In vitro and in vivo inhibition of myeloperoxidase with 5-fluorouracil

OBJECTIVE: Myeloperoxidase (MPO) exists in neutrophils and has an important bactericidal role. During phagocytosis, MPO catalyzes a peroxidative reaction using chloride ion and hydrogen peroxide (H2O2) as substrate. The aim of the present study was to investigate whether 5-fluorouracil (5-FU), a chemotherapeutic agent, has a direct inhibitory effect on MPO and to evaluate some properties of this inhibition. METHODS: The inhibitory effect of 5-FU on MPO was studied in rat tissue, human leukocytes, and leukocytes from cancer patients under 5-FU therapy. MPO was solubilized in a detergent-containing buffer. MPO activity was measured spectrophotometrically through the oxidation of a synthetic substrate tetramethyl benzidine in the presence of H2O2. RESULTS: 5-FU inhibited tissue-associated MPO activity in a dose-dependent but not time-dependent manner with an IC50 value of 0.6 mg/ml. 5-FU also inhibited MPO activity in isolated human leukocytes in a dose-dependent manner, and the IC50 value was 0.75 mg/ml. Using this 5-FU concentration, the inhibitory effect was monitored at different substrate concentrations. Leukocyte MPO activities of patients receiving 5-FU therapy were compared before treatment and after the first, second, and third administration cycles. 5-FU treatment resulted in a significant decrease in leukocyte MPO activity, and repeated 5-FU treatment caused additional decrease. CONCLUSION: Our data showed that 5-FU directly inhibited the MPO activity of human leukocytes in vitro and in vivo. We concluded that, the patients treated with 5-FU should be intensively followed for the risk of infections.     

Rectal Duplication as an Unusual Cause of Chronic Perianal Fistula in an Adult: Report of a Case

Duplication of the rectum is a rare embryologic event, but it should be considered as a possibility when perianal fistulas and abscesses remain resistant to conventional standard surgical treatment modalities over the long term. We report the case of a 57-year-old woman who underwent many operations over 30 years for persistent perianal fistulas. After radiological assay by computed tomography, fistulography, and barium enema studies, we performed surgery to remove a cystic mass in the retrorectal region, which was subsequently found to be a rectal duplication. The patient had an uneventful postoperative course and has been asymptomatic for 3 years.     

Laparoscopic repair of a Morgagni-Larrey hernia: report of three cases

Morgagni-Larrey hernia is a rare type of diaphragmatic hernia, the diagnosis of which is made incidentally by routine chest X-ray film. We describe a technique for the laparoscopic repair of Morgagni-Larrey hernia which was successfully performed in three adult patients; two women and one man. Two of the patients were asymptomatic and had herniation of only omentum into the right hemithorax; however, one was symptomatic and had herniation of the omentum and large bowel. Tension-free closure of the defects was done using Prolene mesh with a hernia stapler, helical fastener, and Endostitch. There were no early complications and the patients were discharged on the fourth postoperative day. The mean follow-up period was 41 months, and there has been no late morbidity or mortality related to this procedure. Using a laparoscopic approach to repair a Morgagni-Larrey hernia provides an excellent view of the surgical field and allows easy manipulation with minimal surgical trauma, followed by rapid recovery of the patient. Received: May 9, 2001 / Accepted: March 5, 2002     

Enteroclysis-guided laparoscopic adhesiolysis in recurrent adhesive small bowel obstructions

The aim of this study was to point out the efficiency of enteroclysis assay in localization of intraabdominal adhesions that impede small bowel transit in patients with recurrent adhesive small bowel obstruction who underwent laparoscopic partial adhesiolysis. Between January 1998 and June 2001, 15 selected patients with recurrent adhesive small bowel obstructions were treated successfully by medical means and evaluated with enteroclysis to define the pathologic adhesive site that impeded bowel transit. If the results of enteroclysis were indicative, they underwent laparoscopic partial adhesiolysis. The mean duration of the laparoscopic procedure was 99 minutes. In one patient conversion to laparotomy occurred because of excessive adhesions, and in another patient a small bowel injury occurred and enterorrhaphy was performed laparoscopically. Mean postoperative hospital stay was 4 days. During a mean follow-up of 17.2 months (range, 6-39), there was no delayed morbidity or recurrence. Identification of the small bowel site of recurrent obstruction with enteroclysis permits limited laparoscopic adhesiolysis. This approach may be a rational alternative to not only open procedures but also complete laparoscopic adhesiolysis without enteroclysis.     

Role of integrins and intracellular adhesion molecule-1 in lung injury after intestinal ischemia-reperfusion

BACKGROUND: We tested the hypothesis that lung injury after intestinal ischemia-reperfusion (IR) requires the activation of CD11/CD18 glycoprotein complex and its ligand, intracellular adhesion molecule-1 (ICAM-1), on pulmonary endothelial surface. METHODS: Rats were assigned to one of six groups including sham operation, intestinal IR (60/120 min) and IR plus treatment with one of the following monoclonal antibodies against CD11a, CD11b, CD18, and ICAM-1. Pulmonary microvascular permeability, neutrophil accumulation, and expression of adhesion molecules were evaluated. RESULTS: Intestinal IR resulted in lung injury characterized by a marked increase in microvascular permeability, neutrophil accumulation and upregulated expression of leukocyte integrins and ICAM-1. The increase in pulmonary microvascular permability and neutrophil accumulation elicited by intestinal reperfusion was effectively prevented by administration of blocking antibodies against ICAM-1, CD11, and CD18. CONCLUSIONS: These results indicate that adhesion molecules contribute to the lung injury after intestinal IR. Immunoneutralization of certain of these adhesion molecules may prevent intestinal IR-induced lung injury.     

Basal Plasma Glucagon Levels of Man

The isolated perfused rat liver can serve as a bioassay system for glucagon, capable of detecting 10 mmug of this agent. Seven 15-ml plasma specimens obtained from different healthy volunteers after an overnight fast were assayed in this system; glucagon could not be detected in any of them, indicating concentrations significantly below 0.67 mmug per ml in all subjects. The effects of administering small doses of glucagon to patients were consistent with these results; imposition of increments to plasma glucagon concentration below 1 mmug per ml induced distinct and sustained increases in blood glucose.Observations of the biologic effects of glucagon, together with data on the rate of its inactivation by the liver, suggest that the basal concentration of this hormone in peripheral plasma probably does not exceed 0.1 mmug per ml.     

Plasma anti-oxidant status and lipid profile in non-gravida women with a history of pre-eclampsia

Objective:  To investigate the total plasma anti-oxidant status, the plasma lipid profile and the uterine artery Doppler velocity waveform in formerly pre-eclamptic women.
Methods:  Thirty-two formerly pre-eclamptic, non-gravida women constituted the study group, while 28 age-matched non-gravida women who had never had pre-eclampsia served as control subjects. On days 17–19 of their menstrual cycle, fasting plasma samples were collected for total anti-oxidant status (TAS) and lipid profile evaluation, and uterine artery Doppler velocity waveform studies were performed. Results were analyzed with Mann–Whitney U -test and Pearson correlation analysis.
Results:  There was no significant difference between the groups in means of the uterine artery Doppler velocity waveforms and the plasma lipid levels, but body mass index values were significant ( P  < 0.005). The TAS value was subnormal in 72% of the formerly pre-eclamptic group and in 35% of the control group. The mean plasma TAS value was 1.20 ± 0.05 mmol/L and was significantly lower in the study group when compared with the control group ( P  < 0.05).
Conclusion:  The current study reveals significantly decreased TAS in women with a history of pre-eclampsia, which may have an important role in pathophysiology.     

Protective and Therapeutic Effect of Molsidomine on Bleomycin-Induced Lung Fibrosis in Rats

We aimed to investigate the preventive and treatment effect of molsidomine (MOL) on bleomycin (BLC)-induced lung injury in rats. Rats were assigned into groups as follows: control group; MOL group, 10 mg/kg MOL was continued orally for 29 day; BLC group, a single intratracheal injection of BLC (2.5 mg/kg), MOL+BLC-preventive group, 10 mg/kg MOL was administered 1 day before the intratracheal BLC injection and continued for 14 days; BLC+MOL-treatment group 10 mg/kg MOL was given on 14th day after the intratracheal BLC injection and continued until sacrifice. All animals were sacrificed on 29th day after BLC administration. The semiquantitative histopathological assessment, tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), total antioxidant status (TAS), total oxidant status (TOS), myeloperoxidase (MPO), and oxidative stress index (OSI) were measured. BLC-provoked histological changes were significantly detected compared to the control group. MOL restored these histological damages in different quantity in the treatment and preventive groups. BLC administration significantly decreased levels of GSH and TAS when compared to controls and these reductions was significantly ameliorated by MOL given prophylactic setting. However, therapeutic MOL administration significantly increased the TAS level decreased by BLC. The levels of MDA, MPO, and TOS were significantly increased with BLM, and these augmentations of MDA and TOS were significantly reduced by MOL given prophylactic setting. Furthermore, the OSI was higher in the BLC group, and this increase was reversed by the MOL administration before and after BLC treatment. In this study, both protective and therapeutic effects of MOL against BLC-induced lung fibrosis were demonstrated for the first time.