સાહિત્યસર્જક ચિનુ મોદી - સમીક્ષાત્મક અધ્યયન

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Synthesis of novel diflunisal hydrazide hydrazones as anti-hepatitis C virus agents and hepatocellular carcinoma inhibitors

Hepatitis C virus (HCV) infection is a main cause of chronic liver disease, leading to liver cirrhosis and hepatocellular carcinoma (HCC). The objective of our research was to develop effective agents against viral replication. We have previously identified the hydrazide hydrazone scaffold as a promising hepatitis C virus (HCV) and hepatocelluler inhibitor. Herein we describe the design a number of 2',4'-difluoro-4-hydroxy-N'-(arylmethylidene) biphenyl-3-carbohydrazide (3a-t) as anti-HCV and anticancer agents. Results from evaluation of anti-HCV activity indicated that most of the synthesized hydrazone derivatives inhibited viral replication in the Huh7/Rep-Feo1b and Huh 7.5-FGR-JCI-Rluc2A reporter systems. Antiproliferative activities of increasing concentrations of 2',4'-difluoro-4-hydroxy-N'-(2-pyridyl methylidene)biphenyl-3-carbohydrazide 3b and diflunisal (2.5-40 mu M) were assessed in liver cancer cell lines (Huh7, HepG2, Hep3B, Mahlavu, FOCUS and SNU-475) with sulforhodamine B assay for 72 h. Compound 3b with 2-pyridinyl group in the hydrazone part exhibited promising cytotoxic activity against all cell lines with IC50 values of 10, 1034 16.21 4.74, 9.29 and 8.33 mu M for Huh7, HepG2, Hep3B, Mahlavu, FOCUS and SNU-475 cells, respectively, and produced dramatic cell cycle arrest at SubG1/G0 phase as an indicator of apoptotic cell death induction. (C) 2015 Elsevier Masson SAS. All rights reserved

Acute Arterial Thromboembolism in Patients with COVID-19 in the New York City Area

© 2020 Elsevier Inc. Background: Coronavirus disease 2019 (COVID-19) predisposes to arterial and venous thromboembolic complications. We describe the clinical presentation, management, and outcomes of acute arterial ischemia and concomitant infection at the epicenter of cases in the United States. Methods: Patients with confirmed COVID-19 infection between March 1, 2020 and May 15, 2020 with an acute arterial thromboembolic event were reviewed. Data collected included demographics, anatomical location of the thromboembolism, treatments, and outcomes. Results: Over the 11-week period, the Northwell Health System cared for 12,630 hospitalized patients with COVID-19. A total of 49 patients with arterial thromboembolism and confirmed COVID-19 were identified. The median age was 67 years (58–75) and 37 (76%) were men. The most common preexisting conditions were hypertension (53%) and diabetes (35%). The median D-dimer level was 2,673 ng/mL (723–7,139). The distribution of thromboembolic events included upper 7 (14%) and lower 35 (71%) extremity ischemia, bowel ischemia 2 (4%), and cerebral ischemia 5 (10%). Six patients (12%) had thrombus in multiple locations. Concomitant deep vein thrombosis was found in 8 patients (16%). Twenty-two (45%) patients presented with signs of acute arterial ischemia and were subsequently diagnosed with COVID-19. The remaining 27 (55%) developed ischemia during hospitalization. Revascularization was performed in 13 (27%) patients, primary amputation in 5 (10%), administration of systemic tissue‐ plasminogen activator in 3 (6%), and 28 (57%) were treated with systemic anticoagulation only. The rate of limb loss was 18%. Twenty-one patients (46%) died in the hospital. Twenty-five (51%) were successfully discharged, and 3 patients are still in the hospital. Conclusions: While the mechanism of thromboembolic events in patients with COVID-19 remains unclear, the occurrence of such complication is associated with acute arterial ischemia which results in a high limb loss and mortality

Synthesis of novel diflunisal hydrazide-hydrazones as anti-hepatitis C virus agents and hepatocellular carcinoma inhibitors

Hepatitis C virus (HCV) infection is a main cause of chronic liver disease, leading to liver cirrhosis and hepatocellular carcinoma (HCC). The objective of our research was to develop effective agents against viral replication. We have previously identified the hydrazideehydrazone scaffold as a promising hepatitis C virus (HCV) and hepatocelluler inhibitor. Herein we describe the design a number of 20,40-difluoro-4-hydroxy-N'-(arylmethylidene) biphenyl-3-carbohydrazide (3a-t) as anti-HCV and anticancer agents. Results from evaluation of anti-HCV activity indicated that most of the synthesized hydrazone derivatives inhibited viral replication in the Huh7/Rep-Feo1b and Huh 7.5-FGR-JCI-Rluc2A reporter systems. Antiproliferative activities of increasing concentrations of 20,40-difluoro-4-hydroxy-N'-(2-pyridyl methylidene)biphenyl-3-carbohydrazide 3b and diflunisal (2.5e40 μM) were assessed in liver cancer cell lines (Huh7, HepG2, Hep3B, Mahlavu, FOCUS and SNU-475) with sulforhodamine B assay for 72 h. Compound 3b with 2-pyridinyl group in the hydrazone part exhibited promising cytotoxic activity against all cell lines with IC50 values of 10, 10.34 16.21 4.74, 9.29 and 8.33 μM for Huh7, HepG2, Hep3B, Mahlavu, FOCUS and SNU-475 cells, respectively, and produced dramatic cell cycle arrest at SubG1/G0 phase as an indicator of apoptotic cell death induction. © 2015 Elsevier Masson SAS

An international experience with single-operator cholangiopancreatoscopy in patients with altered anatomy

Background and study aims: The utility of digital single- operator cholangiopancreatoscopy (D-SOCP) in surgically altered anatomy (SAA) is limited. We aimed to evaluate the technical success and safety of D-SOCP in patients SAA. Patients and methods: Patients with SAA who underwent D-SOCP between February 2015 and June 2020 were retrospectively evaluated. Technical success was defined as completing the intended procedure with the use of D-SOCP. Results: Thirty-five patients underwent D-SOCP (34 D-SOC, 1 D-SOP). Bilroth II was the most common type of SAA (45.7 %), followed by Whipple reconstruction (31.4 %). Twenty-three patients (65.7 %) patients had prior failed ERCP due to the presence of complex biliary stone (52.2 %). A therapeutic duodenoscope was utilized in the majority of the cases (68.6 %), while a therapeutic gastroscope (22.7 %) or adult colonoscope (8.5 %) were used in the remaining procedures. Choledocholithiasis (61.2 %) and pancreatic duct calculi (3.2 %) were the most common indications for D-SOCP. Technical success was achieved in all 35 patients (100 %) and majority (91.4 %) requiring a single session. Complex interventions included electrohydraulic or laser lithotripsy, biliary or pancreatic stent placement, stricture dilation, and target tissue biopsies. Two mild adverse events occurred (pancreatitis and transient bacteremia). Conclusions: In SAA, D-SOCP is a safe and effective modality to diagnose and treat complex pancreatobiliary disorders, especially in cases where standard ERCP attempts may fail

The Groebke-Blackburn-Bienayme Reaction

Imidazo[1,2a]pyridine is a well‐known scaffold in many marketed drugs, such as Zolpidem, Minodronic acid, Miroprofen and DS‐1 and it also serves as a broadly applied pharmacophore in drug discovery. The scaffold revoked a wave of interest when Groebke, Blackburn and Bienaymé reported independently a new three component reaction resulting in compounds with the imidazo[1,2‐a]‐heterocycles as a core structure. During the course of two decades the Groebke Blackburn Bienaymé (GBB‐3CR) reaction has emerged as a very important multicomponent reaction (MCR), resulting in over a hundred patents and a great number of publications in various fields of interest. Now two compounds derived from GBB‐3CR chemistry received FDA approval. To celebrate the first 20 years of GBB‐chemistry , we present an overview of the chemistry of the GBB‐3CR, including an analysis of each of the three starting material classes, solvents and catalysts. Additionally, a list of patents and their applications and a more in‐depth summary of the biological targets that were addressed, including structural biology analysis, is given