Papers by Dharmendra Singh
Journal of biomedical research, 2012
Diabetic neuropathies are a family of nerve disorders caused by diabetes. Symptoms of the disease... more Diabetic neuropathies are a family of nerve disorders caused by diabetes. Symptoms of the disease include nerve palsy, mononeuropathy, mononeuropathy multiplex, diabetic amyotrophy, painful polyneuropathy, autonomic neuropathy, and thoracoabdominal neuropathy. In this study, type 2 diabetes in rats was induced with nicotinamide-streptozotocin. Drug treatment was initiated on the d 15, with the combination regimen of metformin, pioglitazone and glimipiride or metformin and sitagliptin or sitagliptin, amitriptyline and sitagliptin and led to significantly improved glycemic control, increased grip strength and paw jumping response on d 21, 28 and 35 (P < 0.001). Significant increases in blood protein levels and decreases in urinary protein levels were…
TGF‐β1re‐programs TLR4 signaling inL. donovaniinfection: enhancement of SHP‐1 and ubiquitin‐editing enzyme A20
Immunology & Cell Biology, 2011
Visceral leishmaniasis (VL), caused by Leishmania donovani, is a major health concern in India. I... more Visceral leishmaniasis (VL), caused by Leishmania donovani, is a major health concern in India. It represents T-helper type 2 (Th2) bias of cytokines in active state and Th1 bias at cure. However, the role of the parasite in regulating Toll-like receptor (TLR)-mediated macrophage activation in VL patients remains elusive. In this report, we demonstrated that later stages of L. donovani infection rendered tolerance to macrophages, leading to incapability for the production of inflammatory cytokines like tumor necrosis factor (TNF)-α and interleukin (IL)-1β in response to TLR stimulation. Overexpression of transforming growth factor (TGF)-β(1), but not IL-10, resulted in suppressed lipopolysaccharide (LPS)-induced production of TNF-α and downregulation of TLR4 expression in L. donovani-infected macrophages. Recombinant human (rh)TGF-β(1) markedly enhanced tyrosine phosphatase (Src homology region 2 domain-containing phosphatase-1) activity, but inhibited IL-1 receptor-activated kinase (IRAK)-1 activation. Addition of neutralizing TGF-β(1) antibody reversed these effects, and thus suggesting the pivotal role of TGF-β(1) in promoting refractoriness for LPS in macrophages. Surprisingly, the use of a tyrosine phosphatase inhibitor (sodium orthovanadate, Na(3)VO(4)) promoted IRAK-1 activation, confirming the negative inhibitory role of tyrosine phosphatase in macrophage activation. Furthermore, rhTGF-β(1) induced tolerance in infected macrophages by reducing inhibitory protein (IκBα) degradation in a time-dependent manner. In addition, short interfering RNA studies proved that overexpression of A20 ubiquitin-editing protein complex induced inhibitory activity of TGF-β(1) on LPS-mediated nuclear factor-κB activation. Thus, these findings suggest that TGF-β(1) promotes overexpression of A20 through tyrosine phosphatase activity that ensures transient activation of inflammatory signaling pathways in macrophages in active L. donovani infection.
Potato Journal, 2005
The rate of multiplication of seed potato in stage-I ranged between 12.9 to 27.2 tubers per plant... more The rate of multiplication of seed potato in stage-I ranged between 12.9 to 27.2 tubers per plant. Out of 7 varieties, Kufri Anand and Kufri Pukhraj produced the high number of tubers per plant (27.2) in stage-I. The rate of multiplication of these varieties in stage-II was 15.1 to 18.5 tubers per plant. Similarly the weight-wise multiplication rate of these potato cultivar was 5.0 to 6.0 times in stage-III and 4.9 to 6.6 in stage-IV.
BioMed Research International, 2015
Post-kala-azar dermal leishmaniasis (PKDL) is an important factor in kala-azar transmission; henc... more Post-kala-azar dermal leishmaniasis (PKDL) is an important factor in kala-azar transmission; hence its early detection and assessment of effective treatment is very important for disease control. In present study on 60 PKDL cases presented with macular, mixed papulonodular, or erythematous lesions,Leishmania parasiteswere demonstrated microscopically in 91% of papulonodular and 40% of macular lesions. Cellular infiltrates in skin biopsy imprint smears from lesions were mononuclear cells, 25–300/OIF (oil immersion field), predominantly histiocytes with vacuolation, many lymphocytes, some plasma cells, andLeishmaniaamastigotes 0–20/OIF. Cases with no demonstrable parasites were diagnosed on the basis of past history of VL, lesion’s distribution, cytopathological changes, and positive DAT (86.83%). Following antileishmanial treatment with SAG, papulonodular forms of PKDL lesions disappeared clinically but microscopically the mononuclear cells (20–200/OIF) persisted in the dermal lesion...
Genetic Divergence in bread Wheat (Ttriticum aestivum L.) Gersmplasm under Alkali soil
Post-kala-azar dermal leishmaniasis (PKDL), HIV and pulmonary tuberculosis
The National medical journal of India
Post-kala-azar dermal leishmaniasis is usually a sequel to visceral leishmaniasis. A 25-year-old ... more Post-kala-azar dermal leishmaniasis is usually a sequel to visceral leishmaniasis. A 25-year-old woman presented with hypopigmented maculopapular lesions all over the body for the past 4 years without any previous history of visceral leishmaniasis. She was on treatment for leprosy and pulmonary tuberculosis for the past 2 months, but did not show any improvement. Investigations confirmed that she had post-kala-azar dermal leishmaniasis associated with pulmonary tuberculosis and HIV-1 infection. She was started on treatment for the triad of diseases, and showed improvement.
The Journal of antimicrobial chemotherapy, Jan 8, 2015
Silent information regulator 2 (Sir2) is involved in parasite survival and apoptosis. Here, we ai... more Silent information regulator 2 (Sir2) is involved in parasite survival and apoptosis. Here, we aimed to explore the involvement of Sir2 in amphotericin B (AmB) resistance mechanism in Leishmania donovani. The expression levels of Sir2, MDR1 and NAD(+) biosynthetic pathway enzymes in AmB-resistant and -susceptible parasites were measured and total intracellular NAD(+)/NADH ratios were compared. Overexpression and knockout constructs of Sir2 were transfected in AmB-resistant and -susceptible parasites. Both resistant and susceptible parasites were inhibited with sirtinol for 4 h. The deacetylase activity of Sir2, the expression level of MDR1, the rate of AmB efflux, concentrations of reactive oxygen species (ROS) and levels of apoptosis were examined in WT, inhibited and transfected parasites, and the AmB susceptibility of the respective parasites was measured by determining the LD50 of AmB. Levels of mRNA, protein and NAD(+)-dependent deacetylase activity of Sir2 were elevated in res...
BioMed Research International, 2013
Visceral leishmaniasis, caused byLeishmania donovani, is a serious form of leishmaniasis and fata... more Visceral leishmaniasis, caused byLeishmania donovani, is a serious form of leishmaniasis and fatal if untreated. Nearly half of the VL cases are children. There are very few studies of renal function in pediatric visceral leishmaniasis. The aim of this study was to evaluate renal dysfunction by studying glomerular filtration rate (GFR), microalbuminuria, and microscopic examination of urine. Laboratory analysis was performed on blood and urine samples of 40 parasitologically confirmed pediatric VL cases. Laboratory data of urine examination showed albuminuria in 10% (4/40), white blood cells in 20% (8/40), hematuria in 10% (4/40), microalbuminuria in 37.5% (15/40), and decreased GFR in 27.5% (11/40). Renal involvement was manifested in most of the pediatric VL cases. These findings may help clinicians in decision making for safe and suitable antileishmanial treatment particularly in childhood VL.
Earth, Planets and Space, 1998
Large number of high dispersion whistlers recorded at low latitude station Varanasi (L = 1.07) ar... more Large number of high dispersion whistlers recorded at low latitude station Varanasi (L = 1.07) are analysed and it is find out that they have propagated along L 2.12-2.76. This is explained by considering the propagation of whistlers through the earth-ionosphere wave guide after exiting from the duct towards the equator. Using diffusive equilibrium model (DE-1), we have estimated equatorial electron density, total electron content in a flux tube and large scale convective electric fields which are in good agreement with the results reported by other workers from the analysis of mid latitude whistlers. The significance of this paper is to probe mid latitude plasmasphere using whistlers recorded at low latitudes. Further, an attempt has been made to study the propagation mechanism of low latitude whistlers.
Transactions of the Royal Society of Tropical Medicine and Hygiene, 2011
A cohort of 91 asymptomatic individuals with visceral leishmaniasis (VL) were identified during b... more A cohort of 91 asymptomatic individuals with visceral leishmaniasis (VL) were identified during base line screening using recombinant 39-aminoacid antigen (rk-39) and polymerase chain reaction (PCR) conducted from December 2005 to June 2006 involving 997 individuals of two highly endemic villages of Vaishali district, Bihar. The point prevalence of asymptomatic infection was 98 per 1000 persons at baseline. There was no statistically significant difference between rk-39 and PCR positivity rate (P > 0.05), even though PCR positivity alone was found significantly higher (4.2%) than rk-39 positivity alone (2.6%). The monthly follow-up of the asymptomatic cohort revealed a disease conversion rate of 23.1 per 100 persons within a year. There was a statistically significant difference in conversion of disease when individuals were positive by both tests as compared to single tests by rk-39 and PCR (P < 0.01). Disease conversion rate in the subjects residing in households with a history of VL (62%, 13/21) was higher than those residing in the households without a history of VL (38%, 8/21). Most of the identified asymptomatic individuals were from low socioeconomic strata similar to that of VL cases in general. Apart from rk-39, PCR may be considered for screening of asymptomatic Leishmania donovani infection in large-scale epidemiological studies. Screening of asymptomatic cases and their close follow-up to ascertain early detection and treatment of VL may be considered in addition to the existing VL control strategies.
Investigation of the Reaction of Chloroacetyl Chloride with 1,5-Benzothiazepines: Selective Synthesis of Azeto[2,1-d][1,5]benzothiazepines by Green Chemical Methods and Their Biological Activity
Phosphorus, Sulfur, and Silicon and the Related Elements, 2008
An efficient and exclusive synthesis of the tricyclic azeto[2,1-d][1,5]benzothiazepine ring syste... more An efficient and exclusive synthesis of the tricyclic azeto[2,1-d][1,5]benzothiazepine ring system has been developed. By use of microwave irradiation in the presence of basic alumina, the reaction time has been brought down from hours to minutes with improved yields in comparison to conventional heating. Antimicrobial screening of the synthesized compounds has shown promising activity.
Regioselective Synthesis of Diltiazem Analogue Pyrazolo[4,3-c][1,5]benzothiazepines and Antifungal Activity
Phosphorus, Sulfur, and Silicon and the Related Elements, 2010
A dry media procedure has been developed for the synthesis of a series of new class of pyrazolo [... more A dry media procedure has been developed for the synthesis of a series of new class of pyrazolo [4,3-c][1,5]benzothiazepines 6 under microwave irradiation using montmorillonite K10 as solid support. The catalyst can be recovered and reused. Thus, the procedure provides a ...
Pediatric Surgery International, 2004
A case of liver tuberculosis resembling a hemangioendothelioma on computed tomography and clinica... more A case of liver tuberculosis resembling a hemangioendothelioma on computed tomography and clinically masquerading as a tumor is reported. The cause of isolated liver tuberculosis and the importance of an open liver biopsy is discussed, with a review of the literature.
Facile Regioselective Green Synthesis of Triazolo [4,3-a] Pyrimidines in Aqueous Medium
Letters in Organic Chemistry, 2009
INTRODUCTION 1,2,4-Triazole system is a structural unit of many drugs that have antimycotic activ... more INTRODUCTION 1,2,4-Triazole system is a structural unit of many drugs that have antimycotic activity, eg, Fluconazole, Itracona-zole, Voriconzole, Tricyclazole, Furconazole, Hexaconazole, Tetraconazole, Quinconazole, Penconazole [1-2], herbicidal activity, eg, ...
Journal of Trace Elements in Medicine and Biology, 2013
Project: Chronic visceral leishmaniasis (VL) is an increasingly common problem in disease endemic... more Project: Chronic visceral leishmaniasis (VL) is an increasingly common problem in disease endemic states of India. Identification of prognosis risk factor in patients with VL may lead to preventive actions, toward decreasing its mortality in chronic individuals. Though serum Zinc levels are decreased in patients of VL, limited information is available regarding trace elements status in acute and chronic VL patients. The present study was undertaken to compare serum trace elements concentrations in acute and chronic VL patients. Procedure: Acute (mean age = 28.64 years), chronic (mean age = 23.68 years) VL patients and healthy controls (mean age = 23.05 years) who agreed to provide blood specimens for laboratory investigations participated in this study. Serum zinc (Zn), copper (Cu), iron (Fe), magnesium (Mg) and calcium (Ca) were measured spectrophotometrically using chemistry analyzer. Results: Serum Zn concentration was comparatively much decreased in chronic VL than to acute ones (p = 0.007) while serum Mg was higher in chronic VL than acute (p = 0.002) ones. There was no statistically significant difference between acute and chronic VL in serum concentrations of Cu, Fe and Ca. Conclusions: Serum Zn levels were much decreased and serum Mg were increased in chronic VL as compared to acute cases. The serum concentrations of Fe and Ca did not show any difference between two groups. The serum Cu was increased in both groups but more in chronic ones. Serum Zn and Mg could be a potential prognosis factor for chronic VL patients. We hypothesize zinc supplementation as a chemo preventive agent for chronic VL cases, particularly in endemic areas.
Journal of Medical Case Reports, 2009
Introduction: Visceral leishmaniasis, a tropical infectious disease, is a major public health pro... more Introduction: Visceral leishmaniasis, a tropical infectious disease, is a major public health problem in India. Tuberous sclerosis, a congenital neuro-ectodermosis, is an uncommon disease which requires life long treatment. Case presentation: A 15-year-old Indian patient, presented to the outpatient department of our institute with a high-grade fever for two months, splenomegaly and a history of generalized tonicclonic convulsions since childhood. The clinical and laboratory findings suggested visceral leishmaniasis with tuberous sclerosis. The patient was treated with miltefosine and antiepileptics. Conclusion: The patient responded well and in a follow up six months after presentation, she was found free of visceral leishmaniasis and seizures. Diagnosis and treatment of this rare combination of diseases is difficult.
Journal of Clinical Microbiology, 2009
Journal of Clinical Microbiology, 2013
Diagnosis of post-kala-azar dermal leishmaniasis (PKDL), particularly the macular form, is diffic... more Diagnosis of post-kala-azar dermal leishmaniasis (PKDL), particularly the macular form, is difficult when based on microscopy. This study compared the results of nested PCR (91.9% positive samples) with imprint smear microscopy (70.9% positive samples) for 62 PKDL samples. We found that nested PCR, which indicated 87.5% positivity for the macular lesions, compared to 41.6% positivity by imprint smear microscopy, is an efficient method for early diagnosis of PKDL.
Journal of Clinical Microbiology, 2012
Post kala-azar dermal leishmaniasis (PKDL) is a skin manifestation that usually develops after tr... more Post kala-azar dermal leishmaniasis (PKDL) is a skin manifestation that usually develops after treatment of visceral leishmaniasis (VL), a major public health problem in India. The diagnosis and management of PKDL is complex. This is the first case report from India in which PKDL occurred after paromomycin treatment for VL in an Indian patient.
Journal of Biological Chemistry, 2011
Background: RECQL4 is a RecQ helicase mutated in Rothmund-Thomson Syndrome (RTS) and has a functi... more Background: RECQL4 is a RecQ helicase mutated in Rothmund-Thomson Syndrome (RTS) and has a functional role in DNA replication and repair. Results: RECQL4-depleted and RTS patient cells show telomere abnormalities and that RECQL4 interacts with telomeric DNA and related proteins. Conclusion: RECQL4 is involved in telomere maintenance. Significance: The RecQ helicase RECQL4 is involved in telomere replication and maintenance. This establishes a connection between telomere function and a disease with premature aging phenotype.
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Papers by Dharmendra Singh