Health and Environmental Illness Research

Links for 2011-05-19 [del.icio.us]

2011-05-20T00:00:00-07:00

Downregulation of BDNF mRNA in the Hippocampal Dentate Gyrus after Re-exposure to Cues Previously Associated with Footshock
Ann M. Rasmusson, Libin Shi, Ronald Duman
Neuropsychopharmacology (2002), pp. 133-142.
BEYOND INSULIN RESISTANCE AND SYNDROME X: The Oxidative-Dysoxygenative Insulin Dysfunction (ODID) Model
Majid
Chemiluminescence assay of mucosal reactive oxygen metabolites in inflammatory bowel disease.
N. J. Simmonds, R. E. Allen, T. R. Stevens, R. N. Van Someren, D. R. Blake, D. S. Rampton
Gastroenterology (1992)
Obesity, Insulin Resistance, Diabetes, and Cardiovascular Risk in Children
Julia, Stephen
Circulation, Vol. 107 (2003), pp. 1448-1453.
Long-term down-regulation of BDNF mRNA in rat hippocampal CA1 subregion correlates with PTSD-like behavioural stress response.
Nitsan Kozlovsky, Michael A. Matar, Zeev Kaplan, Moshe Kotler, Joseph Zohar, Hagit Cohen
The international journal of neuropsychopharmacology (10 February 2007)
Caffeic acid phenethyl ester inhibits nuclear factor-κB and protein kinase B signalling pathways and induces caspase-3 expression in primary human CD4<sup>+</sup> T cells
L. C. Wang, K. H. Chu, Y. C. Liang, Y. L. Lin, B. L. Chiang
Clinical & Experimental Immunology, Vol. 9999, No. 9999. (2010)

Caffeic acid phenethyl ester (CAPE), an active component in propolis, is known to have anti-tumour, anti-inflammatory and anti-oxidant properties. In this study, the effects of CAPE on the functions of primary human CD4+ T cells were evaluated in vitro. CAPE significantly suppressed interferon (IFN)-03B3 and interleukin (IL)-5 production and proliferation of CD4+ T cells stimulated by soluble anti-CD3 and anti-CD28 monoclonal antibodies in both healthy subjects and asthmatic patients. CAPE inhibited nuclear factor (NF)-03BAB activation and protein kinase B (Akt) phosphorylation, but not p38 mitogen-activated protein kinase (MAPK) phosphorylation in T cells. CAPE also induced active caspase-3 expression in CD4+ T cells; CCR4+CD4+ T cells were more sensitive to CAPE induction than CXCR3+CD4+ T cells. Together, these results indicate that CAPE inhibits cytokin..
DIFFERENTIATION OF CA1 CELL ELEMENTS IN RAT HIPPOCAMPUS ONTOGENESIS
Hana Brichová
Biomed. Papers, Vol. 148, No. 2. (2004), pp. 199-200.
Hippocampal Functions in Post-traumatic Stress Disorder
Darren Weber
Genetic Variation in the Peroxisome Proliferator-Activated Receptor-{gamma}2 Gene (Pro12Ala) Affects Metabolic Responses to Weight Loss and Subsequent Weight Regain
Barbara J. Nicklas, Elisabeth F. van Rossum, Dora M. Berman, Alice S. Ryan, Karen E. Dennis, Alan R. Shuldiner
Diabetes, Vol. 50, No. 9. (1 September 2001), pp. 2172-2176.

This study determined the effects of the peroxisome proliferator-activated receptor (PPAR)-{gamma}2 Pro12Ala variant on body composition and metabolism and the magnitude of weight regain in 70 postmenopausal women (BMI 25-40 kg/m2) who completed 6 months of a hypocaloric diet. At baseline, BMI, percent body fat, intra-abdominal and subcutaneous abdominal fat areas, resting metabolic rate, substrate oxidation, and postprandial glucose and insulin responses were not different between genotypes (Pro/Pro = 56, Pro/Ala and Ala/Ala = 14). The intervention similarly decreased body weight by 8 {+/-} 1% in women homozygous for the Pro allele and by 7 {+/-} 1% in women with the Ala allele (P < 0.0001). Fat oxidation did not change in Pro/Pro women but decreased 19 {+/-} 9% in women with the Ala allele (P < 0.05). Changes in..
Hydrogen sulfide from adipose tissue is a novel insulin resistance regulator.
X. Feng, Y. Chen, J. Zhao, C. Tang, Z. Jiang, B. Geng
Biochemical and biophysical research communications, Vol. 380, No. 1. (27 February 2009), pp. 153-159.

Recent data suggested that endogenous hydrogen sulfide (H(2)S) contributes to the pathogenesis of diabetes. Here, we identified that cystathionine gamma lyase (CSE) was expressed in adipose tissue in rats and endogenously generated H(2)S. The CSE/H(2)S system exists in both rat adipocytes and pre-adipocytes. This system was up-regulated with aging, although a high level of glucose down-regulated the system in a concentration- and time-dependent manner. H(2)S inhibited the basal and insulin-stimulated glucose uptake of mature adipocytes, whereas administration of CSE inhibitors enhanced the glucose uptake of adipocytes. The PI3K but not K(ATP) channel pathway is involved in the inhibitory effect of H(2)S on glucose uptake. Finally, in fructose-induced diabetes in rats, we confirmed the up-regulated CSE/H(2)S system in adipose tis..
Adipose tissue-specific PPARγ deficiency increases resistance to oxidative stress
Weijia Luoa, Jin Caoa, Jie Lia, Weimin He
Experimental Gerontology, Vol. 43, No. 3. (March 2008), pp. 154-163.

The nuclear hormone receptor peroxisome proliferator activated receptor gamma (PPARγ) critically regulates adipogenesis and lipogenesis. Obesity is closely associated with increased oxidative stress, and pharmacological activation of PPARγ by its ligands significantly suppresses oxidative stress in cultured adipocytes. On the other hand, a PPARγ2Pro12Ala polymorphism, which decreases receptor transcription activity, is associated with lower body mass index and increased insulin sensitivity in humans. This mutation is also found to be positively associated with increased human lifespan. Here we show that adipose tissue-specific PPARγ heterozygous mice, which exhibit significant improvement in insulin sensitivity in skeletal muscle, show increased resistance to paraquat-induced oxidative stress. The enhanced oxidative stress tolerance is associated with significant upregulati..
Regulation of PPAR gamma gene expression by nutrition and obesity in rodents.
A. Vidal-Puig, M. Jimenez-Liñan, B. B. Lowell et al.
The Journal of clinical investigation, Vol. 97, No. 11. (1 June 1996), pp. 2553-2561.

The orphan nuclear receptor, peroxisome proliferator-activated receptor (PPAR) gamma, is implicated in mediating expression of fat-specific genes and in activating the program of adipocyte differentiation. The potential for regulation of PPAR gamma gene expression in vivo is unknown. We cloned a partial mouse PPAR gamma cDNA and developed an RNase protection assay that permits simultaneous quantitation of mRNAs for both gamma l and gamma 2 isoforms encoded by the PPAR gamma gene. Probes for detection of adipocyte P2, the obese gene product, leptin, and 18S mRNAs were also employed. Both gamma l and gamma 2 mRNAs were abundantly expressed in adipose tissue. PPAR gamma 1 expression was also detected at lower levels in liver, spleen, and heart; whereas, gamma l and gamma 2 mRNA were expressed at low levels in skeletal muscle. Adipose tissue levels o..
Stress-Induced Changes in Hippocampal Functions
Marian Joels, Harm Krugers, Henk Karst
Ronald (Eds)
In Stress Hormones and Post Traumatic Stress Disorder: Basic Studies and Clinical Perspectives (2007)
In Vivo Response to [agr]1-Adrenoreceptor Stimulation in Human White Adipose Tissue
Michael Boschmann, Gotz Krupp, Friedrich C. Luft, Susanne Klaus, Jens Jordan
Obesity, Vol. 10, No. 6. (June 2002), pp. 555-558.
An overlooked connection: serotonergic mediation of estrogen-related physiology and pathology
Leszek A. Rybaczyk, Meredith J. Bashaw, Dorothy R. Pathak, Scott M. Moody, Roger M. Gilders, Donald L. Holzschu
BMC Women's Health, Vol. 5 (20 December 2005), 12.

Links for 2011-05-18 [del.icio.us]

2011-05-19T00:00:00-07:00

Obstructions for quality care experienced by patients with chronic fatigue syndrome (CFS)--A case study
Ann M. Gilje, Atle Söderlund, Kirsti Malterud
Patient Education and Counseling, Vol. 73, No. 1. (October 2008), pp. 36-41.

Objective To explore obstructions for quality care from experiences by patients suffering from chronic fatigue syndrome (CFS).Methods Qualitative case study with data drawn from a group meeting, written answers to a questionnaire and a follow-up meeting. Purposeful sample of 10 women and 2 men of various ages, recruited from a local patient organization, assumed to have a special awareness for quality care.Results CFS patients said that lack of acknowledgement could be even worse than the symptoms. They wanted their doctors to ask questions, listen to them and take them seriously, instead of behaving degrading. Many participants felt that the doctors psychologized too much, or trivialized the symptoms. Participants described how doctors' lack of knowledge about the condition would lead to long-term uncertainty or maltreatment. Even with doctors who were supporti..
Plasma Vitamin C Level, Fruit and Vegetable Consumption, and the Risk of New-Onset Type 2 Diabetes Mellitus
Anne-Helen, Sheila, Kaytee, Robert, Ailsa, Nita
Arch Intern Med, Vol. 168, No. 14. (2008), pp. 1493-1499.

Background Epidemiologic studies suggest that greater consumption of fruit and vegetables may decrease the risk of diabetes mellitus, but the evidence is limited and inconclusive. Plasma vitamin C level is a good biomarker of fruit and vegetable intake, but, to our knowledge, no prospective studies have examined its association with diabetes risk. This study aims to examine whether fruit and vegetable intake and plasma vitamin C level are associated with the risk of incident type 2 diabetes.

Methods We administered a semiquantitative food frequency questionnaire to men and women from a population-based prospective cohort (European Prospective Investigation of Cancer–Norfolk) study who were aged 40 to 75 years at baseline (1993-1997) when plasma vitamin C level was determined and habitual intake of fruit and vegetables was assessed. During 12 years of follow-up between F..
Invited Commentary: Physical Activity and Vitamin D
Fraser Birrell, Roger M. Francis
Am. J. Epidemiol., Vol. 168, No. 6. (15 September 2008), pp. 587-589.

Exercise and vitamin D are both important for musculoskeletal health. In this issue of the Journal, Scragg and Camargo (Am J Epidemiol 2008;168:577-86) provide a new analysis of relatively old data on physical activity and vitamin D from the Third National Health and Nutrition Examination Survey (1988-1994). This commentary considers the methodological strengths and weaknesses of the study and concludes that the findings are as robust as could reasonably be expected from a cross-sectional design. Consideration is given to whether outdoor exercise is the cause of higher vitamin D levels and, if so, whether mortality gains may accrue from more widespread participation. A note of caution is sounded, given the disappointing results on studies of the prevention of falls and fractures with vitamin D supplementation in community-dwelling populations. However, this is an important observat..
EGCG Inhibits Proliferation of Cardiac Fibroblasts in Rats with Cardiac Hypertrophy
Rui Sheng, Zhen-Lun Gu1, Mei-Lin Xie, Wen-Xuan Zhou, Ci-Yi Guo
Planta Med :, Vol. 10.1055/s-0028-1088387
Iron and calcium in the central nervous system: a close relationship in health and sickness.
Ilaria Pelizzoni, Romina Macco, Daniele Zacchetti, Fabio Grohovaz, Franca Codazzi
Biochemical Society transactions, Vol. 36, No. 6. (1 December 2008), pp. 1309-1312.

Iron and calcium are required for general cellular functions, as well as for specific neuronal-related activities. However, a pathological increase in their levels favours oxidative stress and mitochondrial damage, leading to neuronal death. Neurodegeneration can thus be determined by alterations in ionic homoeostasis and/or pro-oxidative-antioxidative equilibrium, two conditions that vary significantly in different kinds of brain cell and also with aging. In the present review, we re-evaluate recent data on NTBI (non-transferrin bound iron) uptake that suggest a strict interplay with the mechanisms of calcium control. In particular, we focus on the use of common entry pathways and on the way cytosolic calcium can modulate iron entry and determine its intracellular accumulation....
Interferon-{alpha}-induced serotonin uptake in Jurkat T cells via mitogen-activated protein kinase and transcriptional regulation of the serotonin transporter
Chiung-Wen Tsao, Yee-Shin Lin, Juei-Tang Cheng et al.
J Psychopharmacol (16 April 2008), 0269881107082951.

Interferon (IFN)-{alpha} upregulates serotonin (5-HT) uptake and serotonin transporter (5-HTT) messenger ribonucleic acid (mRNA) expression in immune cells, which implies the mechanism underlying IFN-{alpha}-induced depression. However, the signal transduction of this effect remains unclear. We investigated whether the effects of IFN-{alpha} on the functions of 5-HTT were related to mitogen-activated protein kinase (MAPK). By performing Western blotting, real-time reverse transcriptase-polymerase chain reaction and [3H]5-HT labelling, we examined MAPK phosphorylation, 5-HTT mRNA expression and 5-HT uptake in Jurkat T cells. The cells had been cultured for different time periods (1) with IFN-{alpha} alone and (2) preincubated with either MAPK inhibitors or with the selective serotonin reuptake inhibitor, fluoxetine, and subsequently cultured along with IFN-{alpha}. The..
Insulin Regulation in AhR-null Mice: Embryonic Cardiac Enlargement, Neonatal Macrosomia, and Altered Insulin Regulation and Response in Pregnant and Aging AhR-null Females
E. A. Thackaberry, E. J. Bedrick, M. B. Goens et al.
Toxicol. Sci., Vol. 76, No. 2. (1 December 2003), pp. 407-417.

The aryl hydrocarbon receptor (AhR) was originally characterized because of its high affinity binding of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin. However, studies using AhR-null mice have demonstrated the importance of this protein in normal physiology and development. Here we demonstrate that AhR-null embryos develop cardiac enlargement, and that this phenotype is dependent, at least in part, on the maternal genotype. Neonates born to AhR-null females had increased heart weights regardless of the neonatal genotype, an outcome also observed in gestational diabetes. The cardiac hypertrophy markers, beta-myosin heavy chain and atrial natriuretic factor, and the cardiac proliferative index were increased in AhR-null embryos, indicating that the cardiac enlargement is associated with myocyte hypertrophy and hyperplasia, which begin prior to birth. Importantly, two- to three..
Role of transition metals in the pathogenesis of amyotrophic lateral sclerosis.
Willianne I M I. Vonk, Leo W J W. Klomp
Biochemical Society transactions, Vol. 36, No. 6. (1 December 2008), pp. 1322-1328.

ALS (amyotrophic lateral sclerosis) is a devastating progressive neurodegenerative disorder resulting in selective degeneration of motor neurons in brain and spinal cord and muscle atrophy. In approx. 2% of all cases, the disease is caused by a mutation in the Cu,Zn-superoxide dismutase (SOD1) gene. The transition metals zinc and copper regulate SOD1 protein stability and activity, and disbalance of the homoeostasis of these metals has therefore been implicated in the pathogenesis of ALS. Recent data strengthen the hypothesis that these transition metals are excellent potential targets to develop an effective therapy for ALS....
OXIDATIVE STRESS IN METABOLIC SYNDROME
Praveen Sharma, Sandhya Mishra, Peeyush Ajmera, Sandeep Mathur
Indian Journal of Clinical Biochemistry, Vol. 20, No. 1. (2005), pp. 145-149.
IGF-1 protects intestinal epithelial cells from oxidative stress-induced apoptosis.
N. Baregamian, J. Song, M. G. Jeschke, B. M. Evers, D. H. Chung
The Journal of surgical research, Vol. 136, No. 1. (November 2006), pp. 31-37.

BACKGROUND: Reactive oxygen species (ROS) are involved in the pathogenesis of necrotizing enterocolitis (NEC) in premature infants. We have recently found that activation of multiple cellular signaling transduction pathways occurs during ROS-induced intestinal cell apoptosis; the phosphatidylinositol 3-kinase (PI3-K) pathway plays an anti-apoptotic role during this process. Insulin-like growth factor (IGF)-1 activates PI3-K pathway to promote cell survival; however, the effects of IGF-1 treatment during gut injury are not clearly defined. The purpose of this study was to determine whether IGF-1 protects intestinal cells from ROS-induced apoptosis. MATERIALS AND METHODS: Rat intestinal epithelial (RIE)-1 cells were treated with either IGF-1 (100 nm), hydrogen peroxide (H2O2; 500 microm), or combination. Western blotting was performed to assess..
Fibromyalgia in diabetes mellitus.
M. Tishler, T. Smorodin, M. Vazina-Amit, Y. Ramot, M. Koffler, B. Fishel
Rheumatology international, Vol. 23, No. 4. (July 2003), pp. 171-173.

OBJECTIVE: The aim of this study was to evaluate the prevalence of fibromyalgia (FM) in patients with diabetes mellitus (DM). SUBJECTS: The study included 100 consecutive unselected patients with DM attending our diabetes clinic. Patients were divided into two groups: 45 patients with type 1 diabetes and 55 patients with type 2 diabetes. A group of 50 healthy hospital staff members served as controls. The FM was diagnosed according to the 1990 American College of Rheumatology criteria. Counts of 18 tender points were performed by thumb palpation and assessed by dolorimeter. Routine biochemical tests and levels of HbA(1c) were recorded in each patient. RESULTS: The main outcome measure was the association of FM with DM. Fibromyalgia was diagnosed in 17 patients (17%) with DM and in only one (2%) healthy control ( P=0.008). No differences in pa..
Hypothalamo-Pituitary-Adrenal Axis Dysfunction in Chronic Fatigue Syndrome, and the Effects of Low-Dose Hydrocortisone Therapy
A. J. Cleare, J. Miell, E. Heap et al.
J Clin Endocrinol Metab, Vol. 86, No. 8. (1 August 2001), pp. 3545-3554.

These neuroendocrine studies were part of a series of studies testing the hypotheses that 1) there may be reduced activity of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome and 2) low-dose augmentation with hydrocortisone therapy would improve the core symptoms. We measured ACTH and cortisol responses to human CRH, the insulin stress test, and D-fenfluramine in 37 medication-free patients with CDC-defined chronic fatigue syndrome but no comorbid psychiatric disorders and 28 healthy controls. We also measured 24-h urinary free cortisol in both groups. All patients (n = 37) had a pituitary challenge test (human CRH) and a hypothalamic challenge test [either the insulin stress test (n = 16) or D-fenfluramine (n = 21)]. Baseline cortisol concentrations were significantly raised in the chronic fatigue syndrome group for the human CRH test only. Baseline ACT..
Polyphenols restore endothelial function in DOCA-salt hypertension: role of endothelin-1 and NADPH oxidase.
R. Jiménez, R. López-Sepúlveda, M. Kadmiri et al.
Free radical biology & medicine, Vol. 43, No. 3. (1 August 2007), pp. 462-473.

Red wine polyphenols (RWPs) have been reported to exert beneficial effects in preventing cardiovascular diseases, such as hypertension. We studied the effects of chronic treatment with RWPs and apocynin, an inhibitor of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, on blood pressure, endothelial function, and oxidative status in deoxycorticosterone acetate (DOCA)-salt-induced hypertension. Rats were administered RWPs (40 mg/kg) or apocynin (33 microg/kg) daily by gavage for 5 weeks. Plasma catechin levels were detected only after RWP treatment. RWPs and apocynin prevented both the increase in systolic blood pressure and the proteinuria induced by DOCA-salt. Plasma malonyldialdehyde levels, urinary iso-prostaglandin F(2alpha) excretion, aortic superoxide production, and aortic NADPH oxidase activity were found to be increased in anima..
Superoxide dismutase 1 (SOD1) is essential for H2O2-mediated oxidation and inactivation of phosphatases in growth factor signaling
Jose C. Juarez, Mari Manuia, Mark E. Burnett et al.
PNAS (20 May 2008)
Antinociceptive effect of chronic lithium on visceral hypersensitivity in a rat model of diarrhea-predominant irritable bowel syndrome: The role of nitric oxide pathway
Hosein Shamshiri, Pedram Paragomi, Mehrak J. Paydar et al.
Journal of Gastroenterology and Hepatology, Vol. 9999, No. 9999. (2008)

Background and Aim: Lithium, a widely used drug in bipolar-affective disorders, plays gastro-protective roles. The effects of lithium on several tissues are mediated through nitric oxide (NO), which regulates gastrointestinal motility and mucosal integrity. The aim of this study was to investigate the protective effect of chronic lithium administration on visceral hypersensitivity and to investigate the role of NO as a potential mechanism of lithium in a rat model of irritable bowel syndrome.Methods: Colitis was induced by the intracolonic administration of acetic acid. After subsidence of inflammation on the seventh experimental day, nociception and defecation parameters were measured. A subgroup of animals had been pretreated with lithium carbonate (600 mg/L) for 35 days. Thereafter, either a non-selective NO synthase (NOS) inhibitor (N-nitro-L-argini..

Links for 2011-05-17 [del.icio.us]

2011-05-18T00:00:00-07:00

Transient receptor potential TRPA1 channel desensitization in sensory neurons is agonist dependent and regulated by TRPV1-directed internalization
Akopian, N. Armen, Ruparel et al.
The Journal of Physiology, Vol. 583, No. 1. (August 2007), pp. 175-193.
Protease-activated Receptor 2 sensitizes the capsaicin receptor transient receptor potential vanilloid receptor 1 to induce hyperalgesia.
Silvia Amadesi, Jingjiang Nie, Nathalie Vergnolle et al.
Journal of Neuroscience, Vol. 24, No. 18. (5 May 2004)

Inflammatory proteases (mast cell tryptase and trypsins) cleave protease-activated receptor 2 (PAR2) on spinal afferent neurons and cause persistent inflammation and hyperalgesia by unknown mechanisms. We determined whether transient receptor potential vanilloid receptor 1 (TRPV1), a cation channel activated by capsaicin, protons, and noxious heat, mediates PAR2-induced hyperalgesia. PAR2 was coexpressed with TRPV1 in small- to medium-diameter neurons of the dorsal root ganglia (DRG), as determined by immunofluorescence. PAR2 agonists increased intracellular [Ca2+] ([Ca2+]i) in these neurons in culture, and PAR2-responsive neurons also responded to the TRPV1 agonist capsaicin, confirming coexpression of PAR2 and TRPV1. PAR2 agonists potentiated capsaicin-induced increases in [Ca2+]i in TRPV1-transfected human embryonic kidney (HEK) cells and DRG neurons and potentiated cap..
Changes in Motorcycle-Related Head Injury Deaths, Hospitalizations, and Hospital Charges Following Repeal of Pennsylvania's Mandatory Motorcycle Helmet Law
Kristen J. Mertz, Harold B. Weiss
Am J Public Health, Vol. 98, No. 8. (1 August 2008), pp. 1464-1467.

To evaluate the 2003 repeal of Pennsylvania's motorcycle helmet law, we assessed changes in helmet use and compared motorcycle-related head injuries with non-head injuries from 2001-2002 to 2004-2005. Helmet use among riders in crashes decreased from 82% to 58%. Head injury deaths increased 66%; nonhead injury deaths increased 25%. Motorcycle-related head injury hospitalizations increased 78% compared with 28% for nonhead injury hospitalizations. Helmet law repeals jeopardize motorcycle riders. Until repeals are reversed, states need voluntary strategies to increase helmet use. 10.2105/AJPH.2007.123299...
Adherence to Mediterranean diet and risk of developing diabetes: prospective cohort study
M. A. Martinez-Gonzalez, Fuente-Arrillaga, J. M. Nunez-Cordoba et al.
BMJ, Vol. 336, No. 7657. (14 June 2008), pp. 1348-1351.

Objective To assess the relation between adherence to a Mediterranean diet and the incidence of diabetes among initially healthy participants. Design Prospective cohort study with estimates of relative risk adjusted for sex, age, years of university education, total energy intake, body mass index, physical activity, sedentary habits, smoking, family history of diabetes, and personal history of hypertension. Setting Spanish university department. Participants 13 380 Spanish university graduates without diabetes at baseline followed up for a median of 4.4 years. Main outcome measures Dietary habits assessed at baseline with a validated 136 item food frequency questionnaire and scored on a nine point index. New cases of diabetes confirmed through medical reports and an additional detailed questionnaire posted to those who self reported a new diagnosis of di..
Epinephrine: the drug of choice for anaphylaxis. A statement of the World Allergy Organization
S. F. Kemp, R. F. Lockey, F. E. R. Simons
Allergy (August 2008), pp. 1061-1070.

Anaphylaxis is an acute and potentially lethal multi-system allergic reaction. Most consensus guidelines for the past 30 years have held that epinephrine is the drug of choice and the first drug that should be administered in acute anaphylaxis. Some state that properly administered epinephrine has no absolute contraindication in this clinical setting. A committee of anaphylaxis experts assembled by the World Allergy Organization has examined the evidence from the medical literature concerning the appropriate use of epinephrine for anaphylaxis. The Committee strongly believes that epinephrine is currently underutilized and often dosed suboptimally to treat anaphylaxis, is under-prescribed for potential future self-administration, that most of the reasons proposed to withhold its clinical use are flawed, and that the therapeutic benefits of epinephrine exceed the risk when given in appropriate i.m. d..
Traditional acupuncture theories yield null outcomes: a systematic review of clinical trials
H. Moffet
Journal of Clinical Epidemiology, Vol. 61, No. 8. (5 August 2008), pp. 741-747.

OBJECTIVE: This study sought a fair sample of published acupuncture clinical trials to assess whether they provided scientific rationales for their interventions, clearly differentiated their exposures or observed differences in outcomes. STUDY DESIGN AND SETTING: A systematic review of all controlled, clinical trials of acupuncture published in English in 2006 and indexed in PubMed. RESULTS: Seventy-eight acupuncture clinical trials met the screening criteria; 36 had some rationale. Twenty-two studies compared acupuncture to usual care alone or other non-acupuncture controls; 18 (82% of 22) had statistically significant differences in outcomes, but failed to control for placebo effects. Sixteen studies used placebo controls; 11 (69% of 16) had statistically significant differences in outcomes. Forty studies compared acupuncture interventions mainly differentiated according to traditional acupu..
Sustained potentiation by substance P of NMDA-activated current in rat primary sensory neurons
Zi-Zhen Wu, Bing-Cai Guan, Zhi-Wang Li, Qing Yang, Chang-Jin Liu, Jian-Guo Chen
Brain Research, Vol. 1010, No. 1-2. (4 June 2004), pp. 117-126.

This study aimed to explore the modulatory effect of substance P (SP) on the current response mediated by N-methyl--aspartate (NMDA) receptor in rat primary sensory neurons and its time course using whole-cell patch clamp technique. The majority of neurons (179/213, 84.0%) examined were sensitive to NMDA (0.1-1000 [mu]M) with an inward current, and a proportion of the NMDA-sensitive neurons also responded to SP (78/98, 80.0%) with an inward current. Pretreatment with SP potentiated the NMDA-activated current (INMDA) in a non-competitive manner, which is shown in that SP shifted the concentration-response curve for NMDA upwards compared with the control; the maximal value of INMDA increased fourfold, while the EC50 values for both curves were very close (28 vs. 30 [mu]M). Furthermore, this potentiating effect was time-dependent: the amplitude..
Protease-activated receptor-2 activation: a major role in the pathogenesis of Porphyromonas gingivalis infection.
M. Holzhausen, L. C. Spolidorio, R. P. Ellen et al.
The American journal of pathology, Vol. 168, No. 4. (April 2006), pp. 1189-1199.

We have investigated the specific contribution of protease-activated receptor-2 (PAR(2)) to host defense during Porphyromonas gingivalis infection. Culture supernatants from P. gingivalis strains 33277 and W50 provoked Ca(2+) mobilization in cells transfected with PAR(2) (PAR(2)-KNRK) and desensitized the subsequent responses to PAR(2)-selective agonist. In addition, culture supernatants of P. gingivalis E8 (RgpA/RgpB double knockout) did not cause calcium response in PAR(2)-KNRK cells, evidencing the involvement of the arginine-specific cysteine proteases RgpA and RgpB in PAR(2) activation by P. gingivalis. Injection of P. gingivalis into mouse subcutaneous chambers provoked an increased proteolytic activity, which was inhibited by serine protease inhibitors. Fluids collected from chambers of P. gingivalis-injected mice were able to activate PAR(2) an..
Hydrogen Sulfide Attenuates Hepatic Ischemia-Reperfusion Injury: Role of Antioxidant and Anti-Apoptotic Signaling
Saurabh Jha, John W. Calvert, Mark R. Duranski, Arun Ramachandran, David J. Lefer
Am J Physiol Heart Circ Physiol (20 June 2008), 00377.2008.

Hydrogen sulfide (H2S) is an endogenously produced gaseous signaling molecule with diverse physiological activity. The potential protective effects of H2S have not been evaluated in the liver. Therefore, the purpose of the current study was to investigate if H2S could afford hepatoprotection in a murine model of hepatic ischemia and reperfusion (I/R) Injury. Hepatic injury was achieved by subjecting mice to 60 min of ischemia followed by 5 hr of reperfusion. H2S donor (IK1001) or vehicle were administered 5 minutes before reperfusion. H2S attenuated the elevation in serum alanine aminotransferase (ALT) by 68.6% and aspartate aminotransferase (AST) by 70.8% compared to vehicle group. H2S-mediated cytoprotection was associated with an improved balance between reduced glutathione (GSH) vs. oxidized glutathione (GSSG),attenuated the formation of l..
Endogenous Hydrogen Sulfide in Patients With COPD
Ya-Hong Chen, Wan-Zhen Yao, Bin Geng et al.
Chest, Vol. 128, No. 5. (1 November 2005), pp. 3205-3211.

Objectives: COPD is characterized by progressive airway obstruction. Recent studies showed that besides nitric oxide (NO) and carbon monoxide (CO), endogenous hydrogen sulfide (H2S) might be the third signaling gasotransmitter. To clarify the role of endogenous H2S in the pathogenesis of COPD, we investigated the relation of serum H2S level to severity of COPD as defined by lung function and airway inflammation. Methods: Levels of serum H2S and NO, lung function, and cell differential counts in induced sputum were studied in 27 patients with acute exacerbation of COPD (AECOPD), 37 patients with stable COPD, and 13 healthy subjects. Patients with AECOPD had arterial blood gas levels measured and underwent Doppler echocardiography. In addition, in order to clarify the effects of age and smoking status on serum H2S level, we recruited three groups who were age matched to the study gro..
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
Marcello Trevisani, Jan Siemens, Serena Materazzi et al.
Proc Natl Acad Sci (7 August 2007)

TRPA1 is an excitatory ion channel expressed by a subpopulation of primary afferent somatosensory neurons that contain substance P and calcitonin gene-related peptide. Environmental irritants such as mustard oil, allicin, and acrolein activate TRPA1, causing acute pain, neuropeptide release, and neurogenic inflammation. Genetic studies indicate that TRPA1 is also activated downstream of one or more proalgesic agents that stimulate phospholipase C signaling pathways, thereby implicating this channel in peripheral mechanisms controlling pain hypersensitivity. However, it is not known whether tissue injury also produces endogenous proalgesic factors that activate TRPA1 directly to augment inflammatory pain. Here, we report that recombinant or native TRPA1 channels are activated by 4-hydroxy-2-nonenal (HNE), an endogenous alpha,beta-unsaturated aldehyde that is produced when reactive oxygen speci..
A protease activated receptor-2 (PAR-2) activating peptide, tc-LIGRLO-NH2, induces protease release from mast cells: role in TNF degradation
Hashem Alshurafa, Grant Stenton, John Wallace, Morley Hollenberg, Dean A. Befus, Harissios Vliagoftis
BMC Pharmacology, Vol. 4, No. 1. (2004)

BACKGROUND:Mast cell (MC)-derived serine proteases have been implicated in a variety of inflammatory processes. We have previously shown that rat peritoneal MC (PMC) express mRNA for protease activated receptor 2 (PAR-2), a G-coupled receptor activated by trypsin-like proteases. Recent evidence also suggests that MC-induced inflammation can be mediated through PAR. Therefore, we hypothesized that specific PAR-2 agonist peptides (PAR-2ap) induce protease release from PMC.RESULTS:Western blot analysis of PMC supernatants revealed that a PAR-2ap, tc-LIGRLO (10 muM), stimulated the release of rat MC protease (RMCP)-1, RMCP-5 and carboxypeptidase-A. The release was evident by 20 min but further increased up to 8 h. To study the biological effects of protease release we tested supernatants from tc-LIGRLO, tc-OLRGIL (inactive control peptide) and ant..
Heme Oxygenase-2 Protects against Lipid Peroxidation-Mediated Cell Loss and Impaired Motor Recovery after Traumatic Brain Injury
Edward F. Chang, Ronald J. Wong, Hendrik J. Vreman et al.
J. Neurosci., Vol. 23, No. 9. (1 May 2003), pp. 3689-3696.

After traumatic brain injury (TBI), substantial extracellular heme is released from hemoproteins during hemorrhage and cell injury. Heme oxygenase (HO) isozymes are thought to detoxify the pro-oxidant heme to the potent antioxidant, bilirubin. HO-1, the inducible isozyme, is expressed in glial populations after injury and may play a protective role. However, the role of HO-2, the predominant and constitutively expressed isozyme in the brain, remains unclear after TBI. We used a controlled cortical impact injury model to determine the extent and mechanism of damage between HO-2 knock-out (KO) ([-]/[-]) and wild-type (WT) (+/+) mice. The specific cellular and temporal expressions of HO-2 and HO-1 were characterized by immunocytochemistry and Western blots. HO-2 was immunolocalized in neurons both before and after TBI, whereas HO-1 was highly upregulated in glia only aft..
Covalent Modification of Epithelial Fatty Acid-binding Protein by 4-Hydroxynonenal in Vitro and in Vivo. EVIDENCE FOR A ROLE IN ANTIOXIDANT BIOLOGY
Assumpta Bennaars-Eiden, Leeann Higgins, Ann V. Hertzel, Rebecca J. Kapphahn, Deborah A. Ferrington, David A. Bernlohr
J. Biol. Chem., Vol. 277, No. 52. (20 December 2002), pp. 50693-50702.

4-Hydroxynonenal (4-HNE) is a cytotoxic [alpha],[beta]-unsaturated acyl aldehyde that is naturally produced from lipid peroxidation and cleavage in response to oxidative stress and aging. Such reactive lipids covalently modify cellular target proteins, thereby affecting biological structure and function. Herein we report the identification of the epithelial fatty acid-binding protein (E-FABP) as a molecular target for 4-HNE modification both in vitro and in vivo. 4-HNE covalently modified (t1/2 < 60 s) E-FABP in vitro, as revealed by a combination of matrix-assisted laser desorption ionization-time of flight mass spectrometry and immunochemical reactivity using antibodies directed to 4-HNE-protein conjugates. Identification of Cys-120 as the major site of modification was determined through tande..
alpha-Tocopherol, MDA-HNE and 8-OHdG levels in liver and heart mitochondria of adriamycin-treated rats fed with alcohol-free beer.
V. Valls-Belles, M. d. e. l. . C. Torres, L. Boix, P. Muñiz, M. L. Gonzalez-Sanjose, P. Codoñer-Franch
Toxicology, Vol. 249, No. 2-3. (30 July 2008), pp. 97-101.

Different studies indicate that oxidative stress and mitochondrial damage are key factors in different pathogenic process. The aim of this study was to investigate the possible protective role of alcohol-free beer on adriamycin-induced (ADR) heart and liver toxicity using biomarkers of oxidative stress. This effect was compared with the effect of alcohol beer intake and with a control group. Rats were randomly divided into six groups. The first group received no adriamycin, was fed with water and was regarded as the control group; the second group was injected with a ADR (two cycles of 5mg/kg); the third and fourth groups were fed with alcohol-free and beer for 21 days, respectively and the fifth and sixth groups were fed with alcohol-free and beer beginning 7 days before the administration of a first dose of ADR. Beer was ..

Links for 2011-05-16 [del.icio.us]

2011-05-17T00:00:00-07:00

Gene polymorphisms of superoxide dismutases and catalase in diabetes mellitus
Milan Flekac, Jan Skrha, Jirina Hilgertova, Zdena Lacinova, Marcela Jarolimkova
BMC Medical Genetics, Vol. 9 (21 April 2008), 30.
The role of epigenetics in aging and autoimmunity.
Annabelle Grolleau-Julius, Donna Ray, Raymond L. Yung
Clinical reviews in allergy & immunology, Vol. 39, No. 1. (August 2010), pp. 42-50.

The decline in immunocompetence with age is accompanied by the increase in the incidence of autoimmune diseases. Aging of the immune system, or immunosenescence, is characterized by a decline of both T and B cell function, and paradoxically the presence of low-grade chronic inflammation. There is growing evidence that epigenetics, the study of inherited changes in gene expression that are not encoded by the DNA sequence itself, changes with aging. Interestingly, emerging evidence suggests a key role for epigenetics in human pathologies, including inflammatory and neoplastic disorders. Here, we will review the potential mechanisms that contribute to the increase in autoimmune responses in aging. In particular, we will discuss how epigenetic alterations, especially DNA methylation and histone acetylation, are accumulated during aging and how the..
Acute colitis induction by oil of mustard results in later development of an IBS-like accelerated upper GI transit in mice
Edward S. Kimball, Jeffrey M. Palmer, Michael R. D'Andrea, Pamela J. Hornby, Paul R. Wade
Am J Physiol Gastrointest Liver Physiol, Vol. 288, No. 6. (1 June 2005), pp. G1266-1273.

Oil of mustard (OM) is a potent neuronal activator that promotes allodynia and hyperalgesia within minutes of application. In this study, OM was used to induce an acute colitis. We also investigated whether intracolonic OM-induced inflammation alters gastrointestinal (GI) function over a longer time frame as a model of postinflammatory irritable bowel syndrome (PI-IBS). Mice given a single administration of 0.5% OM developed a severe colitis that peaked at day 3, was reduced at day 7, and was absent by day 14. At the peak response, there was body weight loss, colon shrinkage, thickening and weight increases, distension of the proximal colon, and diarrhea. Macroscopic inspection of the distal colon revealed a discontinuous pattern of inflammatory damage and occasional transmural ulceration. Histological exam..
Role of serotonin in the pathophysiology of the irritable bowel syndrome.
Michael D. Crowell
British journal of pharmacology, Vol. 141, No. 8. (April 2004), pp. 1285-1293.

The irritable bowel syndrome (IBS) is a complex disorder that is associated with altered gastrointestinal motility, secretion, and sensation. Serotonin (5-HT) is an important neurotransmitter and paracrine signalling molecule in the gastrointestinal tract. 5-HT release from enterochromaffin (EC) cells initiates peristaltic, secretory, vasodilatory, vagal and nociceptive reflexes. The enteric nervous system (ENS) comprises a semiautonomous effector system that is connected to the central autonomic network. Parasympathetic and sympathetic nerves modulate the ENS via afferent and efferent communications. Ongoing, bidirectional brain-gut interactions involving 5-HT pathways occur that significantly influence the effector systems. Altered 5-HT signalling may lead to both intestinal and extraintestinal symptoms in IBS. 5-HT directly and indirectly affects intestinal motor and secretory functi..
Endothelial nitric oxide attenuates Na+/Ca2+ exchanger-mediated vasoconstriction in rat aorta
Zhao
British Journal of Pharmacology, Vol. 3 (2008)
Exhaled nitric oxide levels in atopic children: relation to specific allergic sensitisation, AHR, and respiratory symptoms.
J. D. Leuppi, S. H. Downs, S. R. Downie, G. B. Marks, C. M. Salome
Thorax, Vol. 57, No. 6. (June 2002), pp. 518-523.

BACKGROUND: Exhaled nitric oxide (eNO), which has been proposed as a measure of airway inflammation, is increased in atopic subjects. This raises the question of whether eNO provides any additional information about airway inflammation in asthmatic subjects, other than as a marker for atopy. A study was undertaken to determine whether eNO levels in a population of atopic children are associated with sensitisation or natural exposure to specific allergens, and to examine the relationship between eNO, airway responsiveness, and current respiratory symptoms. METHODS: Exhaled NO and airway responsiveness to histamine were measured in winter and in summer in 235 children aged 8-14 years who had been classified as atopic by skin prick testing. Current respiratory symptoms, defined as wheeze or cough during the month preceding the test, were measured by a parent completed qu..
Oxidative stress, glutamate, and neurodegenerative disorders
J. T. Coyle, P. Puttfarcken
Science, Vol. 262, No. 5134. (29 October 1993), pp. 689-695.

There is an increasing amount of experimental evidence that oxidative stress is a causal, or at least an ancillary, factor in the neuropathology of several adult neurodegenerative disorders, as well as in stroke, trauma, and seizures. At the same time, excessive or persistent activation of glutamate-gated ion channels may cause neuronal degeneration in these same conditions. Glutamate and related acidic amino acids are thought to be the major excitatory neurotransmitters in brain and may be utilized by 40 percent of the synapses. Thus, two broad mechanisms--oxidative stress and excessive activation of glutamate receptors--are converging and represent sequential as well as interacting processes that provide a final common pathway for cell vulnerability in the brain. The broad distribution in brain of the processes regulating oxidative stress and mediating glutamatergic neurotransmission may expla..
Modulation of Small Intestinal Nitric Oxide Synthase by Gum Arabic
Khalil U. Rehman, Champa N. Codipilly, Raul A. Wapnir
Experimental Biology and Medicine, Vol. 229, No. 9. (1 October 2004), pp. 895-901.

Preceding studies have revealed that gum arabic (GA), a natural proteoglycan ([≥] 250,000 Da), has proabsorptive properties--as shown by increased sodium and water absorption--in normal rats, and especially in two animal models of diarrhea. Because nitric oxide (NO) metabolism is linked to gastrointestinal physiology, the goals of this study were to determine whether GA modulated NO and to determine intestinal function in vivo when NO production was enhanced by L-arginine (Arg), added at either 1 or 20 mM. Mechanistically, the goal was also to determine whether GA was a NO scavenger and a small intestinal NO synthase (NOS) inhibitor. Using a glucose-electrolyte solution in rat jejunal perfusions we found that GA at {+/-}10 lM (2.5 g/l) decreased nitrite and nitrate formation, tending to normalize water, sodium, and glucose absorption when modifi..
Monoterpenes from Paeonia albiflora and Their Inhibitory Activity on Nitric Oxide Production by Lipopolysaccharide-Activated Microglia
Wen-Juan Duan, Jing-Yu Yang, Li-Xia Chen et al.
Journal of Natural Products, Vol. 0, No. 0. (0000)

PMID: 19691309 Eleven new monoterpenes, paeonidangenin (1), paeonidanin A (2), paeonidanin B (3), paeonidanin C (4), paeonidanin D (5), paeonidanin E (6), paeoniflorone (7), 4-O-methylbenzoylpaeoniflorin (8), 4-O-methylgalloylpaeoniflorin (9), 4-O-methyldebenzoylpaeoniflorin (10), and 4-O-methylalbiflorin (11), were isolated from the 60% ethanol extract of the roots of Paeonia albiflora. Their structures were determined primarily on the basis of 1D and 2D NMR techniques and MS studies. Paeonidanins D (5) and E (6) are unprecedented examples of “cage-like” monoterpene dimers. The inhibitory effects of the isolated compounds on nitric oxide production by lipopolysaccharide (LPS)-activated N9 microglia were evaluated....
Antioxidant Properties of Grape Seed Extract on Human Lymphocyte Oxidative Defence
Miroslava

The distribution of polyphenolic compounds in a grape (Vitis vinifera) seed extract (GSE) was determined using LC/ESI-TOF MS, HPLC/DAD, and 13C-NMR. The 17 identified compounds comprised gallic and protocatechuic acid, catetchin and epicatechin monomers, procyanidin oligomers, and procyanidin gallates. This study addresses the in vitro effects of grape seed extract (GSE) on the frequency of micronuclei with reference to the antioxidant status in human lymphocytes. To establish the most effective protective support, we used four different concentrations of GSE, in the range 1 - 6 μg/mL. Treatment of lymphocytes with GSE at a concentration of 2.5 μg/mL induced a significant decrease in the frequency of micronuclei by 40 %, reduction of malonyldialdehyde production by 30 %, while a concentration of 5 μg/mL increased catalase and glutathione S-transferase activity by 10 % and 15 %, respectively. These results demonstrate that GSE may be effective in the prevention of oxidative..
Novel regimen through combination of memantine and tea polyphenol for neuroprotection against brain excitotoxicity
Chang-Mu
Journal of Neuroscience Research, Vol. 9999, No. 9999.
Endothelial Nitric Oxide Synthase Control Mechanisms in the Cutaneous Vasculature of Humans In Vivo.
Dean L L. Kellogg Jr, Joan Liu L. Zhao, Yubo Wu
American journal of physiology. Heart and circulatory physiology (9 May 2008)

Nitric oxide(NO) participates in locally mediated vasodilation induced by increased local skin temperature(Tloc) and in sympathetically mediated vasodilation during whole body heat stress. We hypothesized that endothelial NOS(eNOS) participates in the former, but not the latter response. We tested this hypothesis by examining the effects of the eNOS antagonist, N(G)-amino-L-arginine(LNAA) on skin blood flow(SkBF) responses to increased Tloc and whole body heat stress. Microdialysis probes were inserted into forearm skin for drug delivery. One microdialysis site was perfused with LNAA in Ringers solution, while a second site was perfused with Ringers alone. SkBF (laser-Doppler flowmetry;LDF) and blood pressure(MAP) were monitored and cutaneous vascular conductance calculated(CVC=LDF/MAP). In Protocol 1, Tloc was controlled with LDF/local heating units. Tloc in..
Seven genetic types of ME' found
(5 May 2008)
Hydroxylated Metabolites of the Polybrominated Diphenyl Ether Mixture DE-71 are Weak Estrogen Receptor Alpha Ligands
Minerva
Environmental Health Perspectives (27 May 2008)

Background: Polybrominated diphenyl ethers (PBDEs) are widely found in the environment and are suspected endocrine disruptors. Earlier, we had identified six hydroxylated metabolites of PBDE (OHPBDE) in treated mice.
Objective: We tested the hypothesis that hydroxylated metabolites of PBDEs would interact with and alter
activity of estrogen receptor-alpha (ERô).
Methods: Estrogenicity was tested using two assays: 3H-estradiol (3H-E2) displacement from recombinant
ERô, and induction of reporter gene, ERE-luciferase, in cultured cells. The PBDE mixture DE-71 was
incubated with rat liver microsomes and the resultant metabolite mixture was tested for estrogenic activity.
Relative estrogenic potential of individual hydroxylated PBDE congeners were determined.
Results: Reporter gene activity was increased by DE-71 that had been subjected to microsomal metabolism.
DE-71 did not displace estradiol from ERô but all six of the O..
Pain sensitivity is reduced in borderline personality disorder, but not in posttraumatic stress disorder and bulimia nervosa.
Christian Schmahl, Miriam Meinzer, Andrea Zeuch et al.
The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, Vol. 11, No. 2 Pt 2. (March 2010), pp. 364-371.

Background. Several studies revealed reduced pain sensitivity in patients suffering from borderline personality disorder (BPD) under baseline and stress conditions. To establish whether these findings are specific for BPD, we compared pain thresholds in patients with BPD, posttraumatic stress disorder (PTSD), bulimia nervosa, and healthy controls. Methods. The study included 76 female subjects: 16 patients with BPD, 16 patients with PTSD, 20 patients with bulimia nervosa and 24 healthy controls. Heat and cold pain thresholds were assessed under baseline and stress conditions, using a contact thermode. Mental stress was induced by the Paced Auditory Serial Addition Task. Results. Under baseline conditions, pain thresholds in patients with BPD were signific..

Links for 2011-05-15 [del.icio.us]

2011-05-16T00:00:00-07:00

A proinflammatory chemokine, CCL3, sensitizes the heat- and capsaicin-gated ion channel TRPV1.
Proceedings of the National Academy of Sciences, Vol. 102, No. 12. (22 March 2005), pp. 4536-4541.

Pain, a critical component of host defense, is one hallmark of the inflammatory response. We therefore hypothesized that pain might be exacerbated by proinflammatory chemokines. To test this hypothesis, CCR1 was cotransfected into human embryonic kidney (HEK)293 cells together with transient receptor potential vanilloid 1 (TRPV1), a cation channel required for certain types of thermal hyperalgesia. In these cells, capsaicin and anandamide induced Ca(2+) influx mediated by TRPV1. When CCR1:TRPV1/HEK293 cells were pretreated with CCL3, the sensitivity of TRPV1, as indicated by the Ca(2+) influx, was increased approximately 3-fold. RT-PCR analysis showed that a spectrum of chemokine and cytokine receptors is expressed in rat dorsal root ganglia (DRG). Immunohistochemical staining of DRG showed that CCR1 is coexpressed with TRPV1 in >85% of small-diameter neurons. CCR1 on DRG neurons was f..
Nerve Growth Factor Modifies the Expression of Inflammatory Cytokines by Mast Cells Via a Prostanoid-Dependent Mechanism
Jean S. Marshall, Kaede Gomi, Michael G. Blennerhassett, John Bienenstock
J Immunol, Vol. 162, No. 7. (1 April 1999), pp. 4271-4276.

Nerve growth factor (NGF) is well recognized to have a number of potent effects on mast cells, including increasing mast cell numbers in vivo and inducing mast cell degranulation in vitro. More recently, NGF has been demonstrated to induce PGD2 production by mast cells through the induction of mast cell cyclooxygenase expression. We have observed that NGF at doses as low as 10 ng/ml will induce IL-6 production and inhibit TNF-{alpha} release from rat peritoneal mast cells in the presence of lysophosphatidylserine as a cofactor. NGF synergizes with LPS treatment of peritoneal mast cells (PMC) for the induction of IL-6. Examination of the mechanism of this phenomenon has revealed that NGF can induce both rat PMC and mouse bone marrow-derived cultured mast cells to produce substantial levels of PGE2. This response is maximal at later time points 18-24 h a..
Human skin mast cells rapidly release preformed and newly generated TNF-alpha and IL-8 following stimulation with anti-IgE and other secretagogues.
B. F. Gibbs, J. Wierecky, P. Welker, B. M. Henz, H. H. Wolff, J. Grabbe
Experimental dermatology, Vol. 10, No. 5. (October 2001), pp. 312-320.

Several groups have previously reported that rodent or human leukemic mast cells produce inflammatory cytokines such as TNF-alpha and IL-8 as well as the pro-allergic cytokines IL-4, IL-5 and IL-13. Comparatively little is known, however, regarding the ability of normal human skin mast cells to secrete these factors following either IgE-dependent or IgE-independent modes of activation. We therefore investigated whether normal human skin mast cells produce these cytokines following stimulation by a variety of secretagogues. Enriched isolated skin mast cells released both TNF-alpha and IL-8 following activation with either anti-IgE, SCF, substance P, compound 48/80 or A23187. This release was dose- and time-dependent, with maximal levels being reached within 4 h of stimulation involving, in part, the secretion of preformed stores of both cytoki..
Regulation of cytochrome P450 expression by sphingolipids
A. Merrill
Chemistry and Physics of Lipids, Vol. 102, No. 1-2. (November 1999), pp. 131-139.

Sphingolipids modulate many aspects of cell function, including the expression of cytochrome P450, a superfamily of heme proteins that participate in the oxidation of a wide range of compounds of both endogenous (steroid hormones and other lipids) and exogenous (e.g. alcohol, drugs and environmental pollutants) origin. Cytochrome P450-2C11 (CYP 2C11) is down-regulated in response to interleukin-1β (IL-1β), and this response involves the hydrolysis of sphingomyelin to ceramide as well as ceramide to sphingosine, and phosphorylation of sphingosine to sphingosine 1-phosphate. Activation of ceramidase(s) are a key determinant of which bioactive sphingolipid metabolites are formed in response to IL-1β. Ceramidase activation also appears to account for the loss of expression of CYP 2C11 when hepatocytes are placed in cell culture, and the restoration of expression when they are plated on Matrigel;..
The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease
B. Afzali, G. Lombardi, R. I. Lechler, G. M. Lord
Clinical and Experimental Immunology, Vol. 148, No. 1. (April 2007), pp. 32-46.

Uncommitted (naive) murine CD4+ T helper cells (Thp) can be induced to differentiate towards T helper 1 (Th1), Th2, Th17 and regulatory (Treg) phenotypes according to the local cytokine milieu. This can be demonstrated most readily both in vitro and in vivo in murine CD4+ T cells. The presence of interleukin (IL)-12 [signalling through signal transduction and activator of transcription (STAT)-4] skews towards Th1, IL-4 (signalling through STAT-6) towards Th2, transforming growth factor (TGF)-03B2 towards Treg and IL-6 and TGF-03B2 towards Th17. The committed cells are characterized by expression of specific transcription factors, T-bet for Th1, GATA-3 for Th2, forkhead box P3 (FoxP3) for Tregs and ROR03B3t for Th17 cells. Recently, it has been demonstrated that the skewing of murine Thp towards Th17 and Treg is mutually exclusive. Although human Thp can a..
Oxygen/Glucose Deprivation in Hippocampal Slices: Altered Intraneuronal Elemental Composition Predicts Structural and Functional Damage
Charles P. Taylor, Mark L. Weber, Christopher L. Gaughan, Ellen J. Lehning, Richard M. Lopachin
J. Neurosci., Vol. 19, No. 2. (15 January 1999), pp. 619-629.

Effects of oxygen/glucose deprivation (OGD) on subcellular elemental composition and water content were determined in nerve cell bodies from CA1 areas of rat hippocampal slices. Electron probe x-ray microanalysis was used to measure percentage water and concentrations of Na, P, K, Cl, Mg, and Ca in cytoplasm, nucleus, and mitochondria of cells exposed to normal and oxygen/glucose deficient medium. As an early (2 min) consequence of OGD, evoked synaptic potentials were lost, and K, Cl, P, and Mg concentrations decreased significantly in all morphological compartments. As exposure to in vitro OGD continued, a negative DC shift in interstitial voltage occurred (~5 min), whereas general elemental disruption worsened in cytoplasm and nucleus (5-42 min). Similar elemental changes were noted in mitochondria, except that Ca levels incr..
The connection between Lyme disease, an Inflamed Brain , and Fibromyalgia Syndrome
Gina Nick
Townsend Letters for Doctors (April 2007)
Existence and distinction of acid-evoked currents in rat astrocytes.
Chao Huang, Zhuang-Li L. Hu, Wen-Ning N. Wu et al.
Glia, Vol. 58, No. 12. (September 2010), pp. 1415-1424.

Astrocytes are vital structures that support and/or protect neighboring neurons from pathology. Although it is generally accepted that glutamate receptors mediate most astrocyte effects, acid-evoked currents have recently attracted attention for their role in this regard. Here, we identified the existence and characteristics of acid-sensing ion channels (ASICs) and the transient receptor potential vanilloid type 1 (TRPV1) in astrocytes. There were two types of currents recorded under the application of acidic solution (pH 6.0) in cultured rat astrocytes. Transient currents were exhibited by 10% of the astrocytes, and sustained currents were exhibited by the other 90%, consistent with the features of ASIC and TRPV1 currents, respectively. Western blotting and immunofluorescence confirmed the expression of ASIC1, ASIC2a, ASIC3, and TRPV1 in cultured and in situ astrocytes. Unlike..
Antioxidant and DNA methylation-related nutrients and risk of distal colorectal cancer.
Christina Dawn D. Williams, Jessie A. Satia, Linda S. Adair et al.
Cancer causes & control : CCC, Vol. 21, No. 8. (30 August 2010), pp. 1171-1181.

OBJECTIVE: To investigate the relationship between antioxidant nutrients (vitamins C and E, beta-carotene, selenium) and DNA methylation-related nutrients (folate, vitamins B6 and B12) and distal colorectal cancer risk in whites and African Americans and to examine intakes from food only versus total (food plus dietary supplements) intakes. METHODS: Data are from the North Carolina Colon Cancer Study-Phase II, a case-control study of 945 distal colorectal cancer (including sigmoid, rectosigmoid, and rectum) cases and 959 controls. In-person interviews captured usual dietary intake and various covariates. Multivariate logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: High intakes of each antioxidant and DNA methylation-related nutrient were significantly associated with lower ris..
Vasoprotective effects of resveratrol and SIRT1: attenuation of cigarette smoke-induced oxidative stress and proinflammatory phenotypic alterations
Anna Csiszar, Nazar Labinskyy, Andrej Podlutsky et al.
Am J Physiol Heart Circ Physiol, Vol. 294, No. 6. (1 June 2008), pp. H2721-2735.

The dietary polyphenolic compound resveratrol, by activating the protein deacetylase enzyme silent information regulator 2/sirtuin 1 (SIRT1), prolongs life span in evolutionarily distant organisms and may mimic the cytoprotective effects of dietary restriction. The present study was designed to elucidate the effects of resveratrol on cigarette smoke-induced vascular oxidative stress and inflammation, which is a clinically highly relevant model of accelerated vascular aging. Cigarette smoke exposure of rats impaired the acetylcholine-induced relaxation of carotid arteries, which could be prevented by resveratrol treatment. Smoking and in vitro treatment with cigarette smoke extract (CSE) increased reactive oxygen species production in rat arteries and cultured coronary arterial endothelial cells (CAECs), respectively, which was attenuated by resverat..
TRPV1 receptors and nasal trigeminal chemesthesis
Silver, Clapp, Stone, Kinnamon
Chemical Senses, Vol. 31, No. 9. (2006), pp. 807-812.

The trigeminal nerve responds to a wide variety of irritants. Trigeminal nerve fibers express several receptors that respond to chemicals, including TRPV1 (vanilloid) receptors, acid-sensing ion channels, P2X (purinergic) receptors, and nicotinic acetylcholine receptors. In order to assess whether TRPV1 plays a role in responses to a broad array of substances, TRPV1 (along with green fluorescent protein) was expressed in human embyonic kidney cells (HEK) 293t cells which were then stimulated with diverse trigeminal irritants. Calcium imaging was used to measure responses to capsaicin, amyl acetate, cyclohexanone, acetic acid, toluene, benzaldehyde, (-)-nicotine, (R)-(+)-limonene, (R)-(-)-carvone, and (S)-(+)-carvone. Three irritants (acetic acid and the 2 carvones) stimulated nontransfected controls. Two irritants (capsaicin and cyclohexanone) stimulated only transfected cells. The response could..
Micro- and macrovascular dysfunction evident with the metabolic syndrome
Anita Wilkinson
(8 February 2010)
IL-1 receptor antagonist inhibits monocyte chemotactic peptide 1 generation by human mesangial cells
Zarin Brown, Robert M. Strieter, Guy H. Neild, Robert C. Thompson, Steven L. Kunkel, John Westwick
Kidney Int, Vol. 42, No. 1. (July 1992), pp. 95-101.
Intersecting pathways to neurodegeneration in Parkinson's disease: effects of the pesticide rotenone on DJ-1, alpha-synuclein, and the ubiquitin-proteasome system.
Ranjita Betarbet, Rosa M. Canet-Aviles, Todd B. Sherer et al.
Neurobiology of disease, Vol. 22, No. 2. (May 2006), pp. 404-420.

Sporadic Parkinson's disease (PD) is most likely caused by a combination of environmental exposures and genetic susceptibilities, although there are rare monogenic forms of the disease. Mitochondrial impairment at complex I, oxidative stress, alpha-synuclein aggregation, and dysfunctional protein degradation, have been implicated in PD pathogenesis, but how they are related to each other is unclear. To further evaluated PD pathogenesis here, we used in vivo and in vitro models of chronic low-grade complex I inhibition with the pesticide rotenone. Chronic rotenone exposure in vivo caused oxidative modification of DJ-1, accumulation of alpha-synuclein, and proteasomal impairment. Interestingly, the effects become more regionally restricted such that systemic complex I inhibition eventually results in highly selective degeneration of the nigrostriatal pathway...
Inflammatory murine skin responses to UV-B light are partially dependent on endothelin-1 and mast cells.
M. Metz, V. Lammel, B. F. Gibbs, M. Maurer
The American journal of pathology, Vol. 169, No. 3. (September 2006), pp. 815-822.

Endothelin (ET-1) has been shown to crucially contribute to UV-induced skin responses such as tanning. To test whether ET-1 is also involved in early cutaneous reactions to UV, we assessed ET-1 skin levels in UV-irradiated mice. In correlation with the levels of UV-induced skin inflammation, ET-1 concentrations increased substantially and continually. Moreover, blocking of ET-1 receptors (ETA) resulted in significantly decreased cutaneous inflammation following UV irradiation. When we assessed skin responses to ET-1 injections, we observed prominent mast cell degranulation and mast cell-dependent inflammation. Since mast cells also critically contributed to UV-induced inflammation, we determined the ET-1-dependent inflammatory response to UV in the absence and presence of these cells. Interestingly, ETA blockade did not decrease UV-induced inflammation in mas..

Acupuncture Gets Military Support For Gulf War Illness Treatment

2011-04-24T11:56:00.000-07:00

"The Department of Defense has made a $1.2 million research grant to the New England School of Acupuncture (located in Newton, Massachusetts). The goal of the study is to determine the effectiveness of acupuncture in the treatment of Gulf War Illness (GWI)."Acupuncture Gets Military Support For Gulf War Illness Treatment:

FOXP3(+) CD4(+) Tregs lose suppressive potential but remain anergic during transient inflammation in human.

2011-03-13T06:26:00.000-07:00

A loss of the suppressive function of Tregs have been implicated as a possible contributor to chemical sensitivity. This new study suggests that inflammation can cause a loss of Tregs suppressive function. This suggests that periods where inflammation is higher may contribute to chemical sensitivity.Read Abstract: CiteULike: FOXP3(+) CD4(+) Tregs lose suppressive potential but remain anergic

CiteULike: Isothiocyanates Reduce Mercury Accumulation via an Nrf2-Dependent Mechanism during Exposure of Mice to Methylmercury.

2011-03-11T07:06:00.000-08:00

Compound in broccoli can help prevent toxicity from mercury exposure."Environmental health perspectives (7 March 2011) doi:10.1289/ehp.1003123 Key: citeulike:8979952"CiteULike: Isothiocyanates Reduce Mercury Accumulation via an Nrf2-Dependent Mechanism during Exposure of Mice to Methylmercury.:

Pfizer Touts New Drug for Fibromyalgia, Critics Warn Consumers

2011-03-10T07:32:00.000-08:00

"Pfizer’s new television commercial for the medication Lyrica, features a middle-aged woman who says that her Fibromyalgia (FMS) is real and that she can now live without pain thanks to the medication"Read more: Kalamazoo Shopper::Complete Article:

FDA cracks down on untested cold medicines - BusinessWeek

2011-03-03T06:17:00.000-08:00

"The Food and Drug Administration says it will remove roughly 500 unapproved cold and allergy medications from the market as part of an ongoing campaign cracking down on ineffective prescription medications."Read more: FDA cracks down on untested cold medicines - BusinessWeek:

A brain MRI study of chronic fatigue syndrome: Evidence of brainstem dysfunction and altered homeostasis [preview] – Source: NMR in Biomedicine, March 2011

2011-03-03T06:15:00.000-08:00

New study suggests that astrocyte dysfunction may play a role in chronic fatigue issue. A brain MRI study of chronic fatigue syndrome: Evidence of brainstem dysfunction and altered homeostasis [preview] – Source: NMR in Biomedicine, March 2011: "A brain MRI study of chronic fatigue syndrome: Evidence of brainstem dysfunction and altered homeostasis [preview] – Source: NMR in Biomedicine, March

Researchers Discover Biological Pathway Linked to PTSD - ABC News

2011-02-27T08:22:00.000-08:00

"In both men and women with PTSD, the PAC1 gene was more likely to be modified by a process call 'methylation,' meaning people are not necessarily born susceptible to PTSD but can acquire the vulnerability over time. The finding supports the idea that environmental, genetic and so-called epigenetic factors all contribute to PTSD risk" Watch: Read more: Researchers Discover Biological Pathway

Genetic switch that controls tissue regeneration found

2011-02-25T07:11:00.000-08:00

I have written extensively about the Nrf2 antioxidant system and how it influences overall health, especially in response to environmental contaminants and controllng free radical injury. Looks like research now shows it may influence stem cells too! "It is well known that human body has the ability to heal itself. Thanks to the presence of stem cells, many organs can undergo continuous renewal.

Analysis of common and specific mechanisms of liver function affected by nitrotoluene compounds.

2011-02-25T06:53:00.000-08:00

A common chemical used in industry and medicine causes alterations in a number of pathways that may contribute to environmental-illness-like symptoms. Long-term exposure may contribute to injury. "PloS one, Vol. 6, No. 2. (2011) doi:10.1371/journal.pone.0014662 Key: citeulike:8887114" Read abstract:CiteULike: Analysis of common and specific mechanisms of liver function affected by nitrotoluene

High Cholesterol, Blood Pressure Linked to Early Memory Loss - AOL Health

2011-02-23T11:13:00.000-08:00

"New research finds that high cholesterol and high blood pressure not only put patients at risk for heart disease but are also risk factors for early memory loss and other cognitive problems" Read more:High Cholesterol, Blood Pressure Linked to Early Memory Loss - AOL Health:

Higher Levels of Pain Intensity in Multiple Chemical Sensitvity -Says Study

2011-02-06T11:26:00.000-08:00

"this is the ﬁrst study to show facilitated pain processing in MCS and EC patients with the most abnormal responses in MCS" The Clinical journal of pain, Vol. 27, No. 2. (February 2011), pp. 156-162. Key: citeulike:8774097 Read more: CiteULike: Increased capsaicin-induced secondary hyperalgesia in patients with multiple chemical sensitivity.: Recommended: Chemical Sensitivity: A Guide to

Knockdown of the aryl hydrocarbon receptor attenuates excitotoxicity and enhances NMDA-induced BDNF expression in cortical neurons.

2010-12-22T16:44:00.000-08:00

"that AhR opposingly regulates NMDA receptor-mediated excitotoxicity and neurotrophism possibly by differentially regulating the expression of synaptic and extrasynaptic NMDA receptors."Read more: CiteULike: Knockdown of the aryl hydrocarbon receptor attenuates excitotoxicity and enhances NMDA-induced BDNF expression in cortical neurons.:

BDNF, LRRK and Pink and Environment Play Role in Parkinson's Disease~!

2010-12-22T04:27:00.000-08:00

"PD risk is modulated by both genetic factors including BDNF, PINK, and LRRK and environmental exposures." Read more: CiteULike: Lrrk2 S1647T and BDNF V66M interact with environmental factors to increase risk of Parkinson's disease.:

Cellular mechanism responsible for chronic inflammation, type 2 diabetes uncovered

2010-12-21T13:46:00.000-08:00

Cellular mechanism responsible for chronic inflammation, type 2 diabetes uncovered

Reduction of Signalling of GSK-3B May Reduce Some Problems in Non-alcoholic Liver Disease~!

2010-12-17T05:40:00.000-08:00

High fat diets may caugment environmental illness by disrupting processes in a variety of pathways such as the Nrf2 and contributes to a variety of patholgies including non-alcoholic liver disease. GSK-3b is a protein that can serve as an "on-off switch" for the antioxidant system. A new study shows that knock-down of this protein may provide cells with more resistance to some of the damaging

The Role of Glycogen Synthase Kinase 3 in Regulating IFN-beta-Mediated IL-10 Production

2010-12-17T04:18:00.000-08:00

IL-10 production by IFN-β-stimulated DC was shown to suppress IFN-γ and IL-17 production by myelin oligodendrocyte glycoprotein-specific CD4(+) T cells, and this IL-10-dependent anti-inflammatory effect was enhanced by directly targeting GSK3 in DC. Wang, H. et al. The role of glycogen synthase kinase 3 in regulating ifn-beta-mediated il-10 production. Journal of immunology (Baltimore, Md. :

Cells' Natural Defence Against Cancer-Causing Viruses Discovered

2010-12-16T13:19:00.000-08:00

Cells' Natural Defence Against Cancer-Causing Viruses Discovered

Compound With Potent Effects on the Biological Clock Discovered

2010-12-15T03:41:00.000-08:00

Using automated screening techniques developed by pharmaceutical companies to find new drugs, researchers from UC San Diego and three other research institutions have discovered a molecule with the most potent effects ever seen on the biological clock. Dubbed "longdaysin," for its ability to dramatically slow down the biological clock... Read more: Compound With Potent Effects on the Biological

Proteins in Bone Health, Development and Disease in Environmental Illness

2010-12-13T12:04:00.000-08:00

Proteins in Bone Health, Development and Disease in Environmental Illness

Study: Polymorphisms in Cytokines May Contribute to Autoimmune Disease in Canadian Aboriginal Populations~!

2010-12-12T12:11:00.000-08:00

This has implications for conditions where methylation and polymorphisms that effect control of cytokines as well, including the Nrf2 pathway! Larcombe, L. et al. Differential cytokine genotype frequencies among Canadian Aboriginal and Caucasian populations. Genes and Immunity 6, 140-144 (2004). URL http://dx.doi.org/10.1038/sj.gene.6364157.

New model for the origin of rheumatoid arthritis

2010-12-11T05:58:00.000-08:00

New model for the origin of rheumatoid arthritis

Rheumatoid Arthritis & Anti-Citrulline Antibody: Rheumatology Research is Ongoing

2010-12-11T05:46:00.000-08:00

Rheumatoid Arthritis & Anti-Citrulline Antibody: Rheumatology Research is Ongoing

Wine Compound Improves Symptom of CFS - Study

2010-12-10T09:13:00.000-08:00

Wine Compound Improves Symptom of CFS - Study

Sevoflurane Impairs Olfactory Memory.....

2010-12-10T05:13:00.000-08:00

Comment: I expect that this has important implications on animals as well as, humans. Probably more so in animals that use olfactory cues more than humans. If anestethics can cause changes in olfactive memory it would be interesting to consider how other environmental factors may also influence this ability, the extent and how long the effects last. Kostopanagiotou, G. et al. Sevoflurane

Flavonoids May Modulate BDNF and Amyloid In Alzheimer's ~!

2010-12-09T16:53:00.000-08:00

"stimulating BDNF and reducing Aβ toxicity by natural flavonols provide a therapeutic implication for treatment of AD." Hou, Y. et al. Anti-depressant natural flavonols modulate BDNF and beta amyloid in neurons and hippocampus of double TgAD mice. Neuropharmacology 58, 911-920 (2010). URL http://dx.doi.org/10.1016/j.neuropharm.2009.11.002. Related: Health and Environmental Illness Blog:

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