Levels of benzene concentrations emitted from motor vehicles in various sites in Nibong Tebal, Malaysia

Benzene is classified as carcinogenic compound which is emitted mainly from cars. In this study, benzene was measured at various sites in Nibong Tebal (urban, suburban, town, and rural) of different traffic volume, and traffic counts were performed simultaneously. Monitoring was carried out during the morning and afternoon traffic peaks. The aim of this study is to monitor benzene concentration at several development sites with different traffic flow. The monitoring was done by using indoor air quality meter. The results obtained from monitoring show that the mean concentrations of benzene ranged from 54.7 ppb in the suburban area to 115.1 ppb in the town area. Multiple linear regression analysis correlated the benzene concentrations with traffic volume, temperature, humidity, and time of monitoring as predictors. The results show that R ² of the model was 0.97 in Taman Cowin site, and it was 0.47 in Taman Nibong Tebal Jaya site. Negative correlation was found between benzene concentration and temperature while there was positive correlation with humidity being found through the study. Pearson’s correlation indicates that gasoline vehicular exhaust could be the major source of benzene. The UK Air Quality Standards stipulated that the annual mean of ambient benzene should not exceed 5 ppb or 16.25 μg/m³. The results show that the current concentrations of benzene exceeded the permissible limits set by the UK standards.     

Nitric-oxide-induced inhibition of glyceraldehyde-3-phosphate dehydrogenase may mediate reduced endothelial cell monolayer integrity in an in vitro model blood–brain barrier

The process of nitric-oxide (NO)-induced cellular toxicity may involve energy deprivation since the radical is reported to prevent both mitochondrial oxidative phosphorylation and glycolysis. In order to determine whether these processes are important in NO-induced blood–brain barrier (BBB) dysfunction, we used a cell culture model of the BBB and compared the effects of gaseous NO, potassium cyanide (KCN, a mitochondrial respiratory chain inhibitor) and iodoacetate [IA, an inhibitor of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH)] on endothelial cell ATP content, GAPDH activity and barrier integrity. NO lead to a rapid breakdown in model barrier integrity and resulted in a reduction in endothelial cell ATP content and GAPDH activity. KCN had no effect on endothelial cell ATP content or barrier integrity, while IA, at a concentration that completely blocked endothelial cell GAPDH activity, resulted in a rapid decline in ATP content but did not lead to a decline in barrier integrity until at least 2 h of exposure. These results indicate that inhibition of endothelial cell GAPDH activity rather than mitochondrial respiration causes an energy deficiency and delayed barrier dysfunction. However, the rapid detrimental effects of gaseous NO on barrier integrity cannot be fully explained by endothelial cell energy depletion and may be related to the actions of the free radical and its products on cellular lipids.     

A phase I study of nonmyeloablative chemotherapy and adoptive transfer of autologous tumor antigen-specific T lymphocytes in patients with metastatic melanoma

This report describes a phase I clinical trial using nonmyeloablative, lympho-depleting chemotherapy in combination with adoptive immunotherapy in patients with metastatic melanoma. The chemotherapy-conditioning schedule that induced transient lymphopenia consisted of cyclophosphamide (30 or 60 mg/kg per day for 2 days) followed by fludarabine (25 mg/m(2) per day for 5 days). Immunotherapy for all patients consisted of in vitro expanded, tumor-reactive, autologous T-cell clones selected for high avidity recognition of melanoma antigens. Cohorts of three to six patients each received either no interleukin (IL)-2, low-dose IL-2 (72,000 IU/kg intravenously three times a day to a maximum of 15 doses), or high-dose IL-2 (720,000 IU/kg intravenously three times a day for a maximum of 12 doses). The toxicities associated with this treatment were transient and included neutropenia and thrombocytopenia that resolved in all patients. High dose intravenous IL-2 was better tolerated by patients after chemotherapy than during previous immunotherapy cycles without chemotherapy. No patient exhibited an objective clinical response to treatment, although five patients demonstrated mixed responses or transient shrinkage of metastatic deposits. This study established a nonmyeloablative-conditioning regimen that could be safely administered in conjunction with adoptive T-cell transfer and IL-2 in patients with metastatic melanoma.     

Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 (PPARgamma-2) gene is associated with greater insulin sensitivity and decreased risk of type 2 diabetes in an Iranian population.

BACKGROUND: The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 (PPARgamma-2) gene has been variably associated with insulin resistance, obesity and type 2 diabetes in several populations. However, this association has not been studied in Iranian subjects and we hypothesized that this variation might be associated with insulin resistance, type 2 diabetes and related metabolic traits in this population. METHODS: The Pro12Ala genotypes were determined by PCR-restriction fragment length polymorphism in 696 unrelated subjects including 412 non-diabetic controls and 284 type 2 diabetic patients. RESULTS: The frequency of the Ala allele was 9.4% and 5.9% in controls and type 2 diabetic subjects, respectively [adjusted odds ratio (OR) 0.457, p=0.005]. The Ala allele did not show a significant effect on anthropometric and biochemical parameters in the type 2 diabetic group, whereas in non-diabetic subjects, carriers of the Ala allele had significantly lower fasting insulin (p=0.007) and homeostasis model assessment of insulin resistance (HOMA-IR) (p=0.009) levels compared to Pro/Pro subjects. Multivariate logistic regression analysis showed that Pro12Ala polymorphism was an independent determinant of type 2 diabetes in this population. CONCLUSIONS: Our results for a sample of Iranian type 2 diabetes cases and controls provide evidence that the Pro/Ala genotype of the PPARgamma-2 gene is associated with insulin sensitivity and may also have protective role against type 2 diabetes.     

Clinical trials update from the European Society of Cardiology Meeting 2010: SHIFT, PEARL-HF, STAR-heart, and HEBE-III

This article provides information and a commentary on key trials relevant to the pathophysiology, prevention, and treatment of heart failure (HF) presented at the annual meeting of the European Society of Cardiology held in Stockholm in 2010. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. The SHIFT study supports the use of ivabradine in patients with HF due to left ventricular systolic dysfunction and resting sinus rhythm rate ≥70 b.p.m. despite treatment with beta-blockers or where beta-blockers are contra-indicated. Results from PEARL-HF suggest that the potassium binding polymer RLY5016 may be useful for both prevention and treatment of hyperkalaemia in HF patients with or without concomitant chronic kidney disease. The STAR-heart study provides encouraging observational data about the potential for intracoronary stem cell transplantation in patients with HF. Results from HEBE-III showed no effect of erythropoietin on ejection fraction measured 6 weeks post-MI; although there were fewer cardiovascular events in patients assigned to erythropoietin, the study was too small to provide conclusive evidence of effect.     

Targeting oxidative stress component in the therapeutics of epilepsy

The role of free radical-mediated reactions in human neuropathology continues to attract significant interest. Oxidative injury produced by free radicals may play a role in the initiation and progression of epilepsy and, therapies aimed at reducing oxidative stress may ameliorate tissue damage and favorably alter the clinical course. The prevalence of epilepsy increases with age, and mitochondrial oxidative stress is a leading mechanism of aging and age-related degenerative disease, signifying a further involvement of mitochondrial dysfunction in seizure generation. Oxidative stress occurs when the generation of reactive oxygen species in a system exceeds the body's ability to neutralize and eliminate them, thus creating an imbalance or over abundance of free radicals. Therefore, it is imperative to maintain oxidative balance and control in the brain, and this is tightly regulated by antioxidants. In the last two decades, there has been an explosive interest in the role of antioxidants or neuroprotectants in clinical as well as experimental models of epilepsy. In this regard, the present review is intended to discuss the current state of knowledge pertaining to neuroprotection in epileptic conditions by employing diverse chemical agents including conventional as well as novel anti-epileptic drugs, and to highlight the efficacy of distinct neuroprotective strategies for preventing or treating epilepsy.     

Antinociceptive activity of a synthetic curcuminoid analogue, 2,6-bis-(4-hydroxy-3-methoxybenzylidene)cyclohexanone, on nociception-induced models in mice

Abstract: This study investigated the potential antinociceptive efficacy of a novel synthetic curcuminoid analogue, 2,6‐bis‐(4‐hydroxy‐3‐methoxybenzylidene)cyclohexanone (BHMC), using chemical‐ and thermal‐induced nociception test models in mice. BHMC (0.03, 0.1, 0.3 and 1.0 mg/kg) administered via intraperitoneal route (i.p.) produced significant dose‐related inhibition in the acetic acid‐induced abdominal constriction test in mice with an ID₅₀ of 0.15 (0.13–0.18) mg/kg. It was also demonstrated that BHMC produced significant inhibition in both neurogenic (first phase) and inflammatory phases (second phase) of the formalin‐induced paw licking test with an ID₅₀ of 0.35 (0.27–0.46) mg/kg and 0.07 (0.06–0.08) mg/kg, respectively. Similarly, BHMC also exerted significant increase in the response latency period in the hot‐plate test. Moreover, the antinociceptive effect of the BHMC in the formalin‐induced paw licking test and the hot‐plate test was antagonized by pre‐treatment with the non‐selective opioid receptor antagonist, naloxone. Together, these results indicate that the compound acts both centrally and peripherally. In addition, administration of BHMC exhibited significant inhibition of the neurogenic nociception induced by intraplantar injections of glutamate and capsaicin with ID₅₀ of 0.66 (0.41–1.07) mg/kg and 0.42 (0.38–0.51) mg/kg, respectively. Finally, it was also shown that BHMC‐induced antinociception was devoid of toxic effects and its antinociceptive effect was associated with neither muscle relaxant nor sedative action. In conclusion, BHMC at all doses investigated did not cause any toxic and sedative effects and produced pronounced central and peripheral antinociceptive activities. The central antinociceptive activity of BHMC was possibly mediated through activation of the opioid system as well as inhibition of the glutamatergic system and TRPV1 receptors, while the peripheral antinociceptive activity was perhaps mediated through inhibition of various inflammatory mediators.     

Does COLIA1 SP1-binding site polymorphism predispose women to pelvic organ prolapse?

Introduction and hypothesis  COLIA1 polymorphism is associated with increased risk for stress urinary incontinence. We hypothesize that a similar association exists with pelvic organ prolapse (POP). Methods  Patients with advanced prolapse and healthy controls were evaluated by interview, validated questionnaires, and pelvic examination. DNA was extracted from peripheral blood, and polymerase chain reaction was performed to determine the presence or absence of the polymorphism. Power calculation indicated the need for 36 patients in each arm. Results  The prevalence of the polymorphic heterozygous genotype (GT) in the study and control groups was 33.3% and 19.4%, respectively, leading to an odds ratio of 1.75. This difference, however, did not reach statistical significance (p = 0.27). Conclusions  The COLIA1 polymorphism was not significantly associated with increased risk for POP.