Oxytocin or social housing alleviates local burn injury in rats.

BACKGROUND: Thermal injury may cause distant organ inflammation and multiorgan failure. Oxytocin (OT), a nonapeptide, modulates the immune and inflammatory processes. MATERIALS AND METHODS: To investigate the effects of oxytocin on burn-induced tissue injury, Sprague-Dawley rats were subjected to a partial thickness burn. Immediately after burn, half of the burned rats were placed single in the cages, while others were caged in groups. All the rats then were treated with either OT (5 microg/kg, s.c) or saline twice daily for 5 d. The control rats had no burn injury and received no treatments. On day 5, the rats were decapitated, tissue and serum samples were obtained to score the severity of damage and to assay TNF-alpha levels. RESULTS: Burn trauma resulted in oxidative ileal damage, as evidenced by increased apoptotic rate, increased neutrophil recruitment, and enhanced lipid peroxidation. OT treatment depressed the TNF-alpha level and alleviated dermal degeneration, while attenuating ileal damage. Although a higher degree of skin damage was observed in the animals kept isolated following burn injury, keeping the rats in groups did not affect the level of TNF-alpha or the severity of dermal or ileal injury, but abolished the burn-induced elevations in ileal lipid peroxidation and myeloperoxidase activity. Moreover, OT treatment reduced the ileal apoptosis when applied to rats housed in groups, while the treatment did not alter apoptotic ratio in the isolated rats. CONCLUSION: Oxytocin can be considered as a potential agent in treating burn-induced distant organ injury.

Oxytocin alleviates hepatic ischemia-reperfusion injury in rats.

Various mechanisms have been proposed for the pathogenesis of postischemic hepatic injury, including the generation of reactive oxygen metabolites. Oxytocin (OT) possesses antisecretory, antiulcer effects, facilitates wound healing and has anti-inflammatory properties. Hepatic ischemia-reperfusion (I/R)-injury was induced by inflow occlusion to median and left liver lobes ( approximately 70%) for 30 min of ischemia followed by 1h reperfusion in female Sprague-Dawley rats under anesthesia. I/R group (n=8) was administered intraperitoneally either OT (500 microg/kg) or saline at 24 and 12 h before I/R and immediately before reperfusion. Sham-operated group that underwent laparotomy without hepatic ischemia served as the control. Rats were decapitated at the end of reperfusion period. Hepatic samples were obtained for the measurement of myeloperoxidase (MPO) activity, malondialdehyde (MDA), glutathione (GSH) and collagen levels and histopathological analysis. Tumor necrosis factor-alfa (TNF-alpha) and transaminases (SGOT, SGPT) were assayed in serum samples. I/R injury caused significant increases in hepatic microscopic damage scores, MPO activity, collagen levels, transaminase, serum TNF-alpha levels. Oxytocin treatment significantly reversed the I/R-induced elevations in serum transaminase and TNF-alpha levels and in hepatic MPO and collagen levels, and reduced the hepatic damage scores. OT treatment had tendency to abolish I/R-induced increase in MDA levels, while GSH levels were not altered. These results suggest that OT has a protective role in hepatic I/R injury and its protective effect in the liver appears to be dependent on its inhibitory effect on neutrophil infiltration.

Relationship between overexpression of ras p21 oncoprotein and K-ras codon 12 and 13 mutations in Turkish colorectal cancer patients.

BACKGROUND/AIMS: The activation of ras family genes plays an important role in colorectal tumorigenesis. We investigated the clinicopathological characteristics and point mutations of K-ras oncogene codons 12/13 and ras p21 expression using paraffinembedded materials from cancerous and the surrounding normal tissues of 53 colorectal cancer cases. METHODS: K-ras codons 12 and 13 point mutations were analyzed by PCR-Single- Strand Conformational Polymorphism (SSCP) and followed by DNA sequencing, while ras p21 expression was evaluated using immunohistochemistry. RESULTS: Mutations of K-ras and overexpression of the ras p21 were detected in 11% and 76% of the tumors, respectively. Ras protein level in tumor was increased an average of 4.6-fold over that of normal mucosa. Ras p21 overexpression did not correlate with any of the clinicopathological parameters examined. K-ras gene mutations were found mostly in the presence of a mucinous component within the tumor (p=0.06). Follow-up data were available for 43 patients. There was no statistically significant correlation between these alterations and patient outcomes. CONCLUSIONS: Our data suggest that, apart from K-ras codons 12/13 point mutations, overexpression of the ras family genes is important in the development of the disease but it appears not to be predictive of survival. Furthermore, mucinous secretion in the colorectum may represent a distinct genetic pattern.

Clinical significance of p53, K-ras and DCC gene alterations in the stage I-II colorectal cancers.

BACKGROUND AND AIMS: Genetic alterations of p53, K-ras and DCC genes have a pivotal role in the colorectal cancer progression. The aim of this study was to clarify the association between K-ras mutations, p53 aberrations and DCC loss of heterozygosity (LOH), with the patient outcome and tumor characteristics in 43 stage I-II colorectal cancer patients. METHODS: Mutations in exons 5-8 of the p53 gene and codon 12 and/or 13 of the K-ras gene were assayed by PCR-SSCP and then confirmed by DNA sequencing. DCC LOH was studied by PCR-RFLP, while p53 immunohistochemistry was also made. RESULTS: Mutations of the p53 gene were found in 14 (32.5%) tumors. Five (12%) cases showed mutation of the K-ras gene. Nuclear staining of p53 was found in 22 (51 %) cases. DCC LOH was found in 5 (12%) cases. Cases with guanine to thymine substitution that occurred in K-ras codon 12 and DCC LOH were found to be more aggressive than other cases with codon 12 mutations or DCC wild-type phenotype. Many tumors with p53 over-expression were localized on the left side of the colon (p=0.005). The stage of the tumor was higher in patients who died during the follow-up period, when compared to the ones who have survived. CONCLUSIONS: Although none of these genetic alterations showed a significant prognostic value, specific mutation of K-ras gene and DCC LOH phenotype might have a predictive prognostic implication in colorectal cancer. Furthermore, different etiopathogenetic mechanisms might be involved in the tumorigenesis of the left and right colon.

Laparoscopic cholecystectomy: is it a conscious preference among Turkish patients with symptomatic gallstones?--prospective study.

Laparoscopic cholecystectomy (LC) has the advantages of early return to full daily activity, early return to work, and better cosmetic result, as well as quickly resolving pain. Yet how this information about the procedure influences a patient's attitude toward laparocopy is not known. In this study we analyzed the factors that play role in the decision-making process of patients who choose laparoscopic surgery, and we also evaluated patients' knowledge of laparoscopy and their expectations. A questionnaire was used in evaluating 98 patients suffering from symptomatic cholelithiasis scheduled for elective laparoscopic cholecystectomy between January 2001 and January 2002. Females constituted 81% of the study population. Most of the patients (56%) were housewives. While 45% of the patients had an educational status of primary school degree only, 14% had graduated from a university. Forty-three patients described their level of knowledge about laparoscopy as "low" (had only heard about laparoscopy). In 61% of the patients the surgeon was the sole decision maker about the type of the operation. Almost none of the patients had a preference for the time of discharge from the hospital after surgery, and only three of the actively working patients offered a time interval for return to work. From this study we concluded that most patients have inadequate information about laparoscopic surgery, that the type of operation is dictated mostly by the surgeon, and that early discharge and early return to work are not important for many patients.