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Pancreatic stellate cell: Pandora's box for pancreatic disease biology

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World Journal of gastroenterology 2017年第3期23卷 382-405页

作者： Ratnakar R Bynigeri Aparna Jakkampudi Ramaiah Jangala Chivukula Subramanyam Mitnala Sasikala g venkat rao D Nageshwar Reddy Rupjyoti Talukdar Institute of Basic Sciences Asian Healthcare FoundationHyderabad 500082India Department of Medical gastroenterology Asian Institute of GastroenterologyHyderabad 500082India Department of Surgical gastroenterology Asian Institute of GastroenterologyHyderabad 500082India

Pancreatic stellate cells(PSCs) were identified in the early 1980 s, but received much attention after 1998 when the methods to isolate and culture them from murine and human sources were developed. PSCs contribute to a small proportion of all pancreatic cells under physiological condition, but are essential for maintaining the normal pancreatic architecture. Quiescent PSCs are characterized by the presence of vitamin A laden lipid droplets. Upon PSC activation, these perinuclear lipid droplets disappear from the cytosol, attain a myofibroblast like phenotype and expresses the activation marker, alpha smooth muscle actin. PSCs maintain their activated phenotype via an autocrine loop involving different cytokines and contribute to progressive fibrosis in chronic pancreatitis(CP) and pancreatic ductal adenocarcinoma(PDAC). Several pathways(e.g., JAK-STAT, Smad, Wnt signaling, Hedgehog etc.), transcription factors and mi RNAs have been implicated in the inflammatory and profibrogenic function of PSCs. The role of PSCs goes much beyond fibrosis/desmoplasia in PDAC. It is now shown that PSCs are involved in significant crosstalk between the pancreatic cancer cells and the cancer stroma. These interactions result in tumour progression, metastasis, tumour hypoxia, immune evasion and drug resistance. This is the rationale for therapeutic preclinical and clinical trials that have targeted PSCs and the cancer stroma.

关键词： Pancreatic stellate cells Pancreatic fibrosis Pancreatic cancer stroma Physiological functions Pancreatic stellate cells-cancer-stromal interactions Therapeutic targets

Comprehensive screening for reg1α gene rules out association with tropical calcific pancreatitis

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World Journal of gastroenterology 2007年第44期13卷 5938-5943页

作者： Swapna Mahurkar Seema Bhaskar D Nageshwar Reddy g venkat rao giriraj Ratan Chandak genome Research group Centre for Cellular and Molecular Biology Uppal Road Hyderabad 500 007 India Asian Institute of gastroenterology Punjagutta Hyderabad 500 082 India

AIM: To investigate the allelic and haplotypic association of reg1α gene with tropical calcific pancreatitis (TCP). Since TCP is known to have a variable genetic basis, we investigated the interaction between mutations in the susceptibility genes, SPINK1 and CTSB with reg1α polymorphisms. METHODS: We analyzed the polymorphisms in the reg1α gene by sequencing the gene including its promoter region in 195 TCP patients and 150 ethnically matched controls, compared their allele and haplotype frequencies, and their association with the pathogenesis and pancreaticolithiasis in TCP and fibro-calculous pancreatic diabetes. RESULTS: We found 8 reported and 2 novel polymo-rphisms including an insertion-deletion polymorphism in the promoter region of reg1α. None of the 5' UTR variants altered any known transcription factor binding sites, neither did any show a statistically significant association with TCP. No association with any reg1α variants was observed on dichotomization of patients based on their N34S SPINK1 or L26V CTSB status. CONCLUSION: Polymorphisms in reg1α gene, including the regulatory variants singly or in combination with the known mutations in SPINK1 and/or CTSB genes, are not associated with tropical calcific pancreatitis.

关键词：钙化胰腺炎基因多态现象单体型

Differentiation of Pancreatic Ductal Epithelial Cells into Insulin Like Cell Clusters in Chronic Pancreatitis

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Open Journal of Endocrine and Metabolic Diseases 2015年第12期5卷 177-183页

作者： Pondugala Pavan Kumar gaddipati Radhika g. venkat rao D. Nageshwar Reddy M. Sasikala Asian Health Care Foundation Somajiguda Hyderabad India Asian Institute of gastroenterology Somajiguda Hyderabad India

Background/Aim: Islet regeneration in chronic pancreatitis (CP) is relevant for managing the associated loss of endocrine function. Because ductal epithelial cells were earlier demonstrated to differentiate into pancreatic endocrine mass, we evaluated their proliferation and differentiation in chronic pancreatitis. Methods: Pancreatic ducts were obtained from surgically resected pancreata of 12 patients with chronic pancreatitis and 15 control subjects. CK19 positive ductal cells were evaluated for their proliferating and differentiating abilities upon immunostaining with Ki 67 and hormone positivity for insulin and glucagon, apart from monitoring Pdx 1 expression. Results: In comparison to the controls, a greater number of proliferating pancreatic ductal epithelial cells (PDECs) were observed under conditions of CP. The increase in Pdx1 expressing PDECs (22%) and proliferating Pdx1 expressing PDECs (30%) was significant (P g insulin/glucagon in the exocrine ducts increased significantly in CP as compared to controls (P ?β?cell mass adjacent to the ducts increased by 28%.?Conclusion: Enhanced capability of PDECs to proliferate and differentiate into endocrine mass suggests that PDECs form a source of progenitors for cell based therapy in chronic pancreatitis.

关键词： Chronic Pancreatitis Ductal Epithelial Cells Islet Like Clusters Cell Differentiation

Dietary green Tea Extract and Antioxidants Improve Insulin Secretory Functions of Pancreatic β-Cells in Mild and Severe Experimental Rodent Model of Chronic Pancreatitis

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Open Journal of Endocrine and Metabolic Diseases 2024年第2期14卷 53-72页

作者： galande Sheethal Ranjeet K. Tokala Pavan Pondugala Krishna Vemula Vijayalakshmi venkatesan Pothani Suresh Surya Satyanarayana Singh guduru venkat rao Duvvur Nageshwar Reddy Mitnala Sasikala Basic Science and Translational Research Division Asian Healthcare Foundation AIG Hospitals Hyderabad India Division of Cell and Molecular Biology National institute of Nutrition Hyderabad India National Animal Resource Facility for Biomedical Research Hyderabad India Department of Biochemistry Osmania University Hyderabad India Department of Surgical gastroenterology Asian Institute of Gastroenterology Hyderabad India Department of gastroenterology Asian Institute of Gastroenterology Hyderabad India

Chronic pancreatitis (CP) is a progressive inflammatory disorder of the pancreas. It is predominantly idiopathic (with an unknown cause) in India and mostly due to alcohol in the West. Diabetes that occur secondary to chronic pancreatitis (T3c Diabetes) is often brittle, and is difficult to attain normoglycemia with conventional treatment requiring multiple doses of insulin. Mild and severe model of CP was induced in mice by repeated intraperitoneal injections of cerulein and L-arginine respectively with an intent to study islet dysfunction and develop therapeutic strategy in animal models of CP. Dietary intervention of epigallocatechin-3-gallate (EgCg) was tested in both the models of CP for its beneficial effects on insulin secretory functions. Pancreata collected upon euthanasia were used to study alterations in the morphology of pancreatic parenchyma and inflammation by staining with H&E and fibrotic changes by Masson’s trichrome and picrosirius staining. Insulin secretory functions of islets were evaluated to test the efficacy of the dietary intervention on β-cell functions. Intraperitoneal glucose tolerance test was performed to monitor the glucose homeostasis before and after the dietary intervention. Both the models resulted in CP with dispersed acini, inflammation and fibrosis. The loss of acini and extent of fibrosis was more in L-arginine model. 2-fold improvement in glucose-stimulated insulin secretory functions of islets was observed with 0.5% EgCg dietary intervention in cerulein model of CP and 1.6-fold in L-arginine model of CP. A further improvement in insulin secretion by 3.2-fold was observed with additional dietary supplements like N-acetyl cysteine, curcumin in combination with EgCg. Our results thus demonstrate and highlight the therapeutic potential of dietary green tea (EgCg) supplementation in reversing islet dysfunction and improving glucose homeostasis in experimental chronic pancreatitis in mice.

关键词： Dietary Intervention C57BL6/J Mice Epigallocatechin-3-gallate N-Acetyl Cysteine Curcumin Chronic Pancreatitis Islets glucose Stimulated Insulin Secretion

Seismic safety evaluation methodology for masonry building and retrofitting using splint and bandage technique with wire mesh

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Frontiers of Structural and Civil Engineering 2022年第4期16卷 478-505页

作者： Pravin Kumar venkat rao PADALU Yogendra SINgH Earthquake Engineering Research Center International Institute of Information Technology Hyderabad(IIIT-H)Telangana 500032India Department of Earthquake Engineering Indian Institute of Technology Roorkee(IITR)Uttarakhand 247667India

The paper presents a seismic safety assessment of unreinforced masonry(URM)building using two *** first approach uses the‘Pier Analysis’method,based on the concept of equivalent lateral stiffness,where in-plane and out-of-plane actions are considered *** second approach is developed with the program SAP2000,where the linear response is evaluated using continuum‘finite element modelling’(FEM).Both methods are compared to evaluate the safety of wall piers and the differences in the outcomes under combined gravitational and lateral seismic *** analysis results showed that few wall elements are unsafe in in-plane and out-of-plane *** is also observed that the pier analysis method is conservative compared to FEM,but can be used as a simplified and quick tool in design offices for safety assessment,with reasonable *** safeguard the URM wall piers under lateral loads,a retrofitting technique is adopted by providing vertical and horizontal belts called splints and bandages,respectively,using welded wire mesh(WWM)*** study using the‘Pier Analysis’shows that the lateral load capacity of unsafe URM piers can be enhanced up to 3.67 times and made safe using the applied retrofitting ***,the retrofitting design methodology and recommendations for application procedures to on-site URM buildings are discussed in detail.

关键词： unreinforced masonry seismic in-plane and out-of-plane forces pier analysis finite element modelling splint and bandage technique with wire mesh

Innovative Applications of Post-Tension for Restoration and Rehabilitation of Bridges and Structures--Case Studies in India

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Journal of Civil Engineering and Architecture 2014年第7期8卷 869-880页

作者： Ramesh Kommajosyula Narapraju venkat Ramana rao Varshitha Concrete Technologies Pvt. Ltd. Hyderabad 500 033 India Department of Civil Jawaharlal Nehru Technological University Hyderabad 500085 India

This paper deals with new and innovative case studies of application of post-tensioning for restoration of structures for buildings, bridges and rock stabilization in India. In earlier situations for these types of cases conventional method of repair and rehabilitation has been used. These innovative approaches for restoration have led to enormous saving of cost and time. The advantages of post tensioning are well known in the civil industry and are being used for the last 40 to 50 years. Post tensioning is one of the best methods to induce stresses in the concrete before application of live load and this technique can also be widely used for restoration and rehabilitation of structures. Unlike the use of post-tensioning in new structures there are no definite methods or codes for application in restoration and rehabilitation of structures. For restoration and rehabilitation of structures, PT (post tensioned) technique can be applied in combination with other techniques and materials available. Bridge lifting is a tricky and risky job especially when the superstructure is displaced appreciably by a natural calamity, etc.. Not only the present state of structure needs proper study before commencement of restoration and rehabilitation but also calls for careful execution. This paper deals with case studies of innovative applications of post tensioning in restoration and rehabilitation of structures and restoration of bridge structure in Andaman & Nicobar Island, India affected by Sumatra quake.

关键词：修复程序应用程序桥梁结构案例分析复结构后张创新印度

QbD Approach Method Development for Estimation of Dabigatran Etexilate along with Its Impurities and Identification of Degradants in Capsule Dosage Form

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American Journal of Analytical Chemistry 2016年第6期7卷 494-524页

作者： Hanimi Reddy Bapatu Ravi Kumar Maram Woo Hyung Cho venkat Bhaskar rao Pasagadugula Department of Chemistry JNT University Hyderabad India Dr. Reddy’s Laboratories Ltd. Miyapur India Celltrion Chemical Research Institute Youngin South Korea

The concept of Quality by Design was demonstrated in the development of a stability-indicating assay and related substances method by HPLC for Dabigatran Etexilate Capsules dosage form. Method design, method evaluation, method control and life cycle management were explained by systematic flow chart. Analytical Target Product profile was defined. The method was developed using the Inertsil ODS-3V, 150 mm × 4.6 mm, 5 μm column using the gradient program with ammonium formate buffer as mobile phase A and acetonitrile as mobile phase B. Risk assessment was performed as part of method evaluation. Design of experiment tools was used to optimize the chromatographic conditions. A two-level Full Factorial Design along with Face Centered Central Composite design augmentation was employed and statistical analysis of the experimental data uncovered the significant influential of chromatographic factors. The design space and the contour plot suggest that the current center point parameters can be further modified, resulting in better acceptability of the response parameters. The performance of the optimized method was validated according to current ICH guidelines. Dabigatran Etexilate Capsules was subjected to various stress conditions like oxidative, acid, base, hydrolytic, thermal, humidity, and photolytic degradations and evaluated chromatograms at 220 nm. The degradation products were well separated from each other and main peak, demonstrating the stability-indicating power of the method. One of the major degradant impurities, which are forming in neutral hydrolysis stress condition, is isolated and characterized by using analytical techniques like IR, LC-MS and NMR. Degradation pathway for Dabigatran Etexilate was proposed based on forced degradation data along with reaction mechanism.

关键词： Quality by Design Design of Experiment Dabigatran Etexilate Degradant Impurities

Carobomer Based Controlled Release Designs of Atorvastatin Calcium Tablets Evaluated Using Quality by Design (QbD) Approach

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American Journal of Analytical Chemistry 2017年第3期8卷 189-209页

作者： Arunkanth Krishnakumar Nair Peddakotla venkata Ramana P. venkat Bhaskar rao Bapatu Hanimi Reddy Hari Kishan Reddy ganthi Useni Reddy Mallu Sri Krishnadevaraya University Anantapur India Jawaharlal Nehru Technological University Hyderabad India

The study carried out here was focused on developing conventional monolithic controlled release matrix tablet of Atorvastatin calcium using carbomer as release controlling polymer. This system ensures the drug release at the alkaline pH region where the drug has got maximum solubility. Further the study was concentrated on comparing the impact of gelling agent polyvinyl pyrrolidone on drug release. Quality by design tools were considered during formulation development and the polymer concentrations were optimized adopting the statistical tool, design of experiments (DoE). The optimized formulation of present study exhibited desired controlled drug release characteristics in the alkaline pH conditions and at acidic environment the drug dissolution was minimal as intended.

关键词： Atorvastatin Calcium Tablets Controlled Release Carbomer Release Controlling Polymer gelling Agent Povidone

Influence of Negative Field Cooling on the Exchange Bias Properties of Potassium Split graphene Nanoribbons

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材料科学与工程（中英文A版） 2016年第5期6卷 254-259页

作者： M. venkat Narayana Srinivasa rao Singamaneni Suryanarayana Jammalamadaka Magnetic Materials and Device Physics Laboratory Department of Physics IIT Hyderabad Telangana 502285 India Department of Physics University of Texas at EI Paso EI Paso Texas 79968 USA