In JoVE (1)

Other Publications (22)

Articles by Preeti Chhabra in JoVE

Other articles by Preeti Chhabra on PubMed

S-nitrosothiols Signal Hypoxia-mimetic Vascular Pathology

The Journal of Clinical Investigation. Sep, 2007  |  Pubmed ID: 17786245

NO transfer reactions between protein and peptide cysteines have been proposed to represent regulated signaling processes. We used the pharmaceutical antioxidant N-acetylcysteine (NAC) as a bait reactant to measure NO transfer reactions in blood and to study the vascular effects of these reactions in vivo. NAC was converted to S-nitroso-N-acetylcysteine (SNOAC), decreasing erythrocytic S-nitrosothiol content, both during whole-blood deoxygenation ex vivo and during a 3-week protocol in which mice received high-dose NAC in vivo. Strikingly, the NAC-treated mice developed pulmonary arterial hypertension (PAH) that mimicked the effects of chronic hypoxia. Moreover, systemic SNOAC administration recapitulated effects of both NAC and hypoxia. eNOS-deficient mice were protected from the effects of NAC but not SNOAC, suggesting that conversion of NAC to SNOAC was necessary for the development of PAH. These data reveal an unanticipated adverse effect of chronic NAC administration and introduce a new animal model of PAH. Moreover, evidence that conversion of NAC to SNOAC during blood deoxygenation is necessary for the development of PAH in this model challenges conventional views of oxygen sensing and of NO signaling.

Norovirus Genotype IIb Associated Acute Gastroenteritis in India

Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. Aug, 2008  |  Pubmed ID: 18467163

In India the role of noroviruses in causing gastroenteritis is not well defined.

Epidemiological, Clinical, and Molecular Features of Norovirus Infections in Western India

Journal of Medical Virology. May, 2009  |  Pubmed ID: 19319938

The study was conducted to investigate the molecular epidemiology of noroviruses (NoVs) from western India. A total of 830 fecal specimens were collected during July 2005-June 2007 from children, < or =7 years of age suffering from acute gastroenteritis in Pune, Nagpur, and Aurangabad cities. All the specimens were subjected to RT-PCR, sequencing and phylogenetic analysis for detection and characterization of Genogroup I (GI) and GII NoVs. NoV positivity varied between 6.3% and 12.6% in different cities with the predominance of GII (96.6%). NoV infections were very common in the patients < or =2 years of age. A majority (55%) of the patients suffered from severe disease, however, vomiting was not experienced in 35%. Coinfections with rotaviruses were found in 10% cases. Summer month seasonality supported NoV infections in western India. The phylogenetic analysis of partial RNA polymerase and VP1 (capsid) genes identified 2 GI (GI. 2 and GI.6) and 5 GII (GII.4, GII.6, GII.7, GII.8, and GII.14) genetic clusters with possible occurrence of "2007 new-variant" of GII.4. Six different combinations of RdRp and capsid genes (GII.b/GII.3, GII.b/GII.4, GII.d/GII.3, GII.b/GII.18, GII.1/GII.12 and GII.3/GII.13) were also identified. GII.4 (52%) prevailed in 2005-2006 while the predominance of probable recombinant NoV strains (58%) was noted in 2006-2007 with the contribution of GII.b/GII.3 at 79% level. GII.b/GII.18 type identified in 37% infections in 2005-2006 was completely replaced by GII.b/GII.3 type in 2006-2007. This is the first report that highlights the norovirus epidemiology and strain diversity demonstrating possible circulation of new variants in patients with acute gastroenteritis from western India.

Regenerative Medicine and Tissue Engineering: Contribution of Stem Cells in Organ Transplantation

Current Opinion in Organ Transplantation. Feb, 2009  |  Pubmed ID: 19337146

The Use of Stem Cells in Kidney Disease

Current Opinion in Organ Transplantation. Feb, 2009  |  Pubmed ID: 19337150

Acute and chronic kidney disease is a leading cause of morbidity and mortality worldwide with overall mortality rates between 50 and 80%. An acute shortage of compatible organs coupled with limited adaptability of current dialysis techniques has created a sense of urgency to investigate new alternatives, and the purpose of this review is to provide a concise overview of current stem cell-based strategies in renal repair following acute kidney injury.

Molecular Characterization of a Rare G1P[19] Rotavirus Strain from India: Evidence of Reassortment Between Human and Porcine Rotavirus Strains

Journal of Medical Microbiology. Dec, 2009  |  Pubmed ID: 19679684

This study pertains to the characterization of a human rotavirus strain (NIV929893) with a rare specificity of G1P[19]. Three structural genes (VP4, VP6 and VP7) and one non-structural gene (NSP4) of strain NIV929893 were subjected to RT-PCR for amplification of entire coding regions. All of the amplicons were sequenced to carry out phylogenetic analysis. The complete amino acid sequences of the VP7 and VP4 gene products showed clustering of the VP7 gene with G1 strains of human origin and the VP4 gene with P[19] strains of porcine origin. The two viral proteins VP6 and NSP4, described previously as genetically linked proteins, were shown to be subgroup II and genotype B of human and porcine origins, respectively. The findings of this study provide evidence of reassortment between VP7/VP6 genes of humans and VP4/NSP4 genes of porcine species and an independent segregation of VP6 and NSP4 genes in a group A human rotavirus strain with G1P[19] specificity.

Genetic Diversity of Genotype G1 Rotaviruses Co-circulating in Western India

Virus Research. Dec, 2009  |  Pubmed ID: 19720093

The rotavirus (RV) G1 strains represent the common genotype that causes diarrhea in humans. The aim of this study was to determine the genetic lineages of G1 RV strains circulating in western India during two different time periods, 1991-1994 and 2006 by molecular characterization of VP7 genes. The phylogenetic analysis of VP7 genes showed clustering of G1 strains into lineages I (96.4%) and VIII (3.6%) in 1991-1994 and I (96.2%) and II (3.8%) in 2006. The sublineage IA was predominant (96.4%) in the years 1991-1994, however, was detected only in 44.4% of the strains in 2006 co-circulating with other sublineages IB (44.4%), IC (3.7%), IE (3.7%) and IIB (3.7%). The amino acid substitutions were noted in the previously identified signature codes of sublineages IB and IIB at positions 75 and 55, respectively. The differentiation marker (Q) described for sublineage IB at position 16 was replaced by I in all Indian strains clustered in sublineage IB. The study reports the characterization of G1 RV strains on the basis of distinct lineages and sublineages from India and emphasizes continuous monitoring on the diversity of G1 strains across the Indian population.

Molecular Characterization of Three Novel Intergenotype Norovirus GII Recombinant Strains from Western India

Virus Research. Feb, 2010  |  Pubmed ID: 19941918

The phenomenon of recombination has been widely described among noroviruses (NoVs) in the past few years. In a NoV surveillance study conducted in western India, 3 novel and 3 known combinations of RNA-dependent RNA polymerase (RdRp) and capsid genes were identified in genogroup (G) II NoV strains. The present study pertains to the characterization of three novel intergenotype NoV GII recombinant strains. RT-PCRs were carried out for the amplification of nearly complete RdRp and complete capsid genes spanning ORF1/2 overlap of three strains followed by sequencing of the amplicons. The recombination event was confirmed by phylogenetic analysis using Bayesian MCMC approach, SimPlot analysis and Maximum chi(2) method. Three novel intergenotype (GII) recombinations of GII.b/GII.18, GII.1/GII.12 and GII.3/GII.13 specificities were identified respectively in the strains PC03, PC24 and PC25 for the first time. The breakpoint in the novel recombinants was placed in the vicinity of the 20 bp ORF1/2 overlap, a common hotspot known to exist in NoV recombinants. The capsid genes of all of the 3 recombinants were closely related to their counter parts in reference strains however, a high degree of variation emerged in the polymerase genes especially of PC24 and PC25 in comparison to the reference strains.

Adenosine A(2A) Agonist Administration Improves Islet Transplant Outcome: Evidence for the Role of Innate Immunity in Islet Graft Rejection

Cell Transplantation. 2010  |  Pubmed ID: 20350347

Activation of adenosine A(2A) receptors inhibits inflammation in ischemia/reperfusion injury, and protects against cell damage at the injury site. Following transplantation 50% of islets die due to inflammation and apoptosis. This study investigated the effects of adenosine A(2A) receptor agonists (ATL146e and ATL313) on glucose-stimulated insulin secretion (GSIS) in vitro and transplanted murine syngeneic islet function in vivo. Compared to vehicle controls, ATL146e (100 nM) decreased insulin stimulation index [SI, (insulin)(high glucose)/(insulin)(low glucose)] (2.36 +/- 0.22 vs. 3.75 +/- 0.45; n = 9; p < 0.05). Coculture of islets with syngeneic leukocytes reduced SI (1.41 +/- 0.17; p < 0.05), and this was restored by ATL treatment (2.57 +/- 0.18; NS). Addition of a selective A(2A)AR antagonist abrogated ATL's protective effect, reducing SI (1.11 +/- 0.42). ATL treatment of A(2A)AR(+/+) islet/A(2A)AR(-/-) leukocyte cocultures failed to protect islet function (SI), implicating leukocytes as likely targets of A(2A)AR agonists. Diabetic recipient C57BL/6 mice (streptozotocin; 250 mg/kg, IP) received islet transplants to either the renal subcapsular or hepatic-intraportal site. Recipient mice receiving ATL therapy (ATL 146e or ATL313, 60 ng/kg/min, IP) achieved normoglycemia more rapidly than untreated recipients. Histological examination of grafts suggested reduced cellular necrosis, fibrosis, and lymphocyte infiltration in agonist-treated animals. Administration of adenosine A(2A) receptor agonists (ATL146e or ATL313) improves in vitro GSIS by an effect on leukocytes, and improves survival and functional engraftment of transplanted islets by inhibiting inflammatory islet damage in the peritransplant period, suggesting a potentially significant new strategy for reducing inflammatory islet loss in clinical transplantation.

Complete Genome Characterization of Genogroup II Norovirus Strains from India: Evidence of Recombination in ORF2/3 Overlap

Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases. Oct, 2010  |  Pubmed ID: 20633703

Noroviruses (NoVs) are considered as important causative agents of non-bacterial acute gastroenteritis, worldwide. The data on NoV genomes, their diversity and evolution from Indian subcontinent are not available to date. The present study describes the characterization of full-length genomes of Indian NoV strains for the first time to establish their phylogenetic and evolutionary relationship with those circulating worldwide. Amplification of full-length genomes of three NoV strains (PC15, PC51 and PC52) was carried out using nine overlapping sets of forward and reverse primers. Full-length genomes of all of the three strains were characterized by phylogenetic, SimPlot, selection pressure and hydrophilicity analyses. The strain, PC15 was placed in the GII.4-Hunter subcluster. An intragenotype recombination event between ORFs 2 (new GII.4 variant) and 3 (Den Haag subcluster) of the strain, PC51 was detected for the first time in this study. The strain, PC52 showed the presence of commonly detected intergenotype recombination, GII.b/GII.3. A 16 amino-acid signature code (TDVVYYAGASQPRDDI) was identified in the ORF2 of recombinant GII.3 specificity strains, which may serve as a genetic marker for differentiation of these strains from non-recombinant GII.3 strains. The amino-acid substitutions in the ORF2 of PC51 and PC52 strains in comparison to the reference strains (Toyama1 and TV24) resulted in an increase in the hydrophilicity suggested alterations in the antigenic regions of Indian NoV strains. A unique pattern of amino-acid substitutions was observed within seven subclusters of GII.4 at 19 sites (including 13 sites under positive selection pressure) spanning entire ORF2. The study indicates adaptation of NoVs in the environment to escape the host immune response and to persist in the population. It also provides in-depth analyses of NoV genomes from India and determines the extent of conserved and variable features of the Indian NoV strains.

Anxiety Disorders Among Offenders with Antisocial Personality Disorders: a Distinct Subtype?

Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. Dec, 2010  |  Pubmed ID: 21172099

about 50% of men with antisocial personality disorder (APD) present a comorbid anxiety disorder. Historically, it was thought that anxiety limited criminal activity and the development of APD, but recent evidence suggests that heightened responsiveness to threat may lead to persistent violent behaviour. Our study aimed to determine the prevalence of APD comorbid with anxiety disorders among offenders and the association of these comorbid disorders with violent offending.

Current Status of Immunomodulatory and Cellular Therapies in Preclinical and Clinical Islet Transplantation

Journal of Transplantation. 2011  |  Pubmed ID: 22046502

Clinical islet transplantation is a β-cell replacement strategy that represents a possible definitive intervention for patients with type 1 diabetes, offering substantial benefits in terms of lowering daily insulin requirements and reducing incidences of debilitating hypoglycemic episodes and unawareness. Despite impressive advances in this field, a limiting supply of islets, inadequate means for preventing islet rejection, and the deleterious diabetogenic and nephrotoxic side effects associated with chronic immunosuppressive therapy preclude its wide-spread applicability. Islet transplantation however allows a window of opportunity for attempting various therapeutic manipulations of islets prior to transplantation aimed at achieving superior transplant outcomes. In this paper, we will focus on the current status of various immunosuppressive and cellular therapies that promote graft function and survival in preclinical and clinical islet transplantation with special emphasis on the tolerance-inducing capacity of regulatory T cells as well as the β-cells regenerative capacity of stem cells.

Diversity in the Enteric Viruses Detected in Outbreaks of Gastroenteritis from Mumbai, Western India

International Journal of Environmental Research and Public Health. Mar, 2012  |  Pubmed ID: 22690171

Faecal specimens collected from two outbreaks of acute gastroenteritis that occurred in southern Mumbai, India in March and October, 2006 were tested for seven different enteric viruses. Among the 218 specimens tested, 95 (43.6%) were positive, 73 (76.8%) for a single virus and 22 (23.2%) for multiple viruses. Single viral infections in both, March and October showed predominance of enterovirus (EV, 33.3% and 40%) and rotavirus A (RVA, 33.3% and 25%). The other viruses detected in these months were norovirus (NoV, 12.1% and 10%), rotavirus B (RVB, 12.1% and 10%), enteric adenovirus (AdV, 6.1% and 7.5%), Aichivirus (AiV, 3% and 7.5%) and human astrovirus (HAstV, 3% and 0%). Mixed viral infections were largely represented by two viruses (84.6% and 88.9%), a small proportion showed presence of three (7.7% and 11%) and four (7.7% and 0%) viruses in the two outbreaks. Genotyping of the viruses revealed predominance of RVA G2P[4], RVB G2 (Indian Bangladeshi lineage), NoV GII.4, AdV-40, HAstV-8 and AiV B types. VP1/2A junction region based genotyping showed presence of 11 different serotypes of EVs. Although no virus was detected in the tested water samples, examination of both water and sewage pipelines in gastroenteritis affected localities indicated leakages and possibility of contamination of drinking water with sewage water. Coexistence of multiple enteric viruses during the two outbreaks of gastroenteritis emphasizes the need to expand such investigations to other parts of India.

The Immunosuppressive Role of Adenosine A2A Receptors in Ischemia Reperfusion Injury and Islet Transplantation

Current Diabetes Reviews. Nov, 2012  |  Pubmed ID: 22934547

Activation of adenosine A2A receptors (A2AR) reduces inflammation by generally inhibiting the activation of pro-inflammatory cells, decreasing endothelial adhesion molecule expression and reducing the release of proinflammatory cytokine mediators. Numerous preclinical studies using selective A2AR agonists, antagonists, A2AR knockout as well as chimeric mice have suggested the therapeutic potential of A2AR agonists for the treatment of ischemia reperfusion injury (IRI) and autoimmune diseases. This review summarizes the immunosuppressive actions of A2AR agonists in murine IRI models of liver, kidney, heart, lung and CNS, and gives details on the cellular effects of A2AR activation in neutrophils, macrophages, dendritic cells, natural killer cells, NKT cells, T effector cells and CD4+CD25+FoxP3+ T regulatory cells. This is discussed in the context of cytokine mediators involved in inflammatory cascades. Whilst the role of adenosine receptor agonists in various models of autoimmune disease has been well-documented, very little information is available regarding the role of A2AR activation in type 1 diabetes mellitus (T1DM). An overview of the pathogenesis of T1DM as well as early islet graft rejection in the immediate peri-transplantation period offers insight regarding the use of A2AR agonists as a beneficial intervention in clinical islet transplantation, promoting islet graft survival, minimizing early islet loss and reducing the number of islets required for successful transplantation, thereby increasing the availability of this procedure to a greater number of recipients. In summary, the use of A2AR agonists as a clinical intervention in IRI and as an adjunct to clinical immunesuppressive regimen in islet transplantation is highlighted.

Naturally Occurring Immunoglobulin M (nIgM) Autoantibodies Prevent Autoimmune Diabetes and Mitigate Inflammation After Transplantation

Annals of Surgery. Oct, 2012  |  Pubmed ID: 22964733

To investigate whether polyclonal serum naturally occurring immunoglobulin M (nIgM) therapy prevents the onset and progression of autoimmune diabetes and promotes islet allograft survival.

Stem Cell Therapy to Cure Type 1 Diabetes: from Hype to Hope

Stem Cells Translational Medicine. May, 2013  |  Pubmed ID: 23572052

Type 1 diabetes mellitus (T1D) is a chronic, multifactorial autoimmune disease that involves the progressive destruction of pancreatic β-cells, ultimately resulting in the loss of insulin production and secretion. The goal of clinical intervention is to prevent or arrest the onset and progression of autoimmunity, reverse β-cell destruction, and restore glycometabolic and immune homeostasis. Despite promising outcomes observed with islet transplantation and advancements in immunomodulatory therapies, the need for an effective cell replacement strategy for curing T1D still persists. Stem cell therapy offers a solution to the cited challenges of islet transplantation. While the regenerative potential of stem cells can be harnessed to make available a self-replenishing supply of glucose-responsive insulin-producing cells, their immunomodulatory properties may potentially be used to prevent, arrest, or reverse autoimmunity, ameliorate innate/alloimmune graft rejection, and prevent recurrence of the disease. Herein, we discuss the therapeutic potential of stem cells derived from a variety of sources for the cure of T1D, for example, embryonic stem cells, induced pluripotent stem cells, bone marrow-derived hematopoietic stem cells, and multipotent mesenchymal stromal cells derived from bone marrow, umbilical cord blood, and adipose tissue. The benefits of combinatorial approaches designed to ensure the successful clinical translation of stem cell therapeutic strategies, such as approaches combining effective stem cell strategies with islet transplantation, immunomodulatory drug regimens, and/or novel bioengineering techniques, are also discussed. To conclude, the application of stem cell therapy in the cure for T1D appears extremely promising.

Diversity of Circulating Rotavirus Strains in Children Hospitalized with Diarrhea in India, 2005-2009

Vaccine. Jun, 2013  |  Pubmed ID: 23624096

India accounts for 22% of the 453,000 global rotavirus deaths among children <5 years annually. The Indian Rotavirus Strain Surveillance Network provides clinicians and public health partners with valuable rotavirus disease surveillance data. Our analysis offers policy-makers an update on rotavirus disease burden with emphasis on regional shifts in rotavirus strain epidemiology in India.

Pancreatic Islet Transplantation in Type 1 Diabetes Mellitus: an Update on Recent Developments

Current Diabetes Reviews. Jul, 2013  |  Pubmed ID: 23721158

Type 1 diabetes mellitus is an autoimmune disease that is characterized by the destruction of the islets of Langerhans cells which produce insulin. The current gold standard treatment is exogenous insulin injection, but this is onerous for the patients, and can lead to severe complications. Another approach involves transplanting pancreatic islet cells in order to restore endogenous insulin production under physiologic regulation. Although there has been some success with this treatment plan, there have been several hurdles. The largest hurdle is improving the 5 year survival of the graft, which is currently at 10%. In order to do so, there has been research into better locations for the graft, better isolation techniques, alternate immune suppression regimens, and novel transplantation methodologies utilizing encapsulated grafts. Another hurdle for pancreatic islet transplantation is that current methodologies require islets from several pancreata in order to create one successful graft, which leads to difficulties since there is a limited supply. However, there has been research looking into single donor transplants and porcine xenografts to increase the supply and address this problem. In this article, we review the current state of research regarding pancreatic islet transplantation.

Etiology of Viral Gastroenteritis in Children <5 Years of Age in the United States, 2008-2009

The Journal of Infectious Diseases. Sep, 2013  |  Pubmed ID: 23757337

Although rotavirus and norovirus cause nearly 40% of severe endemic acute gastroenteritis (AGE) in children <5 years of age in the United States, there are limited data on the etiologic role of other enteric viruses in this age group.

Overcoming Barriers in Clinical Islet Transplantation: Current Limitations and Future Prospects

Current Problems in Surgery. Feb, 2014  |  Pubmed ID: 24411187

Viral Gastroenteritis in Rotavirus Negative Hospitalized Children <5 Years of Age from the Independent States of the Former Soviet Union

Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases. Dec, 2014  |  Pubmed ID: 25460823

Rotavirus causes nearly 40% of all hospitalizations for AGE among children <5 years of age in the NIS of the former Soviet Union. The etiologic role of other established gastroenteritis viruses in this age group is unknown.

Characterization of GII.4 Noroviruses Circulating Among Children with Acute Gastroenteritis in Pune, India: 2005-2013

Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases. Jan, 2016  |  Pubmed ID: 26611824

Genogroup II genotype 4 noroviruses (GII.4 NoVs), an important cause of sporadic childhood gastroenteritis worldwide, undergo continuous evolution leading to the periodic emergence of novel variants. The present study was undertaken for surveillance of GII.4 NoVs and identification and characterization of GII.4 variants circulating among children with sporadic gastroenteritis in Pune, India during 2005-2013. Among the 12 GII genotypes detected in the study, GII.4 was predominant. Sequencing and phylogenetic analysis of ORF2 (major capsid protein VP1 gene) of the GII.4 NoVs revealed circulation of seven GII.4 variants, Hunter_2004 (2005-2007), Yerseke_2006a (2006), DenHaag_2006b (2007), Osaka_2007 (2007-2009), Apeldoorn_2007 (2008), New Orleans_2009 (2008-2012) and Sydney_2012 (2013), with the Pune strains grouping with the contemporary global reference strains. The Hunter_2004, Osaka_2007 and New Orleans_2009 variants showed prolonged circulation, with the Hunter_2004 and New Orleans_2009 variants differentiating into temporally separated sub-clusters. Analysis of VP1 sequences and predicted structures of the GII.4 variants identified variant specific amino acid positions, particularly in and near (within 8A(°)) the epitopes A-E, displaying differences in the sequence and physicochemical characteristics of the different variants. Comparison with the reference strains of each of the GII.4 variants revealed up to 11 amino acid substitutions at the variant specific positions in the GII.4 strains from Pune. Amino acid variations were also noted among the strains of the same GII.4 variant in Pune. The strains of different sub-clusters identified in the Hunter_2004 and New Orleans_2009 variants showed differences in sequence and physicochemical properties of either or all of the epitopes A, C and E. The study thus describes the temporal variations and diversity of the GII.4 strains in Pune and emphasizes continuous monitoring and analysis of the GII.4 variants.

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