Role of inflammatory mediators (TNF-α, IL-6, CRP), biochemical and hematological parameters in type 2 diabetes mellitus patients of Kashmir, India.

Background: Type II Diabetes mellitus (T2DM) is a multifactorial disease and a leading cause of premature deaths. Inflammatory cytokines are reported that they have potential to enhance insulin resistance and hence T2DM. Assessment of immunological profile in T2DM patients of Kashmir valley is unclear. So, detection of cytokines is relevant to determine the extent and direction of immune responses. The current research was taken to study the role of inflammatory mediators in T2DM along with insulin sensitivity, biochemical and hematological parameters in mountainous valley of Kashmiri population. Methods: A total of 340 subjects were selected in this study among them 160 were T2DM cases and 180 were healthy controls. Serum expression of inflammatory mediators (TNF-α and IL-6 ) were quantified by ELISA technique, WBC count was measured on Sysmax (Germany) hematology analyzer, biochemical and Immunoassay parameters were done on Abbott c4000 (USA) and Abbott C1000 (USA) fully automatic analyzer. Data was analyzed using statistical 'software SPSS 16.1' (Chicago, IL). For all assessments, p<0.05 were considered statistically significant. Results: The expressions of candidate cytokines (TNF-α, IL-6, CRP, and WBC) were highly significant (p<0.001) in T2DM. Among inflammatory mediators, TNF-α shows a positive correlation (p<0.001) with glycemic profile and insulin sensitivity in T2DM cases in comparison with healthy normal. Biochemical (fasting sugar, HbA1c, insulin resistance, lipid profile) and anthropometric (BMI) parameters were highly significant (p<0.001) in T2DM cases as compared to non-diabetic normal. Conclusion: Low grade inflammation and up regulation of inflammatory mediators has been purported to play a significant role in pathogenesis of T2DM. Our findings confirm that positive correlation of TNF-α and IL-6 with T2DM and insulin sensitivity. These can act as early prediction biomarkers of T2DM. Further studies on wider range of pro and anti- inflammatory cytokines i.e. mediators, in association with other biochemical, immunoassay and hematological parameters are needed to help clinicians manage and treat T2DM effectively.

Sheehan's syndrome presenting as psychosis: a rare clinical presentation.

Sheehan's syndrome (SS) refers to the occurrence of varying degree of hypopituitarism after parturition (1). It is a rare cause of hypopituitarism in developed countries owing to advances in obstetric care and its frequency is decreasing worldwide. However, it is still frequent in underdeveloped and developing countries. Sheehan's syndrome is often diagnosed late as it evolves slowly (2,3). Reports of psychoses in patients with Sheehan's syndrome are rare. Herein, a case report of psychosis in a 31 year old woman who developed Sheehan's syndrome preceded by postpartum haemorrhage is presented. Treatment with thyroxine and glucocorticoids resulted in complete remission after attaining euthyroid and eucortisolemic state.

A case report on bronchoalveolar carcinoma presenting as non-resolving consolidation.

Bronchoalveolar carcinoma presenting as non-resolving consolidation is an uncommon presentation. The typical presentation of bronchoalveolar carcinoma is asymptomatic (solitary nodule) and remains without symptoms even as disease disseminates. We report a case of bronchoalveolar carcinoma presenting as non-resolving consolidation in a young male with productive cough, exertional breathlessness and physical examination revealing the features of right lower consolidation on x-ray chest, with subsequent CT of the chest and bronchoscopic examination revealed bronchoalveolar carcinoma. Patient had a good score and was managed conservatively.

Comparison of hematological parameters in untreated and treated subclinical hypothyroidism and primary hypothyroidism patients.

BACKGROUNDS: Thyroid hormones play an important physiological role in human metabolism. Erythrocyte abnormalities are frequently associated with thyroid disorder. However, they are rarely investigated and related to the subclinical and primary hypothyroidism in Kashmiri Patients. In this study an attempt was made to study hematological parameters in untreated and treated subclinical hypothyroidism and primary hypothyroidism patients. METHODS: This retrospective study included 600 subjects, among which were untreated subclinical hypothyroid (n=110), treated subclinical hypothyroid (n=110), untreated primary hypothyroid (n=100), treated primary hypothyroid (n=100) and euthyroid (n=180). This study was carried out at Department of Biochemistry, Government Medical College Srinagar. The hematological parameters and thyroid profile of the subjects were assessed by the Sysmex (Italy) and ECLIA (Germany) 2010 automatic analyzer. Mean, standard deviation (SD), analysis of variance (Two-way ANOVA), and multiple comparisons were used to report our results, with p<0.05 or p<0.01 considered as statistically significant. RESULTS: In this study group we compared the hematological parameters in these groups, untreated subclinical hypothyroid, treated subclinical hypothyroid, untreated primary hypothyroid, treated primary hypothyroid and euthyroid. We found that hematological parameters like Hb, RBC, MCV, HCT, RDW,RBC% were significantly increased in untreated subclinical hypothyroidism and untreated primary hypothyroidsm, with the p value being less than 0.05 whereas, in treated SCH & Pr. Hypothyroid, results were insignificant. The results reported in these groups as mean±SD, were statistically tested by ANOVA and multiple comparison tests. In untreated subclinical hypothyroid the values were: Hb (10.83±1.33 g/dl), RBC (4.21±0.66 10(6)/µl), MCV (84.56±6.84 fL), HCT (38.5±2.2%), RDW (17.91±2.37 fL), RBC% (84.36±13.2%) and in untreated primary hypothyroid, Hb (10.73±0.86 g/dl), RBC (4.63±0.51 10(6)/µl), MCV (83.34±6.92 fL), HCT (38.6±2.6%), RDW (14.93±5.47 fL), RBC% (92.63±10.30%) suggesting that these patients were at risk of anemia and other erythrocyte abnormalities. MCV is an inexpensive approach to study the types of anemia and explore related information like production, destruction, loss and morphological changes of RBC'S. CONCLUSION: The thyroid dysfunction is frequently associated with anemia in subclinical hypothyroidism and primary hypothyroidism. Subclinical hypothyroidism (SCH) is associated with serious complications. Substantial numbers of patients with the risk of SCH could be getting converted into primary hypothyroidism. Such conditions should be identified and corrected. On the other hand, their presence could move to a thyroid dysfunction, allowing its early management.

Inter-relationship of Pro- and Anti- inflammatory Biomarkers with the development of Type 2 Diabetes Mellitus.

Purpose: There has been growing evidence that inflammatory markers play a role in the development as well as severity of Type 2 diabetes mellitus (T2DM). This study has been designed to decipher the involvement of C-Reactive Protein (CRP), Tumor Necrosis Factor (TNFα), Interleukin-6 (IL-6) and Interleukin-10 (IL-10) in the etiopathogenesis of T2DM. Basic procedures: A total of 480 T2DM cases and 540 healthy controls were recruited for the study. Blood samples were collected from each study subject to measure the serum levels of CRP, TNFα, IL-6 and IL-10. Main findings: We found that serum levels of CRP in mg/dl (4.2 ± 0.9), TNFα in pg/ml (34.5 ± 8.8), IL-6 in pg/ml (19.2 ± 7.2) in T2DM patients were significantly high as compared to control participants (CRP; 1.4 ± 0.6, TNFα; 12.7 ± 3.4, IL-6; 3.1 ± 1.4; P < 0.0001). The serum levels of IL-10 in pg/ml were lower in T2DM cases compared to controls (4.35 ± 1.2 vs. 9.6 ± 1.2). In addition, we observed a significant association of CRP levels with insulin resistance, obesity and dyslipidemia. Increased TNFα levels were strongly associated with female gender, Poor glycemic control and strong family history of diabetes. Poor glycemic control was significantly associated with elevated IL-6 levels. Moreover, significantly reduced IL-10 levels were found in T2DM patients with sedentary lifestyle; low educational and rural background. Conclusions: This study showed a strong relationship between TNFα, IL-6, CRP, IL-10 and T2DM patients of Kashmiri ethnicity, treated at SMHS Hospital. Thus, supporting other studies and showing that cytokines may be good markers for T2DM development.

AT-rich Interaction Domain 1A Gene Variations: Genetic Associations and Susceptibility to Gastric Cancer Risk.

AT-rich interaction domain containing protein 1A (ARID1A), has recently emerged as a novel class of gene which acts as a potent tumor suppressor in numerous types of cancers such as Gastric, Breast, Ovarian, Colorectal, Lung cancers. ARID1A is involved in the regulation of various cellular processes such as proliferation, differentiation and DNA repair, yet its association with the susceptibility of cancer remains unknown. Here, we aimed to analyse the association of the ARID1A variants (Pro912Thr, Gln944Lys and Gln920Ter) with the risk of Gastric cancer (GC) in Kashmiri population. The study included 103 confirmed cases of GC and 163 normal controls. The genotypes were studied using Polymerase Chain Reaction. Different bioinformatic predictive tools were also used to analyse the possible effect of these SNP's on the resultant protein. The Pro912Thr and Gln920Ter variants of ARID1A showed significant difference in genotypic and allelic frequencies between the GC cases and controls (P < 0.05), whereas, the data did not reveal any correlation between Gln944Lys variant and Gastric cancer risk. Both Pro912Thr and Gln920Ter SNP's follow "Dominant mode of inheritance". In Silico analysis predicted that amino acid substitution of Pro912Thr SNP decreases the protein stability thus changing the functional properties of resultant protein, so backing the possibility of damaging effect of this SNP. Our study suggests that Pro912Thr and Gln920Ter SNP's of ARD1A gene are associated with increased risk of GC in Kashmiri population.

Polymorphism of the XRCC3 gene and risk of gastric cancer in a Kashmiri population: a case-control study.

DNA repair plays a critical role in protecting the genome of the cell from the insults of cancer-causing agents. Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with the risk of developing cancer. Inherited polymorphisms of DNA repair genes may contribute to variations in DNA repair capacity and genetic susceptibility to different cancers. The X-ray repair complementing defective repair in Chinese hamster cells 3 (XRCC3) gene is a member of the RAD51 gene family. It encodes an important protein that functions in the homologous recombination repair of a DNA double-strand break. For gastric cancer, the importance of mutations in mismatch repair genes has been well documented, but less is known about other DNA repair pathways in gastric carcinogenesis. In this study, we have focused on the XRCC3 gene, involved in homologous recombinational repair. The Kashmir valley has an increased incidence of gastric cancer and its etiology has not been understood fully as yet. As the Kashmiri population is ethnically and demographically different from that in other parts of the world, the aim of this study was to determine whether a single nucleotide polymorphism of the XRCC3 gene (Thr241Met) of exon 7 can influence the risk of gastric cancer in the population. As many as 80 histopathologically confirmed gastric cancer cases and 70 healthy controls, age, sex, and ethnicity matched for known genotypes of XRCC3 exon 7 were studied. We genotyped for this variant using PCR-restriction fragment length polymorphisms. The XRCC3 genotype and allele frequencies were not significantly different between cases and controls (P=0.92 for the genotype; P=0.72 for the allele). The XRCC3 241Met allele frequency (6.6%) was significantly lower in healthy Kashmiri controls than reported previously in healthy US White controls (38.9%). Compared with the XRCC3 241Thr/Thr genotype, the variant XRCC3 241Thr/Met and Met/Met genotypes were not associated with an increased risk of gastric cancer (adjusted odds ratio=1.19; 95% confidence interval=0.44-3.18). These findings suggest that polymorphisms of XRCC3 Thr241Met may not play a role in the etiology of gastric cancer. Further studies with a larger number of participants and simultaneous measurement of different polymorphisms in DNA repair genes in the same pathway are needed.

Increased prevalence of subclinical hypothyroidism in females in mountainous valley of Kashmir.

BACKGROUND: Iodine-rich diet is necessary for proper thyroid gland function. Subclinical hypothyroidism (SCH) is associated with serious complications. Substantial numbers of patients have risk of SCH getting converted into primary hypothyroidism. OBJECTIVES: The objectives of the present study are to survey dietary iodine intake pattern in ethnic population of Kashmir and to study the prevalence of SCH. MATERIALS AND METHODS: A retrospective, cross-sectional referral hospital study was conducted. Sample size comprised of 2550 patients who were referred to Department of Biochemistry, Government Medical college, Srinagar diagnostic laboratory from OPD and IPD of associated SMHS hospital. Assessment of thyroid function over a period of one year from March 2010 to March 2011 in the serum has been performed by electro-chemiluminescence immunoassay method on ECLIA 2010 fully automatic analyzer. Interview cum questionnaire methods were used to record the patient history and dietary iodine intake pattern. Iodine status of these patients was assessed by measuring urinary iodine excretion. RESULTS: Total patients were 2550 comprising of 44.6% males and 56.4% females. Subjects with elevated and normal thyroid stimulating hormone (TSH) levels in the serum were 30.51 and 69.4% respectively. About 550 patients (21.56%) had subclinical hypothyroidism which includes both males and females. Prevalence of SCH was more in females (81.8%) than in males (18.2%). Most of the patients presenting with SCH were in the age group of 20-65 years. CONCLUSION: The percentage of SCH amongst the study sample patients was 21.56%, which is much higher as compared to other parts of the world. The highest percentage of SCH was found in females (81.8%) as compared to males (18.2%). On the basis of the present study, we suggest that routine screening of selected populations, especially women between 20 and 65 years of age, may be advocated. Further community level awareness programs need to be organized wherein people in mountainous valley of Kashmir are motivated to take salt in iodized form and diet rich in iodine to ensure proper thyroid gland functioning.

Fahr's Disease Presenting as Mania: A Case Report.

Fahr's disease is a rare syndrome characterized by symmetrical and bilateral intracranial calcifications. We report a 21-year-old male who presented with aggression, talkativeness, restlessness, and insomnia of recent onset. His neurological examination was normal. Mental status examination and clinical investigation revealed mania. Brain revealed symmetrical large areas and foci of calcification in bilateral basal ganglia and subcortical regions of cerebral hemispheres. This is the first reported case of mania associated with Fahr's disease in a Kashmiri patient. The description highlights the importance of considering organic causes when encountering patients with mania. The patient was put on mood stabilizers and his abnormal behaviors improved within 4 weeks.