Impact of VEGFA promoter polymorphisms on esophageal cancer risk in North-West Indians: a case-control study.

BACKGROUND: Angiogenesis play a critical role in the development and progression of tumors in solid tumors. Vascular endothelial growth factor (VEGF) is one of the most important endothelial cell mitogen which plays a critical role in normal physiological and tumor angiogenesis. OBJECTIVES: The objective of this case-control study was to investigate the association of VEGF-2578C/A, -2549 I/D, and -460T/C promoter polymorphisms with esophageal cancer risk in North-West Indians. METHODS: In this study, 200 sporadic esophageal cancer patients and 200 healthy, unrelated, age and gender matched controls were analyzed. The genomic DNA was extracted from blood samples using phenol chloroform method. Genotyping of VEGF- 2549I/D polymorphism was carried out by direct polymerase chain reaction (PCR) whereas VEGF -2578C/A and VEGF-460T/C) polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: AA genotype (p = 0.005) and A allele (p = 0.005) VEGF -2578 C/A, II genotype (p = 0.011) and I allele (p = 0.012) of VEGF - 2549 I/D and CC genotype (p = 0.013) and C allele of VEGF-460T/C polymorphisms were significantly associated with increased risk of esophageal cancer. Stratification of data on the basis of gender showed that VEGF -2578 AA genotype (p = 0.001) and A allele (p = 0.001); VEGF -2549 II genotype (p = 0.002) and I allele (p = 0.002) and VEGF- 460CC genotype (p = 0.001) and C allele (p = 0.002) was significantly associated with increased risk of esophageal cancer in female group. Haplotype analysis revealed that A-2578 I- 2549 C- 460 haplotype was significantly associated with increased risk for esophageal cancer in total samples (p = 0.008) as well as in female group (p = 0.001). CONCLUSIONS: The results of present study indicate that VEGF -2578C/A, - 2549I/D and -460T/C polymorphisms were significantly associated with increased risk of esophageal cancer in North-West Indians.

Hydroxychloroquine pre-exposure prophylaxis provides no protection against COVID-19 among health care workers: a cross-sectional study in a tertiary care hospital in North India.

OBJECTIVES: The use of Hydroxychloroquine (HCQ) prophylaxis has been recommended by the National task force constituted by the Indian Council of Medical Research (ICMR) for the prevention of corona virus disease 2019 (COVID-19) among healthcare workers (HCWs). However, this recommendation was based essentially on the preclinical data and limited clinical experience. The aim of this study was to evaluate the efficacy and safety of HCQ as a pre-exposure prophylaxis for COVID-19 infection among Indian HCWs. METHODS: A cross-sectional study was conducted among HCWs of a tertiary care hospital in north India. The HCQ prophylaxis was initiated among 996 HCWs and they were followed up to 8 weeks for conversion to COVID-19 positive status and any adverse drug reaction (ADR). RESULTS: About 10.3% of the study participants were tested positive for COVID-19 which was comparable to the positivity rate among HCWs not taking HCQ prophylaxis (9.7%). CONCLUSIONS: HCQ was well tolerated at a weekly dose of 400 mg for 8 weeks but provided no additional benefit in prevention of COVID-19 among HCWs.

Investigating the role of acute and repeated stress on remote ischemic preconditioning-induced cardioprotection.

OBJECTIVES: To study the effect of acute and repeated stress on cardioprotection-induced by remote ischemic preconditioning (RIPC). MATERIALS AND METHODS: RIPC was induced by giving 4 short cycles of ischemia and reperfusion, each consisting of five min. The Langendorff's apparatus was used to perfuse the isolated rat hearts by subjecting the hearts to global ischemia of 30 min and reperfusion of 120 min. The coronary effluent was collected to measure the levels of lactate dehydrogenase (LDH) and creatine kinase (CK) for the assessment of injury to the myocardium. Myocardial infarct size was measured by the use of triphenyl tetrazolium chloride. Acute stress was induced by subjecting the animals to cold immersion stress for 5 min. However, in the case of stress adaptation, rats were exposed to a homotypic stressor (cold-water immersion stress) each of 5 min duration for five consecutive days. RESULTS: RIPC demonstrated a significant decrease in ischemia-reperfusion-induced myocardial injury in terms of decrease in LDH, CK, and infarct size. However, acute stress for five minutes prior to RIPC significantly abolished its cardioprotective effects. Exogenous administration of adenosine restored RIPC-induced cardioprotective effects in the presence of acute stress. On repeated stress exposure for 5 days, stress adaptation was noted, and there was no effect of repeated stress exposure on RIPC-induced cardioprotection. However, the cardioprotective effects of adenosine were absent in the case of rats subjected to repeated episodes of stress. CONCLUSION: Acute stress, but not repeated stress exposure, may alter the release of adenosine during RIPC, which may be manifested in the form of reduced cardioprotection during ischemic-reperfusion injury.

Dual role of T-type calcium channels in anxiety-related behavior.

T-type calcium channels are low voltage activated calcium channels that are widely expressed in various brain regions including stress-responsive regions. These channels regulate the diverse functions of the central nervous system, and modulation of these channels is shown to modulate the anxiety. Studies have described that modulation of T-type calcium channels may either aggravate or ameliorate anxiety-related behavior, suggesting the dual role of these channels. The studies employing animals with overexpression of T-type calcium channels reported their anxiety-inducing role. Therefore, the blockade of these channels using various pharmacological agents such as ethosuximide, plant extracts of linalool or rosemary, and corticotropin-releasing factor (CRF) is reported to ameliorate anxiety. On the contrary, knockout of the gene encoding these channels predisposes the rodents to anxiety-related disorders, suggesting the anxiety-attenuating role of these channels. It may be possible that these channels in normal or basal state attenuate anxiety, whereas activation of these channels in stressful condition may produce anxiety. The present review describes the dual role of T-type calcium channels in anxiety-related behavior in both preclinical and clinical studies.

Opening of T-type Ca2+ channels and activation of HCN channels contribute in stress adaptation in cold water immersion stress-subjected mice.

AIM: The present study was designed to investigate the possible role of T-type Ca2+ channels and HCN channels in the development of stress adaptation in cold-water immersion stress-subjected mice. MATERIAL AND METHODS: The mice were subjected to cold-water immersion stress by placing them individually in a water tank (depth = 15.5 cm; temperature = 15 ±â€¯2 °C) for 5 min. The mice were subjected to single episode of cold-water immersion stress for inducing acute stress; while for inducing stress adaptation, mice were subjected to repeated episodes of homotypic stressor (5 min) for 5 consecutive days. Animals were administered with ethosuximide (100 and 200 mg/kg, i.p.) and ivabradine (5 and 10 mg/kg, i.p.) before subjecting them to stress for five days. The stress-related behavioral alterations were assessed using the actophotometer, the hole board, the open field and the social interaction tests. The plasma corticosterone levels were quantified as a biochemical parameter of hypothalamic-pituitary-adrenal (HPA) axis activation. RESULTS: Acute stress altered the behavioral and biochemical parameters of the animals. However, repeated stress significantly restored the behavioral and biochemical alterations signifying the development of adaptation. Administration of ethosuximide and ivabradine abolished the restoration of behavioral and biochemical changes in the animals subjected to repeated stress. CONCLUSION: The ethosuximide and ivabradine mediated attenuation of stress adaptation demonstrates that the opening of T-type Ca2+ channels and activation of HCN channels are involved in inducing stress adaptation in repeated stress-subjected animals.