Serum Protein Electrophoresis Bands As Biomarkers for Drug-Sensitive Pulmonary Tuberculosis.

INTRODUCTION: India has the highest cases of tuberculosis worldwide. According to WHO (2022), the incidence of tuberculosis in India is 210 per 100,000 population. Their incidence of new positive smear cases is 75 per 100,000 population per year. In tuberculosis, the level of albumin decreases while globulin increases leading to a low albumin to globulin (A/G) ratio, and electrophoresis of serum proteins are good diagnostic approach and provides essential information for monitoring treatment outcomes. MATERIALS AND METHODS: The present study includes 50 cases of pulmonary tuberculosis and 50 age-sex-matched healthy controls. Initially, serum protein estimation and electrophoresis were performed in newly diagnosed patients and controls. All drugs were given as National Tuberculosis Elimination Programme (NTEP) guidelines and blood samples were collected at two-month, four-month, and six-month intervals, and different serum protein fractions were compared and analyzed. RESULTS: The total serum protein was significantly lower in the cases than in the controls; 6.12±0.61 vs. 7.02±0.56 g/dL (p˂0.0020, t-value=3.12). The mean serum albumin was also significantly lower in the cases compared to the controls; 1.65±0.69 vs. 3.87±0.47g/dL (p˂0.0001, t-value=10.98). The α1 globulin started to rise after four months of treatment and at six months level was 0.262±0.32 g/dL. The level of γ globulin continuously decreases after antituberculous treatment to 1.56±0.67 gm/dL at six months. CONCLUSION: The cause of the decrease in total protein and albumin may be due to malnutrition leading to low cellular immunity. Serum protein level and protein electrophoresis should be analyzed as routine tests in patients before, during, and after treatment. It helps us in identifying patients at risk of pulmonary tuberculosis as well prognosis of the disease. This study is a valuable guide in deciding the effective management of tuberculosis patients with drug treatment plans and appropriate dietary intake. Hence, it highlights the complex relationship that exists between poverty and disease.

Effect of Early Bedside Arm and Leg Cycle Ergometry on Sitting and Standing ability in Hospitalized acute Stroke Patients: A Randomized Controlled Trial.

Objectives: The objective of this study was to evaluate the effect of early bedside arm and leg cycle ergometer exercises as compared to routine physiotherapy on sitting and standing ability in hospitalized acute stroke patients. Materials and Methods: Thirty-four consecutive patients with acute stroke were included in the randomized controlled trial. Patients were divided into two groups based on 1:1 simple randomization Experimental group (n = 18) and control group (n = 16). Experimental Group received arm and leg cycle ergometry along with conventional physiotherapy exercises, while the patients in the control group received conventional physiotherapy exercises. Both the groups received treatment for a total duration of 50 min session, twice a day for 7 days. Preintervention and postintervention measurements were taken for both groups using performance-oriented mobility assessment, postural assessment scale for stroke, Motricity Index, and Trunk control scale. Results: Statistically significant improvement (P < 0.05) was observed in the experimental group and control groupafter intervention among all the outcome measures. Conclusions: Early bedside intervention of cycle ergometer along with routine physiotherapy is effective in improving the sitting and standing abilities, trunk control, and motor function in acute stroke survivors.

B cell lymphoma-2 (BCL-2) homology domain 3 (BH3) mimetics demonstrate differential activities dependent upon the functional repertoire of pro- and anti-apoptotic BCL-2 family proteins.

The B cell lymphoma-2 (BCL-2) family is the key mediator of cellular sensitivity to apoptosis during pharmacological interventions for numerous human pathologies, including cancer. There is tremendous interest to understand how the proapoptotic BCL-2 effector members (e.g. BCL-2-associated X protein, BAX) cooperate with the BCL-2 homology domain only (BH3-only) subclass (e.g. BCL-2 interacting mediator of death, BIM; BCL-2 interacting-domain death agonist, BID) to induce mitochondrial outer membrane permeabilization (MOMP) and apoptosis and whether these mechanisms may be pharmacologically exploited to enhance the killing of cancer cells. Indeed, small molecule inhibitors of the anti-apoptotic BCL-2 family members have been designed rationally. However, the success of these "BH3 mimetics" in the clinic has been limited, likely due to an incomplete understanding of how these drugs function in the presence of multiple BCL-2 family members. To increase our mechanistic understanding of how BH3 mimetics cooperate with multiple BCL-2 family members in vitro, we directly compared the activity of several BH3-mimetic compounds (i.e. ABT-263, ABT-737, GX15-070, HA14.1, TW-37) in biochemically defined large unilamellar vesicle model systems that faithfully recapitulate BAX-dependent mitochondrial outer membrane permeabilization. Our investigations revealed that the presence of BAX, BID, and BIM differentially regulated the ability of BH3 mimetics to derepress proapoptotic molecules from anti-apoptotic proteins. Using mitochondria loaded with fluorescent BH3 peptides and cells treated with inducers of cell death, these differences were supported. Together, these data suggest that although the presence of anti-apoptotic BCL-2 proteins primarily dictates cellular sensitivity to BH3 mimetics, additional specificity is conferred by proapoptotic BCL-2 proteins.

Sphingolipid metabolism cooperates with BAK and BAX to promote the mitochondrial pathway of apoptosis.

Mitochondria are functionally and physically associated with heterotypic membranes, yet little is known about how these interactions impact mitochondrial outer-membrane permeabilization (MOMP) and apoptosis. We observed that dissociation of heterotypic membranes from mitochondria inhibited BAK/BAX-dependent cytochrome c (cyto c) release. Biochemical purification of neutral sphingomyelinases that correlated with MOMP sensitization suggested that sphingolipid metabolism coordinates BAK/BAX activation. Using purified lipids and enzymes, sensitivity to MOMP was achieved by in vitro reconstitution of the sphingolipid metabolic pathway. Sphingolipid metabolism inhibitors blocked MOMP from heavy membrane preparations but failed to influence MOMP in the presence of sphingolipid-reconstituted, purified mitochondria. Furthermore, the sphingolipid products, sphingosine-1-PO(4) and hexadecenal, cooperated specifically with BAK and BAX, respectively. Sphingolipid metabolism was also required for cellular responses to apoptosis. Our studies suggest that BAK/BAX activation and apoptosis are coordinated through BH3-only proteins and a specific lipid milieu that is maintained by heterotypic membrane-mitochondrial interactions.

Vaginal repair of supratrigonal vesicovaginal fistulae--a 10-year review.

INTRODUCTION AND HYPOTHESIS: A 10-year retrospective study was done to determine the outcome of vaginal repair for supratrigonal vesicovaginal fistulae (VVF). METHODS: One hundred thirty-two urinary fistulae were managed from 2001 to 2011 which include 34 ureterovaginal and 98 lower urinary tract fistulae. Fifty-three out of 98 were supratrigonal VVF, 49 were of benign etiology and 4 were malignancy induced. Further analysis of 49 supratrigonal VVF of benign etiology revealed that 38 (77.5%) were of gynecological origin and 11 (22.5%) obstetric. Forty-three were primary and six were recurrent VVF. Thirty (61.2%) supratrigonal VVF were repaired vaginally and 19 (38.8 %) abdominally. Mean follow-up period was 51.7 months. RESULTS: The successful outcome for vaginal and abdominal repair was 86.7% and 100%, respectively (p value = 0.26). Overall, 91.8% supratrigonal VVF were cured at our first attempt. CONCLUSIONS: Majority of supratrigonal VVF can be approached vaginally with success rate comparable to abdominal approach.