René Leriche and "Philosophy of Surgery" in the light of contemporary medical ethics.

Prof. Dr. René Leriche was a famous French surgeon who lived between 1879 and 1955. After working as a vascular surgeon in Lyon, he was appointed professor at the University of Strasbourg in 1924 and later the Paris Collége de France in 1937. Leriche had proposed vascular patches as the ideal treatment for obliterated vascular segments and advocated the necessity of sympathectomy in arterial diseases in the 1920s. He defined "Leriche Syndrome" in 1923 which is known by his name and which develops as a result of incomplete obstruction of the aortic bifurcation. René Leriche wrote a monograph entitled "La Chirurgie de la Douleur-Pain Surgery" in 1940 and he also became a pioneer in the sympathectomy procedure for pain treatment. René Leriche focused on topics that must be remembered again today, including surgery advanced into science, the physiological basis of surgery, research methods, as well as issues such as business technology, humanity in surgery, surgical essence and surgeon's qualifications in the book entitled "La Philosophie de la Chirurgie-Philosophy of Surgery" that he wrote in 1951. In this review, the issues that Prof. Dr. René Leriche addressed in middle of the 20(th) century were revised in the light of contemporary medical ethics.

A randomized controlled trial evaluating early versus traditional oral feeding after colorectal surgery.

OBJECTIVE: This prospective randomized clinical study was conducted to evaluate the safety and tolerability of early oral feeding after colorectal operations. METHODS: A total of 199 patients underwent colorectal surgery and were randomly assigned to early feeding (n = 99) or a regular diet (n = 100). Patients' characteristics, diagnoses, surgical procedures, comorbidity, bowel movements, defecation, nasogastric tube reinsertion, time of tolerance of solid diet, complications, and length of hospitalization were assessed. RESULTS: The two groups were similar in terms of gender, age, diagnosis, surgical procedures, and comorbidity. In the early feeding group, 85.9% of patients tolerated the early feeding schedule. Bowel movements (1.7±0.89 vs. 3.27±1.3), defecation (3.4±0.77 vs. 4.38±1.18) and time of tolerance of solid diet (2.48±0.85 vs. 4.77±1.81) were significantly earlier in the early feeding group. There was no change between the groups in terms of nasogastric tube reinsertion, overall complication or anastomotic leakage. Hospitalization (5.55±2.35 vs. 9.0±6.5) was shorter in the early feeding group. CONCLUSIONS: The present study indicated that early oral feeding after elective colorectal surgery was not only well tolerated by patients but also affected the postoperative outcomes positively. Early postoperative feeding is safe and leads to the early recovery of gastrointestinal functions.

A randomized controlled trial evaluating early versus traditional oral feeding after colorectal surgery

OBJECTIVE: This prospective randomized clinical study was conducted to evaluate the safety and tolerability of early oral feeding after colorectal operations. METHODS: A total of 199 patients underwent colorectal surgery and were randomly assigned to early feeding (n = 99) or a regular diet (n = 100). Patients’ characteristics, diagnoses, surgical procedures, comorbidity, bowel movements, defecation, nasogastric tube reinsertion, time of tolerance of solid diet, complications, and length of hospitalization were assessed. RESULTS: The two groups were similar in terms of gender, age, diagnosis, surgical procedures, and comorbidity. In the early feeding group, 85.9 percent of patients tolerated the early feeding schedule. Bowel movements (1.7±0.89 vs. 3.27±1.3), defecation (3.4±0.77 vs. 4.38±1.18) and time of tolerance of solid diet (2.48±0.85 vs. 4.77±1.81) were significantly earlier in the early feeding group. There was no change between the groups in terms of nasogastric tube reinsertion, overall complication or anastomotic leakage. Hospitalization (5.55±2.35 vs. 9.0±6.5) was shorter in the early feeding group. CONCLUSIONS: The present study indicated that early oral feeding after elective colorectal surgery was not only well tolerated by patients but also affected the postoperative outcomes positively. Early postoperative feeding is safe and leads to the early recovery of gastrointestinal functions.

The effect of CO2 pneumoperitoneum on serum prostate-specific antigen levels in patients undergoing laparoscopic cholecystectomy.

BACKGROUND: Recently, several studies have shown an elevation of serum prostate-specific antigen (PSA) levels after the events associated with presumed pelvic ischemia. Although it has been shown that CO2 pneumoperitoneum during laparoscopic surgery causes splanchnic ischemia, no study has investigated the PSA levels after this procedure. This study aimed to evaluate the effects of CO2 pneumoperitoneum on serum total PSA (tPSA) and free PSA (fPSA) levels in patients undergoing laparoscopic cholecystectomy. METHODS: This study involved 30 men who underwent elective laparoscopic cholecystectomy. Serum tPSA and fPSA levels and f/tPSA ratios were determined the day before surgery (baseline), immediately before insufflation, after desufflation, and 24 hours and 7 days after surgery. RESULTS: Serum tPSA and fPSA values after desufflation and 24 hours after surgery were significantly higher than the values before insufflation and at baseline (P<0.01), whereas the f/tPSA ratio did not change (P>0.05). PSA levels decreased to baseline levels after 7 days. CONCLUSIONS: Our study showed that CO2 pneumoperitoneum during laparoscopic surgery can cause a rise in serum tPSA and fPSA levels. We think that CO2 pneumoperitoneum during laparoscopic surgery should be added to list of the events in which PSA measurements must be interpreted with caution.

[Fournier's gangrene: analysis of risk factors affecting the prognosis and cost of therapy in 18 cases]. / Fournier gangreni: 18 olgudaki prognoza etki eden risk faktörlerinin ve tedavi maliyetinin degerlendirilmesi.

BACKGROUND: Fournier's gangrene (FG) is a rapidly progressive, polymicrobial, synergistic necrotizing fasciitis, and the mortality rate is still high. We aimed to determine the risk factors affecting prognosis and treatment cost. METHODS: Eighteen patients operated for FG during 2003-2007 were investigated retrospectively. Surviving and exitus groups were compared regarding demographic data, etiological factors, laboratory findings, treatment modality, length of hospital stay, and treatment cost. RESULTS: Mean age was 54.5 years, and the female/male ratio was 6/12. Mortality was observed in 6 (33.3%) patients and was significantly high among females (66.6%) (p=0.035). Mean duration of complaint in the exitus group (9+/-3 days) was higher than in survivors (5+/-3 days) (p=0.018). The most frequent comorbid disease was diabetes (39.2%), the most frequent etiology was perianal abscess (55.6%) and the primary location of infection was anorectal region (61.1%). Hyponatremia was significantly high in surviving patients (p=0.039). Mean of FG severity point in the exitus group (6.83) was higher than in survivors (3.17) (p=0.011). The most frequently cultivated microorganism, Escherichia coli (66.6%), was significantly high in the exitus group (p=0.012). The mean number of debridements was 4.67. Fecal diversion was performed in 7 (38.8%) patients. Hospital stay in the surviving group (34.17 days) was higher than in the exitus group (10.50 days) (p=0.002). Treatment cost between groups was indifferent (p>0.05). CONCLUSION: Female gender, duration of complaint, FG severity point, and cultivated microorganism (E. Coli) were thought to affect mortality. FG is a disease that might cause extended hospital stay and high treatment cost.

A randomized clinical study evaluating the need for drainage after Limberg flap for pilonidal sinus.

BACKGROUND: This prospective randomized clinical study was conducted to evaluate the need for drainage after rhomboid excision and a Limberg flap (RELIF) for the treatment of pilonidal sinus. METHODS: One hundred one patients undergoing the RELIF procedure were randomly treated with drainage or not. Operating time, postoperative pain assessed on a visual analogue scale (VAS), total amount of intramuscular analgesic administered, hospital stay, complications, recurrence rate, and patient satisfaction were assessed. RESULTS: The mean operating time (P = 0.036), VAS scores on postoperative day 0 (P = 0.039) and day 1 (P = 0.006), intramuscular analgesic requirement (P = 0.009), mean amount of intramuscular analgesic administered (P = 0.025), complication rate (P = 0.027), and mean hospital stay (P = 0.0001) were significantly reduced in the non-drained group. The recurrence rate was similar in the two groups (P = 0.32). CONCLUSIONS: This study indicates that drain placement after the RELIF procedure might negatively affect the postoperative outcomes of patients with pilonidal sinus. On the basis of these finding, we suggest that the use of drains may not be necessary after the RELIF procedure for the treatment of pilonidal sinus.

An unusual cause of acute abdomen: mesenteric heterotopic pancreatitis causing confusion in clinical diagnosis.

Heterotopic pancreas is defined as the presence of pancreatic tissue that lacks anatomic and vascular continuity with the main body of the pancreas. Frequent symptoms and signs are epigastric pain, abdominal fullness and tarry stools. The most frequent locations of heterotopic pancreas tissue are the stomach and jejunum; however, there are a few reported cases of heterotopic pancreas in the mesentery of the small intestine. Heterotopic pancreas may or may not cause complications related to the pathologic conditions of the pancreas itself. Here we present a case showing an unusual cause of acute abdomen, which caused confusion in the clinical diagnosis preoperatively. The definitive diagnosis was achieved only after histopathologic examination in the postoperative period. Final diagnosis of the patient was mesenteric heterotopic pancreatitis, which was a complication of heterotopic pancreas itself with a rarely seen location. In conclusion, mesenteric heterotopic pancreatitis is seen very rarely and may be an unusual cause of acute abdomen. If the pathologic condition develops in the heterotopic tissue, as in the case of heterotopic pancreas, signs and symptoms of the disease may cause confusion in the clinical diagnosis. We agree that preoperative diagnosis of heterotopic pancreas is still difficult, even in a symptomatic patient.

The monitoring of progress in apoptosis of liver cells in bile duct-ligated rats.

BACKGROUND/AIMS: We aimed to determine the progress of lipid peroxidation and ultrastructural changes established in the rat liver after acute bile duct ligation. METHODS: Groups A1, B1, C1 and D1 were the controls of groups A2, B2, C2 and D2, which represented the 1st, 3rd, 5th and 8th days after bile duct ligation. Serum bilirubin and malondialdehyde, liver malondialdehyde and reduced glutathione levels, and inducible nitric oxide synthase expression were determined. Liver tissue was examined with light and electron microscopy. RESULTS: Serum bilirubin increased progressively. Serum and liver malondialdehyde and inducible nitric oxide synthase expression reached a peak level at day 3, reduced at the 5th day and continued at a constant rate. Reduced glutathione decreased progressively. Ductal proliferation increased progressively to a plateau at day 5. The marked electron microscopic changes were detected at day 3 (B2) and continued constantly. CONCLUSIONS: The first five days after acute bile duct ligation are the most critical.

Effects of sulfasalazine on lipid peroxidation and histologic liver damage in a rat model of obstructive jaundice and obstructive jaundice with lipopolysaccharide-induced sepsis.

BACKGROUND: Sulfasalazine, an inhibitor of cyclooxygenase, 5-lipoxygenase, and nuclear factor κB (NF-κB), has been found to alleviate oxidative damage, proinflammatory cytokine production, bile-duct proliferation, neutrophil infiltration, and fibrosis. Therefore, it may have a potential effect in attenuating lipid peroxidation and histologic liver damage in patients with biliary obstruction and biliary obstruction with sepsis. OBJECTIVE: The aim of this study was to investigate the effect of sulfasalazine on lipid peroxidation and histologic liver damage due to obstructive jaundice (OJ) and to OJ with lipopolysaccharide (LPS)-induced sepsis in an experimental model. METHODS: Male Wistar rats, weighing 150 to 220 g, were randomized into 6 groups: OJ; OJ + LPS; OJ + sulfasalazine; OJ + sulfasalazine + LPS (sulfasalazine administered before sepsis); OJ + LPS + sulfasalazine (sulfasalazine administered after sepsis); and sham. Liver malondialdehyde (MDA) and myeloperoxidase (MPO) activities were assessed to monitor lipid peroxidation and neutrophil infiltration in liver tissue. Histologic liver damage was evaluated with hematoxylin-eosin stained slides. Liver tissue NF-κB and caspase-3 expression were studied immunohistopathologically to evaluate lipid peroxidation, liver damage, and hepatocyte apoptosis. RESULTS: Forty-eight rats were evenly randomized into 6 groups of 8. MDA (P = 0.001), MPO (P = 0.001), NF-κB (P = 0.003), caspase-3 expression (P = 0.002), and liver injury scores (P = 0.002) increased significantly in the OJ group compared with the sham group. Compared with the OJ group, MDA (P = 0.030) and MPO levels (P = 0.001), and liver injury scores (P = 0.033) were decreased significantly in the OJ + sulfasalazine group. In the OJ + sulfasalazine + LPS and OJ + LPS + sulfasalazine groups, MDA (P = 0.008 and P = 0.023, respectively) and MPO (both, P = 0.001) were significantly decreased; however, liver NF-κB, caspase-3 expression, and liver injury scores were not significantly different compared with the OJ + LPS group. There was no significant difference between the OJ + LPS + sulfasalazine and OJ + sulfasalazine + LPS groups in regard to all end points when comparing the effects of sulfasalazine administered before or after sepsis. CONCLUSIONS: Sulfasalazine was associated with decreased neutrophil accumulation and lipid peroxidation in these rats with OJ. Administration of sulfasalazine before or after LPS-induced sepsis was associated with a reduction in lipid peroxidation and neutrophil accumulation; however, it did not attenuate histologic liver damage. There was no difference between the findings when sulfasalazine was administered before or after sepsis in OJ.

Total thyroidectomy is safer with identification of recurrent laryngeal nerve.

OBJECTIVE: To investigate the effect of recurrent laryngeal nerve (RLN) identification on the complications after total thyroidectomy and lobectomy. METHODS: Total 134 consecutive patients undergoing total thyroidectomy or thyroid lobectomy from January 2003 to November 2004 were investigated retrospectively. Patients were divided into two groups: RLN identified (Group A) or not (Group B). The two groups were compared for RLN injury and hypocalcaemia. RESULTS: The numbers of patients and nerves at risk were 71 and 129 in Group A, and 63 and 121 in Group B, respectively. RLN injury in Group A (0) was significantly lower than that in Group B (5 [7.9%]) patients, 7 [5.8%] nerves) for the numbers of patients (P=0.016) and nerves at risk (P=0.006). Temporary hypocalcaemia was significantly higher in Group A than in Group B (14 [24.1%] vs 6 [10.3%], P=0.049). Permanent complications in Group B were significantly higher than those in Group A (13 [20.6%] vs 4 [5.6%], P=0.009). CONCLUSION: RLN injury was prevented and permanent complications were decreased by identifying the whole course and branches of the recurrent laryngeal nerve during total thyroidectomy.

Drainage after total thyroidectomy or lobectomy for benign thyroidal disorders.

OBJECTIVE: This prospective randomized clinical trial was conducted to evaluate the necessity of drainage after total thyroidectomy or lobectomy for benign thyroidal disorders. METHODS: A total of 116 patients who underwent total thyroidectomy or lobectomy for benign thyroidal disorders were randomly allocated to be drained or not. Operative and postoperative outcomes including operating time, postoperative pain assessed by visual analogue scale (VAS), total amount of intramuscular analgesic administration, hospital stay, complications, necessity for re-operation and satisfaction of patients were all assessed. RESULTS: The mean operating time was similar between two groups (the drained and non-drained groups). The mean VAS score was found to be significantly low in the non-drained group patients in postoperative day (POD) 0 and POD 1. The mean amount of intramuscular analgesic requirement was significantly less in the non-drained group. One case of hematoma, two cases of seroma and three cases of transient hypoparathyroidism occurred in the non-drained group, whereas one case of hematoma, two cases of seroma, two cases of wound infections and two cases of transient hypoparathyroidism occurred in the drained group. No patient needed re-operation for any complication. The mean hospital stay was significantly shorter and the satisfaction of patients was superior in the non-drained group. CONCLUSION: These findings suggest that postoperative complications cannot be prevented by using drains after total thyroidectomy or lobectomy for benign thyroid disorders. Furthermore, the use of drains may increase postoperative pain and the analgesic requirement, and prolong the hospital stay. In the light of these findings, the routine use of drains might not be necessary after thyroid surgery for benign disorders.

Liver tissue inducible nitric oxide synthase (iNOS) expression and lipid peroxidation in experimental hepatic ischemia reperfusion injury stimulated with lipopolysaccharide: the role of aminoguanidine.

BACKGROUND: Hepatic ischemia-reperfusion (HIR) is a severe condition that is seen after hepatic arterial injury and in hepatic grafts in living donor transplantation. HIR not only causes liver injury by lipid peroxidation, but also stimulates systemic and portal endotoxemia. Also, lipopolysaccharide (LPS) induces hepatic injury mediated by inducible nitric oxide synthase (iNOS). There is little knowledge on the role of specific iNOS inhibitors in prevention of HIR injury followed by LPS administration. The aim of this study on a LPS induced HIR model was to investigate the effect of aminoguanidine (AG) administration on hepatic tissue iNOS expression and lipid peroxidation when given before or after LPS. METHODS: Six groups were designed; A: Sham, B: HIR, C: HIR + AG, D: HIR + LPS, E: HIR + LPS + AG, F: HIR + AG + LPS. No substance was given to the rats in Group A and B. HIR injury was induced with vascular occlusion for 45 min and reperfusion for 45 min. Drugs were given intraperitoneally 10 min before reperfusion. Serum and tissue analysis for myeloperoxidase (MPO), and malondialdehyde (MDA), and tissue NA+/K+ adenosine 5'triphosphatases (ATPase) and tissue iNOS staining were performed. Permission for this study was obtained from the local Ethics Committee. RESULTS: The level of MPO, MDA, and iNOS staining scores in Group B were significantly higher than Group A and ATPase was lower in Group B (P < 0.05). Contrary to results in Group C, results of MPO, MDA, and iNOS staining scores of Group D was higher than Group B (P < 0.05); however, although iNOS in Group C was lower than Group B, the difference was not significant (P > 0.05). MPO and MDA levels of Groups E and F were significantly lower than Group D. Level of ATPase in Group F was significantly different from Groups D and E. iNOS scoring was low in Group F compared with Group D (P < 0.05). MDA, MPO, and iNOS levels of Group F was lower than Group E, and ATPase of Group F was higher than Group E (P < 0.05). CONCLUSIONS: The results of this study in a LPS induced HIR model showed that LPS after HIR aggravated HIR injury by increasing neutrophil activation and lipid peroxidation both in serum and liver tissue and iNOS in liver, and depleting energy in liver. AG, a selective iNOS inhibitor, ameliorated the negative effects of endotoxemia induced by LPS after HIR; however, energy depletion and iNOS expression in liver tissue were attenuated only when AG was administered prior to LPS. The findings of this study supported the hypothesis that LPS after HIR would aggravate HIR injury and AG would ameliorate this aggravated injury.

The effect of remote ischemic preconditioning on healing of colonic anastomoses.

BACKGROUND: We aimed to investigate the potential protective effect of remote ischemic preconditioning (IPC) on delayed colonic anastomotic healing induced by remote ischemia and reperfusion (I/R) injury. MATERIALS AND METHODS: Forty male Wistar rats were randomly assigned into four groups, each consisting of 10 rats: the control group (C), the remote I/R group [I/R, 40 min of superior mesenteric artery (SMA) occlusion], the preconditioned I/R group (IPC, two cycles of 5 min temporary occlusion of SMA before an ischemic insult of 40 min), and the preconditioned group (PC, two cycles of 5 min temporary occlusion of SMA). Colonic anastomosis was performed immediately after the ischemic insult. Anastomotic healing was assessed on postoperative day 7 by determining anastomotic bursting pressure (ABP), tissue hydroxyproline content, histopathological examination, malondialdehyde (MDA), and nitric oxide levels. RESULTS: Remote I/R injury resulted with significant impairment in anastomotic healing in terms of mean ABP (P = 0.004), hydroxyproline content (P = 0.002), histopathological healing score (P = 0.001), nitric oxide level (P = 0.010), and MDA levels (P = 0.0001) when compared with the control group, but remote IPC did not improve all above mentioned parameters (P = NS for all), except MDA level (P = 0.011) when compared with I/R group. PC alone impaired the ABP (P = 0.0001), but it did not significantly change the other parameters measured (P = NS). CONCLUSIONS: The results of this study showed that remote IPC did not prevent I/R-induced delaying in colonic anastomotic healing.

The effect of octreotide on healing of injured colonic anastomosis with immediate postoperative intraperitoneal administration of 5-Fluorouracil.

PURPOSE: This study was designed to investigate the effect of octreotide on side effects of immediate usage of 5-fluorouracil after colonic anastomosis. METHODS: Forty male Wistar rats were randomly assigned into four groups and underwent standardized left colonic anastomosis. The rats served as control or received intraperitoneal 5-fluorouracil (20 mg/kg daily), subcutaneous octreotide (20 mug/kg daily), or both. Diarrhea and wound complications were noted during the experiment. The colonic anastomoses were assessed for healing on postoperative Day 7 by determining the anastomotic bursting pressure, performing histologic examination, and measuring the tissue hydroxyproline content, serum malondialdehyde, and nitric oxide levels. Intraperitoneal adhesions and anastomotic leakage were also noted. RESULTS: No statistical significant difference was found between the control and octreotide groups for each of the parameters measured. Immediate 5-fluorouracil use resulted with higher adhesion score (P = 0.002), significant depression in anastomotic bursting pressure (P = 0.0001), histopathologic score (P = 0.0001), hydroxyproline content (P = 0.0001), and increasing nitric oxide (P = 0.0001) and malondialdehyde levels (P = 0.0001) compared with the control group. Diarrhea was seen in 80 percent of the 5-fluorouracil group but in neither the control nor octreotide groups (P = 0.0001 for each comparison). However, all these parameters were ameliorated by use of concomitant octreotide and 5-fluorouracil (P = 0.019, P = 0.023, P = 0.0001, P = 0.006, P = 0.0001, and P = 0.013, respectively). In addition, diarrhea was found to be prevented (P = 0.0001). CONCLUSIONS: The results of this study showed that concomitant octreotide use might prevent the side effects of 5-fluorouracil, such as diarrhea, postoperative adhesion, and delaying the anastomotic healing parameters. In addition, it might reduce tissue damage and inflammation.

The effects of exogenous l-carnitine on lipid peroxidation and tissue damage in an experimental warm hepatic ischemia-reperfusion injury model.

BACKGROUND: l-Carnitine is the essential endogenous factor for the transport of long-chain fatty acids from the cytoplasm to within the mitochondrion where the ß-oxidation process takes place. l-Carnitine is a superoxide scavenger and an antioxidant that possesses an anti-ischemic action and a stabilizing effect on cell membranes. It may be of help in liver ischemia reperfusion injury. RESULTS regarding the effects of l-carnitine on liver ischemia and reperfusion injury are few and conflicting. OBJECTIVE: The aim of this study was to investigate the efficacy of exogenous l-carnitine on lipid peroxidation and protecting liver at different stages of experimental total warm hepatic ischemia-reperfusion (TWHIR) procedure in rats. METHODS: This experimental study in healthy, weanling, male Wistar rats (weighing 180-200 g) was conducted at the Experimental Animal Research Laboratory of the Faculty of Medicine of Mersin University, Mersin, Turkey. Rats were randomly divided into 5 groups: (A) Control group; (B) TWHIR procedure only; (C) l-carnitine administered 2 hours before the TWHIR procedure; (D) l-carnitine administered just before the TWHIR procedure; and (E) l-carnitine administered after total warm hepatic ischemia but just before the reperfusion procedure. Total warm hepatic ischemia (via the Pringle maneuver) and reperfusion were performed for 45 and 30 minutes, respectively. l-Carnitine (200 mg/kg) was administered intravenously. At the end of each procedure a blood sample was drawn and total hepatectomy was performed following reperfusion. Malondialdehyde (MDA) and myeloperoxidase (MPO) levels of both plasma and liver tissue, total antioxidant capacity (TAOC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in plasma, and histopathologic examination were analyzed to assess lipid peroxidation and damage in liver tissue. RESULTS: Thirty-four rats (mean [SD]age, 59.26 [1.2]days; mean [SD] weight, 194.1 [5.1] g) were used in the study. There was a significant difference observed between groups A (n = 5) and B (n = 5) for all evaluation parameters. The TWHIR procedure performed in group B was associated with significant increases versus baseline in ALT, AST, MDA, and MPO in plasma, and MDA and MPO in liver tissue, but a significant decrease of TAOC in plasma. ALT, AST, serum and liver MDA, and MPO levels of group B were significantly higher than all groups administered l-carnitine. l-Carnitine administration between total warm hepatic ischemia and reperfusion was associated with a significant attenuation in all parameters. The liver MDA levels of groups C (n = 8) and D (n = 8) were significantly lower than that of group E (n = 8) (mean [SD]: C, 16.53 [3.32] and D, 18.28 [1.67] vs E, 23.05 [3.52]; P = 0.001 and P = 0.016, respectively). The mean (SD) liver MPO level of group C (1.09 [0.16]) was significantly lower than that of groups D (2.12 [0.25]) and E (2.11 [0.28]) (both, P = 0.001). The TAOC of group B (0.77 [0.12]) was significantly lower than that of groups C (1.34 [0.19]) and D (1.08 [0.20]) (P = 0.001 and P = 0.015, respectively). The TAOC of group C was significantly higher than that of the other l-carnitine groups (E, 0.94 [0.13]) (P = 0.023 vs group D; and P = 0.001 vs group E). Histopathologic scores of groups A, C, and E were significantly lower than that of group B, but the difference between groups B and D was not statistically significant. CONCLUSIONS: In this experimental study, administration of exogenous l-carnitine was associated with significantly decreased lipid peroxidation in plasma and liver tissue when administered prior to a TWHIR procedure. In addition, l-carnitine seemed to be more effective with regard to decreasing lipid peroxidation in liver tissue when administered before warm hepatic ischemia. l-Carnitine was associated with significantly decreased leukocyte sequestration in plasma and liver tissue. A significant increase in TAOC was associated with l-carnitine administered prior to ischemia. These observations suggest that l-carnitine might have a protective effect against ischemia-reperfusion injury in rat liver tissue.

Contribution of Rho-kinase in human gallbladder contractions.

Rho/Rho-kinase-mediated pathway has been involved in a variety of physiological processes, including Ca2+ sensitization, which enhances smooth muscle contraction. In this study, first of all we investigated the expression of Rho-kinase (ROCK-2) and then the role of this protein in the control of smooth muscle contraction in the isolated human gallbladder. For this purpose, we examined the effects of a selective Rho-kinase inhibitor, (+)- (R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632, 10(-8)-3x10(-5) M) on carbachol (10(-8)-10(-4) M), cholecystokinin-8 (10(-8) M), endothelin-1 (10(-8) M), histamine (10(-5) M), neurokinin A (10(-7)-10(-6) M), 5-hydroxytryptamine (10(-6)-10(-5) M) and potassium chloride (KCl, 25-50 mM)-induced contractions as well as spontaneous contractile activity. Y-27632 (10(-5) M) significantly reduced 5-hydroxytryptamine, neurokinin A and KCl-induced contractions. Moreover, this Rho-kinase inhibitor (10(-8)-3x10(-5) M, cumulatively) relaxed the contractions produced by cholecystokinin-8, endothelin-1 and histamine in a concentration-dependent manner, being the pEC50 values for Y-27632 5.74+/-0.12, 5.33+/-0.09 and 5.95+/-0.18, respectively. Carbachol (10(-8)-10(-4) M) produced concentration-dependent contractions, which were also inhibited significantly by Y-27632. In addition, the spontaneous contractile activity was suppressed in the presence of Y-27632 (10(-6)-10(-5) M). Moreover, Western blot analysis has revealed that Rho-kinase is expressed in homogenates of the human gallbladder. Taken together, these results show that Rho-kinase is expressed in the human gallbladder, and it has an essential role in agonists and depolarization-induced contractions as well as spontaneous contractile activity.

The effect of aminoguanidine on blood and tissue lipid peroxidation in jaundiced rats with endotoxemia induced with LPS.

Obstructive jaundice (OJ) is a severe condition that leads to several complications. One of the important problems in OJ is the increased incidence of endotoxemia, which is the result of bacterial translocation (BT) and defective host immune response. Lipid peroxidation (LP) is an important problem in OJ and sepsis in which nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) activity are increased and antioxidative activity is decreased. Formation of peroxynitrite (ONOO(-)) anion leads to cellular damage and apoptosis. In this experimental study, we explore the effect of specific iNOS inhibitor aminoguanidine (AG) on blood and tissue (liver and renal) LP and iNOS levels in jaundiced rats with endotoxemia induced with lipopolysaccharide (LPS). Rats were randomized into six groups; group A, sham; group B, obstructive jaundice (OJ); group C, OJ + LPS; group D, OJ + AG; group E, OJ + LPS + AG; group F, OJ + AG + LPS. Serum malondialdehyde (MDA) and serum myeloperoxidase (MPO) activity and liver and renal tissue MDA, MPO, and Na(+)/K(+)-ATPase activity levels were detected in biochemical methods. Liver and renal tissue iNOS levels were examined immunohistopathologically. Serum and tissue MDA and MPO levels and tissue iNOS expression were increased significantly in groups B, C, and E, while tissue ATPase levels were decreased significantly in the same groups. In the group treated with AG (group D), serum and tissue MDA and MPO levels and tissue iNOS expression were decreased while tissue ATPase levels were increased significantly. In group F, if AG was administrated before LPS, we observed that serum and tissue MDA and MPO levels and tissue iNOS expression were decreased while tissue ATPase levels were increased significantly. Thus, our study showed that AG had a protective effect when it was administrated before LPS, but it failed to prevent tissue iNOS expression and LP if there was established endotoxemia in OJ.

Intestinal perforation in Wegener's granulomatosis: a case report.

Wegener's granulomatosis is a disease characterized by a necrotizing vasculitis and granulomatous inflammation. The localized form involves the upper and/or lower respiratory tracts while in the common generalized form there is a widespread necrotizing vasculitis and renal involvement. Although gastrointestinal involvement which has been detected at necropsy in 24% of the cases is an uncommon finding, it might cause severe complications. We report a patient with clinical Wegener's granulomatosis who subsequently developed gastrointestinal perforation. Gastrointestinal perforation was treated with surgical resection and the patient survived under the treatment of cyclophosphamide and prednisolone with no further gastrointestinal complications. The present case indicates that the gastrointestinal complications might be considered in natural history of Wegener's granulomatosis.

The effect of N-acetylcysteine on pulmonary lipid peroxidation and tissue damage.

BACKGROUND: We aimed to investigate the effect of N-acetylcysteine (NAC) on pulmonary lipid peroxidation and tissue damage in experimental obstructive jaundice (OJ) stimulated by lipopolysaccharide (LPS) in this study. MATERIALS AND METHODS: We randomized 40 rats into five groups. Group A: Sham (n = 8); group B: OJ (n = 8); group C: OJ + lipopolysaccharide (LPS; n = 8); group D: OJ + NAC + LPS (n = 8); group E: OJ + LPS + NAC (n = 8). OJ was performed by common bile duct ligation and division in all groups except the sham group. At the fifth day, the rats were jaundiced. At the fifth day of OJ, LPS was injected 10 mg/kg intraperitoneally to the rats and at the tenth day, the rats were sacrificed in group C. In group D; at the fifth day of OJ, NAC was started 100 mg/kg subcutaneously and the same dose NAC injection repeated every day for 5 days. At the tenth day of OJ, LPS was injected 10 mg/kg intraperitoneally to the rats and then after 6 h they were sacrificed. In group E; 10 mg/kg LPS was administered intraperitoneally at fifth day of OJ and after then NAC was started 100 mg/kg subcutaneously and the same dose NAC injection repeated every day for 5 days and at the tenth day, the rats were sacrificed. Tissue samples were harvested through a midline incision, and lungs were resected and examined histopathologically and immunohistochemically for tissue damage scoring. The blood was taken by cardiac puncture and malondialdehyde (MDA), myeloperoxidase (MPO), and levels of total antioxidant status were detected with biochemical methods to evaluate lung tissue damage. RESULTS: Increase in lung and serum MDA and MPO levels, as well as decrease in total antioxidant status, were observed in groups B and C when compared with the sham group (P = 0.0001, for each comparison). Furthermore, the lung tissue damage was observed in the same groups by histopathological examination when compared with sham group. There was significant decrease at serum and lung MPO and MDA levels after the NAC application in groups D and E, when compared with group C (P = 0.0001, for each comparison). Antioxidant status in groups D and E were increased in the presence of NAC (P = 0.0001, for each comparison). Lung histology was prevented relatively in group D when compared with groups B and C. CONCLUSION: Results of the study indicate that NAC has protective effect on pulmonary lipid peroxidation and tissue damage before and after LPS administration.