Development of in vitro screening system for assessment of antifilarial activity of compounds

Evaluation of antifilarial activity of new potential agents in vivo is extremely time consuming and uneconomic. In the present study effort has been made to develop an in vitro screening method using Acanthocheilonema viteae, a subcutaneously dwelling rodent filariid with anaerobic metabolic characteristics like human filariids, W. Bancrofti/Brugia malayi as test parasite. Motility test and tetrazolium (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, MTT) based colorimetric assay were used as parameters in in vitro assay. Results showed that 92.3% of compounds (in vivo active) could be picked up in the in vitro assay when both adults and microfilarae (mf) were used simultaneously. Mf and adult stages separately detected, respectively, 84.6 and 69.2% of in vivo active compounds. The adults and mf separately and both the life stages together exhibited, respectively, 80.0, 50.0 and 80.0% false positive results in the in vitro test with in vivo inactive compounds. It is felt that mf stage when used in in vitro test using motility and MTT assays as parameters would be useful in primary screening of new potential filaricides.     

Hyperinsulinemia and dyslipidemia in non-obese, normotensive offspring of hypertensive parents in northern India.

Insulin resistance contributes to initiation and acceleration of hypertension and atherosclerosis. This study attempted to detect occurrence of pre-hypertensive metabolic abnormalities, including hyperinsulinemia, in the offspring of hypertensive patients. Thirty-eight healthy offspring of hypertensive parents (group I, mean age 23.6+/-3.7 years) and 18 control offspring of normotensive parents (group II, mean age 24.2+/-2.8 years) were clinically examined, subjected to oral glucose tolerance test (OGTT), and the samples were analysed for blood glucose, insulin and lipid profile. Subjects in group I with fasting serum insulin <90 nmol/L constituted group Ia (n = 23, 62%) and those with >90 nmol/L constituted group Ib (n = 15, 38%). Both groups consisted of non-obese and normotensive subjects matched for body mass index and waist-hip ratio. There were no statistically significant differences in blood glucose levels between groups Ia, Ib and II during OGTT. Serum insulin levels during OGTT in group I were significantly higher than in group II (p<0.05), except at 30 min. Fasting insulin and 2 h post-OGTT insulin in group Ib were significantly higher than the other groups. Serum triglyceride levels, though within normal range, were higher in group I than group II (p<0.01). Similarly, high-density lipoprotein cholesterol levels in groups Ia and Ib were lower than those observed in group II (p<0.01). In conclusion, non-obese, normotensive offspring of hypertensive parents were observed to be hyperinsulinemic and dyslipidemic at an early age. These metabolic abnormalities may be associated with hypertension, glucose intolerance and accelerated atherosclerosis in adulthood.     

Inhibition of coal fly ash polycyclic aromatic hydrocarbons and metals induced mixed-function oxidase activity in rat lung and liver by vitamin A and citrate

Administration of benzene-soluble fraction (FAE) and benzene-insoluble fraction (FAR) of fly ash for 3 consecutive days to rats significantly raised cytochrome P-450 levels, aryl hydrocarbon hydroxylase (AHH) activity, and glutathione S-transferase activity in liver. This treatment also significantly increased pulmonary AHH and glutathione S-transferase activity. Intratracheal administration of FAR (5 mg/100 g body weight) alone for 6 consecutive days also significantly increased hepatic cytochrome P-450 levels and the activity of glutathione S-transferase. Intragastric administration of retinyl palmitate (5000 IU/100 g body weight), along with intratracheal FAE and FAR administration, significantly reduced P-450 levels, activity of glutathione S-transferase in liver, and activity of AHH and glutathione S-transferase in lung of rats. Intraperitoneal administration of citrate (40 mg/100 g body weight) along with FAR significantly reduced FAR-induced increase in hepatic cytochrome P-450 levels and glutathione S-transferase activity. The activity of AHH was not affected by these treatments.     

Diethylcarbamazine: effect on lysosomal enzymes and acetylcholine in Wuchereria bancrofti infection

Summary We measured the levels of lysosomal enzymes and acetylcholine in Wuchereria bancrofti - infected asymptomatic microfilaraemic human serum, and found a significant decrease in the activity of β-glucuronidase and acid phosphatase compared to normal serum. Acetylcholine levels were also decreased during infection. However, after giving diethylcarbamazine (6 mg/kg body wt/day) the level of lysosomal enzymes and acetylcholine increased and reached a normal value after two weeks of therapy. It is proposed that parasites secrete acetylcholinesterase in the circulation which degrades acetylcholine. Since acetylcholine stimulates the release of lysosomal enzymes and phagocytosis, the immune response of the host is suppressed during infection. During diethylcarbamazine (DEC) therapy the parasitic enzyme is inhibited by the drug and the normal level of acetylcholine is resumed, which again stimulates the release of lysosomal enzyme and the process of phagocytosis.     

Outcomes of patients with invasive mucinous and tubular carcinomas of the breast

Invasive tubular carcinoma (ITC) and invasive mucinous carcinoma (IMC) of the breast are rare histologic subtypes of breast cancer associated with favorable prognoses. The aim of our study was to investigate the outcomes for these rare subtypes using the National Cancer Database. Female patients diagnosed with ITC or IMC between 2005 and 2014 were analyzed. The primary outcome was overall survival (OS), and we analyzed its association with adjuvant therapy. 2735 patients with ITC and 5602 patients with IMC were identified. ITC presented in younger patients (57 vs. 67 years), had smaller tumors (size <1 cm, 63.1% vs. 25.4%), earlier stage, and less node-positive disease (5% vs. 8.6%), compared with IMC. Older age, government insurance, lower income, treatment in a community cancer program, large tumor size, positive nodal status, and without endocrine therapy were associated with worse OS with either subtype on multivariate analysis. No OS benefit was found for node-positive ITC that received adjuvant chemotherapy compared with those who did not. (5-year OS of 96.0% vs. 91.3%, p = 0.17).OS was improved for IMC that received adjuvant chemotherapy (10-year OS: 82.5% vs. 60.1%, p = 0.008) and endocrine therapy (10-year OS: 86.6% vs. 81.2%, p < 0.001). We concluded that ITC has favorable clinicopathological characteristics and prognosis, even with node-positive disease. ITC and IMC may need to be evaluated independently when administering adjuvant treatment plans.     

Lateral popliteal block in foot and ankle surgery: Comparing ultrasound guidance to nerve stimulation. A prospective randomized trial

BackgroundThe popliteal block has several benefits in foot and ankle surgery. It reduces postoperative pain, limits the use of narcotics and facilitates early discharge. The aim of this prospective randomized trial was to evaluate whether ultrasound guidance improves block characteristics compared to the nerve stimulation technique in lateral popliteal blocks.MethodsPatients were randomized to receive either a lateral popliteal block using neurostimulation or ultrasound guidance. Block performance time, number of needle pricks, number of redirections were recorded. Pain upon admission to and discharge from post anesthesia care unit (PACU) was recorded. Block duration, patient satisfaction, pain at block site and amount of opioids used in PACU and between subsequent followup visits was recorded. Patients were followed for 12 weeks postoperatively.ResultsThere was no statistically significant difference between the two groups in terms of number of pricks, time for the block to wean, pain upon admission to PACU, amount of opioids received in PACU, pain upon discharge from PACU, pain at the operative site, pain at the block site, toe motor function and toe sensation. There was a statistically significant difference in the block procedure performance time between the two groups, with the control group being faster (P < 0.0001). A significantly larger number of patients in the control group required more than three needle redirections (P = 0.0060).ConclusionsThe lateral sciatic popliteal block using nerve stimulation had similar block characteristics and patient satisfaction with a significantly faster performance time compared to the ultrasound guided technique.Level of evidence: Level I, prospective randomized study.     

Variations in Medical Students’ Educational Preferences,Attitudes and Volunteerism during the COVID-19 Global Pandemic

Journal of Community Health - Public health crises require individuals, often volunteers, to help minimize disasters. The COVID-19 pandemic required such activation of individuals, but little is...     

Schistosoma haematobium infection in children in Britain

OBJECTIVE: To highlight the existence of Schistosoma haematobium in certain ethnic minority groups in Britain and in English citizens who have recently visited Africa and the Middle East, so that general practitioners and paediatric nephrologists/urologists are aware of its occurrence and consider it among the differential diagnoses in children presenting with haematuria. PATIENTS AND METHODS: Over a 2-year period, six consecutive boys (mean age 13.5 years, range 8-15) presented with haematuria and were subsequently diagnosed to be infected with S. haematobium. All patients were from Africa and had recently visited their native country. There had all reported paddling in freshwater lakes and streams. RESULTS: Dysuria and haematuria was noted 2-3 months after the infection. Terminal urine samples taken after exercise at midday were positive for S. haematobium ova. Praziquantel anti-schistosomal chemotherapy was effective in treating the infection. CONCLUSION: S. haematobium infection is treatable in the early stages and the changes are reversible before the development of fibrotic lesions, which may result in anatomical obstruction. A terminal urine sample taken at midday after exercise was diagnostic in showing Schistosoma ova in all cases. This infection must be considered in the differential diagnoses of haematuria in some ethnic minority British citizens and in those Britons who have visited Africa or the Middle East in the recent past.