Search

Background and Objectives: We aimed to analyze the impact of prestorage Inline leukodepletion and storage time on interleukin 8 (IL-8) levels in stored buffy coat-depleted packed red blood cell (PRBC) units in the Kashmiri population setting. Methods: A total of 50 donors of Kashmiri origin from North India equally and randomly distributed between Leukodepleted (LD) and non-LD (NLD) arms were recruited in this study. Leukodepletion of PRBCs units was performed using 3rd Generation integrated LD filters and the residual white blood cell (WBC) count was enumerated by FACS using fluorochrome-tagged CD45+ antibodies and IL-8 levels measured by ELISA. Results: In contrast to NLD arm, leukodepletion in the LD arm significantly reduced total leukocyte count (TLC) from pre-LD TLC of 2.25 ± 0.47 x 109/PRBC unit to post LD cell count of 2.40 ± 0.65 x 106/PRBC unit, P = 0.001, i.e., 3 log reduction, P = 0.0001. Contrary to the LD arm, a significant difference in IL-8 levels in NLD arm was observed with 27.15 ± 30.32 pg/mL on day 0, 45.15 ± 36.15 pg/mL on day 14, and on day 28, 37.98 ± 33.05 pg/mL. Furthermore, significant variance (LD vs. NLD) in IL-8 levels was observed at day 0, 14th, and 28th day of storage, with maximum variance observed on day 14th Fstat = 21.46, P = 0.00, depicting prestorage LD have a significant role in suppressing the IL-8 levels in LD stored PRBC units while as in NLD PRBC units with time IL-8 accumulated as its cell source (WBCs) was intact. Conclusion: Inline prestorage leukodepletion by 3rd generation LD filters was uniformly effective in reducing the residual WBC count to desired levels of <5 x 106/unit of PRBC. The significant decrease in TLC and resultant far less accumulation of cytokine (IL-8) in prestorage LD PRBC units of Kashmiri origin, as observed in this study, would be translated into clinical benefits associated with transfusion of LD-PRBC units. [ABSTRACT FROM AUTHOR]

Abstract The development and progression of colorectal cancer (CRC) is a multi-step process, and the Wnt pathways with its two molecular gladiators adenomatous polyposis coli (APC) and β-catenin plays an important role in transforming a normal tissue into a malignant one. In this study, we aimed to investigate the role of aberrations in the APC and β-catenin genes in the pathogenesis of CRC in the Kashmir valley, and to correlate it with various clinicopathological variables. We examined the paired tumour and normal-tissue specimens of 86 CRC patients for the occurrence of aberrations in the mutation cluster region (MCR) of the APC gene and exon 3 of the β-catenin gene by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and/or PCR-direct sequencing. Analysis of promoter hypermethylation of the APC gene was also carried out using methylation-specific PCR (MS-PCR). The overall mutation rate of the MCR of the APC gene among 86 CRC cases was 12.8 per cent (11 of 86). Promoter hypermethylation of APC was observed in 54.65 per cent (47 of 86) of cases. Furthermore, we found a significant association between tumour location, tumour grade and node status and the methylation status of the APC gene (p ≤ 0.05). Although the number of mutations in the APC and β-catenin genes in our CRC cases was very low, the study confirms the role of epigenetic gene silencing of the pivotal molecular gladiator, APC, of the Wnt pathway in the development of CRC in the Kashmiri population.

Background/Aim: Colorectal cancer (CRC) is one of the leading malignancies worldwide and has been reported to show geographical variation in its incidence, even within areas of ethnic homogeneity. The aim of this study was to identify p53 and K-ras gene mutations in CRC patients in a Kashmiri population, and to assess whether these mutations are linked with clinicopathological parameters. Materials and Methods: Paired tumor and normal tissue samples from a consecutive series of 53 patients undergoing resective surgery for CRC were prospectively studied for p53 and K-ras gene mutations by PCR/single strand conformation polymorphism (SSCP). Results: Less than half (45%, 19/42) of the patients presented mutations in the p53 gene. Twenty eight mutations were found in the p53 gene, which comprised of 23 substitutions (17 transitions + 6 transversions), and five insertions. The 23 substitutions constituted 18 missense mutations, two nonsense mutations, and three silent mutations. Of the 28 mutations (7.14%) observed in this study, 2 were not previously reported for CRC samples and were identified as novel p53 mutations. A few patients (22.64%, 12/53) presented with mutations in K-ras, constituting 13 missense mutations, out of which 11 were G→A transitions, one was a G→C transversion, and one a G→T transversion. More than half (61.5%) of the mutations occurred in codon 12 whereas a few (38.5%) occurred in codon 13. One tumor contained missense mutations in both codons. Comparison of the mutation profiles of our patients with those of other ethnic populations and regions reflected both differences and similarities, indicating co-exposure to a unique set of risk factors. Conclusion: Mutations of the p53 and K-ras genes are some of the most common genetic changes in the development of human CRC. The high frequency of p53 gene mutations implicates p53 as a predominant factor for CRC in the high-risk ethnic Kashmiri population.

Objective: Patients with Sheehan syndrome (SS) are predisposed to coronary artery disease (CAD) due to risk factors like abdominal obesity, dyslipidemia and chronic inflammation. In addition to estimate CAD risk enhancers like high sensitive C reactive protein (hsCRP), apolipoprotein B (ApoB) and lipoprotein A [Lp(a)], this study applies Framingham risk score (FRS) and coronary artery calcium (CAC) score to compute a 10‐year probability of cardiovascular (CV) events in SS patients. Design: Case–control study Sixty‐three SS patients, on a stable hormonal replacement treatment except for growth hormone and 65 age, body mass index and parity‐matched controls. Measurements: Measurement of serum hsCRP, ApoB and Lp(a) and estimation of CAC with 16‐row multislice computed tomography scanner. Results: The concentrations of hsCRP, ApoB and Lp(a) were significantly higher in SS patients than in controls (p <.01). After calculating FRS, 95.2% of SS patients were classified as low risk, 4.8% as intermediate risk and all controls were classified as low risk for probable CV events. CAC was detected in 50.7% SS patients and 7.6% controls (p =.006). According to the CAC score, 26.9% SS patients were classified as at risk (CAC > 10) for incident CV events as against 1.6% controls. The mean Multi‐Ethnic Study of Atherosclerosis (MESA) score was significantly higher in patients with SS than controls. CAC corelated significantly with fasting blood glucose (r =.316), ApoB (r =.549), LP(a) (r =.310) and FRS (r =.294). Conclusion: Significant number of asymptomatic SS patients have high coronary artery calcium score and are classified at risk for CAD. [ABSTRACT FROM AUTHOR]

Background: This study was aimed at determining the frequency of thyroid autoimmunity and subclinical hypothyroidism in patients with hyperprolactinemia due to prolactinoma compared to well-matched healthy controls. Methods: This was a cross-sectional study wherein 78 treatment naïve prolactinoma patients and ninety-two healthy control subjects were recruited. Serum prolactin (PRL), thyroid-stimulating hormone (TSH), total thyroxine (T4), circulating anti-thyroid peroxidase (anti-TPO), and anti-thyroglobulin (anti-Tg) antibody levels were measured in all study subjects. Progression of the antibody-positive population to subclinical hypothyroidism was determined. Results: The median PRL level among patients was 166 ng/ml (IQR 85-467) compared to 11.4 ng/ml (IQR 8.5-15.9) in controls (P < 0.001). There was no significant difference in levels of T4 (P = 0.83) and TSH (P = 0.82) between the cases and controls. Overall, 25% of patients had the presence of anti-thyroid antibodies as compared to 20% of controls (P = 0.56). SCH was more common in antibody-positive hyperprolactinemia subjects compared with antibody-positive controls. Conclusion: We did not find an increased prevalence of thyroid autoimmunity among untreated prolactinoma patients compared to healthy controls. At the same time, subclinical hypothyroidism was more common in thyroid antibody-positive patients with hyperprolactinemia than positive controls. [ABSTRACT FROM AUTHOR]

Transforming growth factor‐β (TGF‐β) is a proinflammatory cytokine known to control a diverse array of pathological and physiological conditions during normal development and tumorigenesis. TGF‐β‐mediated physiological effects are heterogeneous and vary among different types of cells and environmental conditions. TGF‐β serves as an antiproliferative agent and inhibits tumor development during primary stages of tumor progression; however, during the later stages, it encourages tumor development and mediates metastatic progression and chemoresistance. The fundamental elements of TGF‐β signaling have been divulged more than a decade ago; however, the process by which the signals are relayed from cell surface to nucleus is very complex with additional layers added in tumor cell niches. Although the intricate understanding of TGF‐β‐mediated signaling pathways and their regulation are still evolving, we tried to make an attempt to summarize the TGF‐β‐mediated SMAD‐dependent andSMAD‐independent pathways. This manuscript emphasizes the functions of TGF‐β as a metastatic promoter and tumor suppressor during the later and initial phases of tumor progression respectively. [ABSTRACT FROM AUTHOR]

Abstract Background The development and progression of colorectal cancer has been extensively studied and the genes responsible have been well characterized. However the correlation between the SMAD4 gene mutations with KRAS mutant status has not been explored by many studies so far. Here, in this study we aimed to investigate the role of SMAD4 gene aberrations in the pathogenesis of CRC in Kashmir valley and to correlate it with various clinicopathological variables and KRAS mutant genotype. Methods We examined the paired tumor and normal tissue specimens of 86 CRC patients for the occurrence of aberrations in MCR region of SMAD4 and exon 1 of KRAS by PCR-SSCP and/or PCR-Direct sequencing. Results The overall mutation rate of mutation cluster region (MCR) region of SMAD4 gene among 86 patients was 18.6% (16 of 86). 68.75% (11/16) of the SMAD4 gene mutants were found to have mutations in KRAS gene as well. The association between the KRAS mutant genotype with SMAD4 mutants was found to be significant (P =< 0.05). Further more, we found a significant association of tumor location, tumor grade, node status, occupational exposure to pesticides and bleeding PR/Constipation with the mutation status of the SMAD4 gene (P =< 0.05). Conclusion Our study suggests that SMAD4 gene aberrations are the common event in CRC development but play a differential role in the progression of CRC in higher tumor grade (C+D) and its association with the KRAS mutant status suggest that these two molecules together are responsible for the progression of the tumor to higher/advanced stage.

Aim: Data about polymorphism in tumor necrosis factor alpha (TNF-α) and its serum levels in chronic obstructive pulmonary disease (COPD) are conflicting. We aimed to evaluate the association of TNF-α 308 G > A polymorphism in patients with COPD in Kashmir (North India), a high burden area and also determined the serum TNF-αlevels in these patients. Materials and Methods: One hundred spirometrically confirmed COPD patients and 163 controls resident from Kashmir valley (North India) were recruited. Genotyping of the promoter region of TNF-α was carried out using polymerase chain reaction restriction fragment length polymorphism. The serum TNF-αwas quantified using the Cytometric Bead Array flex system by flow cytometry. Results were subjected to appropriate statistical treatment and P < 0.05 was considered statistically significant. Results: Ninety one COPD patients (91%) had G/G (wild homozygous) genotype and nine patients (9%) had G/A (heterozygous) genotype. Among the control population, 150 (92%) had G/G genotype and 13 (8%) had G/A genotype. The variant allele "A" was not detected in either of the two groups. Serum levels of TNF- αwere significantly higher in patients compared to control group (8.0 ± 10.1 pg/ml vs. 3.3 ± 0.42 pg/ml, respectively, P = 0.0001). Conclusion: While serum levels of TNF-α are higher in COPD patients compared to the controls, there was no difference in the prevalence of TNF-α 308 polymorphism in the ethnic Kashmiri population with COPD. [ABSTRACT FROM AUTHOR]

Byline: Roohi. Rasool, Irfan. Shera, Saniya. Nissar, Zaffar. Shah, Niyaz. Nayak, Mushtaq. Siddiqi, Aga. Sameer Background: Skin prick test (SPT) is the most effective diagnostic test to detect IgE mediated [...]

Byline: Shakeel. Rehman, A. Sameer, Lubna. Zahoor, Nidda. Syeed, Mahoor. Nanda, Adil. Hafiz, Zaffar. Shah, Mushtaq. Siddiqi Kangri cancer is a unique thermally-induced squamous cell carcinoma (SCC) of skin that [...]

The study was initiated at Entomological Research Institute, Ayub Agricultural Research Institute, Faisalabad, to determine the impact of weather factors in population fluctuation of spotted bollworm Earias sp (E. vittella F and E. insulana B) during 2009 to 2011. On each spot three pheromone traps each ten meters apart were installed in cotton-wheat growing area of Bahawalpur. The data on trapped population of spotted bollworm were recorded fortnightly. The population of the pest remained present throughout the study years. However, the highest peaks were recorded on 10.11.2009 (14.98/trap), on 5.11.2010 (33.22/trap) and on 2.8.2011 (5.60/trap) with maximum, minimum, average temperatures and RH of 32.73°C, 13.00oC, 23.78°C and 66%; 32.47°C, 16.00°C, 24.24°C and 75% and 4.53°C, 26.27°C, 33.40°C and 79.27%, respectively. None of the weather factors showed significant correlation with the pest for individual year and on cumulative basis. Maximum temperature during 2009, relative humidity during 2010, minimum temperature during 2011 and relative humidity on cumulative basis were important resulted in maximum impact i.e. 8.1, 13.9, 15.9 and 7.0 %, respectively in population fluctuation of the pest. [ABSTRACT FROM AUTHOR]

Introduction: Pregnant women represent a typical group susceptible to dietary and mineral deficiencies. This study was sought to assess the efficacy and safety of various doses of 25-hydroxyvitamin D (25[OH]D) supplementation during pregnancy and ratify the inadequacy of the recommended daily allowance for Vitamin D in vulnerable groups. Materials and Methods: A total of 100 pregnant women were included in this open-label, parallel group, prospective, randomized, and controlled trial. Study subjects were assigned to four treatment groups: Group 1 (n = 26), 1000 IU of Vitamin D daily; Group 2 (n = 21), 30,000 IU of Vitamin D monthly; Group 3 (n = 27), 2000 IU of Vitamin D daily; and Group 4 (n = 26), 60,000 IU Vitamin D monthly. Group 1 and 2 were further analyzed together as Group 1K (1000 IU daily and 30,000 IU monthly), and Group 3 and 4 as Group 2K (2000 IU daily and 60,000 IU monthly). The analysis was done on an intention to treat basis. Results: A total of 87 patients completed the study; 21 in Group 1, 25 in Group 2, 18 in Group 3, and 23 in Group 4. The levels of 25(OH)D at baseline ranged from 1.3 to 58.0 with a mean of 24.2 ± 15.1 ng/ml. Postsupplementation, 25(OH)D levels ranged from 11.5 to 70.3 with a mean of 40.2 ± 12.2 ng/ml. The postsupplementation levels of 25(OH)D were higher in Group 2K (42.86 ± 12.83) than in Group 1K (36.96 ± 10.56) with P value of 0.023. Conclusion: We concluded that Vitamin D supplementation with 2000 IU/day or 60,000 IU/month is very effective and safe in achieving Vitamin D sufficiency in pregnant women. [ABSTRACT FROM AUTHOR]

Introduction: Though hypoadiponectinemia and leptin resistance have been proposed as potential factors for weight gain in patients with hyperprolactinemia (HPL), the effects of HPL and cabergoline on these adipocyte-derived hormones are not clear. Aims of this study were (i) to assess the alterations of body fat, leptin, and adiponectin in patients with HPL (ii) effect of cabergoline treatment on these parameters. Methods: Nineteen consecutive patients with prolactinoma (median prolactin [PRL] 118.6 (interquartile range: 105.3) µg/L) and 20 controls were studied in a nonrandomized matched prospective design. The controls were age, gender, and body mass index (BMI) matched. Anthropometric data, metabolic variables, leptin, and adiponectin were studied at baseline and 3 and 6 months after cabergoline treatment. Results: Patients with prolactinoma had increased level of fasting plasma glucose (P < 0.001) as compared to age-, gender-, and BMI-matched healthy controls. Estradiol concentration of controls was higher than that of patients (P = 0.018). Patients with prolactinoma had higher levels of leptin (P = 0.027) as compared to healthy controls without a significant difference in adiponectin levels. There was a significant decrease of body weight at 3 months (P = 0.029), with a further decline at 6 months (P < 0.001) of cabergoline therapy. Furthermore, there was a significant decrement of BMI (P < 0.001), waist circumference (P = 0.003), waist-hip ratio (P = 0.03), total body fat (P = 0.003), plasma glucose (P < 0.001), leptin levels (P = 0.013), and an increase in estradiol concentration (P = 0.03) at 6 months of cabergoline treatment. Conclusion: Patients with prolactinoma have adverse metabolic profile compared to matched controls. Normalization of PRL with cabergoline corrects all the metabolic abnormalities. [ABSTRACT FROM AUTHOR]

Background: Whether Vitamin D supplementation in prediabetes subjects prevents the development of diabetes is a matter of debate, and the results are inconsistent. This open-label, randomized study in subjects with prediabetes evaluated the effect of 12 months of Vitamin D supplementation on glycemic parameters and progression of prediabetes to diabetes in an ethnically homogeneous Kashmiri population. Materials and Methods: A total of 147 subjects were diagnosed as prediabetes out of which 137 subjects were randomized to receive in addition to standard lifestyle measures, either Vitamin D 60,000 IU weekly for 4 weeks and then 60,000 IU monthly (n = 69) or no Vitamin D (n = 68). Fasting plasma glucose (FPG), 2-h plasma glucose and A1C levels were estimated at 0, 6 and 12 months. Changes in FPG, 2-h plasma glucose, A1C level and the proportion of subjects developing diabetes were assessed among 129 subjects. Results: At 12 months, A1C levels were significantly lesser (5.7% ± 0.4%) in the Vitamin D supplemented group when compared with non-Vitamin D supplemented (6.0% ± 0.3%). Similarly, FPG (97 ± 7) and 2-h plasma glucose (132 ± 16) were significantly less in Vitamin D supplemented group as compared with non-Vitamin D supplemented group (FPG = 116 ± 6 and 2-h plasma glucose = 157 ± 25) at 12 months. Nine out of 65 in non-Vitamin D supplemented and seven out of 64 in the Vitamin D supplemented group developed diabetes. Conclusions: Vitamin D supplementation in prediabetes subjects significantly lowered FPG, 2-h plasma glucose and A1C levels. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is characterized by an interaction of various environmental influences especially cigarette smoking and genetic determinants. The prevalence of this disease is ever increasing and characterization of the genetic determinants of the disease has been undertaken globally. The 'A disintegrin and metalloprotease 33' (ADAM 33) gene is one candidate gene that has been studied. Objective: Our objective was to investigate whether single nucleotide polymorphisms in ADAM33 gene are associated with COPD in long-term tobacco smokers in the ethnic Kashmiri population of northern India. Materials and Methods: This was a randomized case-control study, which included 78 stable COPD (GOLD stage11-IV) patients, who were compared with 77 age- and sex-matched long-term tobacco smokers (>20 pack years) without any evidence of COPD. Polymorphic analysis for three single nucleotide polymorphisms (SNPs), (T1, T2, and Q1) of the ADAM33 gene was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by sequencing. The data were analyzed by descriptive statistics and comparative evaluation was done by parametric/ non-parametric tests. Results: The analysis of the T1, T2, and Q1 SNPs, revealed that the frequencies of the T2GG, T1GG, and the Q1AG genotypes were significantly higher in patients with COPD in comparison with the controls (P < 0.001). Similarly, the T1G and T2G allele frequency was higher in the patients than in the controls (p=0.177 and 0.43, respectively). Conclusion: Three SNPs of the ADAM33 gene were significantly associated with COPD in the Kashmiri population of India. This study establishes the possible role of ADAM33 SNPS in the causation of COPD. Further studies across different geographical areas in the country will unravel the contribution of this gene in the causation of COPD in India. [ABSTRACT FROM AUTHOR]