Effect of exposure to high temperatures in the excretion of cadmium and lead

ObjectiveThis study aims to observe the effect on urine and sweat excretion levels of cadmium (Cd) and lead (Pb) in healthy men in a maximum incremental test until exhaustion and repeated exposure to heat.Methodstwenty-nine adult men divided into control group (CG; n = 14) and experimental group (EG; n = 15) performing two maximum tests until exhaustion in normothermia (22 °C) and hyperthermia (42 °C). EG experienced 9 sessions of heat exposure at high temperatures (100 °C) (HEHT). After the nine sessions, the initial tests were repeated in both groups. Urine samples were collected before and after each test. After the hyperthermia tests, sweat samples were gathered.ResultsUrinary Cd increased after initial tests in GC and in hyperthermia in EG (p < 0.05). Urinary excretion of Pb rose after HEHT (p < 0.05). Pb in sweat was higher in EG than in CG after HEHT (p < 0.05).ConclusionHeat exercise and constant exposure to heat can be a valid method to increase the excretion of toxic metals.     

Prostaglandin involvement in hyperthermia induced by sleep deprivation: A pharmacological and autoradiographic study

AimsHyperthermia is a characteristic functional effect of sleep deprivation (SD). We hypothesize here that prostaglandin E2 (PGE2) could be involved in hyperthermia induced by sleep deprivation.Main methodsTo address this issue we examined the effects of a selective cyclo-oxygenase-2 inhibitor (COX-2) agent on hyperthermia induced by SD in rats. We also investigated binding to PGE2 receptors in hypothalamic brain areas of sleep-deprived rats using in vitro autoradiography. Male Wistar rats were deprived of sleep for 96 h using the platform technique. Sleep deprived and control groups received saline or Celecoxib (20, 30 and 40 mg/kg; p.o.) daily during the SD period. Colonic temperature was measured daily.Key findingsResults indicated that core temperature of sleep-deprived rats that receiving saline increased from the first to the fourth day of SD compared to baseline and to the respective control group. However, the hyperthermia induced by SD was not blocked by COX-2 inhibitor at any dose. [³H]PGE2 binding did not differ significantly among the groups in any of a number of hypothalamic areas examined.SignificanceAlthough SD rats showed no response to the COX-2 inhibitor and no alterations in [³H]PGE2 binding, the possibility remains that other prostaglandin system and/or receptor subtypes may be altered by SD.     

Influence of a high-temperature programme on serum,urinary and sweat levels of selenium and zinc

IntroductionThe effect of hyperthermia on the antioxidant system in the human organism is well known.AimThe objective of this study was to observe the effects of heat on the concentration of Se and Zn, elements related to antioxidant systems.MethodsTwenty-nine subjects voluntarily participated in this study. They were divided into a control group (CG; n = 14) and an experimental group (EG; n = 15). All of them underwent two incremental tests until exhaustion in normothermia (22 °C, 20–40%RH) and hyperthermia (42 °C, 20–40%RH). EG experienced nine sessions of repeated heat exposure at high temperatures (100 °C, 20%RH) for three weeks (HEHT). After the intervention, the initial measurements were repeated. Urine and blood samples were collected before and after each test. Additionally, sweat samples were collected after tests in hyperthermia.ResultsThere were no significant changes in serum. An increase in the elimination of Zn and Se in EG was observed in urine after HEHT (p < .05). The elimination of Zn by sweating decreased after HEHT in EG (p < .05).ConclusionsExposure to heat at high temperatures increases the urinary excretion of Se and Zn.     

Quality indicators for hyperthermia treatment: Italian survey analysis

AimNowadays, no Quality Indicators (QI) have been proposed for Hyperthermia treatments. Starting from radiotherapy experience, the aim of this work is to adapt radiotherapy indicators to Hyperthermia and to propose a new specific set of QI in Hyperthermia field.Material and methodsAt first, radiotherapy quality indicators published in literature have been adapted to hyperthermia setting. Moreover, new specific indicators for the treatment of hyperthermia have been defined. To obtain the standard reference values of quality indicators, a questionnaire was sent to 7 Italian hyperthermia Institutes with a list of questions on physical and clinical hyperthermia treatment in order to highlight the different therapeutic approaches.ResultsThree structure, five process and two outcome QI were selected. It has been possible to adapt seven indicators from radiotherapy, while three indicators have been defined as new specific indicators for hyperthermia. Average values used as standard reference values have been obtained and proposed.ConclusionThe survey performed on 7 Italian centres allowed to derive the standard reference value for each indicator. The proposed indicators are available to be investigated and applied by a larger number of Institutes in which hyperthermia treatment is performed in order to monitor the operational procedures and to confirm or modify the reference standard value derived for each indicator.     

Should Food Intake and Circadian Rhythm be Considered When Measuring Serum Calcitonin Level?

ObjectiveTo investigate the relationship between both food intake and circadian rhythmicity and serum calcitonin in the same individuals.MethodsEighteen healthy subjects, 10 males and 8females, aged 22 to 24 years, were recruited. Serum calcitonin level was measured three times: at 0800 after a 9-hour overnight fast, at 0900 postprandially, and at 1700 after another 9-hour fast. The same protocol was repeated once.ResultsThe mean calcitonin levels (at 0800) were 3.92 pg/mL (SD, 2.5 pg/mL) on Day 1 and 3.52 pg/mL (SD, 2.1 pg/mL) on Day 2. Mean postprandial calcitonin (at 0900) was 9.46 pg/mL (SD, 8.6 pg/mL) on Day 1 and 9.91 pg/mL (SD, 6.9 pg/mL) on Day 2. Mean fasting calcitonin in the evening (at 1700) was 6.74 pg/mL (SD, 4.73 pg/mL) on Day 1 and 6.49 pg/mL (SD, 3.57 pg/mL) on Day 2. There was no significant difference in the mean calcitonin level on days 1 and 2 for any of the three time points examined. Statistically significant differences were found between postprandial and evening calcitonin levels and the fasting levels on Day 1 (P = .018 and .015, respectively) and Day 2 (P = .001 and .0009, respectively).ConclusionThese results suggest that serum calcitonin level is significantly influenced by food intake in healthy young subjects and reveal a circadian rhythm, with increased calcitonin level during the afternoon. The timing of blood sampling relative to meals should be integrated into clinical practice and research settings involving serum calcitonin measurements. (Endocr Pract. 2013; 19:620-626)     

Effects of exposure to high temperatures on serum,urine and sweat concentrations of iron and copper

The objective of this research was to determine the acute effect of a maximum test until exhaustion in normothermia and hyperthermia, and after repeated exposure to heat at high temperatures on the homeostasis of Fe and Cu.The sample was composed of twenty-nine male university students. The participants were divided into a control group (CG) and an experimental group (EG). All of them underwent an incremental test until exhaustion in normothermia and hyperthermia before and after the repeated exposure of EG to heat at high temperatures, consisting of 9 heat acclimatisation sessions in the sauna. Samples of urine and blood were taken before and after each test. Additionally, sweat samples were collected in the hyperthermia test. The samples were frozen at −80 °C for further analysis by ICP-MS.None of the metal concentrations in serum were affected by hyperthermia or exposure to heat. Urinary Fe increased in CG in the hyperthermia test before Heat exposure at High Temperature (HEHT)(p < 0.05) and in both groups after HEHT (p < 0.05). In EG there was an increase in the urinary excretion of Cu after HEHT (p < 0.01) in both trials. Fe suffered a decrease in sweat in EG after exposure to heat (p < 0.05).The concentrations of Fe and Cu in serum were not affected by acute exercise and exposure to high temperatures. However, there was a decrease in excretion of Fe in sweat due to HEHT, and an increase in urinary excretion in both. Therefore, we think that in conditions of high temperatures for long periods of time, attention should be paid to the body levels of these metals.     

BDNF serum concentrations in first psychotic episode drug-naïve schizophrenic patients: Associations with personality and BDNF Val66Met polymorphism

AimsTo investigate the relationship among brain derived neurotrophic factor (BDNF) serum concentrations, BDNF Val66Met polymorphism and personality profile in drug-naïve schizophrenic patients with first-episode psychosis (FEP) and healthy participants.Main methodsThis cross-sectional study included fifty FEP patients and fifty healthy participants who served as controls. To study their personality profile the standardized Greek version of the Alternative Five-Factor Zuckerman–Kuhlman Personality Questionnaire (ZKPQ) was administered. Serum BDNF levels were measured and genotyping of BDNF Val66Met polymorphism was performed in patients and healthy subjects.Key findingsFEP patients presented lower BDNF serum concentrations (P = 0.002) and higher scores in ZKPQ Neuroticism (P = 0.001) and Aggression–Hostility (P = 0.002) scales while lower scores in the ZKPQ Sociability scale (P < 0.001) than healthy participants. Multivariate analysis revealed that the odds of being assessed with FEP were 0.4 times lower in those with higher BDNF values (P < 0.001) and 1.8 times greater in those with higher Neuroticism scores (P < 0.001). There were no significant differences with respect to the Val66Met polymorphism between patients and healthy participants.SignificanceReduced BDNF serum concentrations along with higher Neuroticism scores might be associated with FEP. A complex interplay between BDNF serum concentrations, personality traits, BDNF Val66Met polymorphism, and psychotic symptomatology has been arisen but further investigation is needed to better clarify the observed associations.     

Cancer cells resist hyperthermia due to its obstructed activation of caspase 3

AimIt is well known that inducing hyperthermia is a type of cancer treatment but some research groups indicate that this treatment is not effective. This article finds and explains the mechanism of this treatment and its possible problems.BackgroundHyperthermia is commonly known as a state when the temperature of the body rises to a level that can threaten one’s health. Hyperthermia is a type of cancer treatment in which body tissue is exposed to high temperatures (up to 45 °C). Research has shown that high temperatures can damage and kill cancer cells, usually with minimal injury to normal tissues. However, this mechanism is not known.Materials and MethodsWe recently treated cancer cells with different temperatures ranging from 37 °C to 47 °C and further measured their caspase 3 secretion by ELISA, western blot and cell survival rate by microscope.ResultsWe found that most cancer cells are able to resist hyperthermia more than normal cells most likely via non-activation of caspase3. We also found that hyperthermia-treated (≥41°) cancer cells extend a long pseudopod-like extension in comparison to the same cancer cells under normal conditions.ConclusionOur data here indicates that cancer cells have resistance to higher temperatures compared to normal cells via non-activation of caspase 3. This is a significant issue that needs to be brought to attention as the medical community has always believed that a high temperature treatment can selectively kill cancer/tumor cells. Additionally, we believe that the pseudopod-like extensions of hyperthermia-treated cancer cells must be related to its resistance to hyperthermia.     

Physiological and psychological responses in Fire Instructors to heat exposures

AimFire Service Instructors (FSI) are exposed to many repeated periods of high environmental temperatures when training firefighters. Such repeated exposures will impose significant strains on the function of instructors. We aimed to measure the effects of a training programme including repeated exposures to heat, termed “Wears” in the fire service, on the physiological, psychological some immunological markers of Fire Service Instructors.MethodsSix FSI and six physiologically matched controls completed blood and cardiovascular tests pre and post a 4 wk heat instruction training block, controls completed the tests only. FSI were given a 7 wk period of no heat exposure prior to starting the training. Physiological and perceptual measures were taken pre and post the first and last Wear of the 4 wk training protocol.ResultsThere were acute effects of a Wear on core temperature and physiological strain index, as well as measures of fatigue. The acute exposure to heat during a Wear led to a consistent decrease in CRP (−10% to −40%), increased IL6 concentrations 33–45%) as well as increased RPE and TSS. Over the training programme significantly lower quantities of white cells, particularly neutrophils, leukocytes and monocytes were found in the FSI group. Between the start and the end of the 4 week training programme the FSI showed a significantly greater physiological strain index (PSI) to the Wears, which nearly doubled from 2.5 to 4.7 (p<0.05).ConclusionPhysiological and psychological measures indicate that FSI may be experiencing symptoms and changes to their health consistent with an overtraining type condition.     

The effect of encapsulated glutamine on gut peptide secretion in human volunteers

ContextWeight loss and improved blood glucose control after bariatric surgery have been attributed in part to increased ileal nutrient delivery with enhanced release of glucagon-like peptide 1 (GLP-1). Non-surgical strategies to manage obesity are required. The aim of the current study was to assess whether encapsulated glutamine, targeted to the ileum, could increase GLP-1 secretion, improve glucose tolerance or reduce meal size.MethodsA single-center, randomised, double blind, placebo-controlled, cross-over study was performed in 24 healthy volunteers and 8 patients with type 2 diabetes. Fasting participants received a single dose of encapsulated ileal-release glutamine (3.6 or 6.0 g) or placebo per visit with blood sampling at baseline and for 4 h thereafter. Glucose tolerance and meal size were studied using a 75 g oral glucose tolerance test and ad libitum meal respectively.ResultsIn healthy volunteers, ingestion of 6.0 g glutamine was associated with increased GLP-1 concentrations after 90 min compared with placebo (mean 10.6 pg/ml vs 6.9 pg/ml, p = 0.004), increased insulin concentrations after 90 min (mean 70.9 vs 48.5, p = 0.048), and increased meal size at 120 min (mean 542 g eaten vs 481 g, p = 0.008). Ingestion of 6.0 g glutamine was not associated with significant differences in GLP-1, glucose or insulin concentrations after a glucose tolerance test in healthy or type 2 diabetic participants.ConclusionsSingle oral dosing of encapsulated glutamine did not provoke consistent increases in GLP-1 and insulin secretion and was not associated with beneficial metabolic effects in healthy volunteers or patients with type 2 diabetes.     

Plasma Concentrations of Brain-derived Neurotrophic Factor in Patients Undergoing Minor Surgery: A Randomized Controlled Trial

We measured perioperative plasma concentrations of brain-derived neurotrophic factor (BDNF), a major mediator of synaptic plasticity in the central nervous system, in males, 30-65 years old, undergoing lumbar or cervical discotomy. Patients were randomly allocated to a general anesthetic with propofol induction and maintenance or with thiopental induction and isoflurane maintenance. BDNF plasma concentrations were measured before induction (baseline), 15 min after induction but before start of surgery, at skin closure, in the post-anesthetic care unit, and 24 h postoperatively. Data from 26 patients (13 in each group) were analyzed. At each time point, BDNF plasma concentrations showed large variability. At baseline, concentrations were 631 +/- 337 (mean +/- SD) pg ml(-1) in the propofol group and were 549 +/- 512 pg ml(-1) in the thiopental-isoflurane group (P = 0.31). At 15 min, concentrations significantly decreased in the propofol group (247 +/- 219 pg ml(-1), P = 0.0012 compared with baseline) but remained unchanged in the thiopental-isoflurane group (597 +/- 471 pg ml(-1), P = 0.798 compared with baseline). At skin closure and in the post-anesthetic care unit, concentrations were not different from baseline in both groups. At 24 h, concentrations significantly decreased below baseline in both groups (propofol: 232 +/- 129 pg ml(-1), P = 0.0015; thiopental-isoflurane: 253 +/- 250 pg ml(-1), P = 0.016). In the propofol group, there was a weak but statistically significant positive correlation (R2 = 0.38, P = 0.026) between the duration of surgery and BDNF plasma concentrations at skin closure. These data suggest that in males undergoing elective minor surgery, BDNF plasma concentrations show a specific pattern that is influenced by the anesthetic technique and, possibly, by the duration of surgery.     

Influence of repeated hyperthermia on the early development of carcinogen-induced rat mammary cancers; Refinement of a technique for hyperthermia research

• 1.1.|Hyperthermia (c. 41°C) occurs in mammals (e.g. humans) during normal life-history events such as fever and vigorous exercise. The effects of such episodic hyperthermia on early developmental stages of cancer are of potential importance, yet have been investigated hardly at all.
• 2.2.|We injected female Sprague-Dawley rats with the mammary-gland carcinogen 7,12-dimethylbenzathracene and, over a 4-week period before cancer onset, subjected them to 20 1-h episodes of whole-body hyperthermia (41.2°C colonic) to determine effects on subsequent appearance of carcinomas.
• 3.3.|Hyperthermia did not have significant effects on the development of clinical disease in this system, indicating that precancerous or incipient cancerous cells are not susceptible to damage by the levels of hyperthermia associated with normal life-history events.
• 4.4.|For repeated induction of hyperthermia with minimal confounding effects of stress, we refined a technique in which hyperthermia-treated animals, as well as controls, were anesthetized with sodium pentabarbital during thermal treatments, thus suppressing thermoregulation and higher brain functions.

     

The effect of exercise training modality on serum brain derived neurotrophic factor levels in individuals with type 2 diabetes

Introduction

Brain derived neurotrophic factor (BDNF) has been implicated in memory, learning, and neurodegenerative diseases. However, the relationship of BDNF with cardiometabolic risk factors is unclear, and the effect of exercise training on BDNF has not been previously explored in individuals with type 2 diabetes.

Methods

Men and women (N = 150) with type 2 diabetes were randomized to an aerobic exercise (aerobic), resistance exercise (resistance), or a combination of both (combination) for 9 months. Serum BDNF levels were evaluated at baseline and follow-up from archived blood samples.

Results

Baseline serum BDNF was not associated with fitness, body composition, anthropometry, glucose control, or strength measures (all, p>0.05). Similarly, no significant change in serum BDNF levels was observed following exercise training in the aerobic (−1649.4 pg/ml, CI: −4768.9 to 1470.2), resistance (−2351.2 pg/ml, CI:−5290.7 to 588.3), or combination groups (−827.4 pg/ml, CI: −3533.3 to1878.5) compared to the control group (−2320.0 pg/ml, CI: −5750.8 to 1110.8). However, reductions in waist circumference were directly associated with changes in serum BDNF following training (r = 0.25, p = 0.005).

Conclusions

Serum BDNF was not associated with fitness, body composition, anthropometry, glucose control, or strength measures at baseline. Likewise, serum BDNF measures were not altered by 9 months of aerobic, resistance, or combination training. However, reductions in waist circumference were associated with decreased serum BDNF levels. Future studies should investigate the relevance of BDNF with measures of cognitive function specifically in individuals with type-2 diabetes.     

Increased Plasma Levels of Brain Derived Neurotrophic Factor (BDNF) in Patients with Fibromyalgia

Brain-derived neurotrophic factor (BDNF) is involved in neuronal survival and synaptic plasticity of the central and peripheral nervous system. BDNF appears to modulate nociceptive sensory inputs and pain hypersensitivity and has been studied in pathological situations, including chronic pain conditions and major depression. Increased serum BDNF levels have been recently reported in fibromyalgia (FM). In the present study, we assessed plasma BDNF levels in patients with FM and controls. Plasma BDNF was measured from 30 female patients with FM and 30 healthy age- and gender-matched volunteers using an enzyme immunoassay. FM patients showed higher levels of BDNF (FM = 167.1 ± 171.2 pg/mL) when compared with the control group (control = 113.8 ± 149.6 pg/mL) (P = 0.049; Mann–Whitney test). Six out of 30 controls presented superior values to the medium (15/15) of the patients with fibromyalgia (129 pg/mL) (P = 0.029, Fisher exact test). There was no correlation between plasma BDNF levels and age, disease duration, pain score, number of pain points and HAM-D score. Our results confirm previous findings of increased plasma BDNF levels in patients with FM, suggesting that BDNF may be involved in the pathophysiology of Fibromyalgia, despite high levels of depression.     

Fluvoxamine and sigma-1 receptor agonists dehydroepiandrosterone (DHEA)-sulfate induces the Ser473-phosphorylation of Akt-1 in PC12 cells

AimsThe expression of brain-derived neurotrophic factor (BDNF) may be a downstream target of a variety of antidepressant treatments, and selective serotonin reuptake inhibitors (SSRIs) are used clinically for the treatment of depression. BDNF binds to and activates tyrosine kinases receptor (TrkB) to exert its effects. TrkB, after activation by ligands, stimulates phosphoinositide 3-kinase (PI3K). The downstream target of PI3K is Akt-1, a serine-threonine kinase. BDNF has signaling through the PLC-?IP₃/Ca²⁺ pathway. Furthermore, the PLC-?γ/IP₃/Ca²⁺ pathway is regulated by the sigma-1 receptors. Here, we examined whether fluvoxamine (FLV) activated Akt-1 and increased phosphorylation of Akt-1 via sigma-1 receptor in PC12 cells.Main methodsWe examined the effect of the SSRI, FLV and BDNF on the phosphorylation levels of serine-threonine kinase Akt-1 in PC12 cells using immunoblotting techniques.Key findingsTreatment with 10 μM and 100 μM FLV of PC12 cells stimulated a 2.4- and 3.8-fold maximal increase in Ser⁴⁷³-phosphorylated Akt-1 levels at 40 min, respectively. Treatment with 50 ng/ml BDNF also stimulated Ser⁴⁷³ -phosphorylated Akt-1 by 2.6-fold with a maximal increase at 5 min. In addition, the phosphorylation induced by FLV and BDNF was blocked by LY294002, a selective inhibitor of PI3K. The sigma-1 receptor agonists dehydroepiandrosterone (DHEA)-sulfate also stimulated a 2.1-fold increase in the level of Ser473-phosphorylated Akt-1.SignificanceThis study demonstrates that fluvoxamine treatment rapidly increased phosphorylation of Akt-1. And BDNF activated Akt-1 phosphorylation by the TrkB/PI3K/Akt-1 pathway. We conclude that the phosphorylation of Akt-1, downstream of PI3K, was the key to their antidepressant effects.     

A microsphere-based duplex competitive immunoassay for the simultaneous measurements of aldosterone and testosterone in small sample volumes: Validation in human and mouse plasma

BackgroundThe small blood volumes available in rodent studies often limit adequate quantification of all hormones of interest. We report here the development of two new assays combining an extraction step with multiplex immunoassay (MIA) technology for the simultaneous determination of aldosterone and testosterone in 50 μl sample volume.MethodsFollowing solvent extraction, aldosterone and testosterone competitive immunoassays are performed incorporating biotinylated tracers and antibody-coated beads each having a unique fluorescence. Quantification is via addition of streptavidin–R–phycoerythrin (SA–PE). The assays were validated and compared to established methods. Baseline hormone levels in mice from four different strains, and changes after ACTH and HCG stimulation in CD-1 mice are shown.ResultsThe assays are sensitive (aldosterone 15 pg/ml, testosterone 12 pg/ml), reproducible (intra-/inter-assay imprecision aldosterone 5.1–15.6%/9.9–15.8% and testosterone 9.7–10.9%/7.7–11.4%) and correlate significantly to established assays (r = 0.94–0.95). Baseline aldosterone levels varied between strains, but not between the genders. Testosterone was significantly higher in male of all strains except in C57BL/6× NMRI mice. After ACTH injection, aldosterone (median, interquartile range) rose from 354 (261–396) pg/ml to 2008 (875–2467) in male and from 260 (210–576) to 1120 (734–1528) in female CD-1 mice. HCG injection in the same strain increased testosterone in male mice only (3.5 (0.4–8.3) ng/ml to 31.8 (30.4–33.9) ng/ml, P < 0.01).ConclusionsWe describe a MIA for the simultaneous measurement of aldosterone and testosterone in small volumes after extraction. In addition to presenting a new tool for steroid research in rodent models, our data show strain-dependent differences in steroid hormone metabolism in rodents.     

热疗联合奥沙利铂对SW480细胞增殖和凋亡的影响

目的:观察奥沙利铂联合热疗对人结肠癌细胞SW480增殖及凋亡的影响,确定联合用药的效果,为临床方案提供参考。方法:采用MTT(四唑盐)法检测热疗、奥沙利铂及联合用药对细胞增殖的影响;瑞士吉姆萨染色法观察细胞形态;流式细胞仪检测细胞凋亡和周期;Western blot检测Bax、Bcl-2以及Caspase8蛋白表达量变化;q PCR检测Bax、Bcl-2以及Caspase8 m RNA的积累。结果:热疗联合奥沙利铂可以显著抑制细胞增殖,与对照组相比,热疗组、化疗组、联合组细胞凋亡率分别为16.2%、20.5%和36.1%,具有显著性差异(P0.01);细胞学形态中,热疗组细胞发生皱缩,化疗组细胞膜破裂;化疗将细胞阻滞在G2/M期,热疗和联合组将细胞阻滞S期;Western blot和qPCR显示Bax/Bcl-2比值上升,Caspase8表达量增加,联合组三种蛋白的表达量均与对照组具有显著性差异(P0.01)。结论:热疗联合奥沙利铂可以显著促进细胞凋亡,提高治疗效果,为结肠癌的治疗提供参考。     

Evaluation of brain-derived neurotrophic factor in menstrual blood and its identification in human endometrium

The presence of high-affinity brain-derived neurotrophic factor receptor Trk B in mouse and in human fetal oocytes, together with the presence of neurotrophins in human follicular fluid suggests a paracrine role for brain-derived neurotrophic factor (BDNF) in female biology. This study aims to evaluate if BDNF is present and quantitatively determined in human menstrual blood and endometrium. Twenty-one women were studied and subdivided in two groups: A, 11 fertile women (27 ± 2 days cycle length) and B, 10 anovulatory women and/or women with inadequate luteal phase (36 ± 2 days cycle length). In fertile women menstrual BDNF levels was higher than plasma (679.3 ± 92.2 vs 301.9 ± 46.7 pg/ml p <0.001). Similarly, in Group B, BDNF in menstrual blood was higher than plasma (386.1 ± 85.2 vs 166.8 ± 24.1 pg/ml p < 0.001). Moreover, both menstrual and plasma BDNF concentrations in Group A were significantly higher respect to Group B (679.3 ± 92.2 vs 386.1 ± 85.2 pg/ml p < 0.001; 301.9 ± 46.7 vs 166.8 ± 24.1 pg/ml p < 0.001). Immunohistochemistry evidence of BDNF in endometrium, during follicular and luteal phase, was also shown. The detection of BDNF in the human menstrual blood and endometrium further supports the role of this neurotrophin in female reproductive function.     

Specific induction of a 72-kDa heat shock protein protects esophageal mucosa from reflux esophagitis

AimsThe aim of this study is to investigate the expression and cytoprotective function of a 72-kDa heat shock protein (HSP72) using a reflux esophagitis model in rats.Main methodsExpression of HSP60, HSP72, and HSP90 in rat esophageal mucosa was evaluated by Western blot analysis before and after hyperthermia (42.5 °C, 20 min). Rats received the operation to produce reflux esophagitis with or without pretreatment with hyperthermia to induce HSPs. The esophageal mucosal damage was evaluated 12 h after the operation.Key findingsExpression of HSP72 was significantly increased by hyperthermia in rat esophageal mucosa. Reflux esophagitis was dramatically prevented when HSP72 was preinduced by hyperthermia. Furthermore, activation of TNF-α and IL-1β in esophageal mucosa was also suppressed.SignificanceThese results suggested that hyperthermia protects the esophageal mucosa in reflux esophagitis model by inducing HSP72 and suppressing proinflammatory cytokine activation. These findings might suggest that HSP-inducing therapy could be a novel and unique therapy for reflux esophagitis.     

Tumor Necrosis Factor gene polymorphism results in high TNF level in sepsis and septic shock

IntroductionSystemic sepsis releases several cytokines among which tumor necrosis factor alfa (TNFα) has emerged as key cytokine causing septic shock. Single Nucleotide Polymorphisms (SNPs) at positions ?238, ?308, ?376 and +489 in the promoter region of TNF gene exhibit differential association to inflammation and increased TNF production in sepsis.Materials and MethodsThis research work was carried out in 278 critically ill patients and 115 controls. The patients were divided into four groups: Healthy controls, SIRS, Sepsis and Septic shock. Plasma cytokine level was evaluated by ELISA. Specific sequences of TNF gene (?238, ?308, ?376, +489) were amplified using polychromase chain reaction (PCR). SNP detected by BamHiI, NcoI, FokI, TaiI restriction enzymes.ResultsMean plasma TNFα level in healthy Control group was 8.37 ± 2.23 pg/ml, in SIRS group, the mean plasma TNFα level was 77.99 ± 5.51 pg/ml, in Sepsis patients 187.1 ± 14.33 pg/ml and in septic shock 202.2 ± 14.85 pg/ml; range 56.17–417.1 pg/ml. SNP was studied among different patient groups, which showed a higher frequency of mutants among sepsis and shock patients as compared to control.ConclusionPlasma TNF alpha level was significantly high in patients with sepsis and septic shock. SNP of TNF gene showed significant association between polymorphism and development of severe sepsis and septic shock, this would help us in evaluating patients at high risk for septic shock and such patients needed to obtain a rational basis for therapy.