Publications by authors named "Sumit Kar"

89 Publications

Recommendations for the content and management of Certificates of Analysis for reference standards from the GCC for bioanalysis.

Bioanalysis 2021 Apr 13;13(8):609-619. Epub 2021 Apr 13.

Worldwide Clinical Trials, Austin, TX, USA.

The 13th Global CRO Council (GCC) closed forum for bioanalysis was held in New Orleans, LA, USA on 5 April 2019. This GCC meeting was organized to discuss the contents of the 2019 ICH M10 Bioanalytical Method Validation Draft Guideline published in February 2019 and consolidate the feedback of the GCC members. While ICH M10 will cover requirements for reference standards, one of the biggest challenges facing the CRO community is the lack of consistency and completeness of Certificates of Analysis for reference standards used in regulated bioanalysis. Similar challenges exist with critical reagents (e.g., capture and detection antibodies) used for assays supporting biologics. The recommendations provided in this publication are the minimum requirements for the content that GCC members believe should be included in Certificates of Analysis for reference standards obtained from commercial vendors, sponsors and compendial suppliers, for use in regulated bioanalytical studies. In addition, recommendations for internal standards, metabolites and critical reagents are discussed.
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http://dx.doi.org/10.4155/bio-2021-0046DOI Listing
April 2021

Generating Ins2/miR-133aTg Mice to Model miRNA-Driven Cardioprotection of Human Diabetic Heart.

Methods Mol Biol 2021 ;2224:113-121

Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA.

Diabetes mellitus (DM) is caused either due to insulin deficiency (T1DM) or insulin resistance (T2DM). DM increases the risk of heart failure by diabetic cardiomyopathy (DMCM), a cardiac muscle disorder that leads to a progressive decline in diastolic function, and ultimately systolic dysfunction. Mouse models of T1DM and T2DM exhibit clinical signs of DMCM. Growing evidence implicates microRNA (miRNA), an endogenous, non-coding, regulatory RNA, in the pathogenesis and signaling of DMCM. Therefore, inhibiting deleterious miRNAs and mimicking cardioprotective miRNAs could provide a potential therapeutic intervention for DMCM. miRNA-133a (miR-133a) is a highly abundant miRNA in the human heart. It is a cardioprotective miRNA, which is downregulated in the DM heart. It has anti-hypertrophic and anti-fibrotic effects. miR-133a mimic treatment after the onset of early DMCM can reverse histological and clinical signs of the disease in mice. We hypothesized that overexpression of cardiac-specific miR-133a in Ins2 Akita (T1DM) mice can prevent progression of DMCM. Here, we describe a method to create and validate cardiac-specific Ins2/miR-133aTg mice to determine whether cardiac-specific miR-133a overexpression prevents development of DMCM. These strategies demonstrate the value of genetic modeling of human disease such as DMCM and evaluate the potential of miRNA as a therapeutic intervention.
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http://dx.doi.org/10.1007/978-1-0716-1008-4_8DOI Listing
April 2021

2020 White Paper on Recent Issues in Bioanalysis: Vaccine Assay Validation, qPCR Assay Validation, QC for CAR-T Flow Cytometry, NAb Assay Harmonization and ELISpot Validation ( - Recommendations on Immunogenicity Assay Strategies, NAb Assays, Biosimilars and FDA/EMA Immunogenicity Guidance/Guideline, Gene & Cell Therapy and Vaccine Assays).

Bioanalysis 2021 Mar 3;13(6):415-463. Epub 2021 Feb 3.

Intellia Therapeutics, Cambridge, MA, USA.

The 14 edition of the Workshop on Recent Issues in Bioanalysis (14 WRIB) was held virtually on June 15-29, 2020 with an attendance of over 1000 representatives from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations, and regulatory agencies worldwide. The 14 WRIB included three Main Workshops, seven Specialized Workshops that together spanned 11 days in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy and vaccine. Moreover, a comprehensive vaccine assays track; an enhanced cytometry track and updated Industry/Regulators consensus on BMV of biotherapeutics by LCMS were special features in 2020. As in previous years, this year's WRIB continued to gather a wide diversity of international industry opinion leaders and regulatory authority experts working on both small and large molecules to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance and achieving scientific excellence on bioanalytical issues. This 2020 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the Global Bioanalytical Community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2020 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 3) covers the recommendations on Vaccine, Gene/Cell Therapy, NAb Harmonization and Immunogenicity). Part 1 (Innovation in Small Molecules, Hybrid LBA/LCMS & Regulated Bioanalysis), Part 2A (BAV, PK LBA, Flow Cytometry Validation and Cytometry Innovation) and Part 2B (Regulatory Input) are published in volume 13 of Bioanalysis, issues 4 and 5 (2020), respectively.
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http://dx.doi.org/10.4155/bio-2021-0007DOI Listing
March 2021

2020 White Paper on Recent Issues in Bioanalysis: BAV Guidance, CLSI H62, Biotherapeutics Stability, Parallelism Testing, CyTOF and Regulatory Feedback ( - Recommendations on Biotherapeutics Stability, PK LBA Regulated Bioanalysis, Biomarkers Assays, Cytometry Validation & Innovation - Regulatory Agencies' Inputs on Bioanalysis, Biomarkers, Immunogenicity, Gene & Cell Therapy and Vaccine).

Bioanalysis 2021 Mar 29;13(5):295-361. Epub 2021 Jan 29.

Health Canada, Ottawa, ON, Canada.

The 14 edition of the Workshop on Recent Issues in Bioanalysis (14 WRIB) was held virtually on June 15-29, 2020 with an attendance of over 1000 representatives from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations, and regulatory agencies worldwide. The 14 WRIB included three Main Workshops, seven Specialized Workshops that together spanned 11 days in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy and vaccine. Moreover, a comprehensive vaccine assays track; an enhanced cytometry track and updated Industry/Regulators consensus on BMV of biotherapeutics by LCMS were special features in 2020. As in previous years, this year's WRIB continued to gather a wide diversity of international industry opinion leaders and regulatory authority experts working on both small and large molecules to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance and achieving scientific excellence on bioanalytical issues. This 2020 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the Global Bioanalytical Community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2020 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication covers the recommendations on (Part 2A) BAV, PK LBA, Flow Cytometry Validation and Cytometry Innovation and (Part 2B) Regulatory Input. Part 1 (Innovation in Small Molecules, Hybrid LBA/LCMS & Regulated Bioanalysis), Part 3 (Vaccine, Gene/Cell Therapy, NAb Harmonization and Immunogenicity) are published in volume 13 of Bioanalysis, issues 4, and 6 (2021), respectively.
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http://dx.doi.org/10.4155/bio-2021-0005DOI Listing
March 2021

Puzzling Papules over Face: Clinicians Perplexity - A Case of Squamous Cell Carcinoma Impersonating MolluscumContagiosum.

Indian Dermatol Online J 2020 Nov-Dec;11(6):1010-1011. Epub 2020 Nov 8.

Department of Pathology, Mahatma Gandhi Institute of Medical Sciences, Sewagram, Wardha, Maharashtra, India.

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http://dx.doi.org/10.4103/idoj.IDOJ_35_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734985PMC
November 2020

Antimicrobial Susceptibility Trends among Pathogens Isolated from Blood: A 6-Year Retrospective Study from a Tertiary Care Hospital in East Sikkim, India.

J Lab Physicians 2020 Mar 11;12(1):3-9. Epub 2020 Jun 11.

Department of Microbiology, Sikkim Manipal Institute of Medical Sciences, Sikkim Manipal University, Tadong, Sikkim, India.

 Bloodstream infections (BSIs) are one of the frequent nosocomial infections among hospitalized patients. To understand the local epidemiology and evolving antimicrobial drug resistance of blood-borne pathogens, we analyzed the distribution and antibiotic sensitivity profile of organisms causing BSI in our hospital-based study.  We reviewed retrospective data of laboratory-confirmed BSIs, from January 2013 to December 2018. Causative organisms and their antibiotic susceptibility profile of primary and secondary BSI reports were determined from BacT/Alert and Vitek systems findings (bioMérieux). A 6-year multidrug resistance indexing was done to document the resistance pattern of the commonly isolated organisms.  A total of 1,340 (10.2%) BSIs were reported from 13,091 blood cultures. Organisms were frequently isolated from the younger population (≤20 years), especially from ages < 1 year (20.8% of total BSIs). Majority of pathogens were bacterial (97.1%) whereas 2.9% were fungal in origin. Monomicrobial growth was recorded in over 98% of BSIs. Gram-positive and gram-negative bacteria isolated were 518 (39.8%) and 783 (60.2%), respectively. Commonly isolated organisms were coagulase-negative (29.4%), (19.8%), species (13.5%), species (9.4%), and (7.5%). Multidrug-resistance index was observed highest in species followed by and .  Overall, there has been a gradual decline in the reporting of BSI. However, infections by gram-negative bacilli and multidrug-resistant organisms remain persistently high. Ages < 20 years were the vulnerable group, with infants < 1 year contributing to the maximum number of BSI cases caused by both bacteria and fungi. Therefore, additional methods are required to study the origin and causation of these infections, particularly among vulnerable patients.
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http://dx.doi.org/10.1055/s-0040-1712814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419168PMC
March 2020

Bioanalysis Rising Star Award 2020: announcing our finalists.

Bioanalysis 2020 Jun 3;12(12):817-821. Epub 2020 Jul 3.

Celerion, NE, USA.

Over the past 10 years, and Bioanalysis Zone have been proud to host the Bioanalysis Rising Star Award (formerly the New Investigator Award), to recognize and showcase the most promising early-career scientists in our community. The time has now come for you to select your winner for the Bioanalysis Rising Star Award 2020. We are delighted to present our judges' selection of finalists (in alphabetical order): Ashley Ross, University of Cincinnati (OH, USA) Chris Williams, QPS (Groningen, The Netherlands) Danielle Moncrieffe, King's College London (UK) Omar Barnaby, Amgen (CA, USA) Sooraj Baijnath, University of KwaZulu-Natal (South Africa) Sumit Kar, Celerion (NE, USA).
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http://dx.doi.org/10.4155/bio-2020-0130DOI Listing
June 2020

Rapid and robust bioanalytical assays are critical for SARS-CoV-2 therapeutic and vaccine development and beyond.

Bioanalysis 2020 09 26;12(17):1199-1203. Epub 2020 May 26.

Bioanalytical Sciences, Celerion Inc. 621 Rose St, Lincoln, NE 68502, USA.

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http://dx.doi.org/10.4155/bio-2020-0116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255425PMC
September 2020

MMP9 mediates acute hyperglycemia-induced human cardiac stem cell death by upregulating apoptosis and pyroptosis in vitro.

Cell Death Dis 2020 03 13;11(3):186. Epub 2020 Mar 13.

Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, 985850, USA.

Providing a conducive microenvironment is critical to increase survival of transplanted stem cells in regenerative therapy. Hyperglycemia promotes stem cell death impairing cardiac regeneration in the diabetic heart. Understanding the molecular mechanisms of high glucose-induced stem cell death is important for improving cardiac regeneration in diabetic patients. Matrix metalloproteinase-9 (MMP9), a collagenase, is upregulated in the diabetic heart, and ablation of MMP9 decreases infarct size in the non-diabetic myocardial infarction heart. In the present study, we aim to investigate whether MMP9 is a mediator of hyperglycemia-induced cell death in human cardiac stem cells (hCSCs) in vitro. We created MMP9 hCSCs to test the hypothesis that MMP9 mediates hyperglycemia-induced oxidative stress and cell death via apoptosis and pyroptosis in hCSCs, which is attenuated by the lack of MMP9. We found that hyperglycemia induced oxidative stress and increased cell death by promoting pyroptosis and apoptosis in hCSCs, which was prevented in MMP9 hCSCs. These findings revealed a novel intracellular role of MMP9 in mediating stem cell death and provide a platform to assess whether MMP9 inhibition could improve hCSCs survival in stem cell therapy at least in acute hyperglycemic microenvironment.
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http://dx.doi.org/10.1038/s41419-020-2367-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070071PMC
March 2020

Exercise Training Promotes Cardiac Hydrogen Sulfide Biosynthesis and Mitigates Pyroptosis to Prevent High-Fat Diet-Induced Diabetic Cardiomyopathy.

Antioxidants (Basel) 2019 Dec 11;8(12). Epub 2019 Dec 11.

Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.

Obesity increases the risk of developing diabetes and subsequently, diabetic cardiomyopathy (DMCM). Reduced cardioprotective antioxidant hydrogen sulfide (HS) and increased inflammatory cell death via pyroptosis contribute to adverse cardiac remodeling and DMCM. Although exercise training (EX) has cardioprotective effects, it is unclear whether EX mitigates obesity-induced DMCM by increasing H₂S biosynthesis and mitigating pyroptosis in the heart. C57BL6 mice were fed a high-fat diet (HFD) while undergoing treadmill EX for 20 weeks. HFD mice developed obesity, hyperglycemia, and insulin resistance, which were reduced by EX. Left ventricle pressure-volume measurement revealed that obese mice developed reduced diastolic function with preserved ejection fraction, which was improved by EX. Cardiac dysfunction was accompanied by increased cardiac pyroptosis signaling, structural remodeling, and metabolic remodeling, indicated by accumulation of lipid droplets in the heart. Notably, EX increased cardiac H₂S concentration and expression of H₂S biosynthesis enzymes. HFD-induced obesity led to features of type 2 diabetes (T2DM), and subsequently DMCM. EX during the HFD regimen prevented the development of DMCM, possibly by promoting H₂S-mediated cardioprotection and alleviating pyroptosis. This is the first report of EX modulating H₂S and pyroptotic signaling in the heart.
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http://dx.doi.org/10.3390/antiox8120638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943713PMC
December 2019

New approaches for biomarker stability determination in regulated bioanalysis: trending, bridging and incurred samples.

Bioanalysis 2019 Oct 28;11(20):1837-1844. Epub 2019 Oct 28.

Somru BioScience Inc., Innovation Way, BioCommons Research Park, Charlottetown, PE C1E 0B7, Canada.

Determining the stability of biomarkers continues to present challenges. Disease states, complex matrices and differences between recombinant and endogenous analytes require new approaches to maintain stability and measure it. In this report, we determine stability for two assays using trending and statistical analysis. Monitoring trends helps identify out of specification measurements and determine whether concerns are due to the stability of the analyte. We also describe challenges presented when measuring arginase activity in human sputum, a complex matrix, for respiratory diseases. We controlled preanalytical protease activity and collection heterogeneity and monitored incurred sample stability to improve stability of arginine. These new approaches to achieving and determining biomarker stability may provide solutions for increasingly complex biomarker measurements.
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http://dx.doi.org/10.4155/bio-2019-0208DOI Listing
October 2019

Guidelines for evaluating myocardial cell death.

Am J Physiol Heart Circ Physiol 2019 11 16;317(5):H891-H922. Epub 2019 Aug 16.

Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii.

Cell death is a fundamental process in cardiac pathologies. Recent studies have revealed multiple forms of cell death, and several of them have been demonstrated to underlie adverse cardiac remodeling and heart failure. With the expansion in the area of myocardial cell death and increasing concerns over rigor and reproducibility, it is important and timely to set a guideline for the best practices of evaluating myocardial cell death. There are six major forms of regulated cell death observed in cardiac pathologies, namely apoptosis, necroptosis, mitochondrial-mediated necrosis, pyroptosis, ferroptosis, and autophagic cell death. In this article, we describe the best methods to identify, measure, and evaluate these modes of myocardial cell death. In addition, we discuss the limitations of currently practiced myocardial cell death mechanisms.
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http://dx.doi.org/10.1152/ajpheart.00259.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879915PMC
November 2019

Assay validation and clinical performance of chronic inflammatory and chemokine biomarkers of NASH fibrosis.

PLoS One 2019 10;14(7):e0217263. Epub 2019 Jul 10.

Internal Medicine, Gastroenterology and Hepatology Services, Brooke Army Medical Center, San Antonio, TX, United States of America.

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease that can lead to cirrhosis, liver transplant, and even hepatocellular carcinoma. While liver biopsy remains the reference standard for disease diagnosis, analytical and clinical development of non-invasive soluble biomarkers of NASH are of great importance to advance the field. To this end, we performed analytical and clinical validation on a series of pro-inflammatory cytokines and chemokines implicated hepatic inflammation; IL-6, CRP, TNFα, MCP-1, MIP-1β, eotaxin, VCAM-1. Biomarker assays were validated for accuracy and precision. Clinical performance was evaluated in a random sample of 52 patients with biopsy-proven NAFLD/NASH. Patients were categorized into three groups according to their fibrosis stage; advanced (F3-F4), mild (F1-2) and no (F0) fibrosis. Serum IL-6 was increased in patients with advanced fibrosis (2.71 pg/mL; 1.26 pg/mL; 1.39 pg/mL p<0.01) compared to patients with mild or no fibrosis respectively. While, there was no significant difference noted in CRP, TNFα, MCP-1, MIP-1β, eotaxin among the three groups, VCAM-1 levels were increased by 55% (p<0.01) and 40% (p<0.05) in the advanced cohort compared to the mild and no fibrosis groups respectively. VCAM-1 also displayed good clinical performance as a biomarker of advanced fibrosis with an area under the receiver operating curve of 0.87. The VCAM-1 assay demonstrated robust accuracy and precision, and VCAM-1 outperformed IL-6, CRP, TNFα, and the chemokines MCP-1, MIP-1β, and eotaxin as a biomarker of advanced fibrosis in NASH. Addition of biomarkers such as IL-6 and VCAM-1 to panels may yield increased sensitivity and specificity for staging of NASH.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0217263PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619600PMC
February 2020

Hydrogen Sulfide Ameliorates Homocysteine-Induced Cardiac Remodeling and Dysfunction.

Front Physiol 2019 24;10:598. Epub 2019 May 24.

Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, United States.

Patients with diabetes, a methionine-rich meat diet, or certain genetic polymorphisms show elevated levels of homocysteine (Hcy), which is strongly associated with the development of cardiovascular disease including diabetic cardiomyopathy. However, reducing Hcy levels with folate shows no beneficial cardiac effects. We have previously shown that a hydrogen sulfide (HS), a by-product of Hcy through transsulfuration by cystathionine beta synthase (CBS), donor mitigates Hcy-induced hypertrophy in cardiomyocytes. However, the cardiac effects of HS in the context of hyperhomocysteinemia (HHcy) have not been studied. We tested the hypothesis that HHcy causes cardiac remodeling and dysfunction , which is ameliorated by HS. Twelve-week-old male CBS (a model of HHcy) and sibling CBS (WT) mice were treated with SG1002 (a slow release HS donor) diet for 4 months. The left ventricle of CBS mice showed increased expression of early remodeling signals c-Jun and c-Fos, increased interstitial collagen deposition, and increased cellular hypertrophy. Notably, SG1002 treatment slightly reduced c-Jun and c-Fos expression, decreased interstitial fibrosis, and reduced cellular hypertrophy. Pressure volume loop analyses in CBS mice revealed increased end systolic pressure with no change in stroke volume (SV) suggesting increased afterload, which was abolished by SG1002 treatment. Additionally, SG1002 treatment increased end-diastolic volume and SV in CBS mice, suggesting increased ventricular filling. These results demonstrate SG1002 treatment alleviates cardiac remodeling and afterload in HHcy mice. HS may be cardioprotective in conditions where HS is reduced and Hcy is elevated.
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http://dx.doi.org/10.3389/fphys.2019.00598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544124PMC
May 2019

Netherton syndrome: an atypical presentation.

Cutis 2019 04;103(4):E27-E29

Department of Pathology, Mahatma Gandhi Institute of Medical Sciences, Sewagram, Maharashtra, India.

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April 2019

Transgenic Expression of miR-133a in the Diabetic Akita Heart Prevents Cardiac Remodeling and Cardiomyopathy.

Front Cardiovasc Med 2019 24;6:45. Epub 2019 Apr 24.

Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, United States.

Advanced diabetes mellitus (DM) may have both insulin resistance and deficiency (double DM) that accelerates diabetic cardiomyopathy (DMCM), a cardiac muscle disorder. Reduced cardiac miR-133a, a cardioprotective miRNA, is associated with DMCM. However, it is unclear whether increasing miR-133a levels in the double DM heart could prevent DMCM. We hypothesized that increasing cardiac levels of miR-133a could prevent DMCM in Akita, a mouse model of double DM. To test the hypothesis, we created Akita/miR-133aTg mice, a new strain of Akita where miR-133a is overexpressed in the heart, by crossbreeding male Akita with female cardiac-specific miR-133a transgenic mice. We validated Akita/miR-133aTg mice by genotyping and phenotyping (miR-133a levels in the heart). To determine whether miR-133a overexpression could prevent cardiac remodeling and cardiomyopathy, we evaluated cardiac fibrosis, hypertrophy, and dysfunction (P-V loop) in 13-15 week male WT, Akita, Akita/miR-133aTg, and miR-133aTg mice. Our results revealed that miR-133a overexpression in the Akita heart prevents DM-induced cardiac fibrosis (reduced collagen deposition), hypertrophy (decreased beta-myosin heavy chain), and impaired contractility (downregulated calcium handling protein sarco-endoplasmic reticulum-ATPase-2a). These results demonstrate that increased levels of miR-133a in the DM heart could prevent cardiac remodeling. Our P-V loop analysis showed a trend of decreased cardiac output, stroke volume, and ± dp/dt in Akita, which were blunted in Akita/miR-133aTg heart. These findings suggest that 13-15 week Akita heart undergoes adverse remodeling toward cardiomyopathy, which is prevented by miR-133a overexpression. In addition, increased cardiac miR-133a in the Akita heart did not change blood glucose levels but decreased lipid accumulation in the heart, suggesting inhibition of metabolic remodeling in the heart. Thus, miR-133a could be a promising therapeutic candidate to prevent DMCM.
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http://dx.doi.org/10.3389/fcvm.2019.00045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491745PMC
April 2019

Recommendations for classification of commercial LBA kits for biomarkers in drug development from the GCC for bioanalysis.

Bioanalysis 2019 Apr 17;11(7):645-653. Epub 2019 Apr 17.

WuXi Apptec, Plainsboro, NJ, USA.

Over the last decade, the use of biomarker data has become integral to drug development. Biomarkers are not only utilized for internal decision-making by sponsors; they are increasingly utilized to make critical decisions for drug safety and efficacy. As the regulatory agencies are routinely making decisions based on biomarker data, there has been significant scrutiny on the validation of biomarker methods. Contract research organizations regularly use commercially available immunoassay kits to validate biomarker methods. However, adaptation of such kits in a regulated environment presents significant challenges and was one of the key topics discussed during the 12th Global Contract Research Organization Council for Bioanalysis (GCC) meeting. This White Paper reports the GCC members' opinion on the challenges facing the industry and the GCC recommendations on the classification of commercial kits that can be a win-win for commercial kit vendors and end users.
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http://dx.doi.org/10.4155/bio-2019-0072DOI Listing
April 2019

Hydrogen sulfide-mediated regulation of cell death signaling ameliorates adverse cardiac remodeling and diabetic cardiomyopathy.

Am J Physiol Heart Circ Physiol 2019 06 29;316(6):H1237-H1252. Epub 2019 Mar 29.

Department of Cellular and Integrative Physiology, University of Nebraska Medical Center , Omaha, Nebraska.

The death of cardiomyocytes is a precursor for the cascade of hypertrophic and fibrotic remodeling that leads to cardiomyopathy. In diabetes mellitus (DM), the metabolic environment of hyperglycemia, hyperlipidemia, and oxidative stress causes cardiomyocyte cell death, leading to diabetic cardiomyopathy (DMCM), an independent cause of heart failure. Understanding the roles of the cell death signaling pathways involved in the development of cardiomyopathies is crucial to the discovery of novel targeted therapeutics and biomarkers for DMCM. Recent evidence suggests that hydrogen sulfide (HS), an endogenous gaseous molecule, has cardioprotective effects against cell death. However, very little is known about signaling by which HS and its downstream targets regulate myocardial cell death in the DM heart. This review focuses on HS in the signaling of apoptotic, autophagic, necroptotic, and pyroptotic cell death in DMCM and other cardiomyopathies, abnormalities in HS synthesis in DM, and potential HS-based therapeutic strategies to mitigate myocardial cell death to ameliorate DMCM.
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http://dx.doi.org/10.1152/ajpheart.00004.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620689PMC
June 2019

Adaptation of commercial biomarker kits and proposal for 'drug development kits' to support bioanalysis: call for action.

Bioanalysis 2018 Jun;10(12):945-955

Celerion, Inc., Global Bioanalytical Services, 621 Rose Street, Lincoln, NE 68502 USA.

There has been an increased use of commercial kits for biomarker measurement, commensurate with the increased demand for biomarkers in drug development. However, in most cases these kits do not meet the quality attributes for use in regulated environment. The process for adaptation of these kits can be frustrating, time consuming and resource intensive. In addition, a lack of harmonized guidance for the validation of biomarker poses a significant challenge in the adaptation of kits in a regulated environment. The purpose of this perspective is to propose a tiered approach to commercial drug development kits with clearly defined quality attributes and to demonstrate how these kits can be adapted to perform analytical validation in a regulated environment.
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http://dx.doi.org/10.4155/bio-2017-0254DOI Listing
June 2018

Cystatin C Is a More Reliable Biomarker for Determining eGFR to Support Drug Development Studies.

J Clin Pharmacol 2018 10 18;58(10):1239-1247. Epub 2018 May 18.

Global Bioanalytical Services, Celerion, Lincoln, NE, USA.

Glomerular filtration rate (GFR) is routinely used as a surrogate endpoint for the development of investigational drugs in clinical trials. GFR and staging of chronic kidney disease are typically assessed by measuring the concentration of endogenous serum biomarkers such as albumin and creatinine. However, creatinine is subject to high biological variability, and levels of creatinine do not rise until nearly 50% of kidney function is damaged, leading to inaccurate chronic kidney disease staging and false negatives. A newer biomarker for GFR, cystatin C, has been shown to be subject to less biological interference and more sensitive to early declines in kidney function. Cystatin C has also been shown to outperform creatinine as an indicator of true GFR and to add information about the occurrence of acute kidney injury. Comparison studies of cystatin C and creatinine continue to demonstrate its increased accuracy and sensitivity for changes in true GFR. While challenges remain for use of cystatin C, international agencies and working groups continue to validate cystatin C as a biomarker and accompanying GFR estimating equations for diagnostic and drug development use. In this review, we summarize these comparison studies, regulatory and industry guidelines, and clinical trial case studies for use of cystatin C in drug development.
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http://dx.doi.org/10.1002/jcph.1132DOI Listing
October 2018

Phacomatosis cesioflammea in association with von Recklinghausen disease (neurofibromatosis type I).

Cutis 2017 02;99(2):E35-E37

Department of Dermatology, Venereology, and Leprosy, Mahatma Gandhi Institute of Medical Sciences, Sewagram, Wardha, Maharashtra, India.

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February 2017

Extrafacial melasma over forearms.

Indian Dermatol Online J 2016 Jul-Aug;7(4):344-5

Department of Dermatology, Venereology, Leprosy, Mahatma Gandhi Institute of Medical Sciences, Wardha, Maharashtra, India.

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http://dx.doi.org/10.4103/2229-5178.185470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4976433PMC
August 2016

Author's Reply.

Indian J Dermatol 2016 May-Jun;61(3):337-8

Department of Dermatology, Venereology, Leprosy, Mahatma Gandhi Institute of Medical Sciences, Wardha, Maharashtra, India. E-mail:

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http://dx.doi.org/10.4103/0019-5154.182407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885196PMC
June 2016

Hailey-Hailey disease.

Indian Dermatol Online J 2016 Mar-Apr;7(2):147-8

Department of Pathology, Mahatma Gandhi Institute of Medical Sciences, Wardha, Maharashtra, India.

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http://dx.doi.org/10.4103/2229-5178.178090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804597PMC
April 2016

Prevalence of Topical Steroid Misuse Among Rural Masses.

Indian J Dermatol 2016 Jan-Feb;61(1):119

Department of Dermatology, Venereology, Leprosy, Mahatma Gandhi Institute of Medical Sciences, Wardha, Maharashtra, India.

Background: A lot of cosmetic and Ayurvedic products containing unlabeled depigmenting agent and steroids are available readily over the counter sale. The side effects of these products are not documented and can lead to adverse effects of continuous usage.

Objective: By this study, we aimed to find out the true nature of the above problem and it's implication in the Indian rural scenario.

Methodology: All patients attending dermatology department during the period of 3 months from May to June 2013 for skin diseases were enquired about unsupervised use of any cosmetic product on their facial skin, duration of use, any side effect experienced through the prescribed questionnaire.

Results: Total 50 patients were recruited for the study. Out of which, 48% were males and 52% were females. Seventy-four percent of people had applied topical products/steroids in an attempt of attainment of fair complexion, 14% for melasma, 8% for acne induced hyperpigmentation, and 4% for dark circles. About 80% people had obtained one or the other products over the counter sale, 8% had followed the attractive advertisements, 8% had started the application on the recommendation of friends/family while only 4% people had correctly gone through the proper channel to consult a dermatologist.

Conclusion: The problem of topical products or steroids abuse is rampant and significant, and unless and until immediate steps are taken to root out this problem from our setup, the condition will become worse all the more.
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http://dx.doi.org/10.4103/0019-5154.174081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763634PMC
March 2016

Dermatoses due to Quackery: A Case Snippet and Concise Review of Literature.

Indian J Dermatol 2016 Jan-Feb;61(1):75-7

Department of Dermatology, Venereology and Leprosy, Mahatma Gandhi Institute of Medical Sciences, Wardha, Maharashtra, India.

A wide prevalence of socio-religious, cultural, and tribal practices in India often leads to a multitude of skin conditions, which can misled the dermatologists in arriving at a diagnosis. With increasing globalization and migration, the practice of indigenous customs and traditions are crossing boundaries, making it imperative for the dermatologists to be acquainted with the cutaneous side effects of these practices. Here, we report a unique case of thermal burn in a circumferential pattern over the umbilical region, a result of the placement of burning lamp over umbilicus to alleviate abdominal discomfort.
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http://dx.doi.org/10.4103/0019-5154.174029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763699PMC
March 2016

Effects of omega-3 fatty acids in prevention of early preterm delivery: a systematic review and meta-analysis of randomized studies.

Eur J Obstet Gynecol Reprod Biol 2016 Mar 30;198:40-46. Epub 2015 Nov 30.

Women's Health Unit, Royal London Hospital, Bart's Health NHS Trust, London, UK; Women's Health Research Unit, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; Multidisciplinary Evidence Synthesis Hub (MESH), Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

Objective: Preterm birth continues to be the one of the leading causes of infant deaths worldwide. There is a need for effective, easily available, safe and acceptable interventions to prevent preterm delivery, especially before 34 weeks of gestation. Omega-3 fatty acids such as EPA (eicosapentanoic acid) and DHA (docosahexanoic acid) are available as over the counter nutritional supplements, and are taken by women to improve pregnancy outcomes, without any clear recommendations. We undertook a systematic review to assess the effects of omega-3 fatty acids on early (<34 weeks) and any (<37 weeks) preterm delivery.

Methods: We searched MEDLINE, EMBASE and Cochrane Library from inception to 2014 without any language restrictions. Study selection, quality assessment and data extraction were done by two independent reviewers. Results were summarized as relative risks and 95% confidence intervals for dichotomous outcomes and mean differences for continuous outcomes.

Results: Of the nine included trials (5980 women), six (4193 women) evaluated the effects of omega-3 fatty acids on early preterm delivery. The risk of early preterm delivery was reduced by 58% (RR 0.42; 95% CI 0.27-0.66; I(2)=0%; p=0.0002) and any preterm delivery by 17% (RR 0.83; 95% CI 0.70-0.98; I(2)=0%; p=0.03) with the intervention. There was a significant increase in the mean gestational age by 1.95 weeks (95% CI 0.42-3.48 weeks; I(2)=0.47; p=0.01) and mean birth weight by 122.1g (95% CI 47.4-196.8; I(2)=0.84; p=0.001) in the intervention group compared to the controls. Subgroup analysis showed no significant differences in the effects between the groups according to the risk status, dose and timing of the intervention.

Conclusion: Omega-3 fatty acids are effective in preventing early and any preterm delivery. The intervention is simple and easily available and has the potential to influence population based strategies in the prevention of preterm birth.
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http://dx.doi.org/10.1016/j.ejogrb.2015.11.033DOI Listing
March 2016

Linear rays of depigmentation along lymphatics after intralesional corticosteroid therapy.

Indian Dermatol Online J 2015 Nov-Dec;6(6):456-7

Department of Dermatology, Venereology and Leprosy, Mahatma Gandhi Institute of Medical Sciences, Maharashtra, India.

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http://dx.doi.org/10.4103/2229-5178.169728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4693372PMC
January 2016

Acute Hemorrhagic Edema of Infancy.

Indian J Dermatol 2015 Nov-Dec;60(6):624-5

Department of Dermatology, Venereology and Leprosy, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Wardha - 442 102, Maharashtra, India. E-mail:

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http://dx.doi.org/10.4103/0019-5154.169150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681212PMC
December 2015

Authors' Reply.

Indian J Dermatol 2015 Sep-Oct;60(5):515

Department of Dermatology, Venereology and Leprosy, Mahatma Gandhi Institute of Medical Sciences, Wardha, Maharashtra, India. E-mail:

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601431PMC
November 2015