Antithrombin prevents apoptosis by regulating inflammation in the liver in a model of cold ischemia/warm reperfusion injury.

BACKGROUND/AIMS: Hepatic ischemia-reperfusion injury is a major problem in liver surgery. To modulate the complex process of inflammation, additional drugs to add to well-defined organ preserving solutions have been sought. The aim of the current study was to investigate the additive potential of antithrombin (AT) in liver preservation. METHODOLOGY: Female Wistar rats were randomized into four groups: sham (Group I), experiment model (Group II), and treatment groups with AT (250U/kg) administration systematically (Group III) or locally (Group IV) before hepatectomy. UW solution was used for liver preservation for 24h at 4°C. The livers in group II, III and IV were reperfused 1h and histopathological parameters were evaluated microscopically. Apoptosis was assessed with TUNEL test. RESULTS: Karyorrhexis was lower in the local treatment with AT group. Sinusoidal desquamation and mononuclear cell infiltration was higher in the experimental model group. Sinusoidal enlargement was higher in the systemic AT treatment group and neutrophil infiltration to sinusoids was lowest in the local treatment group. Apoptosis of hepatocytes and sinusoidal cells were significantly suppressed in rats that were treated with AT via portal vein infusion. CONCLUSIONS: AT treatment obviously contributed to liver preservation in our model; the effects on apoptosis and inflammation were prominent. Therefore, AT should be considered as a potent agent although its clinical role has yet to be defined in ex-vivo hepatic preservation.

Effects of Probiotic Bacteria on Central Neuronal Activation in Experimental Colitis.

BACKGROUND: Brain-gut axis dysregulation is observed in inflammatory bowel disease. However, the effect of altered gut flora on neuro- immunomodulation and its role in the pathogenesis of inflammatory bowel disease are unknown. The aims of this study are to determine (i) whether colitis modifies the expression of c-fos, a marker of general neuronal activation in the brain and (ii) whether this activation could be modulated by probiotic bacteria. METHODS: In this study, 28 Sprague-Dawley rats were divided into 4 groups: colitis-probiotic group, non-colitis-fed-control group receiv- ing probiotic Lactobacillus delbrueckii subsp. Bulgaricus B3 strain for 7 days, colitis group, and sham group receiving only sodium chlo- ride. Colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid-ethanol. The expression of c-fos was detected by immunohistochemistry in the brain tissue. Cytokines and inflammatory mediators were analyzed in the plasma. Histological scores and oxidative status were analyzed in the colon samples. RESULTS: The inflammatory response was accompanied by increased levels of cytokines, lipid peroxidation activities, c-fos expression in the medial nucleus of the amygdala, and decreased levels of antioxidant enzymes in the colitis (P < .001). Probiotic treatment reversed those effects. Also, histopathologic scores were significantly lower in the probiotic-treated groups compared to the colitis group (P = .035). In contrast, the expression of c-fos was significantly increased in the paraventricular nucleus of hypothalamus in the probiotic- treated rats (P < .001). CONCLUSION: Colitis and intestinal inflammation are associated with the activation of neurons in the limbic system creating stress-like effects in the brain. Probiotics diversely modulate limbic response and hypothalamic axis activity in addition to protective effects in inflammation.

The effect of exopolysaccharide-producing probiotic strains on gut oxidative damage in experimental colitis.

BACKGROUND: Oxidative stress plays a role in disease initiation and progression in inflammatory bowel disease (IBD) and manipulation of this pathway may attenuate disease progress. In this study, the effect of exopolysaccharide (EPS)-producing probiotic bacteria on gut oxidative damage was evaluated in a rat model of experimental colitis. METHODS: Colitis was induced by intracolonic administration of acetic acid. Rats were treated daily with two probiotic strains, L. delbrueckii subsp. bulgaricus B3 strain (EPS of 211 mg/l; high-EPS group) or L. delbrueckii subsp. bulgaricus A13 strain (EPS of 27 mg/l; low-EPS group), which were given directly into the stomach. Non-colitis-fed control and preventative groups were only treated with the high-EPS producing strain. Antioxidant enzyme activities (superoxide dismutase, catalase, total glutathione, reduced glutathione, glutathione disulfide) and lipid peroxidation were measured in colonic tissue samples after a treatment period of 7 days. RESULTS: Significant oxidative damage was associated with a higher level of malondialdehyde (MDA) activity and reduced antioxidant enzyme activities in the colitis model group. All antioxidant enzyme activities were higher in both probiotic-treated groups compared with those of the colitis model group (P < 0.001). Lipid peroxidation was significantly ameliorated in both probiotic groups. The improvement of oxidative stress parameters was significantly more in the high-EPS group than in the low-EPS group (P < 0.001). CONCLUSIONS: EPS-producing probiotic bacteria significantly attenuate oxidative stress in experimental colitis. Increased EPS production gives rise to a better probiotic function. These results suggest that EPS molecules could revaluate probiotic strains and exert their beneficial effects on the host and this may have a therapeutic potential.

Trimetazidine alone or in combination with gemcitabine and/or abraxane decreased cell viability, migration and ATP levels and induced apoptosis of human pancreatic cells.

BACKGROUND: Trimetazidine (TMZ) is an anti-ischemic agent that can inhibit the fatty acid oxidation. It has been stated that inhibition of fatty acid oxidation may be an acceptable approach to cancer treatment. METHODS: We examined the effects of TMZ alone or together with abraxane (ABX) and/or gemcitabine (GEM) on cell viability, apoptosis, adhesion, migration and ATP levels of human pancreatic cancer cell line PANC-1. RESULTS: TMZ significantly reduced the cell viability at higher concentrations. Lower cell viability values were found in cells co-treated with TMZ + GEM, TMZ + ABX and GEM + ABX. The combined treatment of TMZ with ABX and/or GEM significantly increased the apoptosis rates. The highest percentages of apoptosis were found in TMZ + ABX or TMZ + ABX + GEM treatments. TMZ alone or together with ABX and/or GEM significantly reduced the ATP levels. The lowest migration rates were also found at TMZ + ABX and TMZ + ABX + GEM treatments. CONCLUSIONS: Our study is the first study to indicate that TMZ can induce cytotoxicity and apoptosis and reduce migration and ATP levels, especially in cells co-treated with ABX and/or GEM. A combination strategy based on inhibition of fatty acid oxidation and anticancer drugs may be more effective in the treatment of pancreatic cancers.

The effect of trimethazidine on mortality in an experimental acute pancreatitis model1.

BACKGROUND/AIMS: Acute pancreatitis has a high morbidty and mortality. Its physiopathogenesis has not been enlightened up to the present. This study aims to investigate trimetazidine (antiischemic, antioxidant and cardioprotective agent) 's effects on the acute pancreatitis. MATERIALS AND METHODS: In this study, four aqual groups are formed with 43 female Spraque-dawley type rats weighed between230-300 gr (mean 265 gr). 0.9% NaCl is injected intraperitoneally after laparotomy to the Group 1 (n=6). Group 2 (n=6) is control group that without any intervention. Acute pancreatitis is formed in Group 3 (n=16) via injection of Na-taurokolat in the common bile duct. Group 4 (n=15) is being formed pancreatitis and treated with Trimetazidine. In group 4 Trimetazidine 10 mg/kg/day drugs were given, 30 minutes, 24 and 72 hours after formation of acute pancreatitis, in three equal doses by orogastric way. In all groups, the rats have been laparatomised 72 hours later under general anesthesia and pancreas tissues has been extracted and studied histopathologically. Amylase, lipase, lactate dehydrogenase, aspartate transaminase, alanine tranaminase levels in the rats serum and superoxide dismutase, catalase, glutathione, malondialdehyde, nitric oxide, protein carbonyl, glutathione peroxidase levels in the rats tissue also have been looked up. RESULTS: Serum and tissue findings and histopathologically examination of the pancreas tissues show significant decrease in the treatment group compare to study group. CONCLUSION: Trimetazidine protects pancreas tissue and decreases the mortality by significantly lowering the biochemical and histopathological changes in the early stages of acute pancreatitis.

Title.

AIM: We investigated the efficacy of topical phenytoin and capsaicin on random pattern dorsal skin flaps in rats. MATERIAL AND METHOD: Twenty one Wistar rats were used in the study. Random-pattern McFarlane dorsal flaps 3 cm x 10 cm were raised in all the rats .A plastic barrier was placed between the flap and its donor site The flaps were sutured back to the original position with 4/0 nylon sutures. The rats were randomly divided into three groups (n=7). Group I was given only gel, Group II was given 2 gr gel with % 1 phenytoin and Group III was given 2gr gel with %0.1 capsaicin and pure gel. Capsaicin application were used twice a day on 2 consecutive days,subsequently Group III was given only gel on 5 consecutive days. Phenytoin and placebo application were used twice a day on 7 consecutive days. Images were transferred to a computer and ratio of flap necrosis area to total flap area was calculated RESULT: The mean percentage of necrosis in the flaps were 37.27±3.86%, 36.3±6.2%, 23.4±5.9 % in the control, phenytoin and capsaicin groups, respectively. The percentage of flap necrosis was significantly lower in the Capsaicin Group compared to the control group (37.27% vs 23.4%, p<0.01). Although phenytoin had a lower mean percentage of flap necrosins than the control group, this difference was not significant (37.27 vs 36.3 , p>0.05). CONCLUSION: We showed topical capsaicin increased the random pattern skin flap survival in rats whereas topical phenytoin had no positive effect. We believe that further studies are required to investigate the efficiency of topical phenytoin applications. KEY WORDS: Capsaicin, Phenytoin, Skin flaps.

The histopathologic effects of L-carnitine in Sodium Taurocholate Induced Severe Pancreatitis Model.

OBJECTIVE: To evaluate the histopathologic effects of L-carnitine (LC) in an experimental severe pancreatitis (SP) model induced with sodium taurocholate (STC). SUMMARY OF BACKGROUND DATA: LC is an amino acid-like molecule that plays an active role in transporting fatty acids and producing Acetyl CoA in mitochondrial matrix for ß-oxidation to provide energy which is needed for metabolism. It has ameliorative effects on cell injury demonstrated in many studies. The present study focuses on evaluating histopathologic effects of LC in an experimental SP model. METHODS: This experimental study in rats was conducted at the Experimental Animal Research Laboratory of the Faculty of Medicine of Inonu University, Malatya, Turkey. Thirty-two Spraque-dawley male rats were divided into 4 groups in a randomized fashion: control (C) group, L-carnitine (LC) group, pancreatitis (P) group, pancreatitis and L-carnitine (P+LC) group. Pancreatitis was induced by a retrograde pancreatic duct injection of 4% sodium taurocholate and L-carnitine was administered 200 mg/kg/day in treatment group. Rats were euthanized with cardiac puncture under anesthesia at 48th hour of the experiment for biochemical and histopathological examination. RESULTS: In (P+LC) group, the histopathological findings of the pancreatitis were markedly reduced. Acinar cell degeneration was rarely seen. Interlobular and intralobular inflammation and edema was generally mild. The pancreatic damage score of (P+LC) group was significantly lower than that of the (P) group (p<0.05). CONCLUSION: This study revealed that l-carnitine has a significant histopathologic protective effect on acinar cell degeneration in STC-induced SP model in rats.

Restorative proctocolectomy for familial adenomatous polyposis coexisting with colorectal cancer.

The aim of this study was to assess whether restorative proctocolectomy was suitable as an initial procedure for selected familial adenomatous polyposis patients with coexisting colorectal cancer. Six malignancy patients who underwent restorative proctocolectomy for familial adenomatous polyposis were reviewed. At the time of restorative proctocolectomy, cancer was not suspected in four patients. The two remaining familial adenomatous polyposis patients had a known associated colorectal cancer. Operative procedures, pathological findings, complications and long-term follow-up were evaluated. All patients were Stage I-II cancers. There was no mortality or pouch failure. No evidence of tumor recurrence was found and all the patients are still alive and disease-free in follow-up (mean 28 months). As an initial procedure, restorative proctocolectomy for patients with familial adenomatous polyposis with coexisting Stage I-II colorectal cancer seems to be a dependable procedure.

Experimental study on the effects of massive bowel resection on liver function and hepatocyte apoptosis.

BACKGROUND/AIMS: The effects of short-bowel syndrome on liver function and liver morphology independent of parenteral nutrition have not been thoroughly investigated. Our aim was to investigate the effects of massive bowel resection on hepatocyte apoptosis and liver function in rats. MATERIALS AND METHODS: A total of 37 female Sprague-Dawley rats were randomly assigned to five groups: Control (no procedure); Sham 1 [laparotomy (LT)/enterotomy (ET); evaluated on postoperative day (POD) 1]; Sham 2 (LT/ET; evaluated on POD7; Group 1 (80% bowel resection after LT/ET; POD1); and Group 2 (80% bowel resection; POD7). Blood samples were obtained for measuring aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase levels. For assessing hepatocyte apoptosis, liver tissue samples from the median lobe were obtained and used for a terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay. RESULTS: Aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase levels showed statistically significant differences among the five groups. Apoptotic hepatocyte counts there were statistically significant differences among groups for counts made in 20 consecutive high-power fields. However, liver sinusoidal cell apoptosis rates among groups showed statistically significant differences for counts made in 20 consecutive high-power fields, particularly on POD7 in rats undergoing massive bowel resection. CONCLUSION: Parenteral nutrition is not the only factor involved in liver dysfunction after massive bowel resection. Massive bowel resection alone can cause liver abnormalities. Rats undergoing massive small intestinal resection show significant temporal increases in liver sinusoidal cell apoptosis rates.

Comparison of 3D imaging and 2D imaging for performance time of laparoscopic cholecystectomy.

OBJECTIVE: The aim of this study is to evaluate the effect of the Viking 3-dimensional (3D) system on performance time of laparoscopic cholecystectomy. METHODS: Twenty-two patients were included in the study. The groups were standardized using a multiparameters filter (MPF) depending on preoperative ultrasonography and perioperative exploration findings. The 11 patients operated with the Viking 3D system (group A) were compared with 11 patients operated with the Olympus 2D/HD system (group B). RESULTS: The mean performance time was 20.63 ± 5.66 and 30.0 ± 6.03 minutes in the group A (3D) and group B (2D), respectively (P<0.01). CONCLUSIONS: The 3D imaging systems may cause a significant reduction in the performance time of laparoscopic cholecystectomy.

Leakage tests reduce the frequency of biliary fistulas following hydatid liver cyst surgery.

BACKGROUND AND AIM: Biliary fistulas are the most common morbidity (8.2-26%) following hydatid liver surgery. The aim of our study was to reduce the incidence of postoperative biliary fistulas after the suturing of cystobiliary communications by applying a bile leakage test. PATIENTS AND METHODS: A total of 133 hydatid liver cysts from 93 patients were divided into two groups, according to whether the test was performed. Tests were performed on 56 cysts from 34 patients, and the remaining 77 cysts from 59 patients were treated without the test. In both groups, all visible biliary orifices in the cysts were suture ligated, and drains were placed in all cysts. The visibility of the biliary orifices and postoperative biliary drainage through the drains were recorded. Patients in both groups were also compared with respect to the number of days living with the drains, the length of the hospital stay, and secondary interventions related to biliary complications. RESULTS: Biliary orifices were more visible in the tested cysts (13% vs. 48%; P <0.001). Fewer biliary complications occurred in the tested patients (8.8% vs. 27.7%, P = 0.033). The mean drain removal time (4.1 ± 3.3 days vs. 6.8 ± 8.9 days, P < 0.05) and the length of the hospital stay (6.7 ± 2.7 days vs. 9.7 ± 6.3 days, P,0.01) were shorter for the tested patients. None of the patients in the test group required postoperative Endoscopic retrograde cholangiopancreaticography (ERCP) or nasobiliary drainage (0.0% vs. 8.4%, P = 0.09). There were no long-term biliary complications for either group after three years of follow-up. CONCLUSIONS: Identification of biliary orifices with a bile leakage test and the suturing of cystobiliary communications significantly reduced postoperative biliary complications following hydatid liver surgery.

Reversal of the Hartmann procedure through only a stomal orifice.

We performed reversal of the Hartmann procedure only through the stoma site and we did not use either any other incision nor laparoscopic assistance. A total of 8 patients (7 males), ages between 23 and 80 years, were treated by means of a defined technique. The indications of the Hartmann procedure were sigmoid volvulus (4), sigmoid cancer obstruction (2), rectal trauma (1), and Fournier gangrene (one). The duration from the first procedure was a mean of 5 months (range, 2 to 8 months). The length of the rectal stump was at least 5 cm over the pelvic peritoneum and the body mass indices of all patients were less than 30 kg/m². The diameter of the stoma opening was a mean of 50 mm (range, 40 to 55 mm). Incision extensions from the stomal orifice (accepted as conversion) were needed for two cases as a result of injury on the intestine and inability to identify the distal bowel stump (25%). The mean operative blood loss and duration of operation were 50 mL (range, 30 to 100 mL) and 65 minutes (range, 45 to 80 minutes), respectively. Fecal discharge of all patients was weighed before hospital discharge and the length of postoperative hospital stay was a mean of 5.5 days (range, 4 to 9 days). Neither anastomosis leakage nor surgical site infections were observed in any of the patients and all had an uneventful postoperative course. The described technique can be the least invasive one than the previously described techniques for the reversal of the Hartmann procedure by only using the stoma site, particularly for nonobese patients with a long distal rectal stump.

Leakage tests reduce the frequency of biliary fistulas following hydatid liver cyst surgery

BACKGROUND AND AIM: Biliary fistulas are the most common morbidity (8.2-26 percent) following hydatid liver surgery. The aim of our study was to reduce the incidence of postoperative biliary fistulas after the suturing of cystobiliary communications by applying a bile leakage test. PATIENTS AND METHODS: A total of 133 hydatid liver cysts from 93 patients were divided into two groups, according to whether the test was performed. Tests were performed on 56 cysts from 34 patients, and the remaining 77 cysts from 59 patients were treated without the test. In both groups, all visible biliary orifices in the cysts were suture ligated, and drains were placed in all cysts. The visibility of the biliary orifices and postoperative biliary drainage through the drains were recorded. Patients in both groups were also compared with respect to the number of days living with the drains, the length of the hospital stay, and secondary interventions related to biliary complications. RESULTS: Biliary orifices were more visible in the tested cysts (13 percent vs. 48 percent; P <0.001). Fewer biliary complications occurred in the tested patients (8.8 percent vs. 27.7 percent, P = 0.033). The mean drain removal time (4.1±3.3 days vs. 6.8±8.9 days, P<0.05) and the length of the hospital stay (6.7±2.7 days vs. 9.7±6.3 days, P,0.01) were shorter for the tested patients. None of the patients in the test group required postoperative Endoscopic retrograde cholangiopancreaticography (ERCP) or nasobiliary drainage (0.0 percent vs. 8.4 percent, P = 0.09). There were no long-term biliary complications for either group after three years of follow-up. CONCLUSIONS: Identification of biliary orifices with a bile leakage test and the suturing of cystobiliary communications significantly reduced postoperative biliary complications following hydatid liver surgery.

Effects of exopolysaccharide-producing probiotic strains on experimental colitis in rats.

PURPOSE: Inflammatory bowel disease is suggested to result from a dysregulated immune response toward intestinal microflora, which may be restored by probiotic therapy based on the concept of healthy microflora. Ideal probiotic bacteria may be beneficial in inflammatory bowel disease; however, the mechanism of action and the clinical efficacy of probiotic usage are still unclear. In the present study, the effect of exopolysaccharide producing probiotics was evaluated on an experimental colitis model in rats. METHODS: Colitis was induced by intracolonic administration of acetic acid. Then, rats were treated daily with two probiotic strains, Lactobacillus delbrueckii subsp. bulgaricus B3 strain (exopolysaccharide of 211 mg/l: high-EPS group) or Lactobacillus delbrueckii subsp. bulgaricus A13 strain (EPS of 27 mg/l: low-EPS group), which were given into the stomach. The non-colitis-fed control group was only treated with high-exopolysaccharide strain. The model-control and control groups were treated only with tap water. Rats were killed after a seven-day treatment period. Disease activity was quantified by use of histologic scores and colonic myeloperoxidase activity, which is a marker of neutrophil infiltration during inflammation. RESULTS: The enhanced inflammatory response was accompanied by a higher level of myeloperoxidase activity in the colitis group. Histologic scores of colonic damage and myeloperoxidase activity were lower in both probiotic-treated groups compared with those of the colitis control group (P<0.001), although the mentioned scores improved significantly more in the high-EPS group than in the low-EPS group (P<0.001). CONCLUSIONS: Exopolysaccharide-producing probiotics significantly attenuate experimental colitis, which may be mediated by exopolysaccharide in a dose-dependent manner. Therefore, exopolysaccharide-producing probiotics may be a promising therapeutic role in inflammatory bowel disease.