Clinical Objective Dry Eye Tests in a Population of Tannery Workers in North India

Purpose: To analyze the correlation between subjective symptoms and clinical signs of dry eye among tannery workers.

Methods: In this cross-sectional study, three classic clinical tests, namely the fluorescein tear film break-up time (FTBUT) test, the fluorescein staining (FS) test, and the Schirmer test (ST), were performed to assess the clinical signs of dry eye disease in 246 tanners who were found symptomatic for dry eye in a prior ocular surface disease index survey.

Results: All workers were male with a mean age of 35 ± 9 years, and the mean duration of work at tanneries was 8 ± 5 years. Among 246 symptomatic subjects, the FTBUT test, the FS test and the ST were positive in 63.8%, 30.9% and 41.9% workers, respectively. Mean FTBUT and ST scores were 10.6 ± 4.2 seconds and 10.1 ± 7.7mm, respectively. Mean FTBUT for mild, moderate and severe symptom categories differed significantly. Mean ST scores for the mild symptom group were significantly higher than that of the moderate group (p < 0.0001). The FTBUT and ST score showed a strong negative correlation with severity of symptoms (p < 0.0001). A moderate positive correlation was observed between FS positivity and increasing symptom severity (p < 0.0001). The effect of age was insignificant for FTBUT (p = 0.10), while significant for ST score (p < 0.001). The effect of duration of tannery work was significant for both FTBUT and ST scores (p < 0.0001).

Conclusion: Clinical tests correlated well with symptom severity among tanners, and a multifactorial etiology is suggested for dry eye diseases.     

Differential expression of hepatic genes involved in cholesterol homeostasis in high- and low-responding strains of laboratory opossums

Plasma very low-density lipoprotein and low-density lipoprotein (VLDL+LDL) cholesterol levels of 2 partially inbred strains of opossums (Monodelphis domestica) differ markedly when they are fed a high-cholesterol and low-fat (HCLF) diet. High-responding opossums exhibit a dramatic increase (>10-fold) in VLDL+LDL cholesterol, whereas low-responding opossums exhibit a minimal increase (<2-fold) in VLDL+LDL cholesterol. The genes responsible for the accumulation of high levels of plasma VLDL+LDL cholesterol in high-responding opossums have not yet been identified. In this study, we analyzed the expression of genes encoding for (1) 4 bile acid synthesis enzymes (CYP7A1, CYP27A1, CYP8B1, and CYP7B1); (2) 3 cholesterol synthesis enzymes (HMGCR, HMGCS1, and SQLE); (3) the LDL receptor (LDLR); (4) 2 sterol transporters (ABCG5 and ABCG8); and (5) 2 bile acid transporters (ABCB11 and SLC10A1) to determine how the expression of these genes was affected by dietary cholesterol in the 2 strains of opossums. We found differences between high and low responders in the expression of cholesterol synthesis genes on the basal diet, as well as differences in the expression of the CYP27A1, ABCG5, ABCG8, and SLC10A1 genes on the HCLF diet. CYP27A1 messenger RNA levels were lower in the livers of high responders compared with low responders, whereas CYP27A1 messenger RNA levels in extrahepatic tissues were similar in high and low responders on the HCLF diet. Low levels of CYP27A1, ABCG5, and ABCG8 expression in the liver may contribute to hypercholesterolemia in high-responding opossums.     

Limited value of the resting electrocardiogram in assessing patients with recent onset chest pain: lessons from a chest pain clinic.

OBJECTIVE--To evaluate a clinic set up specifically to assess patients with recent onset chest pain, particularly those presenting with a normal resting electrocardiogram. DESIGN--Retrospective review of case notes. SETTING--Cardiac department of a tertiary referral cardiothoracic centre. PATIENTS--250 consecutive patients with recent onset chest pain seen within 24 hours of general practitioner referral. OUTCOME MEASURES--Clinical diagnosis and management. RESULTS--40% of patients were seen within seven days of the onset of symptoms. Twenty seven per cent had non-cardiac symptoms and could be discharged while 60% were considered to have cardiac pain. Sixty six patients (26%) were admitted directly from the clinic and 48 of these underwent coronary angiography within three weeks. Seventy patients (28%) have so far undergone intervention (angioplasty or coronary artery surgery), 22 within one month of presentation. One hundred and nine patients (44%) presented with a normal resting electrocardiogram, 21 of whom were considered to have unstable angina. Forty one of these patients were investigated of whom 37 were found to have significant coronary disease and 26 have undergone intervention. CONCLUSIONS--This experience highlights the inadequacy of a routine electrocardiogram reporting service in patients with recent onset of chest pain. An alternative facility offering immediate and complete cardiac assessment produced patient benefit with early diagnosis and intervention. Investigation of these patients, however, accounted for 5% of cardiac catheterisation laboratory throughput; this was a significant additional and unscheduled workload.     

Chronic physiologic hyperinsulinemia impairs suppression of plasma free fatty acids and increases de novo lipogenesis but does not cause dyslipidemia in conscious normal rats

Type 2 diabetes mellitus and obesity are characterized by fasting hyperinsulinemia, insulin resistance with respect to glucose metabolism, elevated plasma free fatty acid (FFA) levels, hypertriglyceridemia, and decreased high-density lipoprotein (HDL) cholesterol. An association between hyperinsulinemia and dyslipidemia has been suggested, but the causality of the relationship remains uncertain. Therefore, we infused eight 12-week-old male catheterized conscious normal rats with insulin (1 mU/min) for 7 days while maintaining euglycemia using a modification of the glucose clamp technique. Control rats (n = 8) received vehicle infusion. Baseline FFAs were 1.07+/-0.13 mmol/L, decreased to 0.57+/-0.10 (P < .05) upon initiation of the insulin infusion, and gradually increased to 0.95+/-0.12 by day 7 (P = NS vbaseline). On day 7 after a 6-hour fast, plasma insulin, glucose, and FFA levels in control and chronically hyperinsulinemic rats were 32+/-5 versus 116+/-21 mU/L (P < .005), 122+/-4 versus 129+/-8 mg/dL (P = NS), and 1.13+/-0.18 versus 0.95+/-0.12 mmol/L (P = NS); total plasma triglyceride and cholesterol levels were 78+/-7 versus 66+/-9 mg/dL (P = NS) and 50+/-3 versus 47+/-2 mg/dL (P = NS), respectively. Very-low-density lipoprotein (VLDL) + intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and HDL2 and HDL3 subfractions of plasma triglyceride and cholesterol were similar in control and hyperinsulinemic rats. Plasma FFA correlated positively with total (r = .61, P < .005) triglycerides. On day 7 after an 8-hour fast, hyperinsulinemic-euglycemic clamps with 3-3H-glucose infusion were performed in all rats. Chronically hyperinsulinemic rats showed peripheral insulin resistance (glucose uptake, 15.8+/-0.8 v 19.3+/-1.4 mg/kg x min, P < .02) but normal suppression of hepatic glucose production (HGP) compared with control rats (4.3+/-1.0 v 5.6+/-1.4 mg/kg x min, P = NS). De novo tissue lipogenesis (3-3H-glucose incorporation into lipids) was increased in chronically hyperinsulinemic versus control rats (0.90+/-0.10 v 0.44+/-0.08 mg/kg x min, P < .005). In conclusion, chronic physiologic hyperinsulinemia (1) causes insulin resistance with regard to the suppression of plasma FFA levels and increases lipogenesis; (2) induces peripheral but not hepatic insulin resistance with respect to glucose metabolism; and (3) does not cause an elevation in VLDL-triglyceride or a reduction in HDL-cholesterol.     

Isolated interrupted aortic arch accompanied by type B aortic dissection and extensive collateral arteries diagnosed with MDCT angiography

Interrupted aortic arch (IAA) is a rare congenital cardiovascular condition. A patient with uncorrected IAA accompanied by rich collateral arteries can survive to adulthood asymptomatically. However, IAA complicated by aortic dissection is life threatening. Herein, we report a rare case of an isolated IAA accompanied by type B aortic dissection and extensive collateral arteries detected by multidetector computed tomography in a 38-year-old man. The imaging findings of the case are presented, and the utility of multidetector computed tomography in the evaluation of this condition is discussed.     

Diarylheptanoid compounds from Alnus nepalensis express in vitro and in vivo antifilarial activity

A large number of medicinal plants remain to be explored for antifilarial compounds. In the present study a crude methanolic extract of leaves of Alnus nepalensis, chloroform- and n-butanol-partitioned fractions from the crude extract and 6 bioactivity-guided isolated compounds including two new diarylheptanoid from the fractions were assayed for microfilaricidal, macrofilaricidal and female worm sterilizing activity using the lymphatic filariid Brugia malayi in in vitro and in vivo systems. In vitro, the crude methanolic extract exerted better microfilaricidal (LC100: 15.63 μg/ml, IC50: 6.00 μg/ml) than macrofilaricidal (LC100: >250; IC50: 88 μg/ml) activity whereas chloroform and n-butanol fractions were more macrofilaricidal (LC100: 125 and 31.25 μg/ml; IC50: 13.14 and 11.84, respectively) than microfilaricidal (LC100: 250–500 μg/ml, IC50: 44.16 μg/ml). In addition, n-butanol fraction also caused 74% inhibition in MTT reduction potential of the adult worms. In vivo (doses: crude: 100–200 mg/kg; fractions: 100 mg/kg, i.p. × 5 days) the chloroform fraction exerted >50% macrofilaricidal activity whereas methanolic extract and n-butanol fraction produced 38–40% macrofilaricidal action along with some female sterilizing efficacy. Of the 5 diarylheptanoid compounds isolated, alnus dimer, and (5S)-5-hydroxy-1-(4-hydroxyphenyl)-7-(3,4-dihydroxyphenyl)-3-heptanone were found to show the most potent with both macrofilaricidal (LC100: 15.63 μg/ml, IC50: 6.57–10.31 μg/ml) and microfilaricidal (LC100: 31.25–62.5 μg/ml, IC50: 11.05–22.10 μg/ml) activity in vitro. These findings indicate that the active diarylheptanoid compounds may provide valuable lead for design and development of new antifilarial agent(s).     

Inhibition of Wnt/β-catenin pathway overcomes therapeutic resistance to abiraterone in castration-resistant prostate cancer

Abiraterone acetate has been clinically approved for the treatment of patients with advanced-stage prostate cancer. It reduces testosterone production by blocking the enzyme cytochrome P450 17 alpha-hydroxylase. Despite improved survival outcomes with abiraterone, almost all patients develop therapeutic resistance and disease recurrence, progressing to a more aggressive and lethal phenotype. Bioinformatics analyses predicted activation of canonical Wnt/β-catenin and involvement of stem cell plasticity in abiraterone-resistant prostate cancer. Increased expression of androgen receptor (AR) and β-catenin and their crosstalk causes activation of AR target genes and regulatory networks for which overcoming acquired resistance remains a major challenge. Here we show that co-treatment with abiraterone and ICG001, a β-catenin inhibitor, overcomes therapeutic resistance and significantly inhibited markers of stem cell and cellular proliferation in abiraterone-resistant prostate cancer cells. Importantly, this combined treatment abrogated the association between AR and β-catenin; diminished SOX9 expression from the complex more prominently in abiraterone-resistant cells. In addition, combined treatment inhibited tumor growth in an in vivo abiraterone-resistant xenograft model, blocked stemness, migration, invasion, and colony formation ability of cancer cells. This study opens new therapeutic opportunity for advanced-stage castration-resistant prostate cancer patients.     

Cytochrome-C Oxidase I Gene-Based Genetic Divergence and Molecular Phylogeny Among the Species of Fish Genus Channa

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - The freshwater snakehead fishes are members of the family Channidae and order Perciform, which are native to...     

Genetic Structuring in Riverine Population of Channa striata (Bloch, 1793) from India using Cytochrome Oxidase I Gene

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - The freshwater snakehead murrel fish, Channa striata, is a commercially important and potential candidate...