Protective effect of roscovitine on renal ischemia-reperfusion injury.
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Biomedical subjects
Publications and source records attributed to I Sayek.
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Hydatid disease of the liver is still endemic in certain parts of the world. The diagnosis of noncomplicated hydatid cyst of the liver depends on clinical suspicion. Ultrasonography and computed tomography, the most important diagnostic tools, are helpful for determining the complications and planning treatment. The modern treatment of hydatid cyst of the liver varies from surgical intervention to percutaneous drainage or medical therapy. Surgery is still the treatment of choice and can be performed by the conventional or laparoscopic approach. Percutaneous drainage and treatment of the cyst with hypertonic saline or alcohol seems to be a good alternative to surgery in selected cases. Currently, we treat types I and II by ultrasound-guided percutaneous drainage and types IV and V (excluding totally calcified cysts) surgically. Type III cysts can be managed either way depending on the presence of drainable content. We believe that the laparoscopic approach should be limited to noncomplicated cysts.
Currently HIV/AIDS is one of the most difficult challenges for health care professionals. As primary medical care providers, attitudes of the physicians towards HIV/AIDS are of utmost significance. The aim of this research is to determine the attitudes of the surgeons towards HIV/AIDS in their working environment. Data were collected from a self-administered questionnaire given to 128 surgeons. Results revealed that gender, age and professional experience are not significant. This study demonstrated that doctors are worried about contracting HIV/AIDS from the patients. In some circumstances doctors' attitudes, are not clear which may lead to some ethical problems. It is concluded that doctors overestimate the risks and they need special education about HIV/AIDS, as well as professional help to handle their attitudes toward HIV/AIDS.
Many surgical infections are characterized by synergistic polymicrobial mixed infection, for which broad-spectrum antimicrobial therapy is usually administered on an empiric basis. Until relatively recently, standard empiric therapeutic regimens have involved the use of two or more antibiotics, such as aminoglycosides and anti-anaerobic agents, to achieve adequate aerobic and anaerobic coverage. There are often substantial drawbacks, however, such as drug-induced toxicity and high costs of treatment. Evidence from a number of clinical studies suggests that single-agent therapy with beta-lactam/beta-lactamase inhibitor combinations is a suitable and cost-effective alternative to multidrug regimens, as well as to monotherapy with cephalosporins or carbapenems in the treatment of intra-abdominal, gynecologic, and diabetic foot infections, and brain abscesses. These agents are also suitable for use in perioperative prophylaxis and may offer benefits over other agents in terms of reduced incidence of surgical wound infections and lower costs.
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BACKGROUND: The regeneration of normal and cirrhotic liver has been very well demonstrated after partial hepatectomy; although the tissue regenerated by cirrhotic liver is also cirrhotic. The structural differences of the regenerated tissues between normal and cirrhotic livers may also indicate different regeneration capacities. The objective of this study was to compare the regeneration capacities of normal and cirrhotic livers by bromodeoxyuridine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) labeling indices in replicating nuclei and mitotic figures in cells in partially hepatectomized normal and cirrhotic rats and to study the effect of alpha-tocopherol on cirrhotic liver regeneration. METHODS: Five groups of adult Wistar rats comprised normal livers, cirrhotic livers, regenerated normal livers, regenerated cirrhotic livers, and alpha-tocopherol-treated regenerated cirrhotic livers. Cirrhosis was induced by intragastric administration of carbon tetrachloride and phenobarbital in the drinking water of the rats. Liver regeneration capacities in normal and cirrhotic rats and following partial hepatectomy in normal and cirrhotic rats and cirrhotic rats that were administered alpha-tocopherol were evaluated through BrdU incorporation, PCNA labeling, and mitotic indices. RESULTS: BrdU and PCNA labeling and mitotic indices were zero for normal rats and 4.3 +/- 3.5, 6.5 +/- 5, and 2.5 +/- 1.5 for cirrhotic rats, respectively. The values after partial hepatectomy in normal and cirrhotic rats were 46.2 +/- 8.7 and 27.8 +/- 7.5 for BrdU labeling, 83.7 +/- 6.5 and 51.3 +/- 6.8 for PCNA labeling, and 31.8 +/- 4.2 and 18.6 +/- 3.4 for mitotic index, respectively. For the fifth group comprising cirrhotic rats that were administered alpha-tocopherol and had undergone partial hepatectomy, BrdU incorporation, PCNA labeling, and mitotic indices were 37.5 +/- 6.3, 76.5 +/- 6.2, and 27.2 +/- 4.2, respectively. When the cirrhotic liver regeneration group was compared with the normal liver regeneration group, rates of liver regeneration in the cirrhotic group were significantly depressed (P < 0.01). Although the BrdU incorporation and PCNA labeling indices of the alpha-tocopherol-administered cirrhotic liver regeneration group indicated significantly lower rates of liver regeneration when compared with the normal liver regeneration group (P < 0.05), the liver regeneration rates of the alpha-tocopherol-administered cirrhotic group were also significantly higher than those of the cirrhotic liver regeneration group that was not administered alpha-tocopherol (P < 0.01). CONCLUSIONS: Cirrhotic livers revealed a significantly depressed capacity for regeneration following partial hepatectomy. alpha-Tocopherol administration seemed to improve the rates of regeneration in cirrhotic rats with respect to the BrdU incorporation, PCNA labeling, and mitotic indices.
The septic shock-induced decrease in mesenteric blood flow and release of proinflammatory cytokines are among the major pathophysiologic changes presumed to lead to multiple organ dysfunction syndrome (MODS). Increased nitric oxide (NO) levels are associated with both decreased mesenteric blood flow and positive modulation of proinflammatory cytokine release. In this study we aimed to determine the effect of the timing of the inhibition of nitric oxide synthase (NOS) on mesenteric blood flow and serum interleukin-10 (IL-10) concentrations during endotoxin shock. A nonspecific NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME), a specific NOS inhibitor aminoguanidine (AG), or placebo were injected 20 minutes before or 20 minutes after a lipopolysaccharide (LPS) or placebo challenge to Swiss-albino mice, as pretreatment or posttreatment, respectively. At 120 minutes after LPS or placebo injection the mesenteric blood flow was measured, and blood samples from the heart were obtained for IL-10 levels in both groups. Pretreatment and posttreatment with both NOS inhibitors prevented the LPS-induced decrease in mesenteric blood flow. Pretreatment was more effective for this purpose. Pretreatment accentuated the LPS-induced increase in serum IL-10 concentrations, whereas posttreatment had no significant effect. We conclude that the timing of NOS inhibition is important for attenuating some deleterious effects of endotoxin.
OBJECTIVES: An increasing amount of experimental and epidemiological evidence implicates the involvement of oxygen derived radicals in the pathogenesis of cancer development. Oxygen derived radicals are able to cause damage to membranes, mitochondria, and macromolecules including proteins, lipids and DNA. Accumulation of DNA damages has been suggested to contribute to carcinogenesis. It would, therefore, be advantageous to pinpoint the effects of oxygen derived radicals in cancer development. DESIGN AND METHODS: In the present study, we investigated the relationship between oxidative stress and breast cancer development in tissue level. Breast cancer is the most common malignant disease in Western women. Twenty-one breast cancer patients, who underwent radical mastectomy and diagnosed with infiltrative ductal carcinoma, were used in the study. We determined coenzyme Q10 (Q) concentrations, antioxidant enzyme activities (mitochondrial and total superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase), and malondialdehyde (MDA) levels in tumor and surrounding tumor-free tissues. RESULTS: Q concentrations in tumor tissues significantly decreased as compared to the surrounding normal tissues (p < 0.001). Higher MDA levels were observed in tumor tissues than noncancerous tissues (p < 0.001). The activities of MnSOD, total SOD, GSH-Px and catalase in tumor tissues significantly increased (p < 0.001) compared to the controls. CONCLUSIONS: These findings may support that reactive oxygen species increased in malignant cells, and may cause overexpression of antioxidant enzymes and the consumption of coenzyme Q10. Increased antioxidant enzyme activities may be related with the susceptibility of cells to carcinogenic agents and the response of tumor cells to the chemotherapeutic agents. Administration of coenzyme Q10 by nutrition may induce the protective effect of coenzyme Q10 on breast tissue.
Germ line BRCA1 and/or BRCA2 mutations were screened in 50 Turkish breast and/or ovarian cancer patients composed of hereditary, familial, early onset and male cancer groups. Genomic DNA samples were tested by heteroduplex analysis and DNA sequencing. Two truncating BRCA2 mutations, one novel (6880 insG) and one previously reported (3034 delAAAC), were found in two out of six (33%) hereditary breast and/or ovarian cancer patients. A novel truncating (1200 insA) and a missense (2080A-->G) BRCA1 mutation was found in two of 27 (7%) individuals in the early onset group. A total of four (8%) disease-causing mutations in 50 breast cancer patients were identified in BRCA1 and BRCA2 genes. In addition, five BRCA1 sequence variants have been identified in 23 patients. These results indicate that BRCA1 and BRCA2 genes are involved in some, but not all, forms of hereditary predisposition to breast cancer in the Turkish population.
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BACKGROUND: The aim of this study was to investigate the effects of inducible nitric oxide synthase inhibition by aminoguanidine on endotoxin-induced reduction in mesenteric blood flow. METHODS: Twenty Sprague-Dawley rats (180-230 g) allocated into four groups were administered either Escherichia coli endotoxin 1 mg/kg intraperitoneally or its solvent saline and were pretreated with either aminoguanidine (15 mg/kg intraperitoneally 20 min before and 2 h after endotoxin injection) or saline. Some 4 h after endotoxin injection, animals were anaesthetized, arterial blood pressure and mesenteric blood flow were measured and the resistance in the mesenteric vascular beds was then calculated. The effect of phenylephrine (1-30 microg/kg intravenously) on these parameters was also investigated. RESULTS: Endotoxin did not significantly modify the mean arterial blood pressure but decreased mesenteric blood flow by increasing the vascular resistance (mean(s.e.m.) 7.8(1.0) versus 13.7(1.2) mmHg per min per ml for control versus endotoxin groups; n = 5, P = 0.0099). Aminoguanidine alone had no effect on either the mean arterial blood pressure or mesenteric blood flow, but it completely blocked the effects of endotoxin. On the other hand, endotoxin significantly attenuated the responsiveness to phenylephrine which was restored by aminoguanidine. CONCLUSION: The present results indicate that endotoxin decreases the mesenteric vascular blood flow by increasing vascular resistance and decreases responsiveness to phenylephrine. The effects of endotoxin were inhibited by aminoguanidine. The mesenteric vasoconstriction in response to endotoxin might not be explained by the overproduction of nitric oxide; other actions of aminoguanidine may explain its inhibitory effect. Presented in part to the 10th Annual Meeting of the Surgical Infection Society - Europe, Istanbul, Turkey, May 1997
BACKGROUND: The aim of the present study was to evaluate the effects of laparotomy and CO2 insufflation on wound healing in a murine incisional wound healing model. METHODS: Seventy-two male Swiss Albino mice were randomly allocated into three groups of control, laparotomy and CO2 insufflation. A transverse skin incision of 15 mm was made in the dorsum of each mouse, and four interrupted mattress sutures with 4.0 polypropylene thread were laid for wound closure. A median laparotomy was performed in the laparotomy group. CO2 insufflation was performed with an intra-abdominal pressure of 9 mmHg. The retained gas was evacuated from the abdominal cavity at the end of a 60-min period. Mice were killed on the 3rd, 7th and 15th postoperative days. The wound tensile strength and 5-hydroxyproline concentration in the wound tissue were measured. RESULTS: Tensile strength of the incised skin increased as the post-incision period progressed. There was no significant difference between the tensile strengths of the incised skin of control, laparotomy and CO2 insufflation groups throughout the observation period. The skin 5-hydroxyproline concentrations of all groups were not significantly different at the 3rd postoperative day. But laparotomy and CO2 insufflation groups had lower 5-hydroxyproline concentrations at the 7th and 15th postoperative days, when compared to controls (P < 0.02 for 7th and 15th days). CONCLUSION: CO2 insufflation and laparotomy reduce the 5-hydroxyproline concentration of the wound, suggesting a diminished wound healing capacity.
BACKGROUND: Although the effect of locally applied ischemia-reperfusion (I-R) injury on gastrointestinal anastomoses has been studied, to our knowledge there is no previous study that investigates the effect of remote I-R injury on gastrointestinal anastomotic healing. The aim of this study was to investigate and compare the effects of local I-R injury and remote I-R injury on the healing of colonic anastomoses. METHODS: Anastomosis of the right colon was performed in 30 rats that were divided into 5 groups. Group 1 was the control group. In Group 2, I-R was applied to the colonic segment containing the anastomosis. Unilateral lower extremity I-R, unilateral renal I-R, and segmental small intestinal I-R was applied to the rats in Groups 3, 4, and 5, respectively, at the same time as colonic anastomosis. On the fourth postoperative day, animals were killed and bursting pressure and tissue hydroxyproline concentration of the anastomoses were analyzed and compared. RESULTS: The mean bursting pressure values were: 143 mm Hg in Group 1, 40.8 mm Hg in Group 2, 82.8 mm Hg in Group 3, 46.1 mm Hg in Group 4, and 52.3 mm Hg in Group 5 (P <.0001; 1-way analysis of variance). Mean tissue hydroxyproline concentration values were: 5.3 microg/mg in Group 1, 1.6 microg/mg in Group 2, 2.2 microg/mg in Group 3, 1.3 microg/mg in Group 4, and 1.5 microg/mg in Group 5 (P <. 0001, 1-way analysis of variance). Bursting pressure and tissue hydroxyproline concentration values had a good correlation r = 0.86, P <.001, Pearson correlation analysis). CONCLUSIONS: This study showed that I-R injury is a systemic phenomenon, and remote organ I-R can significantly delay anastomotic healing. This has to be kept in mind when constructing an intestinal anastomosis in the presence of local or remote I-R injury.
OBJECTIVE: To investigate the effect of endotoxaemia on rat mesenteric vascular bed and plasma nitrite concentrations, the possible beneficial effect of aminoguanidine (the selective inducible nitric oxide synthase inhibitor) compared with N(G)-nitro-L-arginine methyl ester (L-NAME) (non-selective nitric oxide synthase inhibitor). DESIGN: Randomised experiment. SETTING: University surgical research laboratory, Turkey. SUBJECTS: 75 Wistar rats. INTERVENTIONS: Rats were divided into control (n = 30) and endotoxaemia (n = 42) groups. Endotoxaemia was produced by intraperitoneal injection of lipopolysaccharide 20 mg/kg. Subgroups were given either aminoguanidine or L-NAME. MAIN OUTCOME MEASURES: After 4 hours, isolated perfused mesenteric preparations were obtained and pressor responses to phenylephrine and vasodilatation responses to acetylcholine were evaluated, and plasma nitrite concentrations measured. RESULTS: Pressor response to phenylephrine did not alter but vasodilatation in response to acetylcholine was significantly reduced during endotoxaemia. Pretreatment with aminoguanidine prevented the impairment of the response to acetylcholine. However, L-NAME was ineffective. In the control group, aminoguanidine and L-NAME did not alter the vascular reactivity. The baseline plasma nitrite concentrations in the control group were increased 5-fold during endotoxaemia. This increase was significantly reduced with aminoguanidine but not with L-NAME. CONCLUSION: The protection achieved by aminoguanidine but not L-NAME suggested that nitric oxide produced by inducible nitric oxide synthase had a role in the impairment of endothelial response during endotoxaemia, and confirmed the importance of selective inducible nitric oxide synthase inhibition to achieve beneficial effects in endotoxaemia.
OBJECTIVE: To investigate the effect of various doses of melatonin on reduction in mesenteric blood flow (MBF) and increase in tumour necrosis factor alpha (TNFalpha) concentration caused by injection of lipopolysaccharide (LPS). DESIGN: University Hospital, Turkey. SETTING: Open experimental study. ANIMALS: 59 Swiss albino mice. INTERVENTIONS: Animals were injected with melatonin solvent or 1, 10, 100, or 500 mg/kg melatonin. Ten minutes later control animals were injected with saline, and the experimental group with LPS. MAIN OUTCOME MEASURES: Mesenteric blood flow and serum TNFalpha concentration. RESULTS: In control animals, 100 and 500 mg/kg melatonin reduced MBF. LPS reduced MBF in solvent, 1, and 10 mg/kg melatonin groups. The concentration of TNFalpha was considerably increased in the mice given LPS. Melatonin reduced this response significantly. CONCLUSION: In high doses melatonin directly reduces MBF. It has no protective effect on the LPS-induced decrease in MBF. In lower doses it blocks, but at higher doses reduces, LPS-induced TNFalpha production.
OBJECTIVE: To assess the adhesive potential and incidence of incisional hernia with three meshes. DESIGN: Open experimental study. SETTING: Surgical Research Laboratory, Turkey. ANIMALS: 75 Wistar albino rats INTERVENTIONS: Abdominal walls were excised, and defects closed primarily or with polyglactin 910, polypropylene, or dura mater. Adhesions were graded and hydroxyproline concentrations measured on days 14 and 180. On day 180, the incidence of incisional hernia, and the grades of inflammation and fibrosis were also recorded. RESULTS: The polyglactin 910 group had a higher adhesion grading than the control and dura mater groups on day 14, whereas the polypropylene group had higher adhesion grading than controls. Both polypropylene and polyglactin 910 groups had significantly higher concentration of hydroxyproline than the control and dura mater groups. On day 180, the polypropylene group had a higher adhesion grading than the controls. There were no differences in hydroxyproline concentrations, incidence of hernias, or grading of fibrosis levels among the groups. CONCLUSION: Polyglactin 910 induced more fibrotic adhesions in the early postoperative period whereas polypropylene did in both the early and late postoperative periods.
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OBJECTIVE: To investigate the effect of octreotide, a long-acting analogue of somatostatin, on postoperative adhesion formation, because somatostatin inhibits secretion of some growth factors that have modulatory effects on collagen synthesis. DESIGN: An experimental study. SETTING: Surgical Research and Biochemistry laboratories at Hacettepe University, Ankara, Turkey. SUBJECTS: Male Swiss albino mice. INTERVENTIONS: Both sides of a 5-cm ileal segment from Swiss albino mice were scraped 10 times, and transient ischemia was induced by clamping the segmental artery. Animals were injected subcutaneously with 1 mL/d of saline for 3 days (group 1), a single 5-mL intraperitoneal dose of saline (group 2), subcutaneously with 10 micrograms/kg daily of octreotide for 3 days (group 3) or a single 10 micrograms/kg intraperitoneal dose of octreotide (group 4). In half of the animals repeat laparotomy was performed on postoperative day 5. After adhesions were graded, the scraped ileal segments were excised for determination of hydroxyproline quantity. The same procedure was repeated on postoperative day 14 for the remaining animals. OUTCOME MEASURES: Adhesion grading, hydroxyproline levels. RESULTS: On postoperative day 5, the intraperitoneal octreotide group (group 4) had a significantly lower median adhesion score than groups 1 and 2. On postoperative day 14, both octreotide groups (3 and 4) had a significantly lower median adhesion grading than both saline groups (1 and 2). Hydroxyproline levels of the groups were not significantly different on either day 5 or day 14. CONCLUSION: Octreotide has a beneficial effect in decreasing adhesion formation in the early postoperative period.