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.

Opiate receptor (uOR) is expressed in central nervous system, gastrointestinal tract, male and female reproductive tissues, and immune cells. Morphine, a ligand for opioid receptor family, is known to activate the hypothalamic-pituitary-adrenal axis and release immunosuppressive glucocorticoids. Herein we present that minor changes, in the form of nonsynonymous single nucleotide polymorphisms, in μOR have cumulative impact on receptor-mediated signaling and functions of specific cell type(s). Significant reduction was seen in cells in M and S phases with coactivation of immune receptors with μOR. Flow cytometry-based experiments established a reduction in B and T lymphocytes, NK cells, and macrophages. Differences in types of immune cells were found to be significant to reduce immune response(s) mounted by GG(mutant allele)-bearing individuals. This is the first report on cross-talk between LPS-binding and μOR, explaining the reduction in the number of T and B cells after chronic opiate use and also the association of this impact on immunocytes with functional SNP, rs1799972/118G allele of OPRM1 gene as an explanation for the immune suppression in opiate users. Initially present lower cell titers can be further lowered by exogenous opiates and account for immunosuppression seen in chronic opiate users or after long-term treatment with opiate drugs for chronic pain.

Specimens of the anterior lens capsule with an attached monolayer of lens epithelial cells (LECs) were obtained from patients (n=52) undergoing cataract surgery. Specimens were divided into three groups based on the type of cataract: nuclear cataract, cortical cataract and posterior subcapsular cataract (PSC). Clear lenses (n=11) obtained from donor eyes were used as controls. Expression was studied by immunofluorescence, real-time PCR and Western blot. Statistical analysis was done using the student's t-test. Immunofluorescence results showed punctate localization of Cx43 at the cell boundaries in controls, nuclear cataract and PSC groups. In the cortical cataract group, cytoplasmic pools of Cx43 without any localization at the cell boundaries were observed. Real-time PCR results showed significant up-regulation of Cx43 in nuclear and cortical cataract groups. Western blot results revealed significant increase in protein levels of Cx43 and significant decrease of ZO-1 in all three cataract groups. Protein levels of alpha-catenin were decreased significantly in nuclear and cortical cataract group. There was no significant change in expression of beta-catenin in the cataractous groups. Our findings suggest that ZO-1 and alpha-catenin are important for gap junctions containing Cx43 in the LECs. Alterations in cell junction proteins may play a role during formation of different types of cataract.

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