factor and harm reduction strategies such as needle-exchange programmes and opioid substitution therapy appear effective in decreasing this risk.^[95]^[96]

Post-exposure

A course of antiretrovirals administered within 48 to 72 hours after exposure to HIV positive blood or genital secretions is referred to as post-exposure prophylaxis.^[97] The use of the single agentzidovudine reduces the risk of subsequent HIV infection fivefold following a needle stick injury.^[97] Treatment is recommended after sexual assault when the perpetrator is known to be HIV positive but is controversial when their HIV status is unknown.^[98] Current treatment regimes typically use lopinavir/ritonavir and lamivudine/zidovudine or emtricitabine/tenofovir and may decrease the risk further.^[97] The duration of treatment is usually four weeks^[99] and is frequently associated with adverse effects (with zidovudine in about 70% of cases, including nausea in 24%, fatigue in 22%, emotional distress in 13%, and headaches in 9%).^[26]

Mother-to-child

Programs to prevent the vertical transmission of HIV (from mothers to children) can reduce rates of transmission by 92–99%.^[50]^[95] This primarily involves the use of a combination of antiviral medications during pregnancy and after birth in the infant and potentially includes bottle feeding rather than breastfeeding.^[50]^[100] If replacement feeding is acceptable, feasible, affordable, sustainable, and safe, mothers should avoid breastfeeding their infants; however exclusive breastfeeding is recommended during the first months of life if this is not the case.^[101] If exclusive breastfeeding is carried out, the provision of extended antiretroviral prophylaxis to the infant decreases the risk of transmission.^[102]

Vaccination

As of 2012 there is no effective vaccine for HIV or AIDS.^[103] A single trial of the vaccine RV 144 published in 2009 found a partial reduction in the risk of transmission of roughly 30%, stimulating some hope in the research community of developing a truly effective vaccine.^[104] Further trials of the RV 144 vaccine are ongoing.^[105]^[106]

Management

Main article: Management of HIV/AIDS

There is currently no cure or effective HIV vaccine. Treatment consists of high active antiretroviral therapy (HAART) which slows progression of the disease^[107] and as of 2010 more than 6.6 million people were taking them in low and middle income countries.^[7] Treatment also includes preventative and active treatment of opportunistic infections.

Antiviral therapy

Abacavir – a nucleoside analog reverse transcriptase inhibitor (NARTI or NRTI)

Current HAART options are combinations (or "cocktails") consisting of at least three medications belonging to at least two types, or "classes," ofantiretroviral agents.^[108] Initially treatment is typically a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside analogue reverse transcriptase inhibitors (NRTIs).^[108] Typical NRTIs include: zidovudine (AZT) or tenofovir (TDF) and lamivudine (3TC) or emtricitabine (FTC).^[108]Combinations of agents which include a protease inhibitors (PI) are used if the above regime loses effectiveness.^[108]

When to start antiretroviral therapy is subject to debate.^[14]^[109] Both the World Health Organization, European guidelines and the United States recommends antiretrovirals in all adolescents, adults and pregnant women with a CD4 count less than 350/uL or those with symptoms regardless of CD4 count.^[14]^[108] This is supported by the fact that beginning treatment at this level reduces the risk of death.^[110] The United States in addition recommends them for all HIV-infected people regardless of CD4 count or symptoms, however makes this recommendation with less confidence for those with higher counts.^[111] While the WHO also recommends treatment in those who are co-infected with tuberculosis and those with chronic activehepatitis B.^[108] Once treatment is begun it is recommended that it is continued without breaks or "holidays".^[14] Many people are diagnosed only after the moment treatment ideally should have begun.^[14] The desired outcome of treatment is a long term plasma HIV-RNA count below 50 copies/mL.^[14]Levels to determine if treatment is effective are initially recommended after four weeks and once levels fall below 50 copies/mL checks every three to six months are typically adequate.^[14] Inadequate control is deemed to be greater than 400 copies/mL.^[14] Based on these criteria treatment is effective in more than 95% of people during the first year.^[14]

Benefits of treatment include a decreased risk of progression to AIDS and a decreased risk of death.^[112] In the developing world treatment also improves physical and mental health.^[113] With treatment there is a 70% reduced risk of acquiring tuberculosis.^[108] Additional benefits include a decreased risk of transmission of the disease to sexual partners and a decrease in mother-to-child transmission.^[108] The effectiveness of treatment depends to a large part on compliance.^[14] Reasons for non-adherence include: poor access to medical care,^[114] inadequate social supports, mental illness and drug abuse.^[115] As well the complexity of treatment regimens (due to pill numbers and dosing frequency) and adverse effectsmay create intentional non-adherence.^[116] Adherence is however just as good in low income as high income countries.^[117]

Specific adverse events are related to the agent taken.^[118] Some relatively common ones include: lipodystrophy syndrome, dyslipidemia, and diabetes mellitus especially with protease inhibitors.^[9] Other common symptoms include: diarrhea,^[118]^[119] and an increased risk of cardiovascular disease.^[120] Adverse effects are however less with some of the newer recommended treatments.^[14] Cost may be an issue with some medications being expensive^[121] however as of 2010, 47% of those who needed them were taking them in low and middle income countries.^[7]Certain medications may be associated with birth defects and thus not suitable for women hoping to have children.^[14]

Treatment recommendations for children are slightly different from those for adults. In the developing world, as of 2010, 23% of children who were in need of treatment had access.^[122] Both the World Health Organization and the United States recommend treatment for all children less than twelve months of age.^[123]^[124] The United States recommends in those between one year and five years of age treatment in those with HIV RNA counts of greater than 100,000 copies/mL, and in those more than five years treatments when CD4 counts are less than 500/ul.^[123]

Opportunistic infections

Measures to prevent opportunistic infections are effective in many people with HIV/AIDS. Treatment with antivirals often improves current, as well as decreases the risk of future, opportunistic infections.^[118] Vaccination against hepatitis A and B is advised for all people at risk of HIV before they become infected however may also be given after infection.^[125]Trimethoprim/sulfamethoxazole prophylaxis between four to six weeks of age and finishing breastfeeding in infants born to HIV positive mothers is recommended in resource limited settings.^[122] It is also recommended to prevent PCP when peoples' CD4 count is below 200 cells/uL and in those who have or have previously had PCP.^[126] People with substantial immunosuppression are also advised to receive prophylactic therapy for toxoplasmosis and Cryptococcus meningitis.^[127] Appropriate preventive measures have reduced the rate of these infections by 50% between 1992 and 1997.^[128]

Alternative medicine

In the US, approximately 60% of people with HIV use various forms of complementary or alternative medicine.^[129] The effectiveness of most of these therapies however has not been established.^[130] With respect to dietary advice and AIDS some evidence has shown a benefit from micronutrient supplements.^[131] Evidence for supplementation with selenium is mixed with some tentative evidence of benefit.^[132] There is some evidence that vitamin A supplementation in children reduces mortality and improves growth.^[131] In Africa in nutritionally compromised pregnant and lactating women a multivitamin supplementation has improved outcomes for both mothers and children.^[131] Dietary intake of micronutrients at RDA levels by HIV-infected adults is recommended by the World Health Organization.^[133]^[134] The WHO further states that several studies indicate that supplementation of vitamin A, zinc, and iron can produce adverse effects in HIV positive adults.^[134] There is not enough evidence to support the use of herbal medicines.^[135]

Prognosis

Disability-adjusted life year for HIV and AIDS per 100,000 inhabitants as of 2004.

no data

≤ 10

10–25

25–50

50–100

100–500

500–1000

1000–2500

2500–5000

5000–7500

7500-10000

10000-50000

≥ 50000

HIV/AIDS has become a chronic rather than an acutely fatal disease in many areas of the world.^[136] Prognosis varies between people, and both the CD4 count and viral load are useful for predicted outcomes.^[13] Without treatment, average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype.^[137] After the diagnosis of AIDS, if treatment is not available, survival ranges between 6 and 19 months.^[138]^[139] HAART and appropriate prevention of opportunistic infections reduces the death rate by 80%, and raises the life expectancy for a newly diagnosed young adult to 20–50 years.^[136]^[140]^[141] This is between two thirds^[140] and nearly that of the general population.^[14]^[142] If treatment is started late in the infection prognosis is not as good,^[14] for example if treatment is begun following the diagnosis of AIDS life expectancy is ~10–40 years.^[14]^[136] Half of infants born with HIV die before two years of age without treatment.^[122]

The primary causes of death from HIV/AIDS are opportunistic infections and cancer, both of which are frequently the result of the progressive failure of the immune system.^[128]^[143] Risk of cancer appears to increase once the CD 4 count gets below 500/uL.^[14] The rate of clinical disease progression varies widely between individuals and has been shown to be affected by a number of factors such as a person's susceptibility and immune function;^[144]their access to health care and the presence of co-infections;^[138]^[145] as well as the particular strain (or strains) of the virus involved.^[146]^[147]

Tuberculosis co-infection is one of the leading causes of sickness and death in those with HIV/AIDS being present in a third of all HIV infected people and resulting in 25% of HIV related deaths.^[148] HIV is also the most important risk factors for tuberculosis.^[149] Hepatitis C is another very common co-infection where each disease increases the progression of the other.^[150] The two most common cancers associated with HIV/AIDS are Kaposi's sarcoma and AIDS-related non-Hodgkin's lymphoma.^[143]

Even with anti-retroviral treatment, over the long term HIV-infected people may experience neurocognitive disorders,^[151] osteoporosis,^[152]neuropathy,^[153] cancers,^[154]^[155] nephropathy,^[156] and cardiovascular disease.^[119] It is not clear whether these conditions result from the HIV infection itself or are adverse effects of treatment.

Epidemiology

Main article: Epidemiology of HIV/AIDS

Estimated prevalence of HIV among young adults (15–49) per country as of 2011.^[157]

HIV/AIDS is a global pandemic.^[158] As of 2010 approximately 34 million people have HIV worldwide.^[7] Of these approximately 16.8 million are women and 3.4 million are less than 15 years old.^[7] It resulted in about 1.8 million death in 2010, down from 3.1 million in 2001.^[7]

Sub-Saharan Africa is the region most affected. In 2010, an estimated 68% (22.9 million) of all HIV cases and 66% of all deaths (1.2 million) occurred in this region.^[159] This means that about 5% of the adult population is infected^[160] and it is believed to be the cause of 10% of all deaths in children.^[161]Here in contrast to other regions women compose nearly 60% of cases.^[159] South Africa has the largest population of people with HIV of any country in the world at 5.9 million.^[159] Life expectancy has fallen in the worst-affected countries due to HIV/AIDS; for example, in 2006 it was estimated that it had dropped from 65 to 35 years in Botswana.^[8]

South & South East Asia is the second most affected; in 2010 this region contained an estimated 4 million cases or 12% of all people living with HIV resulting in approximately 250,000 deaths.^[160] Approximately 2.4 million of these cases are in India.^[159] Prevalence is lowest in Western and Central Europe at 0.2% and East Asia at 0.1%.^[160]

In 2008 in the United States approximately 1.2 million people were living with HIV, resulting in about 17,500 deaths. The Centre for Disease Control and Prevention estimated that in 2008 20% of infected Americans were unaware of their infection.^[162] In the United Kingdom as of 2009 there where approximately 86,500 cases which resulted in 516 deaths.^[163] In Canada as of 2008 there were about 65,000 cases which results in 53 deaths.^[164] Between the first recognition of AIDS in 1981 and 2009 it has led to nearly 30 million deaths.^[6]

History

Main article: History of HIV/AIDS

Discovery

AIDS was first clinically observed in 1981 in the United States.^[21] The initial cases were a cluster of injecting drug users and homosexual men with no known cause of impaired immunity who showed symptoms of Pneumocystis carinii pneumonia (PCP), a rare opportunistic infection that was known to occur in people with very compromised immune systems.^[165] Soon thereafter, an unexpected number of gay men developed a previously rare skin cancer called Kaposi's sarcoma (KS).^[166]^[167] Many more cases of PCP and KS emerged, alerting U.S. Centers for Disease Control and Prevention (CDC) and a CDC task force was formed to monitor the outbreak.^[168]

In the early days, the CDC did not have an official name for the disease, often referring to it by way of the diseases that were associated with it, for example, lymphadenopathy, the disease after which the discoverers of HIV originally named the virus.^[169]^[170] They also used Kaposi's Sarcoma and Opportunistic Infections, the name by which a task force had been set up in 1981.^[171] At one point, the CDC coined the phrase "the 4H disease", since the syndrome seemed to affect Haitians, homosexuals, hemophiliacs, and heroin users.^[172] In the general press, the term "GRID", which stood for gay-related immune deficiency, had been coined.^[173] However, after determining that AIDS was not isolated to the gay community,^[171] it was realized that the term GRID was misleading and the term AIDS was introduced at a meeting in July 1982.^[174] By September 1982 the CDC started referring to the disease as AIDS.^[175]

Robert Gallo, co-discoverer of HIV in the early eighties among (from left to right) Sandra Eva, Sandra Colombini, and Ersell Richardson.

In 1983, two separate research groups led by Robert Gallo and Luc Montagnier independently declared that a novel retrovirus may have been infecting AIDS patients, and published their findings in the same issue of the journal Science.^[176]^[177] Gallo claimed that a virus his group had isolated from an AIDS patient was strikingly similar in shape to other human T-lymphotropic viruses (HTLVs) his group had been the first to isolate. Gallo's group called their newly isolated virus HTLV-III. At the same time, Montagnier's group isolated a virus from a patient presenting with swelling of the lymph nodes of the neck and physical weakness, two characteristic symptoms of AIDS. Contradicting the report from Gallo's group, Montagnier and his colleagues showed that core proteins of this virus were immunologically different from those of HTLV-I. Montagnier's group named their isolated virus lymphadenopathy-associated virus (LAV).^[168] As these two viruses turned out to be the same, in 1986, LAV and HTLV-III were renamed HIV.^[178]

Origins

Both HIV-1 and HIV-2 are believed to have originated in non-human primates in West-central Africa and were transferred to humans in the early 20th century.^[4] HIV-1 appears to have originated in southern Cameroon through the evolution of SIV(cpz), a simian immunodeficiency virus (SIV) that infects wild chimpanzees (HIV-1 descends from the SIVcpz endemic in the chimpanzee subspecies Pan troglodytes troglodytes).^[179]^[180] The closest relative of HIV-2 is SIV(smm), a virus of the sooty mangabey (Cercocebus atys atys), an Old World monkey living in litoral West Africa (from southern Senegalto western Côte d'Ivoire).^[61] New World monkeys such as the owl monkey are resistant to HIV-1 infection, possibly because of a genomic fusion of two viral resistance genes.^[181] HIV-1 is thought to have jumped the species barrier on at least three separate occasions, giving rise to the three groups of the virus, M, N, and O.^[182]

There is evidence that humans who participate in bushmeat activities, either as hunters or as bushmeat vendors, commonly acquire SIV.^[183] However, SIV is a weak virus which is typically suppressed by the human immune system within weeks of infection. It is thought that several transmissions of the virus from individual to individual in quick succession are necessary to allow it enough time to mutate into HIV.^[184] Furthermore, due to its relatively low person-to-person transmission rate, SIV can only spread throughout the population in the presence of one or more of high-risk transmission channels, which are thought to have been absent in Africa prior to the 20th century.

Specific proposed high-risk transmission channels, allowing the virus to adapt to humans and spread throughout the society, depend on the proposed timing of the animal-to-human crossing. Genetic studies of the virus suggest that the most recent common ancestor of the HIV-1 M group dates back to circa 1910.^[185] Proponents of this dating link the HIV epidemic with the emergence of colonialism and growth of large colonial African cities, leading to social changes, including a higher degree of sexual promiscuity, the spread of prostitution, and the accompanying high frequency of genital ulcer diseases (such as syphilis) in nascent colonial cities.^[186] While transmission rates of HIV during vaginal intercourse are low under regular circumstances, they are increased many fold if one of the partners suffers from an sexually transmitted infection resulting in genital ulcers. Early 1900s colonial cities were notable due to their high prevalence of prostitution and genital ulcers, to the degree that, as of 1928, as many as 45% of female residents of eastern Kinshasa were thought to have been prostitutes, and, as of 1933, around 15% of all residents of the same city were infected by one of the forms of syphilis.^[186]

An alternative view holds that unsafe medical practices in Africa during years following World War II, such as unsterile reuse of single use syringes during mass vaccination, antibiotic and anti-malaria treatment campaigns, were the initial vector that allowed the virus to adapt to humans and spread.^[184]^[187]^[188]

The earliest well documented case of HIV in a human dates back to 1959 in the Congo.^[189] The virus may have been present in the United States as early as 1966,^[190] but the vast majority of infections occurring outside sub-Saharan Africa (including the U.S.) can be traced back to a single unknown individual who got infected with HIV in Haiti and then brought the infection to the United States some time around 1969.^[191] The epidemic then rapidly spread among high-risk groups (initially, sexually promiscuous men who have sex with men). By 1978, the prevalence of HIV-1 among gay male residents of New York and San Francisco was estimated at 5%, suggesting that several thousand individuals in the country had been infected.^[191]

Society and culture

Stigma

Ryan White became a poster child for HIV after being expelled from school because he was infected.

Main article: Discrimination against people with HIV/AIDS

AIDS stigma exists around the world in a variety of ways, including ostracism, rejection, discrimination and avoidance of HIV infected people; compulsory HIV testing without prior consent or protection of confidentiality; violence against HIV infected individuals or people who are perceived to be infected with HIV; and thequarantine of HIV infected individuals.^[192] Stigma-related violence or the fear of violence prevents many people from seeking HIV testing, returning for their results, or securing treatment, possibly turning what could be a manageable chronic illness into a death sentence and perpetuating the spread of HIV.^[193]

AIDS stigma has been further divided into the following three categories:

Instrumental AIDS stigma—a reflection of the fear and apprehension that are likely to be associated with any deadly and transmissible illness.^[194]
Symbolic AIDS stigma—the use of HIV/AIDS to express attitudes toward the social groups or lifestyles perceived to be associated with the disease.^[194]
Courtesy AIDS stigma—stigmatization of people connected to the issue of HIV/AIDS or HIV- positive people.^[195]

Often, AIDS stigma is expressed in conjunction with one or more other stigmas, particularly those associated with homosexuality, bisexuality, promiscuity, prostitution, and intravenous drug use.^[196]

In many developed countries, there is an association between AIDS and homosexuality or bisexuality, and this association is correlated with higher levels of sexual prejudice such as anti-homosexual/bisexual attitudes.^[197] There is also a perceived association between AIDS and all male-male sexual behavior, including sex between uninfected men.^[194] However, the dominant mode of spread worldwide for HIV remains heterosexual transmission.^[198]

Economic impact

Main articles: Economic impact of HIV/AIDS and Cost of HIV treatment

Changes in life expectancy in some hard-hit African countries.

Botswana Zimbabwe Kenya South Africa Uganda

HIV/AIDS affects the economics of both individuals and countries.^[161] The gross domestic product of the most affected countries have decreased due to the lack of human capital.^[161]^[199] Without proper nutrition, health care and medicine, large numbers of people die from AIDS-related complications. They will not only be unable to work, but will also require significant medical care. It is estimated that as of 2007 there where 12 million AIDS orphans.^[161] Many are cared for by elderly grandparents.^[200]

By affecting mainly young adults, AIDS reduces the taxable population, in turn reducing the resources available for public expenditures such as education and health services not related to AIDS resulting in increasing pressure for the state's finances and slower growth of the economy. This results in a slower growth of the tax base, an effect that is reinforced if there are growing expenditures on treating the sick, training (to replace sick workers), sick pay and caring for AIDS orphans. This is especially true if the sharp increase in adult mortality shifts the responsibility and blame from the family to the government in caring for these orphans.^[200]

At the household level, AIDS results in both the loss of income but also increased spending on healthcare. A study in Côte d'Ivoire showed that households with an HIV/AIDS patient, spent twice as much on medical expenses as other households. This additional expenditure also leaves less income to spend on education and other personal or family investment.^[201]

Religion and AIDS

Main article: Religion and HIV/AIDS

The topic of religion and AIDS has become highly controversial in the past twenty years, primarily because some religious authorities have publicly declared their opposition to the use of condoms.^[202]^[203] The religious approach to prevent the spread of AIDS according to a report by American health expert Matthew Hanley titled The Catholic Church and the Global Aids Crisis argues that cultural changes are needed including a re-emphasis on fidelity within marriage and sexual abstinence outside of it.^[203]

Some religious organisations have claimed that prayer can cure HIV/AIDS. In 2011, the BBC reported that some churches in London were claiming that prayer would cure AIDS, and the Hackney-based Centre for the Study of Sexual Health and HIV reported that several people stopped taking their medication, sometimes on the direct advice of their pastor, leading to a number of deaths.^[204] The Synagogue Church Of All Nations advertise an "anointing water" to promote God's healing, although the group deny advising people to stop taking medication.^[204]

Media portrayal

Main article: Media portrayal of HIV/AIDS

One of the first high profile cases of AIDS was the American Rock Hudson, a gay actor who had been married and divorced earlier in life, who died on 2 October 1985 having announced that he was suffering from the virus on 25 July that year. He had been diagnosed during 1984.^[205] A notable British casualty of AIDS that year was Nicholas Eden, a gay politician and son of the late prime minister Anthony Eden.^[206] On November 24, 1991, the virus claimed the life of British rock star Freddie Mercury, lead singer of the band Queen, who died from an AIDS related illness having only revealed the diagnosis on the previous day.^[207] However he had been diagnosed as HIV positive during 1987.^[208] One of the first high profile heterosexual cases of the virus was Arthur Ashe, the American tennis player. He was diagnosed as HIV positive on 31 August 1988, having contracted the virus from blood transfusions during heart surgery earlier in the 1980s. Further tests within 24 hours of the initial diagnosis revealed that Ashe had AIDS, but he did not tell the public about his diagnosis until April 1992.^[209] He died, aged 49, as a result on 6 February 1993.^[210]

Therese Frare's photograph of gay activist David Kirby, as he lay dying from AIDS while surrounded by family, was taken in April 1990. LIFE magazine said the photo became the one image "most powerfully identified with the HIV/AIDS epidemic." The photo was displayed in LIFE magazine, was the winner of the World Press Photo, and acquired worldwide notoriety after being used in aUnited Colors of Benetton advertising campaign in 1992.^[211] Andy Lippincott's death from AIDS in the comic strip Doonesbury on May 24, 1990, ran on the obituary page of the The San Francisco Chronicle, and Andy also received a square in the NAMES Project AIDS Memorial Quilt.^[212]

Denial, conspiracies, and misconceptions

Main articles: AIDS denialism and Misconceptions about HIV/AIDS

A small group of individuals continue to dispute the connection between HIV and AIDS,^[213] the existence of HIV itself, or the validity of HIV testing and treatment methods.^[214]^[215] These claims, known as AIDS denialism, have been examined and rejected by the scientific community.^[216] However, they have had a significant political impact, particularly in South Africa, where the government's official embrace of AIDS denialism (1999-2005) was responsible for its ineffective response to that country's AIDS epidemic, and has been blamed for hundreds of thousands of avoidable deaths and HIV infections.^[217]^[218]^[219] Operation INFEKTION was a worldwide Soviet active measures operation to spread information that the United States had created HIV/AIDS. Surveys show that a significant number of people believed – and continue to believe – in such claims.^[220]

There are many misconceptions about HIV and AIDS. Three of the most common are that AIDS can spread through casual contact, that sexual intercourse with a virgin will cure AIDS, and that HIV can infect only homosexual men and drug users. Other misconceptions are that any act of anal intercourse between two uninfected gay men can lead to HIV infection, and that open discussion of homosexuality and HIV in schools will lead to increased rates of homosexuality and AIDS.^[221]^[222]

Research

"AIDS research" redirects here. For the journal formerly known as AIDS Research, see AIDS Research and Human Retroviruses.

Research to improve current treatments includes decreasing side effects of current drugs, further simplifying drug regimens to improve adherence, and determining better sequences of regimens to manage drug resistance. However, only a vaccine is thought to be able to halt the pandemic. This is because a vaccine would cost less, thus being affordable for developing countries, and would not require daily treatment.^[223] However, after over 20 years of research, HIV-1 remains a difficult target for a vaccine,^[223]^[224] and there is as yet no cure.

Stem cell transplantation

In 2007, Timothy Ray Brown,^[225] a 40-year-old HIV-positive man, also known as "the Berlin Patient", was given a stem cell transplant as part of his treatment for acute myeloid leukemia(AML).^[226] A second transplant was made a year later after a relapse. The donor was chosen not only for genetic compatibility but also for being homozygous for a CCR5-Δ32 mutation that confers resistance to HIV infection.^[227]^[228] After 20 months without antiretroviral drug treatment, it was reported that HIV levels in Brown's blood, bone marrow, and bowel were below the limit of detection.^[228] The virus remained undetectable over three years after the first transplant.^[226] Although the researchers and some commentators have characterized this result as a cure, others suggest that the virus may remain hidden in tissues^[229] such as the brain (which acts as a viral reservoir).^[230] Stem cell treatment remains investigational because of its anecdotal nature, the disease and mortality risk associated with stem cell transplants, and the difficulty of finding suitable donors.^[229]^[231]

Immunomodulatory agents

Complementing efforts to control viral replication, immunotherapies that may assist in the recovery of the immune system have been explored in past and ongoing trials, including IL-2 and IL-7.^[232]

The failure of vaccine candidates to protect against HIV infection and progression to AIDS has led to a renewed focus on the biological mechanisms responsible for HIV latency. A limited period of therapy combining anti-retrovirals with drugs targeting the latent reservoir may one day allow for total eradication of HIV infection.^[233] Researchers have discovered an abzyme that can destroy the protein gp120 CD4 binding site. This protein is common to all HIV variants as it is the attachment point for B lymphocytes and subsequent compromising of the immune system.

Sumber : www.wikipedia.org/

dangers of smoking

noreply@blogger.com (Rep Oi Tj) — Wed, 30 Jan 2013 20:46:00 +0000

Natural News) Shocking new research reveals that a specific type of lung cancer many smokers develop comes from tiny tears in their lung tissue caused by microscopic glass fibers, also known as glass wool, found in many conventional cigarette filters. These rips in the epithelial (soft) tissue fuel the development of tumors and cancerous cells due to the constant overload of toxins, namely pesticides, nicotine and ammonia, contained in commercial cigarette smoke.

The filters of typical commercial cigarettes contain microscopic, needle-shaped shards of glass wool (like fiberglass insulation) which escape into the mouth and throat, and then lodge with tobacco tar in the lung tissue, surrounding the alveoli (tiny air sacs) and lead to COPD (chronic obstructive pulmonary disease), emphysema and eventually lung cancer.

A physician's assistant (PA) and an intensive care nurse at a major hospital reviewed the damaged lung tissue of several cigarette smokers and said the x-rays looked identical to those of patients exposed to asbestos, and that diagnostic imaging revealed what looked like "ground glass" which settled in the soft tissue near the bottom of the lungs (GGO - ground glass opacity). The interviewed nurse said, "When lung tissue is damaged over and over, it develops lesions, and the cancer plants itself in there like seeds." (http://www.appliedradiology.com)

According to the PA, the tiny shards penetrate the "lipid bilayer, then embed in the lung tissue, causing the tissue to harden and eventually lose its ability to absorb oxygen." This damage fuels the development of the same type of lung cancer (mesothelioma) associated with asbestos poisoning. He also explained how smoking destroys the cilia (tiny hairs) that help push excretions/mucus out, and how when smokers sleep, their breathing patterns relax and the "tar deposits creep in on damaged air sacs called blebs, eventually rupturing and collapsing them." This is why when smokers awake in the morning they can experience unproductive coughing fits and/or bronchial spasms.

(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1766058/)

Why Fiberglass?

The cigarette filter (butt) acts as a buffer from the extreme heat of the cigarette's burning chemicals, which can exceed 1700 degrees Fahrenheit during inhale. Fibrous glass has the heat-resistant qualities of asbestos, which makes it an efficient material for insulation; however, if you've ever been in an attic and got insulation on your skin, you already know how irritating the glass fiberscan be, so now imagine what it's doing to the inside of a smoker's lungs.

Up to 12,000 microscopic glass fibers are tightly bound together, which explains why filters take between 10 to 15 years to disintegrate. If the filter were simply cotton rolled tightly in paper, a few rainstorms would break it up and wash it away within weeks. Filters are also constructed to catch the tar and the tobacco particles from coming through, but not entirely.

Although fiberglass is not the same as asbestos, it can be just as damaging to the human body. The long, very narrow fibers penetrate deep into lung tissue and remain there. One study conducted with rats showed that fibrous glass is a potent carcinogen, leading to changes in the DNA genetic structure and breaking down the immune system. This is one reason smoker's fight colds, the flu, sinus and bronchial infections for much longer periods of time than non-smokers. (http://tpx.sagepub.com/content/19/4-1/482.full.pdf)

60 years of BIG LIES from BIG TOBACCO

Independent studies reveal that commercial cigarettes with defective filters have been marketed for over 60 years. Mesothelioma, a deadly cancer that develops in the protective lining of the lungs, abdomen, and/or the cavity around the heart, is most commonly associated with asbestos poisoning, but now research reveals that more than 10% of those cases are now associated with cigarette smokers with NO history of exposure to asbestos.

The tobacco industry has been negligent in failing to perform toxicological examinations to assess human health risks from inhaling and ingesting these synthetic micro-particles released from conventional cigarette filters. The recent "warning ads" about the effects of smoking are not educational, nor do they help smokers understand strategies for cessation at all. The $54 million campaign full of "stark and graphic advertisements" is nothing more than a ploy to pretend like the U.S. Center for Disease Control (CDC) is trying to help with this massive, preventable health crisis. (http://www.cnn.com)

Thanks to absolutely no regulations regarding the ingredients used for manufacturing cigarettes, smokers are susceptible to multiple forms of lung disease, including desquamative interstitial pneumonitis from ground glass infiltration of the soft tissues, bronchoalveolar cell carcinoma, and pulmonary fibrosis, which are all revealed from specific lung biopsies (HR-CT scans). (http://www.radiologyassistant.nl/en/42459cff38f02)

Since the U.S. government doesn't help smokers quit, who does?

Once a smoker realizes what they've really got themselves into, they can prepare physically and mentally for quitting. 14AndOut is a 60 minute video download which addresses all angles of the smoking addiction, including chemical addiction, behavioral habits, and nutrition for cleansing the lungs and blood. No other program is so unique that fully addresses replenishing nutrientsthat have been severely depleted by the 4,000 commercial cigarette chemicals. A preview trailer and testimonials are available at the following link: (http://premium.naturalnews.tv/14AndOut__TV.htm)

14AndOut is a holistic program which is comprehensive and inexpensive, and teaches the smoker how to wean his/herself off cigarettes entirely in 14 days or less. The short course explains how smokers who have switched to e-cigs are still damaging their liver and kidneys by ingesting nicotine, which is the main chemical that feeds the vicious cycle of the smoking addiction. If you're a smoker with a deep desire to escape the nicotine prison, 14AndOut is the way to extend your life.

Sumber : http://www.naturalnews.com/

Terjadi Kecelakaan di daerah Bawen - semarang

noreply@blogger.com (Rep Oi Tj) — Mon, 28 Jan 2013 21:05:00 +0000

Pagi tadi tepatnya tgl 28-01-2013 telah terjadi kecelakaan di jalur bawen - semarang antara tiga buah kendaraan bermotor, yaitu truk bermuatan barang styrofoam, truk pasir, dan mobil kijang, ini menyebabkan jalur solo-semarang, yogyakarta-semarang macet total sampai kurang lebih 5 km beberapa saat (lebih dari 3 jam).Ini disebabkan pada esok pagi jalan sedang rame-ramenya orang akan pergi beraktivitas, dan sedang dilakukannya evakuasi terhadap mobil dan korban.

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PEDIATRIC CLINIC DONATION AND ANNOUNCEMENT FOR NEW CHARITY CAMPAIGN 'BE MY FRIEND'

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dangers of smoking

Why Fiberglass?

60 years of BIG LIES from BIG TOBACCO

Since the U.S. government doesn't help smokers quit, who does?

Terjadi Kecelakaan di daerah Bawen - semarang