The Effect of the iNOS Inhibitor S-Methylisothiourea and Hyperbaric Oxygen Treatment on Radiation Colitis in Rats.

INTRODUCTION: External radiotherapy is one of the main treatment modalities for a variety of malignancies. However, the lower gastrointestinal tract is sensitive to the ionizing radiation. Hyperbaric oxygen treatment (HOT) has been suggested as a viable treatment for refractory radiation colitis, but the effect of S-Methylisothiourea (SMT) in the radiation colitis have not reported. To investigate the effect of SMT, HOT and the combination of both in an acute radiation-induced enterocolitis model. METHODS: Sixty Sprague-Dawley rats were divided randomly into five equal groups. A single dose of gamma irradiation (25 Gy) was administered through the colorectal region to anesthetized rats. In the control group, we applied 2 ml of saline solution intraperitoneally for five days. In the HOT group, 100-per-cent oxygen at 2.5 atm pressure was applied for five days. In the SMT group, 10 mg/kg/day of SMT was applied intraperitoneally for five days. In the HOT+SMT group, HOT and SMT were both applied in the same dosages as in the preceding two groups. At the end of five days, the rats were sacrificed and colon samples were collected for histological grading. Blood samples were collected to test for : tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), IL-1ß, transforming growth factor-ß (TGF-ß) and intercellular adhesion molecule-1 (ICAM-1) mRNA. RESULTS: The TNF-α, IL-1ß, IL-10 and TGF-ß levels were reduced by SMT, HOT and HOT+SMT applications (p < 0.05). However ICAM-1 mRNA levels were not significantly lower (p:0.19). The microscopic scores differed significantly between the SMT, HOT and HOT+SMT groups and the control group. There was significant improvement histologically, especially in the HOT+SMT group. When we compared the weight of the rats before and after the study, weight loss was significantly lower in the SMT, HOT and HOT+SMT groups compared with the control group (p < 0.05). CONCLUSION: HOT and SMT together were significantly more effective in preventing weight loss and in reducing inflammation and the severity of colitis histology when compared with HOT and SMT separately.

New end-to-end microvascular anastomosis with geometrically adaptable ends technique: an experimental study on rats.

OBJECTIVE: The aim of this study was to develop an effective arterial anastomosis model with a high patency rate and low operation time. We introduced a new end-to-end microvascular anastomosis with geometrically adaptable ends. METHODOLOGY: In this technique, two triangular flaps were prepared at the end of the vessels and four stitches applied on the tip of those flaps. During this study, 15 new technique anastomoses were compared to 15 conventional 8 stitches anastomoses in 30 rat femoral arteries. Operating time, patency rates and number of stitches with consequential effects on the vessel wall were analyzed statistically. The anastomotic patency of both groups was assessed by: (1) in vivo observation using the milking test under the operating microscope and (2) flow study using laser Doppler ultrasound. Healing was assessed by the light and electron microscopy. RESULTS: According to statistical results and compared to the conventional method, the new technique was associated with a significant time savings (mean 18 vs 26 minutes, p < 0.001). The patency rates were equivalent to the conventional technique by observation and laser Doppler ultrasound (p > 0.05). Histological evaluation of both techniques showed that rats operated with the new technique healed faster and with less endothelial damage. CONCLUSIONS: This new "Geometrically Adaptable Ends Technique" is faster, easier to perform and a reliable method with patency and flow characteristics similar to those of the conventional end-to-end anastomoses (Fig. 7, Ref. 20).

Dipyrone increases the blood flow of arterial dorsal skin flaps.

BACKGROUND: Findings have shown that dipyrone has a beneficial effect on skin flap survival. A pharmacologic explanation for this effect points to its vascular smooth muscle-relaxing effect. This study evaluated the effect of dipyrone on blood flow and thus survival of rat random dorsal skin flaps. METHODS: For this study, 27 male Wistar albino rats were randomly assigned to control (treated with sterile saline) and treatment (treated with dipyrone 100 mg/kg) groups. A random dorsal skin flap measuring 4 x 10 cm was raised in each animal. The edges of the flap were sutured back into their original place. Dipyrone treatment continued at 100 mg/kg per day during the 7-day observation period. Blood flow was recorded by laser Doppler preoperatively (baseline), immediately after the flap was sutured back to its original position (acute), and on postoperative day 7. The degree of necrosis was evaluated by the grid method on day 7. Mean percentage necrosis and minimum laser Doppler readings were compared between the two groups. RESULTS: A significant increase in blood flow was observed in the dipyrone group at the acute phase but not on postoperative day 7. The percentage of the necrotic area was lower in the treatment group. However, it did not reach the significance level (p = 0.09). CONCLUSION: Dipyrone significantly increases [corrected] skin blood flow at the acute phase of flap elevation although the necrotic area does not reach the significance level.

The diffusion of nimesulide gel into synovial fluid: a comparison between administration routes.

BACKGROUND: Nimesulide is available in gel formulation and applied mainly for topical pain management. However, its passage to the synovial fluid is not yet clear. The aim of this study was to evaluate if topical administered nimesulide passes into the synovial fluid and to compare its concentration with the oral nimesulide administration regimen. METHODS: Synovia and plasma nimesulide concentrations were investigated in patients after topical (Sulidin gel 1%) and oral (Mesulid tablet) drug administration. 34 adult outpatients who were scheduled to have an arthroscopic knee examination for mainly meniscal tears repair and who had knee pain during this period were enrolled in the first part of the study. One group received topical nimesulide gel to the skin of the knee whereas the second group received oral 2 x 100 mg nimesulide tablets, 4-7 days before the planned arthroscopy. Synovial fluid and plasma samples were taken simultaneously during the arthroscopy and analyzed using HPLC. In addition, an open-label pilot study was performed to investigate the efficacy and safety of 1-week administration of nimesulide gel. 63 knee osteoarthritis patients were asked to complete the WOMAC Osteoarthritis Index questionnaire before and 1 week after use of Sulidin gel applied 3 times daily. RESULTS: Synovia and plasma nimesulide concentrations were 19.7 +/- 8.6, 11.8 +/- 3.0 and 1958.8 +/- 397.5, 3631.9 +/- 799.3 ng/ ml for topical and oral administration groups, respectively. There was a significant (paired Student's t-test) improvement after 1 week nimesulide treatment in all WOMAC Osteoarthritis Index parameters measured. CONCLUSION: Nimesulide passes into the synovial fluid after topical administration and may have potential benefits in knee osteoarthritis treatment. The actual efficacy and safety of topical nimesulide gel administration should be investigated in a long-term, randomized, placebo-controlled clinical trial.

Effect of Candida albicans septicemia on the cardiovascular function of rabbits.

Candida albicans is an opportunistic pathogen that causes life-threatening systemic infection in immunocompromised host. However, little is known about the effects of yeast on the cardiovascular functions. This study examined the effects of C. albicans septicemia on the heart and vessel functions and nitric oxide (NO) production in infected rabbits. Anaesthetized animals were challenged with intravenous C. albicans (6 x 10(8)/kg) or saline and the blood pressure of rabbits were measured over 5 h. After that response of the isolated thoracic aorta, right atrium and left papillary muscle were recorded. Blood pressure significantly decreased in the infected rabbits during the septicemia but in the control animals it was stable. The blood nitrite levels and NO-synthases (eNOS, iNOS) expression and tissue nitrite levels in the heart and aorta were similar in the both groups. In the aorta isolated from C. albicans-infected rabbits, acetylcholine-induced endothelium-dependent relaxation was decreased, but contractions induced by phenylephrine were potentiated. The NOS inhibitor, L-N(G)-nitro-arginine methyl ester (L-NAME)-induced contraction increase in the right atrium was depressed by the yeast-infection. In the heart and aorta, microscopic examination revealed no tissue invasion of C. albicans. These results indicate the ability of C. albicans-induced septicemia to destroy NO-related responses of the heart and aorta and may have important implications for functional damage to endothelium and the regulation of cardiovascular functions. In addition, NOS induction and NO over-production are not stimulated by systemic C. albicans infection, which would alter the host immune reaction and homeostasis.

Insulin independence following isolated islet transplantation and single islet infusions.

OBJECTIVE: To restore islet function in patients whose labile diabetes subjected them to frequent dangerous episodes of hypoglycemic unawareness, and to determine whether multiple transplants are always required to achieve insulin independence. SUMMARY BACKGROUND DATA: The recent report by the Edmonton group documenting restoration of insulin independence by islet transplantation in seven consecutive patients with type 1 diabetes differed from previous worldwide experience of only sporadic success. In the Edmonton patients, the transplanted islet mass critical for success was approximately more than 9,000 IEq/kg of recipient body weight and required two or three separate transplants of islets isolated from two to four cadaveric donors. Whether the success of the Edmonton group can be recapitulated by others, and whether repeated transplants using multiple donors will be a universal requirement for success have not been reported. METHODS: The authors report their treatment with islet transplantation of nine patients whose labile type 1 diabetes was characterized by frequent episodes of dangerous hypoglycemia. RESULTS: In each of the seven patients who have completed the treatment protocol (i.e., one or if necessary a second islet transplant), insulin independence has been achieved. In five of the seven patients only a single infusion of islets was required. To date, only one recipient has subsequently lost graft function, after an initially successful transplant. This patient suffered recurrent hyperglycemia 9 months after the transplant. CONCLUSIONS: This report confirms the efficacy of the Edmonton immunosuppressive regimen and indicates that insulin independence can often be achieved by a single transplant of sufficient islet mass.

The effect of dipyrone on survival of skin flaps.

The effect of dipyrone on the skin flap survival was studied in a model of an epigastric island flap with a random extension on the opposite side in 23 rats. Dipyrone was given intraperitoneally one hour before the skin flap was raised. At the end of the operation the depth of penetration of the fluorescein dye in the skin flap was assessed visually from photographic records and the flap survival area was measured by a grid method on the seventh postoperative day. There was a significant reduction in the amount of ischaemic necrosis of the skin flap after a single dose of dipyrone 50 mg/kg (p < 0.001). These data suggest that dipyrone is a useful agent in the prevention and treatment of ischaemia and necrosis of the skin flap.

Role of tumour necrosis factor in lung injury caused by intestinal ischaemia-reperfusion.

BACKGROUND: Despite the well known inflammatory effects of tumour necrosis factor alpha (TNF), the mechanism of TNF-mediated lung injury following ischaemia-reperfusion (I/R) is still unclear. In this study, the role of TNF in the development of acute lung injury following intestinal I/R was investigated. METHODS: Male Wistar rats underwent either sham operation (n = 10), 1 h of superior mesenteric artery occlusion and 2 h of reperfusion (I/R, n = 10), or pretreatment with anti-TNF polyclonal antibody 2 mg/kg and I/R (n = 6). Lung injury was evaluated by Evans blue dye concentration, immunohistochemical staining and morphometric analysis. Intestinal injury was assessed by Evans blue dye concentration and histological examination. RESULTS: Intestinal I/R resulted in lung injury characterized by an increase in Evans blue dye concentration, neutrophil sequestration, and obvious staining for expression of pulmonary CD11b and CD18. Pretreatment of animals with anti-TNF antibody led to a reduction in the sequestration of neutrophils, and a decrease in expression of pulmonary intracellular adhesion molecule 1 and CD18. Anti-TNF antibody pretreatment also reduced the intestinal microvascular injury but not histological grade after intestinal I/R. CONCLUSION: Treatment with an anti-TNF antibody resulted in a significant attenuation of lung injury following intestinal I/R. The data indicate that TNF is an important trigger for upregulation of pulmonary endothelial and neutrophil adhesion molecules after intestinal I/R.

Intestinal ischemia and reperfusion impairs vasomotor functions of pulmonary vascular bed.

OBJECTIVE: To investigate the effects of intestinal ischemia and reperfusion (I/R) on the pulmonary vascular endothelium and smooth muscle. SUMMARY BACKGROUND DATA: Respiratory failure is an important cause of death and complications after intestinal I/R. Although the mechanism of respiratory failure in this setting is complex and poorly understood, recent studies of lung injury suggest that endothelial dysfunction may play a significant role. METHODS: A rat model of acute lung injury was studied after 60 minutes of superior mesenteric arterial occlusion followed by either 120 or 240 minutes of reperfusion. The pulmonary vasomotor function was examined in isolated lungs perfused at a constant flow rate. RESULTS: Sixty minutes of intestinal ischemia followed by 120 or 240 minutes of reperfusion led to a significant reduction in the ability of the pulmonary vasculature to respond to angiotensin II, acetylcholine, and calcium ionophore but not to nitroglycerin. The vasoconstriction response to N(G)-nitro-L-arginine methyl ester, which is a measure of basal nitric oxide release, was diminished in the 240-minute reperfusion group. Intestinal I/R was also associated with pulmonary leukosequestration and increased pulmonary microvascular leakage. CONCLUSIONS: Basal and agonist-stimulated release of nitric oxide from the pulmonary vascular endothelium and the ability of pulmonary smooth muscle to contract in response to angiotensin II were impaired by intestinal I/R. Such functional impairment in both pulmonary vascular endothelium and smooth muscle may contribute to the alveolocapillary dysfunction and pulmonary hypertension found in acute lung injury after intestinal I/R.

Effects of agmatine on ethanol withdrawal syndrome in rats.

Effects of agmatine, which is an endogenous polyamine metabolite formed by decarboxylation of L-arginine, have been investigated on the ethanol withdrawal syndrome in rats. Adult male Wistar rats were used in the study. Ethanol (7.2% v/v) was given to the rats by a liquid diet for 21 days. Agmatine (20, 40, 80 and 160 mg/kg) and saline were injected to rats intraperitoneally 30 min before ethanol withdrawal testing. After 30th min, 2nd and 6th h of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs which included locomotor hyperactivity, agitation, stereotyped behavior, wet dog shakes and tremor were recorded or rated. A second series of injections was given at 6 h after the first one, and subjects were then tested for audiogenic seizures. Agmatine caused dose-dependent and significant inhibitory effects on stereotyped behaviors, wet dog shakes and tremors during the observation period. It did not cause any significant change in motor coordination of naive (not ethanol-dependent) rats. Our results suggest that agmatine attenuates withdrawal syndrome in ethanol-dependent rats; thus, this drug may be beneficial in the treatment of ethanol dependence.

The vasorelaxant effect of dipyrone on an experimental cerebral vasospasm model in rabbits.

Cerebral vasospasm is an important clinical phenomenon associated with a high mortality rate and therefore any promising findings in the laboratory deserve assessment in clinical practice. Dipyrone (Metamizol) has been in clinical use for its non-narcotic analgesic effect since 1922. In addition to its analgesic effect, dipyrone has been shown to possess spasmolitic activity in various smooth muscle organs. In our recent study, it was shown that dipyrone also has a relaxing effect in vascular smooth muscle preparations and that the smooth muscle relaxing effect on the rabbit thoracic aorta was produced by one of dipyrone's spontaneous degradation products. The present study was designed to examine the possible effects of dipyrone on the rabbit basilar artery in a model of cerebral vasospasm. Dipyrone was shown to have a clear spasmolitic effect in the rabbit basilar artery vasospasm produced by an intracisternal injection of autologous blood. This effect was apparent with either local or intravenous administration of dipyrone. These data suggest that dipyrone is potentially useful in the treatment of patients suffering from cerebral vasospasm in combination with other agents or alone.

Inhibition of endothelium-dependent relaxation by Candida albicans.

This study examines the effects of Candida albicans on acethylcholine-induced, endothelium-dependent relaxation of thoracic aorta of rabbits, precontracted by phenylephrine (10(-7) M). Isolated vessel rings were incubated with C. albicans, Saccharomyces cerevisiae, or their mannans, and endothelium-dependent relaxation was measured by the induction of acethylcholine. Endothelium-dependent relaxation remained unaffected after 3 hours by either C. albicans or S. cerevisiae, or their mannans. After 24 hours, however, incubation with C. albicans had completely abolished relaxation, whereas relaxation was decreased by mannan of C. albicans and continued unaffected by S. cerevisiae. In contrast, no change was registered with a 24 hours incubation of C. Albicans in a sodium nitroprusside-induced, endothelium-independent, vascular smooth muscle relaxation. Microscopical investigation of the morphological structure of vessel walls revealed penetration of C. albicans on the intimal surface after 3 hours incubation and infiltration of the yeast through the vessel wall after 24 hours. No changes in vessel morphology occurred after 3 or 24 hours with S. cerevisiae or the mannan of C. albicans. These results show the ability of C. albicans to inhibit endothelium-dependent, but not endothelium-independent, relaxation of vascular smooth muscle and may have important implications for functional damage to endothelial cells and the regulation of vessel tone and blood flow.

Pharmacological characterization of metamizol-induced relaxation in phenylephrine-precontracted rabbit thoracic aorta smooth muscle.

Metamizol produced a dose- and time-dependent relaxation in rabbit thoracic aorta smooth muscle that was precontracted by phenylephrine. Such a relaxation was not observed with indomethacin, which is also a nonsteroidal anti-inflammatory drug. The relaxing effect of metamizol was independent of the presence of vascular endothelium. Tetraethylammonium (a calcium-activated potassium channel inhibitor), glybenclamide (an ATP-dependent potassium channel inhibitor), indomethacin (a cyclooxygenase inhibitor), and methylene blue (a soluble guanylate cyclase inhibitor) did not have any effect on metamizol-induced relaxation response. Metamizol did not produce any relaxation effect on aortic smooth muscle when KCl (30, 60, and 117 mM KCl) was used instead of phenylephrine to precontract the preparation. Ouabain (a Na-K ATPase pump inhibitor) showed a dose-dependent inhibition on metamizol's relaxation response. However, in potassium-free medium, which is an alternative way to block the Na-K ATPase pump, no inhibition in metamizol-induced relaxation response was observed. When metamizol was incubated for 2 h in organ-bath conditions before evaluating its relaxing effect, it produced a relatively faster relaxation, indicating that the relaxing effect of metamizol is produced by one of its (active) spontaneous degradation products (possibly 4-methylaminoantipyrine).

Pharmacokinetics of phenprobamate after oral administration to healthy subjects.

Phenprobamate (CAS 673-31-4) is a centrally acting skeletal-muscle relaxant agent. There are only two studies in the literature about the pharmacokinetics of phenoprobamate in man. The inconsistency between the results of these studies can be attributed partly to the different analytical methodologies used. A sensitive, specific and reproducible HPLC-assay, which may increase the reliability of the pharmacokinetic studies of phenprobamate in plasma, has been developed recently. The objective of this investigation was to assess the single-dose kinetics of phenprobamate in human and to determine the pharmacokinetic parameters of clinical and regulatory concern. The plasma pharmacokinetics of phenprobamate have been investigated following single oral administration at a dose of 800 mg in eleven healthy volunteers.

The effects of L-arginine and iloprost on the viability of random skin flaps in rats.

The effects of an intravenous infusion of L-arginine as a physiological precursor of endothelium-derived relaxing factor/nitric oxide (EDRF/NO), iloprost (a stable prostacyclin (PGI2) analogue), and L-arginine combined with iloprost on skin viability were studied in 9 x 3 cm random pattern skin flaps in rats. Intravenous infusion of all drugs was started at the beginning of the operation and continued for 60 minutes. At the end of infusion period the depth of fluorescein dye penetration in the skin flap was assessed visually from photographic records, and the flap survival area was measured by the grid method at the seventh postoperative day. There was a significant reduction in distal necrosis of random skin flaps after intravenous infusion of L-arginine, iloprost, and L-arginine combined with iloprost (p < 0.01). Possible mechanisms that may be responsible for impairment of endothelium-dependent vasodilation and vasospasm in the microvasculature of random skin flap and their prevention with L-arginine and iloprost include restoration of the depleted stores of NO which in turn causes vasodilatation and has an antithrombotic effect.

The determination of diethylstilbestrol (DES) in the faeces and tissues of chickens treated with DES and in the faeces and tissue samples of calves, lambs and chickens collected from various areas of Turkey.

Diethylstilbestrol (DES) analyses were carried out on muscle, liver, kidney and faeces samples of 20 control and 20 experimental broilers to which 5 mg DES/day had been given orally for a period of 7 days. The treated samples were analysed using the Radioimmunoassay method. The removal time of DES from the tissues was determined. Five days following the final administration of DES, its faecal concentration was 151 ppb. However, 7 days after the final administration faecal DES concentrations increased again. On the first day after the final DES administration, DES concentrations in the liver, muscle and kidney were 0.78, 0.74 and 1.33 ppb, respectively. While these values measured on the final day were within the range of the control values. There was an increase of DES in plasma at the end of the experimental period. A total of 1811 muscle, liver, kidney and faeces samples of calves, lambs and chickens and feed samples collected from various areas in Turkey were analysed for the presence of DES. Positive samples for chicken feed was 36.9%. Also 1.9% of the chicken faeces samples were DES positive. All other samples were negative for DES.

[Antibiotic-resistant microorganisms isolated from the urine of patients with suspected urinary tract infections]. / Uriner enfeksiyon süpheli hastalarin idrarlarindan izole edilen mikroorganizmalar ve antibiyotik duyarliliklari.

In our study 5331 urine specimen have been examined. In 22 of the total 2 types of bacteria have been isolated and in the cultures of 1167 patients colony counts over than 100.000/ml. have been determined. These are 599 Escherichia coli, 161 Hemolytic Escherichia coli, 104 Klebsiella, 93 Proteus, 81 Pseudomonas, 65 Staphylococcus epidermidis, 44 Staphylococcus aureus, 24 Enterobacter, 18 Enterococcus. 602 of the infected patients were women and 565 were men. According to antibiogram results microorganisms were mostly resistant to Tetracycline (97.7%), subsequently to Ampicillin (87.5%) and to Trimethoprim-sulfamethoxazole (72.8%). Ofloxacin (97.7%), Ceftriaxone (86.4%) and Cefotaxime (86.1%) were found effective on these organisms.

[Microbiological analysis of some cosmetics on the market]. / Piyasadaki bazi kozmetiklerin mikrobiyolojik arastirmasi.

In this study we have examined contamination of cosmetics by microorganisms. 14 samples from 64 cosmetics were found bacteria more than normally. 9 of 38 shampoo, 2 of 15 hand cream, 1 of 5 hair cream and 2 of 14 hair tonic have been isolated microorganisms more than 10(3) bacteria. Of 14 isolates were 3 Pseudomonas aeruginosa, 2 Escherichia coli, 2 Staphylococcus aureus, 5 Bacillus subtilis and 2 Enterobacter. In addition, antibiotic susceptibility of bacteria were presented in Table 2.