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1.  Exploring Trends in Forensic Odontology 
Background: Forensic odontology nowadays has become a developing science and is of great importance to society. It is important that dental practitioners should have a proper knowledge of forensics as the need has increased greatly over the last decades due to the unprecedented demand from the criminal justice including terrorism in Kashmir valley (J&K India).
Materials and Methods: Data was collected based on questionnaire survey among qualified dental practitioners related to their awareness of forensic odontology.
Results: A total number of 235 dental practitioners responded to the questionnaire. Results showed that there was a low confidence, in handling of forensic odontology related cases among dental practitioners and majority of dental practitioners were not having any formal training in forensic odontology.
Conclusion: Each dental practitioner has a responsibility to understand the forensic implications associated with the practice of his profession and thus he should work sincerely enough so to ensure his contribution in the field of forensic odontology.
doi:10.7860/JCDR/2014/9976.5273
PMCID: PMC4316332  PMID: 25654026
Bite marks; Child abuse; Dental practitioners; Mass disaster
2.  Leptin antagonist ameliorates chronic colitis in IL-10−/− mice 
Immunobiology  2013;218(12):1439-1451.
Background
Although the etiology of two major forms of inflammatory bowel disease (IBD), Crohn’s disease (CD) and ulcerative colitis (UC) are unknown and evidence suggests that chronic intestinal inflammation is caused by an excessive immune response to mucosal antigens. Previous studies support the role for TGF-β1 through 3 in the initiation and maintenance of tolerance via the induction of regulatory T cells (Tregs) to control intestinal inflammation. Leptin, a satiety hormone produced primarily by adipose tissue, has been shown to increase during colitis progression and is believed to contribute to disease genesis and/or progression.
Aim
We investigated the ability of a pegylated leptin antagonist (PG-MLA) to ameliorate the development of chronic experimental colitis.
Results
Compared to vehicle control animals, PG-MLA treatment of mice resulted in an (1) attenuated clinical score; (2) reversed colitis-associated pathogenesis including a decrease in body weight; (3) reduced systemic and mucosal inflammatory cytokine expression; (4) increased insulin levels and (5) enhanced systemic and mucosal Tregs and CD39+ Tregs in mice with chronic colitis. The percentage of systemic and mucosal TGF-β1, -β2 and -β3 expressing CD4+ T cells were augmented after PG-MLA treatment. The activation of STAT1 and STAT3 and the expression of Smad7 were also reduced after PG-MLA treatment in the colitic mice. These findings clearly suggest that PG-MLA treatment reduces intestinal Smad7 expression, restores TGF-β1-3 signaling and reduces STAT1/STAT3 activation that may increase the number of Tregs to ameliorate chronic colitis.
Conclusion
This study clearly links inflammation with the metabolic hormone leptin suggesting that nutritional status influences immune tolerance through the induction of functional Tregs. Inhibiting leptin activity through PG-MLA might provide a new and novel therapeutic strategy for the treatment of IBD.
doi:10.1016/j.imbio.2013.04.020
PMCID: PMC3778116  PMID: 23726523
Inflammation; Inflammatory bowel disease (IBD); Leptin; Antagonist; Pegylated; Ulcerative Colitis (UC); Crohn’s Disease (CD)
3.  Role of abd-A and Abd-B in Development of Abdominal Epithelia Breaks Posterior Prevalence Rule 
PLoS Genetics  2014;10(10):e1004717.
Hox genes that determine anteroposterior body axis formation in all bilaterians are often found to have partially overlapping expression pattern. Since posterior genes dominate over anterior Hox genes in the region of co-expression, the anterior Hox genes are thought to have no function in such regions. In this study we show that two Hox genes have distinct and essential functions in the same cell. In Drosophila, the three Hox genes of the bithorax complex, Ubx, abd-A and Abd-B, show coexpression during embryonic development. Here, we show that in early pupal abdominal epithelia, Ubx does not coexpress with abd-A and Abd-B, while abd-A and Abd-B continue to coexpress in the same nuclei. The abd-A and Abd-B are expressed in both histoblast nest cells and larval epithelial cells of early pupal abdominal epithelia. Further functional studies demonstrate that abd-A is required in histoblast nest cells for their proliferation and suppression of Ubx to prevent first abdominal segment like features in posterior segments while in larval epithelial cells it is required for their elimination. We also observed that these functions of abd-A are required in its exclusive as well as the coexpression domain with that of Abd-B. The expression of Abd-B is required in histoblast nest cells for their identity while it is dispensable in the larval epithelial cells. The higher level of Abd-B in the seventh abdominal segment, that down-regulates abd-A expression, leads this segment to be absent in males or of smaller size in females. We also show that abd-A in histoblast nest cells positively regulates expression of wingless for the formation of the abdominal epithelia. Our study reveals an exception to the rule of posterior prevalence and shows that two different Hox genes have distinct functions in the same cell, which is essential for the development of abdominal epithelia.
Author Summary
The spatially non-overlapping function of Hox genes is known to determine Antero-posterior body axis in all the bilaterians. The expression of Hox genes is found to be overlapping in several cases. According to the posterior prevalence rule, posterior Hox genes suppress the function of anterior Hox genes in the overlapping expression domains. Our findings show an exception to the rule of posterior prevalence. We show that in the overlapping expression domains of abd-A and Abd-B in early pupal abdominal epithelia, both the genes have essential roles. While abd-A is required for cell proliferation, Abd-B determines the segmental identity.
doi:10.1371/journal.pgen.1004717
PMCID: PMC4207640  PMID: 25340649
4.  The Emerging Role of Leptin Antagonist as Potential Therapeutic Option for Inflammatory Bowel Disease 
Inflammatory bowel disease (IBD) is a chronic relapsing immune-mediated inflammatory disorder that affects millions of people around the world. Leptin is a satiety hormone produced primarily by adipose tissue and acts both centrally and peripherally. Leptin has been shown to play a major role in regulating metabolism, which increases during IBD progression. Leptin mediates several physiological functions including elevated blood pressure, tumorogenesis, cardiovascular pathologies and enhanced immune response in many autoimmune diseases. Recent development of a leptin mutant antagonist that blocks leptin activity raises great hope and opens up new possibilities for therapy in many autoimmune diseases including IBD. To this end, preliminary data from an ongoing study in our laboratory on pegylated leptin antagonist mutant L39A/D40A/F41A (PEG-MLA) treatment shows an inhibition of chronic colitis in IL-10−/− mice. PEG-MLA effectively attenuates the overall clinical scores, reverses colitis-associated pathogenesis including a decrease in body weight, and decreases systemic leptin level. PEG-MLA induces both central and peripheral leptin deficiency by mediating the cellular immune response. In summary, after blocking leptin activity, the correlative outcome between leptin-mediated cellular immune response, systemic leptin levels, and amount of adipose tissue together may provide new strategies for therapeutic intervention in autoimmune diseases, especially for intestinal inflammation.
doi:10.3109/08830185.2013.809071
PMCID: PMC4159716  PMID: 23841494
Crohn’s disease (CD); inflammation; inflammatory bowel disease (IBD); leptin antagonist; pegylated leptin; ulcerative colitis (UC)
5.  Alternative Medicines as Emerging Therapies for Inflammatory Bowel Diseases 
Inflammatory bowel disease (IBD) can be divided into two major categories, ulcerative colitis (UC) and Crohn disease (CD). While the main cause(s) of IBD remain unknown, a number of interventional and preventive strategies have been proposed for use against CD and UC. Many reports have focused on the use of alternative natural medicines as potential therapeutic interventions in IBD patients with minimal side effects. While the use of alternative medicines may be effective in IBD patients that are refractory to corticosteroids or thiopurins, alternative treatment strategies are limited and require extensive clinical testing before being optimized for use in patients.
doi:10.3109/08830185.2011.642909
PMCID: PMC4138959  PMID: 22251008
bromelain; Crohn disease (CD); curcumin; inflammation; inflammatory bowel disease (IBD); polyphenols; pomegranate; resveratrol; rutin; ulcerative colitis (UC)
6.  Use of Cannabinoids as a Novel Therapeutic Modality Against Autoimmune Hepatitis 
Vitamins and hormones  2009;81:487-504.
Autoimmune hepatitis is a severe immune mediated chronic liver disease with a prevalence range between 50 and 200 cases per million in Western Europe and North America and mortality rates of up to 80% in untreated patients. The induction of CB1 and CB2 cannabinoid receptors during liver injury and the potential involvement of endocannabinoids in the regulation of this process have sparked significant interest in further evaluating the role of cannabinoid systems during hepatic disease. Cannabinoids have been shown to possess significant immunosuppressive and anti-inflammatory properties. Cannabinoid abuse has been shown to exacerbate liver fibrogenesis in patients with chronic hepatitis C infection involving CB1 receptor. Nonetheless, CB2 receptor activation may play a protective role during chronic liver diseases. Thus, differential targeting of cannabinoid receptors may provide novel therapeutic modality against autoimmune hepatitis. In this review, we summarize current knowledge on the role of endocannabinoids and exocannabinoids in the regulation of autoimmune hepatitis.
doi:10.1016/S0083-6729(09)81019-4
PMCID: PMC4139007  PMID: 19647124
7.  Carcinogenic lead chromate induces DNA double-strand breaks in human lung cells 
Mutation research  2005;586(2):160-172.
Hexavalent chromium (Cr(VI)) is a widespread environmental contaminant and a known human carcinogen, generally causing bronchial cancer. Recent studies have shown that the particulate forms of Cr(VI) are the potent carcinogens. Particulate Cr(VI) is known to induce a spectrum of DNA damage such as DNA single strand breaks, Cr-DNA adducts, DNA-protein crosslinks and chromosomal aberrations. However, particulate Cr(VI)-induced DNA double strand breaks (DSBs) have not been reported. Thus, the aim of this study was to determine if particulate Cr(VI)-induces DSBs in human bronchial cells. Using the single cell gel electrophoresis assay (comet assay), showed that lead chromate-induced concentration dependent increases in DSBs with 0.1, 0.5, 1 and 5 μg/cm2 lead chromate inducing a 20, 50, 67 and 109% relative increase in the tail integrated intensity ratio, respectively. Sodium chromate at concentrations of 1, 2.5 and 5 μM induced 38, 78 and 107% relative increase in the tail integrated intensity ratio, respectively. We also show that genotoxic concentrations of lead chromate activate the ataxia telangiectasia mutated (ATM) protein, which is thought to play a central role in the early stages of DSB detection and controls cellular responses to this damage. The H2A.X protein becomes rapidly phosphorylated on residue serine 139 in cells when DSBs are introduced into the DNA by ionizing radiation. By using immunofluorescence, we found that lead chromate-induced concentration-dependent increases in phosphorylated H2A.X (r-H2A.X) foci formation with 0.1, 0.5, 1, 5 and 10 μg/cm2 lead chromate inducing a relative increase in the number of cells with r-H2A.X foci formation of 43, 51, 115 and 129%, respectively.
doi:10.1016/j.mrgentox.2005.06.002
PMCID: PMC4136752  PMID: 16112599
Hexavalent chromium; DNA double strand breaks; ATM; Smc1; Lead chromate
8.  Cannabinoids Receptor-2 (CB2) agonist ameliorates colitis in IL-10−/− mice by attenuating the activation of T cells and promoting their apoptosis 
Toxicology and applied pharmacology  2011;258(2):256-267.
Inflammatory bowel disease (IBD) is a chronic intestinal inflammation caused by hyperactivated effector immune cells that produce pro-inflammatory cytokines. Recent studies have shown that the cannabinoid system may play a critical role in mediating protection against intestinal inflammation. However, the effect of cannabinoid receptors induction after chronic colitis progression has not been investigated. Here, we investigate the effect of cannabinoid receptor-2 (CB2) agonist, JWH-133, after chronic colitis in IL-10−/− mice. JWH-133 effectively attenuated the overall clinical score, reversed colitis-associated pathogenesis and decrease in body weight in IL-10−/− mice. After JWH-133 treatment, the percentage of CD4+ T cells, neutrophils, mast cells, natural killer (NK1.1) cells, and activated T cells in the LP of colitis mice declined after JWH-133 treatment in the intestinal lamina propria (LP) and mesenteric lymph nodes (MLN). JWH-133 was also effective in ameliorating dextran sodium sulphate (DSS)-induced colitis. In this model, JWH-133 reduced the number and percentage of macrophages and IFN-γ expressing cells that were induced during colitis progression. Treatment with aminoalkylindole 6-iodopravadoline (AM630), a CB2 receptor antagonist, reversed the colitis protection provided by JWH-133 treatment. Also, activated T cells were found to undergo apoptosis following JWH-133 treatment both in-vivo and in-vitro. These findings suggest that JWH-133 mediates its effect through CB2 receptors, and ameliorates chronic colitis by inducing apoptosis in activated T cells, reducing the numbers of activated T cells, suppressing induction of mast cells, NK cells, and neutrophils at sites of inflammation in the LP. These results support the idea that the CB2 receptor agonists may serve as a therapeutic modality against IBD.
doi:10.1016/j.taap.2011.11.005
PMCID: PMC4117838  PMID: 22119709
Cannabinoid-2 receptors; JWH 133; Colitis; inflammatory bowel disease
9.  Genome Sequencing of Ralstonia solanacearum Biovar 3, Phylotype I, Strains Rs-09-161 and Rs-10-244, Isolated from Eggplant and Chili in India 
Genome Announcements  2014;2(3):e00323-14.
Ralstonia solanacearum Indian strains Rs-09-161 and Rs-10-244 were isolated from the coastal region of Goa and from the Andaman Islands. We report the draft genome sequences of these representative isolates infecting solanaceous vegetables in India.
doi:10.1128/genomeA.00323-14
PMCID: PMC4038872  PMID: 24874667
10.  Dysregulation in microRNA Expression Is Associated with Alterations in Immune Functions in Combat Veterans with Post-Traumatic Stress Disorder 
PLoS ONE  2014;9(4):e94075.
While the immunological dysfunction in combat Veterans with post-traumatic stress disorder (PTSD) has been well documented, the precise mechanisms remain unclear. The current study evaluated the role of microRNA (miR) in immunological dysfunction associated with PTSD. The presence of peripheral blood mononuclear cells (PBMC) and various lymphocyte subsets in blood collected from PTSD patients were analyzed. Our studies demonstrated that the numbers of both PBMC and various lymphocyte subsets increased significantly in PTSD patients. When T cells were further analyzed, the percentage of Th1 cells and Th17 cells increased, regulatory T cells(Tregs) decreased, while Th2 cells remained unaltered in PTSD patients. These data correlated with increased plasma levels of IFN-γ and IL-17 while IL-4 showed no significant change. The increase in PBMC counts, Th1 and Th17 cells seen in PTSD patients correlated with the clinical scores. High-throughput analysis of PBMCs for 1163 miRs showed that the expression of a significant number of miRs was altered in PTSD patients. Pathway analysis of dysregulated miRs seen in PTSD patients revealed relationship between selected miRNAs and genes that showed direct/indirect role in immunological signaling pathways consistent with the immunological changes seen in these patients. Of interest was the down-regulation of miR-125a in PTSD, which specifically targeted IFN-γ production. Together, the current study demonstrates for the first time that PTSD was associated with significant alterations in miRNAs, which may promote pro-inflammatory cytokine profile. Such epigenetic events may provide useful tools to identify potential biomarkers for diagnosis, and facilitate therapy of PTSD.
doi:10.1371/journal.pone.0094075
PMCID: PMC3997344  PMID: 24759737
11.  Carriage prevalence of carbapenem-resistant Enterobacteriaceae in stool samples: A surveillance study 
Background
With more people being exposed to antibiotics, intestinal microflora faces constant pressure of antibiotic selection, which has resulted in the emergence of multidrug resistant strains. This may pose a severe problem as intestinal Enterobacteriaceae members are commonly implicated in human infections.
Aims
This surveillance study was undertaken to investigate the carriage of carbapenem-resistant Enterobacteriaceae (CRE) in the gastrointestinal tract among patients attending the outpatient clinic in a tertiary care center of East Delhi, India.
Method
We performed a prospective surveillance study to screen 242 Enterobacteriaceae isolates for carbapenemase production from the stool samples of 123 outpatients attending a tertiary care hospital in East Delhi over a four-month period.
Results
Twenty-four (9.9 per cent) isolates demonstrated carbapenemase activity among 242 screened Enterobacteriaceae isolates. Four stool samples had two isolates of different species, both eliciting this feature and therefore indicating presence of multiple carbapenem-resistant Enterobacteriaceae (CRE) isolates in a single sample.
Conclusion
Screening for carriage of CRE in stools of patients undergoing elective or emergency gastrointestinal surgical procedures, with haematological malignancies taking chemotherapy, or those planned for bone marrow transplantation can guide clinicians about gut colonisation of multidrug-resistant Enterobacteriaceae as these groups of patients are at risk of possible endogenous infection.
doi:10.4066/AMJ.2014.1926
PMCID: PMC3941578  PMID: 24611074
Carbapenem resistant Enterobacteriaceae; gut colonisation; prophylactic antibiotic
12.  MicroRNA let-7e is associated with the pathogenesis of experimental autoimmune encephalomyelitis 
European journal of immunology  2012;43(1):104-114.
MicroRNAs (miRNAs) play important roles in the regulation of immune responses. There is evidence that miRNAs also participate in the pathogenesis of multiple sclerosis (MS), but how the miRNAs regulate the pathogenesis of MS is still under investigation. The identification of new members of the miRNA family associated with the pathogenesis of MS could facilitate early diagnosis and treatment. Here we show that the level of miRNA let-7e is significantly upregulated in experimental autoimmune encephalomyelitis (EAE), an animal model of MS using miRNA array and quantitative real-time PCR. The expression of let-7e was mainly in CD4+ T cells and infiltrated mononuclear cells of central nervous system, and highly correlated with the development of EAE. We found that let-7e silencing in vivo inhibited encephalitogenic Th1 and Th17 cells and attenuated EAE, with reciprocal increase of Th2 cells; overexpression of let-7e enhanced Th1 and Th17 cells and aggravated EAE. We also identified IL-10 as one of the functional targets of let-7e. Together, we propose that let-7e is a new miRNA involved in the regulation of encephalitogenic T-cell differentiation and the pathogenesis of EAE.
doi:10.1002/eji.201242702
PMCID: PMC3650085  PMID: 23079871
MicroRNA; mir-let-7e; EAE/MS; Th1/Th2 cells; Cell differentiation
13.  Estimation of serum β2-microglobulin in potentially malignant disorders and squamous cell carcinoma of the oral cavity: A clinicopathological study 
Dental Research Journal  2014;11(1):109-113.
Background:
Tumor markers are substances, which quantitatively changes in serum, during the tumor development, one such tumor marker is serum β2-microglobulin (β2-m). The aim of this study was to establish the role of β2-m as a biochemical parameter for diagnosis and prognosis of oral carcinoma by estimation of serum β2-m levels in potentially malignant lesions, conditions, and oral squamous cell carcinoma.
Materials and Methods:
The study was carried out on 48 subjects (16 control, 8 oral submucous fibrosis, 8 oral leukoplakia, and 16 oral squamous cell carcinoma patients of different stages), conducted at department of Oral Medicine, Kothiwal Dental College, Moradabad, India. Under aseptic precautions, 5 ml venous blood was drawn and serum was separated. Estimation of β2-m level in serum was carried out by enzyme linked immunosorbent assay. The data were analyzed by using the statistical package for social sciences (SPSS 17.0) software. Cases and controls were tested for statistical significance with one-way ANOVA with post-hoc Tukey's HSD. Values of P < 0.05 were considered significant.
Results:
The mean serum β2-m level in the control group was 1.173 ± 0.059, in potentially malignant lesions/conditions group was 1.688 ± 0.137 and in oral squamous cell carcinoma group was 2.835 ± 0.0313. This progressive increase in serum β2-m level was found to be highly significant (P value < 0.001). Results of Receiver operating characteristic analysis showed β2-m as a 100% sensitive and specific biomarker for oral squamous cell carcinoma.
Conclusion:
The present study establishes β2-m as a specific biological tumor marker for diagnostic and prognostic evaluation of oral squamous cell carcinoma.
PMCID: PMC3955303  PMID: 24688569
β2-microglobulin; enzyme linked immunosorbent assay; squamous cell carcinoma; tumor markers
14.  Training module for cheiloscopy and palatoscopy in forensic odontology 
Introduction:
Studies of lip prints and palatal rugae, dates back to late 19th and early 20th centuries and since then, various methods of classification and analysis were introduced, however systematic recording and analysis of data is still need to improve further, to arrive at flawless and meaningful conclusions. Moreover, the awareness among dental personnel regarding the practical knowledge of cheiloscopy and palatoscopy is ambiguous. So, efforts have been made to introduce training module to improve the education of cheiloscopy and palatoscopy for dental students.
Aims and Objective:
1. To prepare training module for cheiloscopy and palatoscopy. 2. To assess the efficacy of designed training module.
Materials and Methods:
Training module was used to train the dental students. Random matching of lip and palatal rugae patterns was carried out by dental students before and after training. Pre- and post-training matched results were then compared. Intraobserver variability assessed by comparing first and second assessment of lip print and palatal rugae patterns.
Results:
It was inferred statistically that training module had improved the ability to identify individuals based on lip prints and palatal rugae, with insignificant intraobserver variation.
doi:10.4103/0975-1475.127768
PMCID: PMC3970386  PMID: 24695814
Lip print; palatal rugae; training module
15.  Expression, Regulation and Function of MicroRNAs in Multiple Sclerosis 
MicroRNAs (miRNAs) are single-stranded 19-25 nucleotide-long RNAs and have an important role in post-transcriptional gene silencing. It has been demonstrated that miRNAs are dysregulated in patients with multiple sclerosis (MS). For instance, miR-21, miR-142-3p, miR-146a, miR-146b, miR-155 and miR-326 were up-regulated in both peripheral blood mononuclear cells (PBMCs) and brain white matter lesions from MS patients and mouse model as well. These up-regulated miRNAs may be used as a signature for MS and play critical roles in MS pathogenesis. Moreover, miR-15a, miR-19a, miR-22, miR-210 and miR-223 were up-regulated in both regulatory T cells (Tregs) and other samples such as plasma, blood cells, PBMCs and brain white matter tissues from MS patients, suggesting that these up-regulated miRNAs and Tregs may also play a role in MS pathogenesis. Contrarily, other miRNAs such as miR-15a, miR-15b, miR-181c and miR-328 were down-regulated in MS. Drugs such as interferon-β and glatiramer acetate for MS treatment may regulate miRNA expression and thus have benefits for MS patients. The dysregulated miRNAs such as miR-155 and miR-326 may be used as diagnostic markers and therapeutic targets for MS.
doi:10.7150/ijms.8647
PMCID: PMC4057480  PMID: 24936144
miRNA; multiple sclerosis; biomarker; therapeutic target; gene expression; gene regulation
16.  Detoxification of Croton tiglium L. seeds by Ayurvedic process of Śodhana 
Ancient Science of Life  2014;33(3):157-161.
Objective:
Croton tiglium seeds, known as Jamālgoṭa in Hindi, Marathi, and Urdu is well-known for its toxicity (severe purgative action). In Ayurvedic texts, the plant is known as Kumbhinī and is used for the treatment of constipation after Śodhana (detoxification process) of the seeds with Godugdha (cow milk).
Material and Methods:
In the present study, C. tiglium seeds were purified with cow milk as reported in Ayurvedic classics. Phorbol esters equivalent to phorbol-12-myristate-13-acetate (PMA) and crotonic acid contents were quantified by high-performance liquid chromatography method in the seeds of C. tiglium before and after the purification process.
Results:
The content of the phorbol ester equivalent to PMA in unpurified and purified sample was found to be 5.2 mg/100 g and 1.8 mg/100 g of dried seeds of C. tiglium, respectively. The quantity of crotonic acid in unpurified seeds of C. tiglium was found to be 0.102 mg/100 g of dried seeds while it was absent in the purified seed extract of C. tiglium.
Conclusion:
The toxicity of C. tiglium seeds may be due to the presence of phorbol esters and crotonic acid along with other constituents. These constituents are oil soluble and may be removed by cow milk during the process of Śodhana. Reduction in the level of these constituents after the purification decreases the toxicity of C. tiglium seeds. Reduction in the oily content from the seeds of C. tiglium during the purification process is also supported by the results obtained from the physiochemical parameters.
doi:10.4103/0257-7941.144619
PMCID: PMC4264303  PMID: 25538350
Croton tiglium; crotonic acid; phorbol ester; purification
17.  The Severity of Experimental Autoimmune Cystitis Can be Ameliorated by Anti-CXCL10 Ab Treatment 
PLoS ONE  2013;8(11):e79751.
Background
Interstitial cystitis (IC), more recently called painful bladder syndrome (PBS) is a complex disease associated with chronic bladder inflammation that primarily affects women. Its symptoms include frequent urinary urgency accompanied by discomfort or pain in the bladder and lower abdomen. In the United States, eight million people, mostly women, have IC/PBS. New evidence that autoimmune mechanisms are important in the pathogenesis of IC/PBS triggered interest.
Methodology/Principal Findings
SWXJ mice immunized with a homogenate of similar mice’s urinary bladders develop an autoimmune phenotype comparable to clinical IC with functional and histological alterations confined to the urinary bladder. Using the murine model of experimental autoimmune cystitis (EAC), we found that serum levels of CXCR3 ligand and local T helper type 1 (Th1) cytokine are elevated. Also, IFN-γ-inducible protein10 (CXCL10) blockade attenuated overall cystitis severity scores; reversed the development of IC; decreased local production of CXCR3 and its ligands, IFN-γ, and tumor necrosis factor-α (TNF-α); and lowered systemic levels of CXCR3 ligands. Urinary bladder CD4+ T cells, mast cells, and neutrophils infiltrates were reduced following anti-CXCL10 antibody (Ab) treatment of mice. Anti-CXCL10 Ab treatment also reversed the upregulated level of CXCR3 ligand mRNA at urinary bladder sites. The decreased number and percentage of systemic CD4+ T cells in EAC mice returned to normal after anti-CXCL10 Ab treatment.
Conclusion/Significance
Taken together, our findings provide important new information about the mechanisms underlying EAC pathogenesis, which has symptoms similar to those of IC/PBS. CXCL10 has the potential for use in developing new therapy for IC/PBS.
doi:10.1371/journal.pone.0079751
PMCID: PMC3836899  PMID: 24278169
18.  Minor salivary glands and dental caries: Approach towards a new horizon 
Introduction:
Reduction of functioning minor salivary glands may contribute to emergence of mucosal infections, mucosal ulceration, and possibly dental caries. A study was, therefore, designed to understand the exact role of minor salivary gland secretions over dental caries.
Methodology:
We studied the average labial distribution of functional minor salivary glands using various pre-defined locations, counted the minor salivary gland secretion imprints, and correlated the decayed missing filledlevels in subjects. The functional level and amount of secretion of minor salivary gland were evaluated. The radial immunodiffusion was performed by Diffu-Plate kit and the dimensions of the ring were correlated with the amount of immunoglobulin A in saliva.
Results:
The mean number of functional labial minor salivary glands, amount of secretion, level of glycoprotein secretion, and immunoglobulin A secretion levels could very well dictate the functional status and role of minor salivary glands over caries assessment.
Conclusion:
The above-mentioned tests could be of major significance in routine diagnosis of the most common oral disease, i.e., dental caries.
doi:10.4103/0976-9668.117000
PMCID: PMC3783781  PMID: 24082733
Radial immunodiffusion; salivary immunoglobulin A; unstimulated whole saliva
19.  Effect of rate-adaptive pacing on performance and physiological parameters during activities of daily living in the elderly: results from the CLEAR (Cylos Responds with Physiologic Rate Changes during Daily Activities) study 
Europace  2013;15(6):849-856.
Aims
For most elderly pacemaker patients, evaluation of rate-adaptive pacing using treadmill and bicycle tests is impractical and not representative of typical daily activities. This study was designed to compare the performance and physiological response of the closed-loop stimulation (CLS) rate-adaptive sensor to accelerometer (XL) and no rate sensor (DDD) during typical daily activity testing.
Methods and results
Subjects recently implanted with a Cylos pacemaker completed timed activities of daily life testing, which included walking, sweeping, and standing from a seated position. Activity performance and physiological response from each sensor mode was evaluated for subjects requiring ≥80% pacing. Overall, 74 subjects needed ≥80% pacing during at least one test. An increase in the area swept (CLS vs. XL, 1.67 m2 difference, P = 0.009; CLS vs. DDD, 1.59 m2 difference, P = 0.025) and a decrease in the prevalence of orthostatic hypotension (OH) after standing 1 min (CLS vs. XL, odds ratio = 0.16, P = 0.006; CLS vs. DDD, odds ratio = 0.18, P = 0.012) was observed in the CLS mode as compared with XL and DDD. No statistical difference in walk distance was observed between CLS and XL or CLS and DDD.
Conclusion
In acute testing, as compared with XL and DDD, CLS provides a more physiological response during the performance of activities of daily living for subjects with ≥80% pacing. This is clinically reflected in better performance during the sweep test as well as a decrease in the prevalence of OH in our elderly population.
Clinicaltrials.gov identifier: NCT00355797
doi:10.1093/europace/eus425
PMCID: PMC3663333  PMID: 23419655
Rate-adaptive pacing; Closed-loop stimulation; Accelerometer; Orthostatic hypotension
20.  Role of resveratrol-induced CD11b+ Gr-1+ myeloid derived suppressor cells (MDSCs) in the reduction of CXCR3+ T cells and amelioration of chronic colitis in IL-10−/− mice 
Brain, behavior, and immunity  2011;26(1):72-82.
Resveratrol, a naturally occurring polyphenol has received significant attention as a potent anti-inflammatory agent. Inflammatory bowel disease (IBD) is a chronic intestinal inflammation caused by hyperactivated effector immune cells that produce pro-inflammatory cytokines. Myeloid derived suppressor cells (MDSCs) are a heterogeneous population characterized by the co-expression of CD11b+ and Gr-1+ and have long been known for their immunosuppressive function. We report that resveratrol effectively attenuated overall clinical scores as well as various pathological markers of colitis in IL-10−/− mice by down regulating Th1 responses. Resveratrol lessened the colitis-associated decrease in body weight and increased levels of serum amyloid A (SAA), CXCL10 and colon TNF-α, IL-6, RANTES, IL-12 and IL-1β concentrations. After resveratrol treatment, the percentage of CXCR3 expressing T cells was decreased in the spleen, mesenteric lymph nodes (MLN), and intestinal lamina propria (LP). However, the percentage and absolute numbers of CD11b+ and Gr-1+cells in the lamina propria (LP) and spleen were increased after resveratrol treatment as compared with the vehicle treatment. Co-culture of resveratrol induced CD11b+ Gr-1+ cells with T cells, attenuated T cell proliferation, and most importantly reduced IFN-γ and GM-CSF production by LP derived T cells from vehicle treated IL-10−/− mice with chronic colitis. The current study suggests that administration of resveratrol into IL-10−/− mice induces immunosuppressive CD11b+ Gr-1+ MDSCs in the colon, which correlates with reversal of established chronic colitis, and down regulation of mucosal and systemic CXCR3+ expressing effector T cells as well as inflammatory cytokines in the colon. The induction of immunosuppressive CD11b+ Gr-1+ cells by resveratrol during colitis is unique, and suggests an as-yet-unidentified mode of anti-inflammatory action of this plant polyphenol.
doi:10.1016/j.bbi.2011.07.236
PMCID: PMC3506001  PMID: 21807089
Inflammation; Resveratrol; Colitis; CXCR3; CD11b+ and Gr-1+ and MDSCs
22.  Revealing anti-cariogenic efficacy of smokeless tobacco: A pilot study 
Background:
The tobacco plant, Nicotiana tabacum, has been responsible for more deaths than any other herb. However, the literature has also been endowed with its use as “holy herb” since the pre-Columbian era. Used for treating pain, poisonous bites, ulcers, nasal polyps, and basal cell carcinoma; it also acts as an important ingredient of commercially available toothpastes; and even used as tobacco vaccines against Streptococcus species as highlighted in the literature.
Aims and Objectives:
(1) To elicit the anti-microbial property of tobacco against Streptococcus mutans, if any, in raw smokeless tobacco. (2) To study the relationship of duration and growth inhibition efficacy of smokeless tobacco.
Materials and Methods:
Extracts were prepared by centrifugation of mixed raw smokeless tobacco with Ringer's lactate solution and with saliva. The extracts were placed in wells prepared on Mitis salivarius culture plate and incubated at 37°C for 24 h after 0 h, 1 h, and 2 h of extract preparation. The inhibition zones were measured on the underside of plate using the vernier calipers.
Results:
Smokeless tobacco has a statistically significant zone of inhibition, which proves its anti-microbial activity against S. mutans. However, the mean zones of inhibition were greater for Ringer's lactate and tobacco group as compared to test samples (saliva and tobacco) with subsequent reduction of inhibition zones with an increase in duration.
Conclusion:
The anti-microbial property of extensive tobacco resources can be utilized from their extracts in order to balance the deterioration it had caused to mankind.
doi:10.4103/0973-029X.110727
PMCID: PMC3687190  PMID: 23798831
Anti-cariogenecity; Streptococcus mutans;  tobacco
23.  Resveratrol (trans-3,5,4'-trihydroxystilbene) suppresses EL4 tumor growth by induction of apoptosis involving reciprocal regulation of SIRT1 and NF-κB 
Molecular nutrition & food research  2011;55(8):1207-1218.
Scope
Understanding the molecular mechanisms through which natural products and dietary supplements exhibit anticancer properties is crucial and can lead to drug discovery and chemoprevention. The current study sheds new light on the mode of action of Resveratarol (RES), a plant-derived polyphenolic compound, against EL-4 lymphoma growth.
Methods and results
Immuno-compromised NOD/SCID mice injected with EL-4 tumor cells and treated with RES (100 mg/kg body weight) showed delayed development and progression of tumor growth and increased mean survival time. RES caused apoptosis in EL4 cells through activation of aryl hydrocarbon receptor (AhR) and upregulation of Fas and FasL expression in vitro. Blocking of RES-induced apoptosis in EL4 cells by FasL mAb, cleavage of caspases and PARP, and release of cytochorme c, demonstrated the participation of both extrinsic and intrinsic pathways of apoptosis. RES also induced upregulation of SIRT1 and downregulation of NF-kB in EL4 cells. SiRNA-mediated down regulation of SIRT1 in EL4 cells increased the activation of NF-kB but decreased RES-mediated apoptosis, indicating the critical role of SIRT1 in apoptosis via blocking activation of NF-kB.
Conclusion
These data suggest that RES-induced SIRT1 upregulation promotes tumor cell apoptosis through negative regulation of NF-kB, leading to suppression of tumor growth.
doi:10.1002/mnfr.201000576
PMCID: PMC3516994  PMID: 21520490
Cancer; Lymphoma; Resveratrol; AhR; Fas; FasL; Apoptosis; Extrinsic pathway; Intrinsic pathway
24.  Distribution of Aedes albopictus (Diptera, Culicidae) in southwestern Pacific countries, with a first report from the Kingdom of Tonga 
Parasites & Vectors  2012;5:247.
Background
Aedes (Stegomyia) albopictus is currently one of the most notorious globally invasive mosquito species. Its medical importance is well documented, and its fast expansion throughout most continents is being monitored with concern. It is generally assumed that its expansion through the Western Pacific island countries has not progressed since its establishment in Fiji in 1989. However, the current status of Ae. albopictus in the Pacific region is largely unknown.
Findings
According to data from the literature and our own observations, Ae. albopictus is currently present in the following countries of the southern Pacific region: Papua New Guinea, Solomon Islands, Fiji, and the Kingdom of Tonga, where it was first detected in July 2011. It is absent from New Caledonia and French Polynesia where routine entomological surveillance is carried out, and was not detected during entomological work in 2007, either on the Cook Islands or on the Wallis and Futuna Islands. The species was not reported from American Samoa in 2004, but it is mentioned as probably present in Vanuatu. This is the first report of Ae. albopictus in Tonga.
Conclusions
The introduction and establishment of Ae. albopictus in Tonga was expected due to the geographical proximity of this country to Fiji where the species is strongly established. The pathway of introduction is unknown. The expansion of Ae. albopictus in the Pacific region poses an increasing threat to public health given the role this mosquito plays as primary vector of emerging infectious diseases such as Chikungunya fever.
doi:10.1186/1756-3305-5-247
PMCID: PMC3497854  PMID: 23130961
Aedes albopictus; Vector; Distribution; Pacific islands; Tonga; Introduction
25.  Prenatal Exposure to TCDD Triggers Significant Modulation of microRNA Expression Profile in the Thymus That Affects Consequent Gene Expression 
PLoS ONE  2012;7(9):e45054.
Background
MicroRNAs (miRs) are a class of small RNAs that regulate gene expression. There are over 700 miRs encoded in the mouse genome and modulate most of the cellular pathways and functions by controlling gene expression. However, there is not much known about the pathophysiological role of miRs. TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), an environmental contaminant is well known to induce severe toxicity (acute and chronic) with long-term effects. Also, in utero exposure of fetus to TCDD has been shown to cause thymic atrophy and alterations in T cell differentiation. It is also relevant to understand “the fetal basis of adult disease” hypothesis, which proposes that prenatal exposure to certain forms of nutritional and environmental stress can cause increased susceptibility to clinical disorders later in life. In the current study, therefore, we investigated the effects of prenatal exposure to TCDD on miR profile in fetal thymocytes and searched for their possible role in causing thymic atrophy and alterations in the expression of apoptotic genes.
Methodology/Principal Findings
miR arrays of fetal thymocytes post exposure to TCDD and vehicle were performed. Of the 608 mouse miRs screened, 78 miRs were altered more than 1.5 fold and 28 miRs were changed more than 2 fold in fetal thymocytes post-TCDD exposure when compared to vehicle controls. We validated the expression of several of the miRs using RT-PCR. Furthermore, several of the miRs that were downregulated contained highly complementary sequence to the 3′-UTR region of AhR, CYP1A1, Fas and FasL. Also, the Ingenuity Pathway Analysis software and database was used to analyze the 78 miRs that exhibited significant expression changes and revealed that as many as 15 pathways may be affected.
Conclusions/Significance
These studies revealed that TCDD-mediated alterations in miR expression may be involved in the regulation of its toxicity including cancer, hepatic injury, apoptosis, and cellular development.
doi:10.1371/journal.pone.0045054
PMCID: PMC3443208  PMID: 23024791

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