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Favipiravir-induced Liver Injury in Patients with Coronavirus Disease 2019

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Journal of Clinical and Translational Hepatology 2021年第2期9卷 276-278页

作者： Pramod Kumar Anand Kulkarni Mithun Sharma padaki nagaraja rao Duvvuru Nageshwar Reddy Department of Hepatology and Liver Transplantation Asian Institute of Gastroenterology HospitalsHyderabadIndia Department of Gastroenterology Asian Institute of Gastroenterology HospitalsHyderabadIndia

Favipiravir,an antiviral,was given restricted emergency use approval to treat coronavirus disease 2019(COVID-19)in many *** the clinical efficacy of favipiravir in COVID-19 remains uncertain,the approval was based on findings from in vitro studies and a clinical trial.1 Limited data from studies of the Ebola virus and influenza disease showed a favorable safety profile.2 Herein,we provide the first report of drug-induced liver injury(DILI)due to favipiravir in patients treated for COVID-19.

关键词： clinical approval Liver

Pooled genetic analysis in ultrasound measured non-alcoholic fatty liver disease in Indian subjects:A pilot study

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World Journal of Hepatology 2014年第6期6卷 435-442页

作者： Vishnubhotla Venkata Ravi Kanth Mitnala Sasikala padaki nagaraja rao Urmila Steffie Avanthi Kalashikam Rajender rao Duvvuru Nageshwar Reddy Asian Healthcare Foundation Hyderabad 500082India Asian Institute of Gastroenterology Hyderabad 500082India Division of Endocrinology and Metabolism National Institute of NutritionTarnakaHyderabad 500082India

AIM: To investigate genetic susceptibility in Indian subjects with non-alcoholic fatty liver disease(NAFLD) by performing a pooled genetic ***: Study subjects(n = 306) were recruited and categorized into NAFLD and control groups based on ultrasound findings of fatty infiltration. Of the 306 individuals, 156 individuals had fatty infiltration and thus comprised the NAFLD group. One hundred and fifty(n = 150) individuals were normal, without fatty infiltration of the liver, comprising the control group. Blood samples, demographic and anthropometric data from the individuals were collected after obtaining informed consent. Anthropometric data, blood glucose, lipids and liver function tests were estimated using standard methods. Genome wide association stud-ies done to date on NAFLD were identified, 19 single nucleotide polymorphisms(SNPs) were selected from these studies that were reported to be significantly associated with NAFLD and genotyping was performed on the Sequenom platform. Student's t test for continuous variables and χ2 test was applied to variant carriers from both groups. Required corrections were applied as multiple testing was *** The mean age of the control group was 39.78 ± 10.83 and the NAFLD group was 36.63 ± 8.20 years. The waist circumference of males and females in the control and NAFLD groups were 80.13 ± 10.35; 81.77 ± 13.65 and 94.09 ± 10.53; 92.53 ± 8.27 respectively. The mean triglyceride and alanine transaminase(ALT) levels in the control and NAFLD groups were 135.18 ± 7.77; 25.39 ± 14.73 and 184.40 ± 84.31; 110.20 ± 67.05 respectively. When χ2 test was applied to the number of individuals carrying the variant risk alleles between the control and NAFLD group, a significant association was seen between rs738409 of the patatin-like phospholipase domain containing 3(PNPLA3) gene(P = 0.001), rs2073080 of the PARVB gene(P = 0.02), rs2143571 of SAMM50 gene(P = 0.05) and rs6487679 of the pregnancy zone protein(PZP) gene(P = 0.0

关键词： Non-alcoholic fatty liver disease Genome wide association studies Genetic association Hepatic steatosis Genotyping Single nucleotide polymorphisms Susceptibility

Genetics of non-alcoholic fatty liver disease: From susceptibility and nutrient interactions to management

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World Journal of Hepatology 2016年第20期8卷 827-837页

作者： Vishnubhotla Venkata Ravi Kanth Mitnala Sasikala Mithun Sharma padaki nagaraja rao Duvvuru Nageshwar Reddy Asian Healthcare Foundation a Research Wing of Asian Institute of Gastroenterology Asian Institute of Gastroenterology

Genetics plays an important role in determining the susceptibility of an individual to develop a disease. Complex, multi factorial diseases of modern day(diabetes, cardiovascular disease, hypertension and obesity) are a result of disparity between the type of food consumed and genes, suggesting that food which does not match the host genes is probably one of the major reasons for developing life style diseases. Non-alcoholic fatty liver is becoming a global epidemic leading to substantial morbidity. While various genotyping approaches such as whole exome sequencing using next generation sequencers and genome wide association studies have identified susceptibility loci for non-alcoholic fatty liver disease(NAFLD) including variants in patatin-like phospholipase domain containing 3 and transmembrane 6 superfamily member 2 genes apart from others; nutrient based studies emphasized on a combination of vitamin D, E and omega-3 fatty acids to manage fatty liver disease. However majority of the studies were conducted independent of each other and very few studies explored the interactions between the genetic susceptibility and nutrient interactions. Identifying such interactions will aid in optimizing the nutrition tailor made to an individual's genetic makeup, thereby aiding in delaying the onset of the disease and its progression. The present topic focuses on studies that identified the genetic susceptibility for NAFLD, nutritional recommendations, and their interactions for better management of NAFLD.

关键词： Transmembrane 6 superfamily member 2 gene Patatin-like phospholipase domain containing 3 gene Genotyping Nutrient interactions Non-alcoholic fatty liver disease Genetic susceptibility

Regional differences in genetic susceptibility to nonalcoholic liver disease in two distinct Indian ethnicities

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World Journal of Hepatology 2017年第26期9卷 1101-1107页

作者： Govardhan Bale Avanthi Urmila Steffie Vishnubhotla Venkata Ravi Kanth padaki nagaraja rao Mithun Sharma Mitnala Sasikala Duvvur Nageshwar Reddy Asian Healthcare Foundation Asian Institute of Gastroenterology

AIM To validate the association of variants in PNPLA3(rs2281135) and TM6SF2(rs58542926) genes with ultrasound detected non-alcoholic fatty liver disease(NAFLD).METHODS A total of 503 individuals with and without fatty infiltration were recruited. Fatty infiltration was confirmed based on ultrasound findings. Anthropometric data and blood samples were collected from the study group. DNA was isolated from peripheral blood, quality and quantity was assessed by gel electrophoresis and spectrophotometer respectively. Genotyping of the variants in PNPLA3 and TM6SF2 genes was carried out by employing taqman probes(C_15875080_10 for PNPLA3 and C_8946351_10 for TM6SF2 SNP) on real time PCR(Stepone-Lifetechnologies). Genotype data was tested for deviations from Hardy-Weinbergequilibrium. χ~2 test was used to analyze the statistical significance of the difference in genotype distribution of the studied variants in patients and controls and the strength of association was expressed as odds ratio(95%CI). A two-tailed P value of ≤ 0.05 was considered statistically significant. RESULTS The study group comprised of 503 individuals of which 256 had fatty infiltration and 247 without fatty infiltration and thus formed the patient and control groups respectively. As the patient group could be divided in to two distinct ethnicities(ancestral South Indians-ASI and North-East Indians-NEI), further recruitment of control cohort and association analyses was carried out based on ethnicities. Of the 256 with fatty infiltration 93 were ASI and 163 were NEI and of the 247 controls 138 were ASI and 109 were NEI. As expected, there were significant differences in the anthropometric and other clinical data between the control and the patient groups. However significant differences within the ethnicities were also noted. While rs2281135 in PNPLA3 gene was significantly associated(P = 0.03) with higher risk(odds 1.9, 95%CI: 1.5-3.14, P = 0.03) of NAFLD in NEI ethnicity, rs58542926 in TM6SF2 gene wa

关键词： Transmembrane 6 superfamily 2 Patatinlike phospholipase domain-containing protein 3 Fatty infiltration Genetic susceptibility Ethnicity Nonalcoholic fatty liver disease Cirrhosis Single nucleotide polymorphism

Autologous mobilized peripheral blood CD34^+ cell infusion in non-viral decompensated liver cirrhosis

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World Journal of Gastroenterology 2015年第23期21卷 7264-7271页

作者： Mithun Sharma padaki nagaraja rao Mitnala Sasikala Mamata Reddy Kuncharam Chimpa Reddy Vardaraj Gokak BPSS Raju Jagdeesh R Singh Piyal Nag D Nageshwar Reddy Department of Gastroenterology and Hepatology Asian Institute of Gastroenterology Asian Healthcare Foundation Asian Healthcare Foundation Department of Interventional Radiology Asian Institute of Gastroenterology

AIM: To study the effect of mobilized peripheral blood autologous CD34 positive(CD34+) cell infusion in patients with non-viral decompensated ***: Cirrhotic patients of non-viral etiology were divided into 2 groups based on their willingness to be listed for deceased donor liver transplant(DDLT)(control, n = 23) or to receive autologous CD34+ cell infusion through the hepatic artery(study group, n= 22). Patients in the study group were admitted to hospital and received granulocyte colony stimulating factor injections 520 μg/d for 3 consecutive days to mobilize CD34+ cells from the bone marrow. On day 4,leukapheresis was done and CD34+ cells were isolated using CliniMAC magnetic cell sorter. The isolated CD34+ cells were infused into the hepatic artery under radiological guidance. The patients were discharged within 48 h. The control group received standard of care treatment for liver cirrhosis and were worked up for DDLT as per protocol of the institute. Both groups were followed up every week for 4 wk and then every month for 3 ***: In the control and the study group, the cause of cirrhosis was cryptogenic in 18(78.2%) and16(72.72%) and alcohol related in 5(21.7%) and6(27.27%), respectively. The mean day 3 cell count(cells/μL) was 27.00 ± 20.43 with a viability of 81.84± 11.99%. and purity of 80%-90%. Primary end point analysis revealed that at 4 wk, the mean serum albumin in the study group increased significantly(2.83± 0.36 vs 2.43 ± 0.42, P = 0.001) when compared with controls. This improvement in albumin was,however, not sustained at 3 mo. However, at the end of3 mo there was a statistically significant improvement in serum creatinine in the study group(0.96 ± 0.33 vs 1.42 ± 0.70, P = 0.01) which translated into a significant improvement in the Model for End-Stage Liver Disease score(15.75 ± 5.13 vs 19.94 ± 6.68,P = 0.04). On statistical analysis of secondary end points, the transplant free survival at the end of 1 mo and 3 mo did not show

关键词： CD34 cell infusion Stem cell Cirrhosis Model for end-stage liver disease Liver transplantation

Identification of circulating CD90^+ CD73^+ cells in cirrhosis of liver

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World Journal of Stem Cells 2011年第7期3卷 63-69页

作者： Mitnala Sasikala Pugazhelthi Surya Gaddipati Radhika Pondugala Pavan Kumar Mekala Subba rao Rathindra Mohan Mukherjee padaki nagaraja rao D Nageshwar Reddy Institute of Basic Sciences and TranslationalResearch Asian Health Care Foundation Asian Institute of Gastroenterology

AIM:To identify circulating CD90 + CD73 + CD45 cells and evaluate their in vitro proliferating ***:Patients with cirrhosis(n=43),and healthy volunteers(n=40)were recruited to the *** cells were isolated and cultured from the peripheral blood of controls and cirrhosis ***-like cells that appeared in cultures were analyzed for morphological features,enumerated by flow cytometry and confirmed by immunocytochemistry(ICC).Colony forming efficiency(CFE)of these cells was assessed and expressed as a ***:In comparison to healthy volunteers,cells obtained from cirrhotic patients showed a significantincrease(P<0.001)in the percentage of CD90+CD73+ CD45 cells in *** cells also showed 10 fold increases in *** cytometry and ICC confirmed that the proliferating cells expressed CD90 + CD73 + in the cultures from cirrhosis ***:These results indicate the presence of circulating CD90 + CD73 + CD45 cells in patients with liver cirrhosis that have the potential to proliferate at a higher rate.

关键词： CD90+ CD73+ CD45 cells Liver cirrhosis Proliferation Colony forming efficiency

Assessment of high-gain quadratic boost converter with hybrid-based maximum power point tracking technique for solar photovoltaic systems

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Clean Energy 2022年第4期6卷 632-645页

作者： Veerabhadra S.nagaraja rao M S Ramaiah University of Applied Sciences Department of Electrical EngineeringBangaloreIndia

Solar photovoltaic(SPV)modules have a low output voltage and are ***,it is critical that the SPV system has an adequate DC-DC converter to regulate and improve the output voltage to get maximum output *** meet load requirements,the voltage must be increased,necessitating the use of energy-efficient power electronic *** performance of an SPV system coupled to a high-gain quadratic boost converter(HG-QBC)with a load is investigated in this *** suggested HG-QBC for the SPV system at a lower value of duty ratio provides high voltage gain with a boost factor of four *** analytical comparison is carried out with the various existing boost converters in terms of the components and the boost *** issue of locating the maximum power generation point from the SPV system is *** a result,choosing an appropriate maximum power point tracker(MPPT)-based technique to obtain the peak power output of the SPV system under the rapidly varying atmospheric conditions is *** determine the highest output power of an SPV system,a hybrid-based MPPT with a neural network assisted by a perturb and observe(P&O)technique is *** the HG-QBC,a comparison of the proposed MPPT with a traditional P&O-based MPPT is *** comparative analysis takes into account rise time,settling time and voltage *** output voltage and power characteristics of the proposed model are analysed under constant and varying irradiation conditions using MATLAB®/Simulink®.The results of a hybrid-based MPPT show that the oscillations are minimum at the maximum power point with fewer ripples of 0.20%and a settling time of 1.2 s in comparison with the other two techniques.

关键词： neural network maximum power point tracker renewable energy sources power electronic converters solar photovoltaic and high-gain quadratic boost converter

Switching angle optimization and fault analysis of a multistring-multilevel inverter for renewable-energy-source applications

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Clean Energy 2022年第6期6卷 907-930页

作者： Savitha M S.nagaraja rao MS Ramaiah University of Applied Sciences Department of Electrical EngineeringBangaloreIndia

In this paper,a multistring-multilevel inverter(M-MLI)for renewable-energy-source applications has been proposed with reduced switch count and harmonics along with single-switch fault analysis for various *** requires only‘m+1’power switches for‘m’voltage *** proposed work achieves the fine-tuning of switching angles using a metaheuristic technique,*** teaching-learning-based optimization algorithm(TLBOA),to mitigate the total harmonic distortion(THD)of the ***,the proposed TLBOA has been compared with conventional modulation techniques such as equal phase(EP),half-equal phase(HEP),near-level control(NLC)and Newton-Raphson(NR)to verify the effectiveness of TLBOA for various voltage levels in terms of%voltage-THD(%V-THD),computational time and *** fine-tuning the switching angles,the%V-THD is improved significantly when compared with EP,HEP,NLC and NR modulation *** an 11-level single-phase M-MLI,the%V-THD using TLBOA at 0.91 modulation index(MI)is 5.051%.The lower-order harmonics,i.e.5,7,11 and 13,are eliminated to improve the power ***,MLIs are often prone to failure,resulting in waveform *** extreme reduction in power quality impacts the load and significant damage is *** location of the open-circuit fault to be identified becomes more tedious under the faulty conditions with increased switch counts and voltage levels since the mathematical modelling fails to address the scenario in less computational ***,the machine-learning approach,*** vector machine(SVM)with Bayesian optimization,has been discussed to locate the faulty ***,the proposed M-MLI configuration has been modelled,simulated and validated using MATLAB®and Simulink®.The results of the M-MLI configuration have been verified for 7,9 and 11 levels using TLBOA along with fault analysis using the SVM approach.

关键词： TLBO fault resilience multistring-multilevel inverters renewable-energy applications

Wind energy conversion system using perturb&observe-based maximum power point approach interfaced with T-type three-level inverter connected to grid

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Clean Energy 2022年第4期6卷 534-549页

作者： Pranupa S A.T.Sriram S.nagaraja rao M S Ramaiah University of Applied Sciences BangaloreIndia

In this paper,the performance of a permanent magnet synchronous generator(PMSG)-based wind energy conversion system(WECS)supplied to an uncontrolled rectifier-fed boost converter(BC)interfaced with a three-phase T-type three-level inverter(TLI)has been *** proposed WECS involves three converters,namely an uncontrolled rectifier that is used for conversion from AC to DC;a BC supplied by a PMSG-fed rectifier used to enhance the voltage gain;and a grid-connected three-phase T-type TLI is proposed to eliminate power-quality issues with synchronization of grid voltage and *** main goal of this research is to model and control the grid-connected T-type TLI using a d-q synchronous frame for wind energy for regulating the DC-link voltage and transferring the generated wind power from the BC to the ***,the perturb&observe(P&O)-based maximum power point(MPP)approach is recommended to keep track of the MPP for a BC that is supplied from a PMSG-based WECS under constant and variable wind *** proposed PMSG-based WECS interfaced with grid-connected T-type TLI using d-q control has been computationally modelled,simulated and validated with constant and variable speeds using MATLAB®and Simulink®.It is confirmed that the P&O-based MPP approach ensures maximum power for varying wind speeds,and the total harmonic distortion of the T-type TLI grid current value is 3.18%,which is within IEEE-519 ***,with grid synchronization,the power factor of the T-type TLI is maintained at unity to avoid power-quality issues.

关键词： boost converter grid synchronization perturb&observe T-type three-level inverter wind turbine