Savaş Demirbilek

Small-Dose Capsaicin Reduces Systemic Inflammatory Responses in Septic Rats

We investigated the influence of small- and large-dose capsaicin in modulating systemic inflammatory responses during different stages of sepsis in rats. Rats were divided into six groups: group C, control; group S, sepsis; group CLC, small dose of capsaicin (1 mg/kg subcutaneously); group SLC, small dose of capsaicin plus sepsis; group CHC, large dose of capsaicin (150 mg/kg subcutaneously); group SHC, large dose of capsaicin plus sepsis. Rats were made septic by cecal ligation and puncture (CLP). Each group was subdivided into two subgroups. The animals were killed at 9 or 18 h after CLP. Plasma concentrations of calcitonin gene-related peptide (CGRP), tumor necrosis factor (TNF)-&agr;, interleukin (IL)-6, IL-10, and total nitrite/nitrate (NOx) were measured. Superoxide dismutase and malondialdehyde (MDA) were determined in liver, lung, and heart tissues. CGRP was increased in groups S, CLC, and SLC when compared with the other groups. In the SLC group, plasma concentrations of TNF-&agr;, IL-6, NOx, and tissue MDA levels were reduced and IL-10 level was increased when compared with groups S and SHC 18 h after CLP (P < 0.05). Small-dose capsaicin treatment increased antiinflammatory IL-10 levels and attenuated the increases in proinflammatory cytokines, NOx, and tissue MDA in septic rats.

Reduced neuronal innervation in the distal end of the proximal esophageal atretic segment in cases of esophageal atresia with distal tracheoesophageal fistula

BackgroundEsophageal dysmotility is a common occurence after surgical repair of proximal esophageal atresia (EA) and distal tracheoesophageal fistula (TEF). The etiology of this motility disorder, however, remains controversial. Esophageal dysmotility also is present in isolated TEF or EA before surgery, suggesting a congenital cause. However, there is no information available in the literature with regard to the intramural nervous system of the human esophagus in EA-TEF.Patients and MethodsWe examined the distal end of proximal esophageal atretic segment of neonates undergoing EA-TEF repair for intrinsic neuronal innervation. Using specific antibodies, we studied neuronal markers of specimens from nine cases of EA-TEF and 9 cases of normal esophagus by immunohistochemistry using neurofilament (NF), synaptophysin (SY), S100, and glial cell line-derived neurotrophic factor (GDNF).ResultsIn the atretic segment, specimens staining with hematoxylin and eosin showed that there were marked hypoganglionosis and immature ganglion cells in the myenteric plexus. GDNF immunoreactivity in the atretic esophagus were markedly reduced in both the muscular layer and myenteric plexus. SY and NF-immunorective nerve fibers were distributed throughout the myenteric plexus of the normal esophagus, but the scarcity of these immunoreactive nerve fibers in the atretic esophagus was apparent. In contrast, the density of immunorective nerve fibers for S100 in the myenteric plexus and muscular layer was increased in the distal end of the atretic esophagus.ConclusionWe concluded that the distribution of ganglion cells and some nerve fibers in the distal end of the atretic esophageal segment is deficient. Inadequate and abnormal neuronal innervation of the esophagus could be related to the esophageal dysmotility seen in EA. Because GDNF is a survival factor for central and peripheral neurons, defective expression of GDNF could have an important role in the defective and/or abnormal neuronal innervation of atretic esophageal segment.