Browsing by Author "Sanjeev K. Gupta"

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A functional single nucleotide polymorphism -1562c>t in the matrix metalloproteinase-9 promoter is associated with type 2 diabetes and diabetic foot ulcers
(2013) Kanhaiya Singh; Neeraj K. Agrawal; Sanjeev K. Gupta; Kiran Singh
Impaired neovascularization is the hallmark of type 2 diabetes, which results in various macro- and microvascular complications and the development of foot ulcerations later in life. Matrix metalloproteinases (MMPs) are the key enzymes which influence matrix remodeling. Here, we aim to investigate that whether single nucleotide polymorphism (SNP -1562C>T) (rs3918242) in the promoter region of MMP-9 gene, which alters the transcriptional activity of MMP-9 is associated with type 2 diabetes and diabetic foot ulcers (DFUs). This case-control study was composed of 730 individuals, out of which 463 patients were with type 2 diabetes mellitus (T2DM) and 267 were nondiabetic healthy controls (non-DM controls). T2DM patients were subclassified as 149 cases without any secondary complications (T2DMNSC), 110 with DFUs, 204 T2DM patients having one or the other secondary complications. Genotyping for -1562C>T SNP in MMP-9 gene was done by polymerase chain reaction-restriction fragment length polymorphism method and sequencing. SNP -1562C>T of MMP-9 gene showed a significant association with T2DM and DFU. The allele distribution differed significantly between patients and normal control group (odds ratio = 1.82, P =.00005, 95% confidence interval = 1.36-2.42 for T2DM vs control and odds ratio = 2.112, P =.00048, 95% confidence interval = 1.38-3.126 for DFU vs control) indicating strong association of SNP -1562C>T of MMP-9 gene with T2DM and DFU in an Indian population. SNP -1562C>T in the promoter of the MMP-9 gene results in increased expression at the level of the transcription. To the best of our knowledge, this is the first report that suggests that SNP -1562C>T in the promoter of the MMP-9 gene is associated with T2DM and DFU. An increased MMP-9 production from high expressing T allele may promote matrix degradation. © 2013 The Author(s).
Analysis of histological features in needle core biopsy of breast useful in preoperative distinction between fibroadenoma and phyllodes tumour
(2010) J Mike Morgan; Anthony G Douglas-Jones; Sanjeev K. Gupta
Aims: Fine Needle Aspiration Cytology (FNAC) has been replaced by Needle core biopsy (NCB) as the pathological investigation of choice in pre-operative diagnosis of breast lesions. Despite the greater yield of material with spatial information, the distinction between fibroepithelial lesions of the breast, fibroadenoma (FA) and benign phyllodes tumour (PT), remains problematic. The aim of this study was to confirm a set of histological features which may assist in the pre-operative distinction between FA and PT on NCB and to explore novel strategies to refine the analysis of the data. Methods: Previously defined histological criteria were applied to 112 NCBs of fibroepithelial lesions of the breast. Contingency tables for frequency analysis, logistic regression, receiver operating characteristic (ROC) and linear discriminant analysis were used. Results: Frequency analysis identifying significant differences agreed with published data. Correct categorisation was possible in 95% of cases using logistic regression analysis (age and mitotic index) and in 94% using discriminant analysis (age, mitoses and %stroma). ROC analysis identified cut off values (between FA and PT) for age (50-55 years), %stroma (85-90) and mitoses (≥1/2.2 mm2). Conclusion: The results confirm previously published observations and provide novel putative predictive tools, to be tested prospectively. © 2010 Blackwell Publishing Limited.
Association of functional SNP-1562C > T in MMP9 promoter with proliferative diabetic retinopathy in north Indian type 2 diabetes mellitus patients
(Elsevier Inc., 2017) Kanhaiya Singh; Prabhjot Goyal; Manju Singh; Sujit Deshmukh; Divyesh Upadhyay; Sri Kant; Neeraj K. Agrawal; Sanjeev K. Gupta; Kiran Singh
Objective Retinal angiogenesis is a hallmark of diabetic retinopathy. Matrix Metalloproteinases (MMPs) are involved in degradation of extracellular matrix (ECM). Functional SNP-1562C > T in the promoter of the MMP-9 gene results increase in transcriptional activity. The present work was designed to evaluate the contribution of functional SNP-1562C > T of MMP-9 gene to the risk of proliferative diabetic retinopathy (PDR) in type 2 diabetes mellitus (T2DM) patients in north Indian Population. Methods This Case control study comprised of a total of 645 individuals in which 320 were T2DM patients out of which 73 had PDR, 98 had non- proliferative diabetic retinopathy (NPDR), 149 T2DM cases without any eye related disease (DM) and 325 non diabetic healthy individuals as controls (non DM controls). Genotyping for SNP-1562C > T of MMP-9 was done by polymerase chain reactions followed by restriction analyses with specific endonucleases (PCR-RFLP). DNA sequencing was used to ascertain PCR-RFLP results. Results T allele frequency in PDR patients was 32.1%, 20.4% in NPDR, 15.4% in DM and 13.7% in controls. Statistically significant difference was observed in both allele and genotype distribution between the PDR versus non-DM control group (p < 0.0001 by T allele; p = 0.002 by TT and p < 0.0001 by CT genotype). Conclusions The present study suggests that the functional SNP-1562C > T in the promoter of the MMP-9 gene could be regarded as a major risk factor for PDR as increased MMP-9 production from high expressing T allele may promote retinal angiogenesis. © 2017 Elsevier Inc.
Association of toll-like receptor 4 polymorphisms with diabetic foot ulcers and application of artificial neural network in DFU risk assessment in type 2 diabetes patients
(2013) Kiran Singh; Kanhaiya Singh; Vivek Kumar Singh; Neeraj K. Agrawal; Sanjeev K. Gupta
The Toll-Like receptor 4 (TLR4) plays an important role in immunity, tissue repair, and regeneration. The objective of the present work was to evaluate the association of TLR4 single nucleotide polymorphisms (SNPs) rs4986790, rs4986791, rs11536858 (merged into rs10759931), rs1927911, and rs1927914 with increased diabetic foot ulcer (DFU) risk in patients with type 2 diabetes mellitus (T2DM). PCR-RFLP was used for genotyping TLR4 SNPs in 125 T2DM patients with DFU and 130 controls. The haplotypes and linkage disequilibrium between the SNPs were determined using Haploview software. Multivariate linear regression (MLR) and artificial neural network (ANN) modeling was done to observe their predictability for the risk of DFU in T2DM patients. Risk genotypes of all SNPs except rs1927914 were significantly associated with DFU. Haplotype ACATC (P value = 9.3E-5) showed strong association with DFU risk. Two haplotypes ATATC (P value = 0.0119) and ATGTT (P value = 0.0087) were found to be protective against DFU. In conclusion TLR4 SNPs and their haplotypes may increase the risk of impairment of wound healing in T2DM patients. ANN model (83%) is found to be better than the MLR model (76%) and can be used as a tool for the DFU risk assessment in T2DM patients. © 2013 Kanhaiya Singh et al.
Association of variant rs7903146 (C/T) single nucleotide polymorphism of TCF7L2 gene with impairment in wound healing among north indian type 2 diabetes population: A case-control study
(2013) Kiran Singh; Kanhaiya Singh; Neeraj K. Agrawal; Sanjeev K. Gupta
The variants of transcription factor 7-like 2 (TCF7L2) gene have been shown to be associated with type 2 diabetes mellitus (T2DM) and its several secondary complications. Here, we aimed to examine the possible role of one of the common variant of this gene, rs7903146 (C/T), with impairment of wound healing in cases with T2DM. A total of 750 individuals, including 322 patients with T2DM and 120 patients with diabetic foot ulcers (DFUs) and 308 controls, were analyzed for rs7903146 variant of the TCF7L2 gene. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism. For rs7903146 variant, TT genotype frequency in patients with DFU was 10.8% and in controls was 5.2%. Risk genotype (TT) frequencies showed statistically significant difference between the DFU patients versus non-DM control group (odds ratio = 2.44, P =.037, 95% confidence interval = 1.05-5.64) compared with nonrisk genotype (CC + CT). In the present study, a positive significant association between DFU and the TT genotype of rs7903146 (C/T) variant of TCF7L2 gene was found. © The Author(s) 2013.
Case Report: a Rare Case of Bilateral Spigelian with Bilateral Inguinal Hernia
(Springer, 2021) Prakhar Jaiswal; Seema Khanna; Sanjeev K. Gupta; Satendra Kumar
Spigelian hernia is an uncommon hernia which occurs through a defect in the spigelian aponeurosis. An 84-year-old gentleman presented to us with uncomplicated bilateral spigelian hernia with bilateral direct inguinal hernia. The patient underwent an open pre-peritoneal mesh repair under spinal anesthesia. Bilateral spigelian hernia with bilateral inguinal hernia is a rare occurrence which led us to publish this case report. © 2020, Association of Surgeons of India.
Decreased expression of heat shock proteins may lead to compromised wound healing in type 2 diabetes mellitus patients
(Elsevier Inc., 2015) Kiran Singh; Kanhaiya Singh; Neeraj K. Agrawal; Sanjeev K. Gupta; Gyanendra Mohan; Sunanda Chaturvedi
Background Heat shock proteins (HSPs) are inducible stress proteins expressed in cells exposed to stress. HSPs promote wound healing by recruitment of dermal fibroblasts to the site of injury and bring about protein homeostasis. Diabetic wounds are hard to heal and inadequate HSPs may be important contributors in the etiology of diabetic foot ulcers (DFU). Objective To analyze the differential expression of HSPs and their downstream molecules in human diabetic wounds compared to control wounds. Methods Expressional levels of HSP27, HSP47 and HSP70 and their downstream molecules like TLR4, p38-MAPK were seen in biopsies from 101 human diabetic wounds compared to 8 control subjects without diabetes using RT-PCR, western blot and immunohistochemistry. Results Our study suggested a significant down regulation of HSP70, HSP47 and HSP27 (p value = < 0.001 for HSP70; p value = 0.007 for HSP47; p value = 0.007 for HSP27) in DFU along with their downstream molecules TLR4 and p38-MAPK (p value = 0.006 for p38-MAPK; p value = 0.02 for TLR4). HSP70 levels were significantly lower in male subjects and their levels increased significantly with the grades of wound on Wagner's scale. Infection status of the wounds was found to be significantly associated with the increased levels of HSP70 and HSP27 in infected diabetic wounds. Conclusions Our study demonstrates that the down regulation of HSPs in diabetic wounds is associated with wound healing impairment in T2DM subjects. © 2015 Elsevier Inc. All rights reserved.
Detecting aerobic bacterial diversity in patients with diabetic foot wounds using ERIC-PCR: A preliminary communication
(2009) Surya K. Singh; K. Gupta; S. Tiwari; Shailesh K. Shahi; S. Kumar; A. Kumar; Sanjeev K. Gupta
The polymicrobial nature of diabetic foot infection is a reflection of the immune compromised state of the host.The methods of microbial identification based on colony morphology and biochemical characteristics have limitations as they may not differentiate the diverse microorganisms that infect foot wounds. The aim of the present study was to find out the bacterial diversity in diabetic foot infections at genetic level by finger printing, that is, ERIC-PCR (enterobacterial repetitive intergenic consensus -polymerase chain reaction). Nine patients with infected diabetic foot ulcers were recruited to the study. Pus and tissue samples were collected from the wound site. Aerobic bacteria were isolated employing standard microbiological culture methods and their genetic variability was analyzed using the ERIC-PCR. Sensitivity test for these isolates against commonly used antibiotics were performed using disc diffusion method. The standard microbiological culture technique yielded 38 morphotypes of bacteria and their genetic diversity was confirmed by ERIC-PCR assay. Analysis of the similarity index using NTSYSpc 2.1 software revealed 34 types of banding pattern among these isolates. Based on the similarity index these isolates were divided into 7 groups. As many as 8 types of aerobic bacterial isolates were detected from a single patient using the above technique compared with 2 on routine culture analysis. Genetically diverse isolates showed differential sensitivity pattern against commonly used antibiotics in the assay. The observed diversity at genetic level is attributed to variable sensitivity pattern of these isolates against the class of antibiotics. A molecular technique such as ERIC-PCR is a more sensitive detection method than conventional techniques, the potential of which needs to be fully understood.
Diabetic foot: A continuing challenge
(Springer New York LLC, 2013) Sanjeev K. Gupta; Surya K. Singh
Diabetes is rapidly emerging as the new global epidemic. The prevalence of diabetes is expected to double in the next three decades. Diabetic foot (DF) is a major complication of long standing diabetes, accounting for nearly 35% of all hospital admissions in diabetic clinics. It also accounts for nearly 80% of all nontraumatic amputations of the lower limb. Due to its significant morbidity and mortality, DF has a staggering economic impact not only on the individual and his family but also the society. The aetiopathogenesis of DF is multifactorial and is related to per ipheral neuropathy leading to the insen sate foot with foot deformities, peripheral vascular disease and infection in addition to the reduced immunity seen in these patients. The clinical evaluation of the DF in addition to the detailed examination of foot deformities and the ulcers should focus on identifying loss of protective sensation using simple clinical tests as well as an examination of the vascular integrity by a simple hand held Doppler device. Patients of DF should be managed by a multidisciplinary team which in addition to clinic al specia lists should also include a podiatrist and trained nursing staff. The basic tenets of treatment include of floading, wound bed preparation using repeated debridement, treating local and systemic infection and to identify and correct vascular impairment if it is present. Once the ulcer has healed, recurrences are common and patient education for foot care is of paramount importance as is an annual examination in a dedic ated foot clinic. Once an ulcer develops it should be promptly referred to a specialist unit. © 2012 Landes Bioscience and Springer Science+Business Media.
Differential expression of matrix metalloproteinase-9 gene in wounds of type 2 diabetes mellitus cases with susceptible -1562c>t genotypes and wound severity
(SAGE Publications Inc., 2014) Kiran Singh; Neeraj K. Agrawal; Sanjeev K. Gupta; Gyanendra Mohan; Sunanda Chaturvedi; Kanhaiya Singh
Coordinated extracellular matrix deposition is a prerequisite for proper wound healing which is mainly orchestrated by matrix metalloproteinases (MMPs). Diabetic wounds generally show compromised wound healing cascade and abnormal MMP9 concentration is one of the cause. Our group have recently shown that the polymorphism -1562 C>T in the promoter region of MMP9 gene is associated with pathogenesis of wound healing impairment in T2DM patients. In present study we have done expression profiling of MMP9 gene in the wound biopsy of DFU cases. Expression level of MMP9 mRNA was then compared with susceptible -1562 C>T genotypes (TT and CT) as well as with different grades of wounds. We also screened the promoter region of MMP9 gene to see the methylation state of CpGs present there. Our study suggests that levels of MMP9 mRNA increase significantly with the wound grades. Moreover, the MMP9 levels in diabetic wounds were also dependent on -1562 C>T polymorphism in the promoter region of MMP9. Diabetic wounds also showed a significant unmethylated status of MMP9 promoter compared to control wounds. In conclusion, The risk genotypes of -1562 C>T polymorphism along with lack of methylation of CpG sites in MMP9 gene promoter may result in altered expression of MMP9 in wounds of T2DM cases resulting into nonhealing chronic ulcers in them. © 2014 The Author(s).
Environmental adaptation of small-seeded lentils (Lens culinaris) in Indian climates: Insights into crop–environment interactions, mega-environments, and breeding approaches
(John Wiley and Sons Inc, 2025) Ashok Kumar S. Parihar; Shailesh K. Tripathi; Kali Krishna Hazra; Amrit Lamichaney; Debjyoti Sen Gupta; Jitendra Kumar; Anil Kumar Singh; Jai Dev Sharma; Parvez Sofi; Ajaz A. Lone; S. Samuel Jeberson; Ashok M.Praveen Kumar; Sarvjeet P. Singh; Harsh Kumar Dikshit; Murlidhar Aski; Sumer Singh Punia; Manoj Katiyar; Anil Kumar Singh; Subhash Chandra; Chandra Shekhar Mahto; Hironya Kumar Borah; Amitava Banerjee; Arpita K. Das; Deepak V. Singh; Sanjeev K. Gupta; Girish Prasad Dixit
This study aimed to evaluate the impact of diverse environments on agronomic traits of small-seeded lentils in India and to identify strategic environment(s) for crop improvement using empirical approaches. Sixteen small-seeded lentil genotypes were tested across 16 locations, covering North Hill Zone (NHZ), North Western Plain Zone (NWPZ), and North Eastern Plain Zone (NEPZ). Crop yield exhibited a quadratic response to maximum temperature during flowering (TMAXF) and minimum temperature during reproductive period (TMINRP), indicating that both higher and lower TMAXF (optimal = 23.5°C) and TMINRP (optimal = 12.0°C) negatively affected yield. Low temperatures extended crop duration, and correlation analysis confirmed that environment-induced variations in vegetative or maturity periods significantly influenced yield, as further validated by regression models and principal component analysis. While an extended reproductive period increased seed weight, its association with grain yield was non-significant. Among the tested zones, NWPZ recorded the highest average yield (1359 kg ha−1), while NEPZ (1269 kg ha−1) demonstrated greater yield consistency across locations. Genotype, environment, and genotype-by-environment interaction (GEI) contributed 6%, 53%, and 36% of the total yield variation, respectively. Biplot analysis identified three distinct mega-environments, with Durgapura (NWPZ), Varanasi (NEPZ), Faizabad (NEPZ), and Berthin (NHZ) emerging as ideal testing sites. This study highlights the significant influence of diverse agroclimatic conditions on crop yield and emphasizes the need for region-specific breeding to harness positive GEI (at mega-environment scale) and to prioritize early flowering and optimal seed traits to achieve broader adaptability across Indian climates. © 2025 The Author(s). Crop Science © 2025 Crop Science Society of America.
Gastrointestinal Stromal Tumors (GIST): an Overview
(Springer, 2021) Sanjeev K. Gupta; Nisha Rateria
Gastrointestinal stromal tumors are rare mesenchymal tumors of the alimentary tract with varied clinical presentation ranging from small asymptomatic tumors detected incidentally to large palpable abdominal masses which may present with gastrointestinal bleeding, perforation, or obstruction. CT abdomen is the imaging modality of choice. Treatment depends upon the size, location and risk stratification. Complete surgical excision is the treatment of choice for resectable tumours. The discovery of c-kit mutations and tyrosine-kinase inhibitors has revolutionized the treatment of locally advanced, metastatic and recurrent tumors. © 2020, Association of Surgeons of India.
Genetic alterations in toll-like receptor 4 signaling pathway and impairment of wound healing in patients with type 2 diabetes
(SAGE Publications Inc., 2014) Kiran Singh; Kanhaiya Singh; Vivek Kumar Singh; Neeraj K. Agrawal; Sanjeev K. Gupta
[No abstract available]
Genetic and epigenetic alterations in Toll like receptor 2 and wound healing impairment in type 2 diabetes patients
(Elsevier Inc., 2015) Kiran Singh; Kanhaiya Singh; Neeraj K. Agrawal; Sanjeev K. Gupta; Gyanendra Mohan; Sunanda Chaturvedi
Aim Persistent hyperglycemic microenvironment in type 2 diabetes mellitus (T2DM) leads to the development of secondary complications like wound healing impairment. Proper co-ordination of innate immune system plays an integral role in wound healing. Toll like receptors (TLRs) are prominent contributors for the induction of the innate immune and inflammation response. TLR2 is an important extracellular member in mammalian TLR family and has been shown to be a potent player in the wound healing mechanism. Methods Expressional status of TLR2 was seen in wounds of T2DM cases with respect to the severity of wounds in 110 human lower extremity wounds. The methylation status of TLR2 promoter was also examined. Results Although TLR2 transcripts were downregulated in T2DM wounds compared to control, their levels tend to increase with the severity of T2DM wounds. The methylation status of TLR2 gene promoter was not significantly different among different grades of wounds in T2DM subjects. The CpG sites investigated were totally or partially methylated in majority of DFU cases. Conclusion TLR2 down regulation in wounds of T2DM patients compared to non diabetic patients may lead to development of non healing chronic ulcers in them. © 2015 Elsevier Inc. All rights reserved.
Increased expression of endosomal members of toll-like receptor family abrogates wound healing in patients with type 2 diabetes mellitus
(Blackwell Publishing Ltd, 2016) Kanhaiya Singh; Neeraj K. Agrawal; Sanjeev K. Gupta; Gyanendra Mohan; Sunanda Chaturvedi; Kiran Singh
The inflammatory phase of wound healing cascade is an important determinant of the fate of the wound. Acute inflammation is necessary to initiate proper wound healing, while chronic inflammation abrogates wound healing. Different endosomal members of toll-like receptor (TLR) family initiate inflammatory signalling via a range of different inflammatory mediators such as interferons, internal tissue damaged-associated molecular patterns (DAMPs) and hyperactive effector T cells. Sustained signalling of TLR9 and TLR7 contributes to chronic inflammation by activating the plasmacytoid dendritic cells. Diabetic wounds are also characterised by sustained inflammatory phase. The objective of this study was to analyse the differential expression of endosomal TLRs in human diabetic wounds compared with control wounds. We analysed the differential expression of TLR7 and TLR9 both at transcriptional and translational levels in wounds of 84 patients with type 2 diabetes mellitus (T2DM) and 6 control subjects without diabetes using quantitative real-time polymerase chain reaction (RT-PCR), western blot and immunohistochemistry. TLR7 and TLR9 were significantly up-regulated in wounds of the patients with T2DM compared with the controls and were dependent on the infection status of the diabetic wounds, and wounds with microbial infection exhibited lower expression levels of endosomal TLRs. Altered endosomal TLR expression in T2DM subjects might be associated with wound healing impairment. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.
Increased expression of TLR9 associated with pro-inflammatory S100A8 and IL-8 in diabetic wounds could lead to unresolved inflammation in type 2 diabetes mellitus (T2DM) cases with impaired wound healing
(Elsevier Inc., 2016) Kanhaiya Singh; Neeraj K. Agrawal; Sanjeev K. Gupta; Pratima Sinha; Kiran Singh
Background Type 2 diabetes mellitus (T2DM) is characterized by persistent hyperglycemia which causes a chain of abrupt biochemical and physiological changes. Immune dys-regulation is the hallmark of T2DM that could contribute to prolonged inflammation causing transformation of wounds into non-healing chronic ulcers. Toll like receptor - 9 (TLR9) is a major receptor involved in innate immune regulation. TLR9 activation induces release of pro-inflammatory molecules like S100A8 and interleukin-8 (IL-8) by myeloid cells causing migration of myeloid cells to the site of inflammation. We hypothesized that pro-inflammatory S100A8 and IL-8 proteins could cause persistent inflammation in chronic wounds like diabetic foot ulcer (DFU) and may contribute to impaired wound healing in T2DM patients. Materials and Methods Expression of TLR9 and its downstream effector molecules S100A8, and IL-8 were analyzed in chronic diabetic wound and non-diabetic control wound tissue samples by semiquantitative reverse transcriptase - polymerase chain reaction (RT-PCR), quantitative RT-PCR, western blot and immunofluorescence. CD11b+CD33+ myeloid cells were analyzed by flow cytometry. Results TLR9 message and protein were higher in diabetic wounds compared to control wounds (p = 0.03, t = 2.21 for TLR9 mRNA; p = < 0.001, t = 4.21 for TLR9 protein). TLR9 down-stream effector molecules S100A8 and IL-8 were also increased in diabetic wounds (p = 0.003, t = 3.1 for S100A8 mRNA; p = 0.04, t = 2.04 for IL-8). CD11b+ CD33+ myeloid cells were decreased in T2DM as compared to non-diabetic controls (p = 0.001, t = 3.6). DFU subjects had higher levels of CD11b+ CD33+ myeloid cells as compared to non-DFU T2DM control (p = 0.003, t = 2.8). Infection in the wound microenvironment could be the cause of increase in CD11b+CD33+ myeloid cells in DFU (p = 0.03, t = 2.5). Conclusion The up-regulation of myeloid cell-derived pro-inflammatory molecules S100A8 and IL-8 in combination with lower levels of CD11b+ CD33+ myeloid cells may cause the impairment of wound healing in T2DM subjects leading to chronic ulcers. © 2016 Elsevier Inc. All rights reserved.
Infective subcutaneous emphysema after laparoscopic rectopexy: A rare complication
(2008) Puneet; Santosh K. Mahalik; Sanjeev K. Gupta
Subcutaneous emphysema after laparoscopic surgery is not uncommon but infection of the subcutaneous space because of gas forming organisms causing emphysema after a laparoscopic procedure is an extremely rare entity. We report a case of infective subcutaneous emphysema after laparoscopic rectopexy. © 2008 by Lippincott Williams & Wilkins.
Interaction of dihydrofolate reductase and aminoglycoside adenyltransferase enzyme from Klebsiella pneumoniae multidrug resistant strain DF12SA with clindamycin: A molecular modelling and docking study
(2013) Shailesh K. Shahi; Vinay K. Singh; Ashok Kumar; Sanjeev K. Gupta; Surya K. Singh
Klebsiella pneumoniae strain DF12SA (HQ114261) was isolated from diabetic foot wounds. The strain showed resistance against ampicillin, kanamycin, gentamicin, streptomycin, spectinomycin, trimethoprim, tetracycline, meropenem, amikacin, piperacillin/tazobactam, augmentin, co-trimoxazole, carbapenems, penicillins and cefoperazone, and was sensitive to clindamycin. Molecular characterization of the multidrug-resistance phenotype revealed the presence of a class 1 integron containing two genes, a dihydrofolate reductase (DHFR) (PF00186), which confers resistance to trimethoprim; and aminoglycoside adenyltransferase (AadA) (PF01909), which confers resistance to streptomycin and spectinomycin. A class 1 integron in K. pneumoniae containing these two genes was present in eight (18.18 %) out of 44 different diabetic foot ulcer (DFU) patients. Hence, there is a need to develop therapeutics that inhibit growth of multidrug resistant K. pneumoniae in DFU patients and still achieve amputation control. Am attempt was made to create a 3D model and find a suitable inhibitor using an in silico study. Rational drug design/testing requires crystal structures for DHFR and AadA. However, the structures of DHFR and AadA from K. pneumoniae are not available. Modelling was performed using Swiss Model Server and Discovery Studio 3.1. The PDBSum server was used to check stereo chemical properties using Ramachandran plot analysis of modeled structures. Clindamycin was found to be suitable inhibitor of DHFR and AadA. A DockingServer based on Autodock & Mopac was used for docking calculations. The amino acid residues Ser32, Ile46, Glu53, Gln54, Phe 57, Thr72, Met76, Val78, Leu 79, Ser122, Tyr128, Ile151 in case of DHFR and Phe34, Asp60, Arg63, Gln 64, Leu68, Glu87, Thr89, Val 90 for AadA were found to be responsible for positioning clindamycin into the active site. The study identifies amino acid residues crucial to 'DHFR and AadA -drug' and 'DHFR and AadA -inhibitor' interactions that might be useful in the ongoing search for a versatile DHFR and AadA -inhibitor. © 2012 Springer-Verlag Berlin Heidelberg.
Leg Ulcers in the Tropics
(2002) Sanjeev K. Gupta; Vijay K. Shukla
Leg ulcers are an important clinical condition and are often difficult to treat. The treatment has to continue for long periods, and the associated morbidity leads to significant loss of work. The successful treatment of leg ulcers or chronic wounds depends upon accurate diagnosis and treatment of the underlying cause. In Western societies, most leg ulcers are due to venous insufficiency, arterial disease, neuropathy (usually diabetic), or some combination of these factors. In tropical countries, however, there have been no large series of leg ulcers reported. The prevalence of leg ulcers and etiology are unknown. In this article, a short review is presented of the etiology and management of lower extremity ulcers as seen in the tropical countries. © 2002, Sage Publications. All rights reserved.
Perforated typhoid enteritis in children
(BMJ Publishing Group, 1994) Vineeta Gupta; Sanjeev K. Gupta; Vijay K. Shuklal; Saroj Gupta
A prospective study of 65 patients with perforated typhoid enteritis managed operatively over a 3 year period at a university hospital is presented. There were 45 males and 20 females with ages ranging from 5 to 15 years. Presenting symptoms were fever, abdominal pain, vomiting and either diarrhoea or constipation. All the patients were subjected to surgery and 56 (86%) underwent two-layer bowel closure after freshening of ulcer margins. The overall mortality rate in this study was 20% and was adversely influenced by the increasing duration of perforation, presence of shock and faecal peritonitis. Early surgery after prompt and adequate resuscitation is life saving. However, prevention of typhoid fever by providing safe drinking water and better sanitary conditions appears to offer the best chance of decreasing the high rates of mortality and morbidity of this deadly disease.