Alterations in intestinal permeability and endotoxemia in severe acute pancreatitis.

Background: Intestinal permeability increases early in the course of acute pancreatitis and is associated with sepsis and organ failure. Aim: To evaluate the intestinal permeability (IP) and anti-endotoxin antibodies immunoglobulin G and A (AEA IgG and A) in severe acute pancreatitis (SAP) as compared to healthy controls and determine their significance in relation to various complications of SAP. Methods: IP was measured by urinary lactulose/mannitol (LM) excretion ratio and antiendotoxin antibodies by Endocab ELISA kit at days one and seven of admission (D1 and D7). Results: Thirty one patients of SAP [mean age (42.0±15.8) years, APACHE II scores (8.8±5.4) and CT severity index (6.4±2.0)] were included in this study. Infected pancreatic necrosis was detected in 13 (42%) patients of whom three died. Six died of persistent organ failure. Median values of LM ratio at D1 and D7 were similar to those in healthy controls. Patients experiencing complications [organ failure (4/9, 44%), infected pancreatic necrosis (5/10, 50%) and death (1/ 2, 50%)] manifested a substantial increase in their intestinal permeability at D7. Anti-endotoxin antibodies IgG were lower (p=0.003) in patients than the controls at admission. AEA IgG were lower (p=0.03) in non-survivors as compared to survivors at D7. Conclusion: Patients experiencing complications of severe acute pancreatitis showed an increase in intestinal permeability. Higher endotoxemia predicted poor outcome in severe acute pancreatitis.

Analysis of single nucleotide polymorphisms of CRYGA and CRYGB genes in control population of western Indian origin.

Aim: Polymorphisms in gamma-crystallins ( CRYG ) can serve as markers for lens differentiation and eye disorders leading to cataract. Several investigators have reported the presence of sequence variations within crystallin genes, with or without apparent effects on the function of the proteins both in mice and humans. Delineation of these polymorphic sites may explain the differences observed in the susceptibility to cataract observed among various ethnic groups. An easier Restriction Fragment Length Polymorphism (RFLP)-based method has been used to detect the frequency of four single nucleotide polymorphisms (SNPs) in CRYGA / CRYGB genes in control subjects of western Indian origin. Materials and Methods: A total of 137 healthy volunteers from western India were studied. Examination was performed to exclude volunteers with any ocular defects. Polymerase chain reaction (PCR)-RFLP based method was developed for genotyping of G198A (Intron A), T196C (Exon 3) of CRYGA and T47C (Promoter), G449T (Exon 2) of CRYGB genes. Results: The exonic SNPs in CRYGA and CRYGB were found to have an allele frequency 0.03 and 1.00 for ancestral allele respectively, while frequency of non-coding SNP in CRYGA was 0.72. Allele frequency of T90C of CRYGB varied significantly ( P = 0.02) among different age groups. An in-silico analysis reveals that this sequence variation in CRYGB promoter impacts the binding of two transcription factors, ACE2 (Member of CLB2 cluster) and Progesterone Receptor (PR) which may impact the expression of CRYGB gene. Conclusions: This study establishes baseline frequency data for four SNPs in CRYGA and CRYGB genes for future case control studies on the role of these SNPs in the genetic basis of cataract.

Correlation of circulatory immunoglobulin levels with Mu opiate receptor allele.

Opiates are known to induce immunosuppression in their users (addicts). Evidences supporting their role in suppressing a variety of immunological end points in addicts have been reported by several investigators. In the present study, we investigated the changes in serum immunoglobulin (Ig) levels and their correlation with Mu opiate receptor (MOR) genotypes. Eighty-seven users and forty-five non-users were recruited for the study. Genomic DNA, isolated from the peripheral blood, was used for genotyping for C17T and A118G polymorphism using PCR-RFLP method. The frequency of A and G alleles in non-users was 89% and 11% respectively, whereas in addicts, it was 67% and 33% respectively. Case control analysis between groups revealed that 118G allele was associated with opioid dependence [Chi square (chi2) = 13.56, odds ratio (OR) = 3.90, confidence interval 95% (CI 95%) = 1.80-8.67, p = 0.000231]. C17T polymorphism showed no association with opioid dependence [(chi2) = 0.9, OR = 2.49, CI 95% = 0.528-16.12, p = 0.343]. Mean Ig levels, both IgG (student's t-test = 2.2738, p = 0.007) and IgA (student's t-test = 2.848, p = 0.0051) differed between opiate users and nonusers. IgG and IgA levels were also significantly different in individuals with different MOR genotypes. Immunosuppression was observed in AA genotype-bearing individuals, while no suppression was seen in AG and GG genotypes bearing individuals. In case of C17T polymorphism, both CC and CT genotypes bearing individuals showed immunosuppression, as judged by circulating Ig levels.