Prevalence of hepatitis A virus and hepatitis E virus in the patients presenting with acute viral hepatitis in Rohtak, Haryana, India

Background: Hepatitis A virus (HAV) and hepatitis E virus (HEV) cause acute hepatitis in humans and are transmitted mainly through the fecal-oral route. They pose major health problems in developing countries. This study was done to determine prevalence of HAV and HEV in patients presenting with AVH and the co-infection of HAV and HEV in these patients.Methods: The study was conducted in the virology research and diagnostic laboratory, PGIMS Rohtak during the study period of August 2017-December 2018. The study population included sera of individuals from all age group who were suspected of acute viral hepatitis (AVH). All the sera were screened for IgM antibody to HEV and HAV using IgM capture ELISA.Results: HEV IgM ELISA test   was performed in 307 patients (mean age 34 years;), with an overall seroprevalence rate of 138(44.9%). HAV antibodies were detected in 109 subjects, with a median age of 9.5 years the seroprevalence of HAV was 34 (31.1%). HEV seropositivity was highest in the age group 20-30 years. Mean age was 34 years whereas the interquartile range was from 14-71 years. HAV infection was positive mainly in the age group <10 years. With interquartile range from 6-16 years. Out of total 34 patients positive for HAV infection males were 20 (58.8%), whereas females were 14(41.1%). HEV IgM was positive in 138 patients, out of which male were 96 (69.56%) and females were 42 (30.43%). HEV IgM was positive in 138 patients, out of which male were 96 (69.56%) and females were 42 (30.43%). HAV and HEV seen to be prevalent all with highest predominance seen towards the end of monsoons (August and September) and beginning of winters.Conclusions: The present study also points toward HEV being the prime etiological agent for outbreaks of acute hepatitis in the studied region of Haryana (Rohtak), India. A comparatively lower HAV prevalence may be the consequence of an overall declining trend due to improved living standards and environmental hygiene

A comparative study of antihyperglycemic effect of Gymnema sylvestre and metformin in streptozotocin induced diabetic rats

Background: Diabetes mellitus (DM) is a metabolic disorder that has the phenotype of hyperglycemia. According to World Health Organization (WHO) there were 65.1 million diabetics in India in 2013, International Diabetes Federation estimates this to increase to 190 million by 2035. Although a number of drugs are available for treatment of DM, their cost and safety profile are major concern. Medicinal plants are used by clinicians for treatment of diabetes. Gymnema sylvestre (GS) extract has been reported to increase insulin levels in diabetic rats. This study was designed to compare the antihyperglycemic effect of Gymnema sylvestre with metformin.Methods: Diabetes was induced in Sprague-Dawley rats using streptozotocin 45mg/kg. Methanolic extract of Gymnema sylvestre 120mg/kg p.o. prepared using Soxhlet apparatus.Results: GS extract reduced blood glucose levels but not statistically significant. GS extract increased HDL and triglycerides, reduced both serum ALT and AST but no statistical significance seen. Metformin significantly increased serum urea, which was not seen in GS extract group. GS extract showed regenerative changes in pancreas, liver and kidney.Conclusions: The study investigation demonstrates that methanolic extract of GS possesses antihyperglycemic and hypolipidaemic activity and so it can be considered as a promising natural remedy in a prediabetic state and in mild hyperlipidaemia to prevent its progression. Increase in β cell regeneration activity could be a probable mechanism of action. However, further long term clinical studies are recommended to define its possible role in diabetes mellitus and hyperlipidaemia. Role of GS as a potential hepatoprotective agent also needs further evaluation

Long-Term Treatment with Extended-Release Carbidopa– Levodopa (IPX066) in Early and Advanced Parkinson’s Disease: A 9-Month Open-Label Extension Trial

Background and Objective IPX066 is a multiparticulate extended-release formulation of carbidopa–levodopa, designed to produce prolonged therapeutic levodopa plasma concentrations. This 9-month open-label extension study assessed its long-term safety and clinical utility in early and advanced Parkinson’s disease (PD). Methods Participants were enrolled from two phase III IPX066 studies and one open-label phase II study. Early PD patients were titrated to an appropriate dosing regimen while advanced patients started with regimens established in the antecedent studies. Adjustment was allowed throughout the extension. Clinical utility measures included the Unified Parkinson’s Disease Rating Scale (UPDRS) and Patient Global Impression (PGI) ratings. Results Among 268 early PD patients, 53.4 % reported adverse events (AEs) and 1.1 % (three patients) discontinued due to AEs; the most frequent AEs were nausea (5.6 %) and insomnia (5.6 %). Among 349 advanced patients, 60.2 % reported AEs and 3.7 % (13 patients) discontinued due to AEs; the most frequent AEs were dyskinesia (6.9 %) and fall (6.6 %). At month 9 (or early termination), 78.3 % of early patients were taking IPX066 three times daily (median: 720 mg/day) and 87.7 % of advanced patients were taking IPX066 three or four times daily (median: 1450 mg/day). Adjusting for 70 % bioavailability relative to immediate-release (IR) carbidopa–levodopa, the median dosages correspond to *500 and *1015 mg/day of IR levodopa in early and advanced PD, respectively. Based on the plasma profiles previously observed in PD patients, the IPX066 regimens in the extension can be estimated to provide a levodopa Cmax (maximum plasma drug concentration) similar to or lower than that provided by IR regimens during the antecedent trials. UPDRS and PGI findings showed sustained treatment effects throughout the extension. Conclusion During 9 months of extended use, IPX066 exhibited a safety/tolerability profile consistent with dopaminergic PD therapy

Long-term treatment with extended-release carbidopa-levodopa (IPX066) in early and advanced Parkinson's Disease : a 9-month open-label extension trial

Background and Objective IPX066 is a multiparticulate extended-release formulation of carbidopa–levodopa, designed to produce prolonged therapeutic levodopa plasma concentrations. This 9-month open-label extension study assessed its long-term safety and clinical utility in early and advanced Parkinson’s disease (PD). Methods Participants were enrolled from two phase III IPX066 studies and one open-label phase II study. Early PD patients were titrated to an appropriate dosing regimen while advanced patients started with regimens established in the antecedent studies. Adjustment was allowed throughout the extension. Clinical utility measures included the Unified Parkinson’s Disease Rating Scale (UPDRS) and Patient Global Impression (PGI) ratings. Results Among 268 early PD patients, 53.4 % reported adverse events (AEs) and 1.1 % (three patients) discontinued due to AEs; the most frequent AEs were nausea (5.6 %) and insomnia (5.6 %). Among 349 advanced patients, 60.2 % reported AEs and 3.7 % (13 patients) discontinued due to AEs; the most frequent AEs were dyskinesia (6.9 %) and fall (6.6 %). At month 9 (or early termination), 78.3 % of early patients were taking IPX066 three times daily (median: 720 mg/day) and 87.7 % of advanced patients were taking IPX066 three or four times daily (median: 1450 mg/day). Adjusting for 70 % bioavailability relative to immediate-release (IR) carbidopa–levodopa, the median dosages correspond to *500 and *1015 mg/day of IR levodopa in early and advanced PD, respectively. Based on the plasma profiles previously observed in PD patients, the IPX066 regimens in the extension can be estimated to provide a levodopa Cmax (maximum plasma drug concentration) similar to or lower than that provided by IR regimens during the antecedent trials. UPDRS and PGI findings showed sustained treatment effects throughout the extension. Conclusion During 9 months of extended use, IPX066 exhibited a safety/tolerability profile consistent with dopaminergic PD therapy

Highlights From the Annual Meeting of the American Epilepsy Society 2022

With more than 6000 attendees between in-person and virtual offerings, the American Epilepsy Society Meeting 2022 in Nashville, felt as busy as in prepandemic times. An ever-growing number of physicians, scientists, and allied health professionals gathered to learn a variety of topics about epilepsy. The program was carefully tailored to meet the needs of professionals with different interests and career stages. This article summarizes the different symposia presented at the meeting. Basic science lectures addressed the primary elements of seizure generation and pathophysiology of epilepsy in different disease states. Scientists congregated to learn about anti-seizure medications, mechanisms of action, and new tools to treat epilepsy including surgery and neurostimulation. Some symposia were also dedicated to discuss epilepsy comorbidities and practical issues regarding epilepsy care. An increasing number of patient advocates discussing their stories were intertwined within scientific activities. Many smaller group sessions targeted more specific topics to encourage member participation, including Special Interest Groups, Investigator, and Skills Workshops. Special lectures included the renown Hoyer and Lombroso, an ILAE/IBE joint session, a spotlight on the impact of Dobbs v. Jackson on reproductive health in epilepsy, and a joint session with the NAEC on coding and reimbursement policies. The hot topics symposium was focused on traumatic brain injury and post-traumatic epilepsy. A balanced collaboration with the industry allowed presentations of the latest pharmaceutical and engineering advances in satellite symposia

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

Susceptibility of glucose-6-phosphate dehydrogenase deficient red cells to primaquine, primaquine enantiomers, and its two putative metabolites: II. Effect on red blood cell membrane,lipid peroxidation, MC-540 staining, and scanning electron microscopic studies

The effects of primaquine (PQ), its enantiomers [(+)PQ,(-)PQ] and hydroxy metabolites [5-hydroxyprimaquine (5HPQ) and 6-desmethyl-5-hydroxyprimaquine (6D5HPQ)] on cell membranes of glucose-6-phosphate dehydrogenase (G-6-PD) deficient red cells were studied in vitro. There was no significant effect of PQ on the malonyldialdehyde (MDA) content of normal and heterozygous red cells, but it caused a significant increase in MDA in G-6-PD deficient red cells (P &lt; 0.05). There was no noticeable difference between the effects of the two enantiomers on this variable (P &gt; 0.05). Compared to PQ, the hydroxy metabolites produced a significantly greater increase in MDA in all the groups studied (P &lt; 0.001). Of the two hydroxy metabolites, 6D5HPQ was more toxic than 5HPQ. Staining with MC 540 showed that exposure to PQ, its enantiomers and two putative metabolites produced significant fluorescence, indicating that the drug produces marked alterations in membrane fluidity. Although the fluorescence was seen both in normal and heterozygous cells, the effect was marked in hemizygous deficient red cells (P &lt; 0.001). Scanning electron microscopic (SEM) studies revealed that PQ enantiomers had a stomatocytic effect on red cells of normal, heterozygous and hemizygous G-6-PD deficient red cells, whereas the putative metabolites had an echinocytic effect. The effects were most pronounced in G-6-PD deficient red cells

Susceptibility of glucose-6-phosphate dehydrogenase deficient red cells to primaquine enantiomers and two putative metabolites-I: effect on reduced glutathione, methemoglobin content and release of hemoglobin

The effects of the primaquine (PQ) enantiomers, (+)PQ and (-)PQ, and two putative metabolites [5-hydroxyprimaquine (5HPQ) and 6-desmethyl-5-hydroxyprimaquine (6D5HPQ)] on methemoglobin (Met Hb) and glutathione content and release of hemoglobin into plasma from glucose-6-phosphate dehydrogenase (G-6-PD) deficient red cells were studied in vitro. The results show that a 1.5 mM concentration of (-)PQ produced a significantly greater increase in Met Hb content and decrease in reduced glutathione (GSH) level than did (+)PQ. However, the release of plasma hemoglobin was greater with (+)PQ than with (-)PQ. The hydroxy derivatives of primaquine, 5HPQ and 6D5HPQ, were significantly more active than PQ. Their individual effects differed; whereas 5HPQ produced significantly greater reduction in GSH compared to 6D5HPQ, the effect of 6D5HPQ on Met Hb content and release of plasma hemoglobin was greater than that of 5HPQ. The qualitative effects of these compounds on normal, heterozygous and hemizygous G-6-PD deficient red cells were similar, but quantitatively the effects were greatest on hemizygous G-6-PD deficient cells and intermediate on heterozygous cells

Structural hemoglobin variants: mutation, hematology and its application in prenatal diagnosis

Referred cases of Genetics OPD, SGPGI between 1988-2000 were screened for cause of anemia. Out of which one hundred and ninety eight individuals were found as abnormal hemoglobin variants and associated with β-thalassemia mutations viz: EβT, SβT, DβT. These phenotypes were of severe type. Hematology and mutation analysis were performed in these subjects by ARMS-PCR technique. Due to high prevalence of IVS I-5 (G-C) mutation, most of the structural variants (69%) were found associated with this mutation. Severity of the thalassemia syndromes (EβT, SβT, DβT) emphasized the need of establishment of prenatal diagnosis for common structural hemoglobin variants along with beta thalassemia mutations