Supplementation with high-dose ascorbic acid improves intestinal anastomotic healing.

BACKGROUND/AIM: Ascorbic acid modulates tissue healing but the value of ascorbic acid supplementation during anastomotic healing remains unclear. We examined the role of ascorbic acid treatment in experimental intestinal resection. METHODS: Male Wistar albino rats (n = 30) were divided into three groups: sham treatment (group 1), and daily ascorbic acid treatment with 100 mg/kg (group 2) or 200 mg/kg (group 3) via the intramuscular route. Following sacrifice on the 7th postoperative day, bursting pressure of the anastomoses was measured. Hydroxyproline assessment and histological analysis were carried out. RESULTS: The bursting pressure values of groups 2 (171.4 +/- 4.3 mm Hg) and 3 (196.4 +/- 2.2 mm Hg) were higher than that of group 1 (139.1 +/- 4.1 mm Hg; p < 0.05). In addition, the hydroxyproline level of group 3 (249.2 +/- 25.1 microg/mg) was higher than that of groups 1 (157.9 +/- 14.9 microg/mg) and 2 (187.9 +/- 14.8 microg/mg; p < 0.05). The histopathological scores indicated improved healing in groups 3 (6.0 +/- 0.2) and 2 (4.4 +/- 0.4), compared to group 1 (2.7 +/- 0.3; p < 0.05). CONCLUSION: In the present study, supraphysiologic doses of ascorbic acid improved anastomotic healing. Therefore, vitamin C supplementation poses as a beneficial treatment in the context of collagen accumulation, inflammatory response, and anastomotic strength. However, the clinical value of high-dose ascorbic acid supplementation in the clinical setting is yet to be established.

Everolimus and mycophenolate mofetil sensitize human pancreatic cancer cells to gemcitabine in vitro: a novel adjunct to standard chemotherapy?

BACKGROUND/AIMS: Gemcitabine improves survival in pancreatic adenocarcinoma. A variety of drugs have been tested to potentiate gemcitabine treatment for pancreatic cancer cells. Two major immunosuppressive drugs, mycophenolate mofetil (MMF) and everolimus (RAD001) have been shown to exert an anti-tumoral effect, but their ability to sensitize human pancreatic cell lines during gemcitabine treatment remains unclear. We examined the effects of everolimus and MMF on gemcitabine-treated MiaPaCa and Panc-1 cell lines. METHODS: MiaPaCa and Panc-1 human pancreatic tumor cell lines were subjected to everolimus (0.001-1 microg/ml) or MMF (0.1-100 microg/ml) treatment in combination with gemcitabine (1-10(6) nM). Western blot analysis was performed for Panc-1 cells in the presence or absence of TGF-beta1 and different treatments: 0.1-100 muicro/ml MMF and 0.1-100 microg/ml everolimus. The antiproliferative effect of the treatment was assessed by BrdU test. The results were evaluated by two-way analysis of variance followed by post-hoc tests, and nonlinear regression analysis for dose-response rates. RESULTS: As expected, standard treatment doses of gemcitabine decreased proliferation dose-dependently. Everolimus increased the actual EC(50) response to gemcitabine treatment (1-10(3) nM) to as much as 83.1 and 82.1% in MiaPaCa and Panc-1 cell lines, respectively. Likewise, concomitant administration with MMF altered the EC(50) of gemcitabine treatment in MiaPaCa cell lines to values between 76.8 and 85.2% for doses of >or=1 microg/ml. Even the minor dose of MMF (0.1 microg/ml) increased the antiproliferative effect of gemcitabine by 43.5% for MiaPaCa and 42.4% for Panc-1 cells. In addition, treatment of Panc-1 cells with MMF (0.1-100 microg/ml) dose-dependently inhibited TGF-beta1-induced collagen expression. CONCLUSION: We found an overadditive antiproliferative effect of both MMF and everolimus in gemcitabine-treated MiaPaCa and Panc-1 cells in vitro, and an additional inhibitory effect of MMF on TGF-beta1-induced collagen type I expression. Interestingly, both the sensitizing effect of pancreatic cancer cells to gemcitabine treatment and the inhibition of collagen type I expression could be achieved by clinically feasible doses of everolimus and MMF. The use of these drugs is promising as a novel adjunct to standard chemotherapy.

The right method for midline laparotomy: what is the best choice for wound healing?

BACKGROUND: The techniques used for midline laparotomy affect healing in surgical wounds, but the relationship between cold scalpel and haemostatic methods (harmonic scalpel, diathermy) regarding wound healing remains unclear. There are also limited studies concerning the effects of harmonic scalpel on abdominal fascia. This study was aimed at comparing myofascial wound healing following laparotomy incision on fascia by cold scalpel (CS), harmonic scalpel (HS), and diathermy in terms of hydroxyproline content, inflammatory changes and tensile strength. MATERIALS AND METHODS: Twenty-seven male Wistar albino rats underwent midline laparotomy either with cold scalpel (CS), harmonic scalpel (HS) or diathermy. Fascia incisions were closed with continuous 4/0 polypropylene and skin incisions were closed with interrupted 4/0 polypropylene stitches. On the 7th postoperative day, the abdominal walls of the rats were tested for tensile strength. In addition, each abdominal fascia was evaluated for inflammation scores and hydroxyproline levels. RESULTS: HS caused less inflammation and necrosis in abdominal fascia compared to the diathermy group (p < 0.01 and p < 0.05, respectively), whereas the CS group showed no difference in inflammation scores, but had significantly lower necrosis scores than the HS and diathermy groups (p < 0.05 and p < 0.001, respectively). Hydroxyproline content of the fascia did not differ among groups, while the tensile strength of the wound was obviously higher in the CS group (p < 0.001). CONCLUSION: HS causes less inflammatory reaction and necrosis than diathermy, but more necrosis than CS. Fascia incisions with CS gains tensile strength faster than in other groups. HS appears to cause less tissue injury than diathermy and also has comparable results for wound healing. Further clinical studies on the impact of HS in fascia incisions are needed.

Nitric oxide as an independent regulatory factor in regenerating rat liver.

Nitric oxide production and lipid peroxidation modulate the proliferating activity of liver cells, but the relationship between enhanced nitric oxide production, lipid peroxidation, and liver regeneration remains unclear. We examined the role of nitric oxide and lipid peroxidation on experimental liver regeneration. Thirty-five male Wistar albino rats underwent a sham operation (I), partial hepatectomy alone (II, IV), partial hepatectomy and daily N-nitro-L-arginine methyl ester (L-NAME) treatment for 24-hrs (III) or 48-hrs (V). Liver tissue concentrations of catalase, nitrite and nitrate, glutathione, and serum levels of alaninaminotransferase and bilirubin were measured. CD34, Ki-67 and proliferating cell nuclear antigen were evaluated in liver samples. Compared with other groups, both of the L-NAME groups had decreased tissue nitric oxide concentrations. Nitrate and nitrite (nitric oxide) concentrations were higher in partial hepatectomy-alone groups, as were CD34 counts and proliferation indexes. Partial hepatectomy elevated catalase, and glutathione levels in all groups compared to the sham-operated controls. In conclusion, nitric oxide inhibition impaired hepatic regeneration following partial hepatectomy. An obvious effect of nitric oxide on lipid peroxidation in the context of hepatocyte and endothelial cell proliferation could not be demonstrated. Thus, while lipid peroxidation could influence some steps in liver regeneration, nitric oxide poses as an independent regulatory factor in regenerating rat liver.

The effects of nitric oxide supplementation and inhibition on bacterial translocation in bile duct ligated rats.

Obstructive jaundice promotes bacterial translocation from the gut, but the role of nitric oxide is controversial in this process. We studied the effects of nitric oxide synthase substrate, L-arginine, and nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester, on bacterial translocation in bile duct ligated rats. The animals were randomized into five groups; control, sham, common bile duct ligation alone, nitric oxide inhibition, and nitric oxide supplementation. Obstructive jaundice was performed with common bile duct ligation. L-arginine or N(G)-nitro-L-arginine methyl ester was injected once daily for 14 days. Blood bilirubin level, liver histology, and bacterial translocation to the mesenteric lymph nodes as well as to the liver were assessed. The L-arginine supplemented group had the lowest bacterial translocation rate, but the most prominent hepatic fibrosis. Nitric oxide inhibition increased bacterial translocation to the mesenteric lymph nodes. Therefore, the administration of nitric oxide donor or inhibitor acts as a significant regulatory factor for bacterial translocation in obstructive jaundice.

Does pharmaconutrition with L-arginine and/or alpha-tocopherol improve the gut barrier in bile duct ligated rats?

BACKGROUND/AIM: Nitric oxide supplementation and antioxidant therapy modulate gut barrier function, but the relationships between enhanced nitric oxide production, antioxidant administration, and biliary obstruction remain unclear. We evaluated the role of nitric oxide and alpha-tocopherol supplementation in bile duct ligated rats. METHODS: Fifty male Wistar albino rats underwent sham operation (group I; control animals) or bile duct ligation (groups II, III, IV, and V). The ligation groups received the following regimens: standard pellet diet (group II), pellet diet plus intramuscularly administered alpha-tocopherol (group III), and L-arginine-enriched pellet diet without (group IV) or with (group V) alpha-tocopherol. Nitric oxide, malondialdehyde, and alpha-tocopherol concentrations were assessed at the end of 3 weeks. Liver and intestinal samples were scored histologically. Mesenteric lymph node and liver cultures were assessed for bacterial translocation. RESULTS: The liver malondialdehyde concentration was highest in group III. The nitric oxide content in the liver was higher in groups III and V, as were the blood alpha-tocopherol levels. Bacterial translocation was evident following bile duct ligation, but did not differ among the treatment groups. Intestinal histology revealed that group III had the lowest villus height, that group V had the least villus count, and that group II had the highest mucous cell count. The fibrosis scores were higher in groups IV and V. CONCLUSIONS: An obvious effect of alpha-tocopherol (with or without L-arginine) on the gut barrier could not be demonstrated. Moreover, the L-arginine-enriched diet promoted fibrosis in the liver. Thus, while biliary duct obstruction triggers bacterial translocation, nitric oxide and/or alpha-tocopherol supplementation did not seem to improve the gut barrier in our model.

Is synchronous bowel anastomosis safe?

In this study, we investigated the effects of synchronous anastomosis on intestinal healing in experimental colonic resection. Sprague-Dawley rats were randomized into 3 groups; control (group I), single anastomosis (group II) and synchronous (double) anastomosis (group III). Single and proximal anastomoses were located 3 cm distal to caecum, and distal anastomoses were done 3 cm distal to them. On the 7th postoperative day, bursting pressure, hydroxyproline level and histology of the anastomotic site were assessed. Bursting pressures and hydroxyproline levels indicated that impaired healing of proximal anastomoses in group III was evident. Proximal anastomoses in group III had the lowest hydroxyproline value and bursting pressure level. Significant fibrosis was observed in the histological examination of distal anastomoses in group III. Double colonic anastomoses is not as safe as single anastomoses and involves additional risk. The healing of proximal anastomosis is significantly altered after experimental synchronous resection.

Perforation of the stomach due to chest tube complication in a patient with iatrogenic diaphragmatic rupture.

Diagnosis of diaphragmatic injury is difficult. A case of iatrogenic diaphragmatic rupture is reported in which perforation of a herniated stomach occurred following left lobectomy and partial resection of the diaphragm for lung cancer. On the second postoperative day, bile-stained fluid coming out from the chest tube revealed gastrointestinal leakage. This rare complication of chest tube insertion, early diagnosis and treatment are emphasized.

[Effectiveness of the Mannheim Peritonitis Index in patients with peritonitis]. / Peritonitli hastalarda Mannheim peritonit indeksinin etkinligi.

Classification of patients regarding to outcome in early periods of peritonitis or intra-abdominal sepsis, has always been a primary goal of intensive care physicians. In order to predict outcome, a wide variety of scoring systems have been proposed. Mannheim Peritonitis Index (MPI) is one of the most effective scoring systems and its predictive value has been shown previously. Three hundred and twenty five patients that were admitted to Emergency Services in both Ege and Dokuz Eylül University Hospitals between 1995 and 1999, have been evaluated retrospectively by using patient records. Among them, 258 patients (79.4%) have been discharged in well condition and 67 patients died (20.6%). In the latter, MPI scores were always equal or more than 26. Mean MPI scores were 30.23 7.05 and 18.55 6.67 in exitus group and discharged group respectively. When all descriptive factors in MPI have been evaluated separately, every predictor was revealed statistically significant differences between exitus and discharged groups. It has been concluded that MPI is effective scoring system in terms of predicting final outcome in patients with peritonitis and intraabdominal sepsis.

[Case report: foreign body causing a penetrating neck injury]. / Olgu sunumu: yabanci cisme bagli penetran boyun yaralanmasi.

A 30 year old man is admitted to the emergency section with the complaint of bleeding from the neck after an industrial explosion. A laceration, 5 cm's in length, is seen on 'zone II', near the medial border of the anterior jugular triangle. The patient was hemodynamically stable, but there was active bleeding from the laceration. A round mass is detected with palpation adjacent to the bifurcation of carotis. The wound is explored under anesthesia with endotracheal intubation. Major vessels and other vital structures found to be undamaged. Many authors suggest mandatory exploration for the neck wounds that penetrated the platysma, while others prefer exploration for selected cases on the basis of diagnostic studies. Immediate exploration is indicated in the presence of active bleeding, and diagnostic studies should be reserved for haemodynamically stable patients. Injury of major vessels might be tamponaded by foreign bodies, therefore blind removal of the objects may cause life-threatening hemorrhage. Endotracheal intubation is appropriate in the management of airway, as for convenient surgical approach.

The prophylactic and therapeutic effects of glutamine- and arginine-enriched diets on radiation-induced enteritis in rats.

BACKGROUND: Recent studies indicated that glutamine and arginine support the mucosal barrier in several ways. This experimental study hypothesized that administration of glutamine- and arginine-enriched diets before abdominal radiation therapy would provide a radioprotective effect on intestinal mucosa, and this would augment the therapeutic effectiveness provided by postirradiation administration. MATERIALS AND METHODS: A rat model of radiation enteritis was designed with a single dose of 1100 cGy to the abdomen. Thirty-five rats were randomized into five groups of seven. A 7-day glutamine-enriched diet for Group I and a 7-day arginine-enriched diet for Group II were administered both pre- and postradiation. For Groups III and IV, the same glutamine and arginine diets were given, respectively, postradiation only. Group V was fed a glutamine- and arginine-free diet and was the control group. The rats underwent laparotomy for culture of mesenteric lymph nodes and removal of segments of ileum, jejenum, and colon for microscopic examination. RESULTS: Bacterial translocation was significantly higher in Group V (P < 0.05), while intestinal villus count and villus height were significantly higher in all of the groups fed glutamine and arginine when compared with the control group (P < 0.0001 and P < 0.05, respectively). CONCLUSION: Both arginine- and glutamine-enriched diets have protective effects on gut mucosa in the postirradiation state; however, pre- and postirradiation administration together does not provide superior protection versus postradiation administration alone.