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Sepsis is associated with global cardiac dysfunction and with high mortality rate. The development of septic cardiomyopathy is due to complex interactions of damage-associated molecular patters, cytokines, and complement activation products. The aim of this study was to define the effects of sepsis on cardiac structure, gap junction, and tight junction (TJ) proteins. Sepsis was induced by cecal ligation and puncture in male C57BL/6 mice. After a period of 24 h, the expression of cardiac structure, gap junction, and TJ proteins was determined. Murine HL-1 cells were stimulated with LPS, and mRNA expression of cardiac structure and gap junction proteins, intracellular reactive oxygen species, and troponin I release was analyzed. Furthermore, pyrogenic receptor subtype 7 (P2X7) expression and troponin I release of human cardiomyocytes (iPS) were determined after LPS exposure. In vivo, protein expression of connexin43 and α-actinin was decreased after the onset of polymicrobial sepsis, whereas in HL-1 cells, mRNA expression of connexin43, α-actinin, and desmin was increased in the presence of LPS. Expression of TJ proteins was not affected in vivo during sepsis. Although the presence of LPS and nigericin resulted in a significant troponin I release from HL-1 cells. Sepsis affected cardiac structure and gap junction proteins in mice, potentially contributing to compromised cardiac function.

Objective: st th To evaluate the thyroid prole(T4,FT4 and TSH) in term and preterm neonates at 1 week after birth and during follow up at 4 week. Material and Method: This prospective observational hospital based study was conducted with 30 term(>37 completed week) and 30 preterm neonates(from 28 to 36 week 6days) with exclusion criteria of maternal thyroid disease or neonates with co-morbidity or signicant congenital st th anomalies. Serum T4,FT4 and TSH level were measured at 1 week and 4 week of postnatal age and results are analysed statistically. Results: st th We found TSH was elevated more in preterm than in term neonates in the 1 week, which decreased in both the groups at the 4 week . T4 st th and FT4 were signicantly higher in the term neonates than in preterm in the 1 week. During follow up in the 4 week, T4 and FT4 decreases in st term and increases in preterm so that the FT4 level almost matches in both the group at the end of 1 month. Conclusion: Our study shows that T4, FT4 and TSH has a signicant relationship with gestational age. Premature infants are born with higher th levels of TSH and lower levels of FT4 and T4 than term, which almost normalizes at 4 week.

The humoral serine proteases of the complement system and the coagulation system play central roles during the events of an inflammatory response. While the complement system confers immunoprotective and -regulatory functions, the coagulation cascade is responsible to ensure hemostatic maintenance. Although these two systems individually unfold during inflammation, several studies have reported on the “crosstalk” between components of the complement and the coagulation system in the fluid phase. However, both cascades are usually initiated on or in close proximity to foreign or activated surfaces, and there is increasing evidence for interacting complement and coagulation proteins on various superficial areas on endothelium, circulating entities like platelets, leukocytes, microparticles and pathogens, and even on artificial surfaces. This review aims at summarizing these interactions to complete the picture.

Dysfunction of the gut-blood barrier plays an important role in many diseases, such as inflammatory bowel disease, hemorrhagic shock (HS), or burn injury. However, little is known about gut barrier dysfunction after hemodynamically instable polytrauma (PT). Therefore, we aimed to evaluate the effects of PT and HS on remote intestinal damage and barrier dysfunction, especially regarding the role of zonula occludens protein 1 (ZO-1) as an important tight junction protein.Male C57BL/6 mice were subjected to either PT (thorax trauma, closed head injury, soft tissue injury, and distal femoral fracture), 60 min of pressure-controlled HS (30 ± 5 mmHg), or PT+HS, or sham procedures.Animals of all trauma groups showed an increase in abdominal girth and dilation of the intestine during the experimental period, which was largest in the PT+HS group. Increased blood-tissue permeability to albumin (assessed by Evans blue dye) was found in the HS group. Experimental groups showed a slight increase in plasma concentration of intestinal fatty acid binding protein and some intestinal damage was histologically detectable. Of note, PT+HS animals revealed significantly reduced expression of ZO-1 in intestinal epithelial cells. In an in-vitro model, stimulation of human colon epithelial cells with peptidoglycan, but not with lipopolysaccharide, resulted in elevated secretion of pro-inflammatory cytokines, reflecting inflammatory activity of the intestinal epithelium.Taken together, PT and HS lead to increased permeability of the gut-blood barrier. Bacterial components may lead to production of inflammatory and chemotactic mediators by gut epithelial cells, underlining the role of the gut as an immunologically active organ.

The established paradigm of stress axis is not only borne by the hypothalamic-pituitary-adrenal (HPA) axis. There are various “fine-tuners” in the form of neuromodulators whose intricate functioning is under active investigation. Two such neuromodulators, namely nociceptin and orexin are interesting candidates to further evaluate their respective roles and possible cross-talk in due course of stress. In addition, apart from this outlook toward stress, immune stress is also perceived as an impending threat to the physiology and probably implicates the HPA axis in ways that we fail to comprehend with our current crux of knowledge. Sepsis or system inflammatory response syndrome is an exemplary of such an immune stress where the role of the HPA axis has been evidentially supported. An interesting question which arises is how would neurologically perceived stress and sepsis be guided by various neuromodulators. The scope of this review is to evaluate the existing literature where we look at the role of nociceptin and orexin in guiding the complex etiology of stress and sepsis, respectively. Extensive review has suggested, there also might be a hypothetical “cross-talk” between nociceptin and orexin, though this again has to be supported by further investigations.