Hypoxia-Induced Inflammatory Chemokines in Subjects with a History of High-Altitude Pulmonary Edema

High altitude hypoxia is known to induce an inflammatory response in immune cells. Hypoxia induced inflammatory chemokines may contribute to the development of high altitude pulmonary edema (HAPE) by causing damage to the lung endothelial cells and thereby capillary leakage. In the present study, we were interested to know whether chronic inflammation may contribute to HAPE susceptibility. We examined the serum levels of macrophage inflammatory protein-1α (MIP-1α), monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 in group (1) HAPE Susceptible subjects (n = 20) who had past history of HAPE and group (2) Control (n = 18) consist of subjects who had stayed at high altitude for 2 years without any history of HAPE. The data obtained confirmed that circulating MCP-1, MIP-1α were significantly upregulated in HAPE-S individuals as compared to the controls suggestive of chronic inflammation. However, it is not certain whether chronic inflammation is cause or consequence of previous episode of HAPE. The moderate systemic increase of these inflammatory markers may reflect considerable local inflammation. The existence of enhanced level of inflammatory chemokines found in this study support the hypothesis that subjects with past history of HAPE have higher baseline chronic inflammation which may contribute to HAPE susceptibility.     

Molecular Mycobacteriology and Expansion in Disease Diagnosis

Molecular diagnostic tools for tuberculosis (TB) have evolved quickly with new innovations which can provide unprecedented opportunities for the rapid, sensitive and specific diagnosis of M. tuberculosis in clinical specimens and the status of its drug sensitivity. Microscopy and culture methods can not be replaced but the molecular assays can be applied in parallel with any new molecular tests for the diagnosis of TB. For extra pulmonary specimens, the use of the amplification methods is advocated, since rapid and accurate laboratory diagnosis is critical. Customization of the diagnostic usefulness of a molecular assay, according to the ease, reliability and need for health care sector is of immense value in a modern clinical mycobacteriology laboratory.     

Evaluation of polymerase chain reaction for rapid diagnosis of clinically suspected tuberculous pleurisy

Pleural effusion is one of the commonest presentations of tuberculosis, the clinical manifestations being typically abrupt resembling bacterial pneumonia. Since delayed hypersensitivity is the underlying immune response, bacterial load is very low. Owing to these facts, tuberculous pleurisy as an extra-pulmonary disease poses a diagnostic dilemma. The conventional bacteriological methods rarely detect Mycobacterium tuberculosis in pleural fluid and are of limited use in diagnosis of tuberculous pleurisy. We evaluated the efficacy of polymerase chain reaction (PCR) in the diagnosis of tuberculous pleurisy by targeting the gene segment coding for MPB64 protein specific forMycobacterium tuberculosis. Based on the clinical criteria, 82 patients with lymphocytic exudative pleural effusion were included in the study. Patients were analyzed in two groups; one group consisting of 48 patients of tubercular pleural effusion confimed by various diagnostic procedures and another group of 34 patients comprising of non-tubercular pleural effusion. There were no false positive results by PCR and the specificity worked out to be 100%. Twenty two patients tested positive for Mantoux with a sensitivity of 45%. ZN-staining for AFB was found in samples from 15 patients (20% sensitivity). ADA was positive for 28 patients with a sensitivity of 53%. PCR was positive for 32/48 patients (67% sensitivity). Thus, PCR was found to be more sensitive than any other conventional method in diagnosis of clinically suspected tubercular pleurisy.     

Evaluation of adenosine deaminase activity and lipid peroxidation levels in diabetes mellitus

There was increase in erythrocyte lipid peroxidation and adenosine deaminase (ADA) activity in red blood cells (RBC's), white blood cells (WBC's) and plasma, in 30 patients of confirmed diabetes mellitus, 10 each of insulin dependent diabetes mellitus (IDDM or type I), non-insulin dependent diabetes mellitus (NIDDM or type II) and diabetes with ketoacidosis when compared with 20 healthy individuals (controls). Glycosylated hemoglobin A1c%, plasma free fatty acid (FFA) and glycerol levels were also elevated in all the cases when compared with controls. The increase was more in diabetic ketoacidosis group. Significant positive correlations were seen between erythrocyte lipid peroxidation and ADA activities in RBC's, WBC's and plasma. It is suggested that decreased tissue adenosine levels due to increase in ADA activity, is related to the severity of hyperglycemia and lipid peroxidation in diabetes mellitus.     

Effect of Certain Antibiotics Against Filarial Parasite <Emphasis Type="Italic">Brugia malayi</Emphasis> In Vitro: Possible Role of Oxidative Stress

WHO-Tropical Disease Research scheme highlighted the need for development of new anti-filarial drugs. Certain antibiotics have recently been found effective against Wolbachia, co-existing symbiotically with filarial parasites. Inflammatory response entails oxidative mechanism to educe direct anti-microbial effect. In the present study microfilariae were maintained in vitro in medium supplemented with varying concentrations of tetracycline, doxycycline (20–100 μg/ml) or ciprofloxacin (50–250 μg/ml) separately to find out any involvement of oxidative mechanism in the anti-filarial effect of these antibiotics. Loss of motility of the microfilariae was measured after 48 h and correlated with the levels of MDA, nitric oxide and protein-carbonylation. Significant loss of microfilarial motility was recorded with increasing concentration of tetracycline and doxycycline but with ciprofloxacin the effect was not marked. Agents with high antifilarial activity revealed significant association with oxidative parameters in a dose dependent manner. The result suggests that oxidative effect might be exploited to design novel antifilarial drug candidate.     

Moderately high altitude habitation modulates lipid profile and alkaline phosphatase activity in aged <Emphasis Type="Italic">Khasis</Emphasis> of Meghalaya

The indigenous Khasis inhabit different geographical and climatic locations of Meghalaya. In this study, we intended to find out whether habitation in moderately high altitude place has any effect on the lipid and liver profile amongst the aged Khasis. The level of various serum parameters under lipid and liver profile were analyzed and compared from aged (65–70 years) male Khasi residents of moderately high (Shillong city) and low (Byrnihat) altitude places. Results obtained from the lipid profile data show decreased total serum cholesterol (29%), triglyceride (27%) and LDL-cholesterol (42%) level in the old Khasis of Shillong compared to Byrnihat. Furthermore, the alkaline phosphatase activity was significantly raised (47%) in the old Khasis from Shillong as against Byrnihat. The decreased level of total cholesterol, triglyceride and LDL-cholesterol in old Khasis from Shillong may be due to living and acclimatization in high altitude with low annual temperature. Moderately high elevation could have acted as a stressor, thereby reducing the level of serum cholesterol, triglyceride and LDL-cholesterol, which may put them at a lower risk of cardiovascular diseases. In comparison, old residents of Byrnihat with high cholesterol, triglyceride and LDL-cholesterol levels may elevate their risk of coronary complications. The raised alkaline phosphatase activity amongst the old Khasis of Shillong could be due to increased bone and/or intestinal turnover as a result of living in high altitude, which, however, may elevate the risk of osteoporosis. Taken together, we conclude that low cholesterol, triglyceride and LDL-cholesterol levels, accompanied with high alkaline phosphatase activity amongst the old Khasis of Shillong, could be due to the influence of high altitude and mild climatic conditions that prevails.     

Effect of calcium channel blockers on stress-induced visceral, endocrinological and immune responses

In the present study effects of five commonly used calcium channel blockers (CCBs) belonging to different chemical classes have been investigated on stress-induced modulation of some visceral, endocrinological and immunological parameters in rats and mice. Restraint stress (RS) produced gastric mucosal lesions, increased plasma corticosterone levels and reduced antiSRBC antibody titre, a measure of humoral immune response and % leucocyte migration inhibition (% LMI) and foot pad thickness, measures of cell-mediated immunity. Nimodipine (10, 20 40 mg/kg, i.p.) and flunarizine (10, 20, 40 mg/kg, i.p.) antagonised the effect of RS on gastric ulcerogenesis and plasma corticosterone levels but failed to modulate the stress-induced suppression of both humoral and cell-mediated immune responses. Thus, CCBs appear to modulate stress-induced visceral, endocrinological and immune responses, albeit in a differential manner.     

Inhibitory effect of metalloporphyrins in conjunction with cholesterol on hepatic phospholipase A2 activityin vivo in rats

We investigated the effect of cholesterol and the metalloporphyrins cobalt mesoporphyrin (CoMP) and chromium protoporphyrin (CrPP) on phospholipase A₂ (PLA₂) activity and the consequent hepatic mitochondrial stability as well as on lipid concentrations. Our studies revealed that on administration of cholesterol, CrPP, CoMP as well as simultaneous adminstration of cholesterol and CrPP, there was an inhibition of PLA₂ activity. These moieties may therefore, be agents for preventing destabilisation of the mitochondrial membrane and the consequent pathological conditions which may arise due to membrane lysis. Our results revealed that cholesterol administration increased phospholipid concentration, albeit by modest amounts. Although the independent administration of metalloporphyrins led only to minor elevations in phospholipid concentration, the simultaneous administration of cholesterol and CrPP generated a steep elevation in the concentration of total phospholipid. Since cholesterol inhibits PLA₂ activity it has the potential of being therapeutic agent for preventing the pathological conditions which may arise due to membrane lysis.     

Global and regional cardiac function in lifelong endurance athletes with and without myocardial fibrosis

The aim of the present study was to compare cardiac structure as well as global and regional cardiac function in athletes with and without myocardial fibrosis (MF). Cardiac magnetic resonance imaging with late gadolinium enhancement was used to detect MF and global cardiac structure in nine lifelong veteran endurance athletes (58?±?5 years, 43?±?5 years of training). Transthoracic echocardiography using tissue-Doppler and myocardial strain imaging assessed global and regional (18 segments) longitudinal left ventricular function. MF was present in four athletes (range 1–8?g) and not present in five athletes. MF was located near the insertion points of the right ventricular free wall on the left ventricle in three athletes and in the epicardial lateral wall in one athlete. Athletes with MF demonstrated a larger end diastolic volume (205?±?24 vs 173?±?18?ml) and posterior wall thickness (11?±?1 vs 9?±?1?mm) compared to those without MF. The presence of MF did not mediate global tissue velocities or global longitudinal strain and strain rate; however, regional analysis of longitudinal strain demonstrated reduced function in some fibrotic regions. Furthermore, base to apex gradient was affected in three out of four athletes with MF. Lifelong veteran endurance athletes with MF demonstrate larger cardiac dimensions and normal global cardiac function. Fibrotic areas may demonstrate some co-localised regional cardiac dysfunction, evidenced by an affected cardiac strain and base to apex gradient. These data emphasize the heterogeneous phenotype of MF in athletes.