Histological alterations in cavernous tissue after radical prostatectomy

PURPOSE: Radical prostatectomy often results in erectile dysfunction because of lesions to the erectile nerves. In this study we evaluated histomorphological alterations in cavernous smooth muscle and collagen content after radical prostatectomy. MATERIALS AND METHODS: A total of 19 patients between 57 and 69 years old with prostate adenocarcinoma and normal erectile function, as reported and validated by RigiScan (UroHealth Systems, Laguna Niguel, California) testing, underwent corpora cavernosa biopsy in the operating room before radical prostatectomy, and 2 and 12 months after surgery. No patient underwent hormone therapy before or after surgery and none was diabetic. Elastic fibers (manual counting), muscle specific actin (immunostaining) and collagen content (computerized morphometric imaging) were measured in the 3 biopsies. RESULTS: In all cases the first postoperative histological assessment revealed some disorganization. Trabecular elastic fibers (p <0.0003) and smooth muscle fibers were decreased and collagen content was significantly increased (p <0.0003) compared with preoperative biopsies. One year after surgery elastic fibers (p <0.0003) and smooth muscle fibers were decreased and collagen content was significantly increased (p <0.0003) compared with the first postoperative biopsy. Moreover, organized collagen and trabecular protocollagen deposits were increased. CONCLUSIONS: Progressive fibrosis in the corpora cavernosa after radical prostatectomy probably results from denervation and/or an ischemic process, which is caused in turn by the ligation of anomalous pudendal artery branches or of venous plexuses that drain to or from the corpora cavernosa. Fibrosis and the subsequent loss in elasticity and function of erectile tissue probably together cause erectile dysfunction.     

An insulin sensitizer improves the free radical defense system potential and insulin sensitivity in high fructose-fed rats.

Recently there has been growing interest in the effects of antioxidants on insulin activity. In the present study, we investigated the effect of metformin on free radical activity and insulin sensitivity in high fructose-fed rats, a diet that leads to insulin resistance. The animals were divided into four groups (n = 16 per group; experiment duration = 6 weeks): the control (C) group received a standard diet; the control metformin (CM) group was fed a control diet and received metformin (200 mg x kg(-1) x day(-1) in water); the fructose control (FT) group was fed a diet in which fructose composed 56.8% of the total carbohydrates; and the fructose metformin (FM) group received high-fructose diet and metformin (200 mg x kg(-1) x day(-1) in water). The glucose clamp technique was used to determine insulin sensitivity in eight animals per group. Metabolic and oxidative stress parameters were measured in the remaining rats. In the FT rats, insulin resistance, lower red cell CuZn superoxide dismutase activity and lower blood reduced glutathione were observed. Metformin treatment improved both the insulin activity and the antioxidant defense system. In the CM group, metformin had no effect on metabolic parameters, but improved red cell antioxidant enzyme activities and the blood GSH level, which suggests that it has an antioxidant activity independent of its effect on insulin activity.     

Erythrocyte defense mechanisms against free oxygen radicals in haemodialysed uraemic children

Changes in erythrocyte lipid peroxidation (measured as the concentration of malonyl dialdehyde), glutathione metabolism, antioxidant enzyme activities (glutathione peroxidase, catalase, and superoxide dismutase), the oxidized products of haemoglobin (Hb), and hydrogen peroxide (H₂O₂)-induced haemolysis were studied in six children with chronic renal failure treated with serial acetate and bicarbonate haemodialysis (HD). Ten age- and sex-matched children acted as controls. Malonyl dialdehyde levels were significantly higher and antioxidant enzyme activities lower in uraemic red blood cells (RBCs) compared with controls (P<0.05). Incubation of RBCs for 1 h with acetylphenylhydrazine induced a decrease in the concentration of reduced glutathione (P<0.001) and an increase in the level of oxidized products of Hb (P<0.001), but only in the uraemic patients. The H₂O₂ haemolysis test revealed a mild (n=3) to increased (n=3) haemolysis in the uraemic RBCs. Oxidative haemolysis is probably a multifactorial process in uraemic patients, and may be an important risk factor in HD therapy.     

皮肤软组织扩张后的自由基水平变化

Ｓ－Ｄ大白鼠背部置入２０ｍｌ扩张器，扩张２３～２５天，于最后一次扩张（总量达２０ｍｌ）前、扩张后１ｈ、６ｈ、１２ｈ和２４ｈ分别测定扩张皮肤组织中ＳＯＤ活性和ＭＤＡ含量。结果表明：ＳＯＤ活性和ＭＤＡ含量扩张后１ｈ、６ｈ及１２ｈ与扩张前比较差异有非常显著性（Ｐ＜０．０１）；至扩张后２４ｈ基本回复到扩张前水平（Ｐ＞０．０５）。探讨组织扩张自由基形成机理，为安全、快速、有效地进行皮肤组织扩张提供新的思路。     

实验性精索静脉曲张睾丸组织自由基水平的测定观察

本实验以Wistar大鼠人工复制精索静脉曲张病理模型。2、3个月后,处死动物,摘取睾丸,应用电子自旋共振技术(ESR)检测睾丸组织自由基相对水平并观察了丙二醛(MDA)含量的变化。结果显示,精索静脉曲张组(VG)左、右睾丸氧自由基水平均显著高于对照组(CG),差异有非常显著性意义。其中2个月时VG左右睾丸增高最显著,分别高于3个月时的双侧VG(P<0.01,P<0.05);睾丸MDA含量2月、3月VG双侧均显著高于CG(P<0.05)。实验结果表明,在精索静脉曲张发病过程中,睾丸组织产生大量的氧自由基并启动胞膜的脂质过氧化,从而对睾丸的生精细胞产生毒性作用。提示早期损伤程度较重。这也从一方面支持了尽早治疗可减轻精索静脉曲张睾丸功能障碍的观点。     

A free radical scavenger reduces hematoma-induced flap necrosis in Fischer rats

Free radicals have been shown to play an important role in hematoma-induced flap necrosis. The present study investigated the effect of deferoxamine, a free radical scavenger and iron chelator, on flap necrosis. A 4 X 2 cm dorsal flap was raised in Fischer inbred rats, and 3 cc of blood from inbred donors was instilled beneath the flap. Saline-treated control animals (Group 1) were compared with two experimental groups. In Group 2, deferoxamine 150 mg/kg was administered 15 minutes before surgery and every 8 hours for 5 days. In Group 3, deferoxamine was given every 8 hours for 3 days before surgery and every 8 hours for 5 days postoperatively. Flap necrosis was assessed on postoperative day 5. Group 2 had significantly less necrosis, 18.6%, than the control group, 64.0% (p less than 0.001). Group 3, with 36.0% necrosis, also showed improvement (p less than 0.05). Group 2 and Group 3 were not significantly different. Deferoxamine, a safe and well-tolerated free radical scavenger, greatly enhanced flap survival, presumably by the neutralization of damaging free radical species and by chelation of iron.     

The effect of the pneumoperitoneum on the peritoneal defense mechanisms in diabetic rats

To investigate the effects of pneumoperitoneum on the peritoneal defense mechanism induced by streptozocin infusion during laparoscopic surgery in diabetic rats and to show the importance of regulation of diabetes for peritoneal defense mechanisms. One hundred twenty-six Sprague-Dawley male rats were allocated into six groups each consisting of 21 rats: group 1, nondiabetic sham laparotomy (control); group 2, nondiabetic pneumoperitoneum (control); group 3, uncontrolled diabetes plus sham laparotomy; group 4, controlled diabetes plus sham laparotomy; group 5, uncontrolled diabetes plus pneumoperitoneum; and group 6, controlled diabetes plus pneumoperitoneum. Diabetes was constituted by intraperitoneal infusion of one dose of 60 mg/kg streptozotocin, and diabetes was regulated (in groups 4 and 6) by subcutaneous injection of 10 IU/kg insulin in the morning and evening after the blood glucose measurements since the fourth day. Peritoneal fluid samples were taken at the zero, second, and sixth hours after sham laparotomy for groups 1, 3, and 4 and after pneumoperitoneum for groups 2, 5, and 6 on the seventh day. Total peritoneal cell count, antibacterial activity of the peritoneal fluid, and types of phagocytic cells in the peritoneal fluid were assessed. Peritoneal cell count was found to be lower in uncontrolled diabetes due to high blood glucose levels (>200 mg/dL), which led to slow migration of phagocytic cells into the peritoneum. Pneumoperitoneum had augmented the effect on phagocytic cell migration to the peritoneum compared with the sham laparotomy in controlled diabetic rats. Uncontrolled and controlled diabetes have adverse effects on peritoneal defense mechanism killing functions by interfering with the antimicrobial activity of peritoneal fluid.     

Alterations in free radical tissue-defense mechanisms in streptozocin-induced diabetes in rat. Effects of insulin treatment

We investigated the possible involvement of reactive oxygen radical-related processes in chronic (12-wk) diabetes induced in rats by streptozocin (STZ). Diabetes was associated with significantly increased activities of catalase (CAT), glutathione reductase (GSSG-RD), and CuZn-superoxide dismutase (SOD) in the pancreas and of CAT and GSSG-RD in the heart. On the other hand, the liver of diabetic rats showed a generalized decrease in CAT, glutathione peroxidase (GSH-PX), and SOD as well as in the levels of reduced glutathione (GSH). Diabetic kidney also showed decreases in CAT and SOD, but the activities of GSH-PX were increased. Insulin treatment (9-12 U/kg body wt) that was started after 8 wk of diabetes and continued for 4 wk reversed all of the foregoing alterations in tissue antioxidant status. Our results suggest the presence of increased oxidative stress in uncontrolled diabetes as manifested by the marked alterations in tissue antioxidant enzyme activities, the magnitude of which increased with the degree of emaciation. The complex patterns of changes observed in the various tissues examined are believed to be the result of compensatory increases in enzyme activities (usually involving enzymes whose activity in control tissues is low) and direct inhibitory effects, possibly resulting from an increased tissue-oxidant activity. Our findings support the view that tissue antioxidant status may be an important factor in the etiology of diabetes and its complications.     

Natural host defense mechanisms.

Severe injury, whether the result of a major accident, a large burn, or a complicated surgical operation, often results in sepsis. Under such conditions both specific and nonspecific host defense systems are affected. The individual facets of major concern are chemotaxis, phagocytosis, intracellular killing, complement depletion, and depression of humoral and cellular mediated immunity. The most profound changes occur in cell-mediated immunity. Within a few hours o injury, the number of circulating T cells becomes depleted, concomitantly thoracic duct lymphocytes are markedly reduced. This change is not only quantitative but functional. The clinical impact of these deficient host defense mechanisms lies in the fact that low virulent organisms may become a lethal threat to the injured patient. Currently, investigators are attempting to reverse thse deficiencies through the use of immunotherapy.     

L-arginine and free radical scavengers increase cerebral blood flow and brain tissue nitric oxide concentrations after controlled cortical impact injury in rats

To examine the mechanism of the increase in cerebral blood flow induced by L-arginine administration after traumatic brain injury, the cerebral hemodynamic effects of L-arginine, D-arginine, and the free radical scavengers superoxide dismutase (SOD) and catalase were compared in the controlled cortical impact injury model in rats. Animals were anesthetized with isoflurane. Measured parameters included mean blood pressure, intracranial pressure, cerebral blood flow using laser Doppler flowmetry (LDF) and brain tissue nitric oxide (NO) concentrations using an NO electrode. L-arginine, but not D-arginine, administration resulted in a significant increase in tissue NO concentrations and an improvement in LDF at the impact site, compared to control animals given saline. Administration of SOD alone and in combination with catalase resulted in a significant increase in brain tissue NO concentrations. However, LDF was consistently improved only when both SOD and catalase were given. These studies support the theory that L-arginine administration improves post-traumatic cerebral blood flow by increasing NO production. Free radical production after trauma may also contribute to the reduction in CBF by inactivating NO.     

Effects of endurance training on antioxidant defense mechanisms and lipid peroxidation in testis of rats

Male rats were equally divided into trained rest (TR), trained exhaustive exercise (TE), untrained rest (UR), and untrained exhaustive exercise (UE). Endurance training consisted of treadmill running for 1.5 h/d, 5 days a week for 8 weeks reaching the speed of 2.1 km/h at the fortieth week. For acute exhaustive exercise, graded treadmill running was conducted reaching the speed of 2.1 km/h at 95th min, 10% uphill, continued until exhaustion. Testicular tissue malondialdehyde (MDA), antioxidant potential (AOP) levels, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST), glutathione reductase (GR) and catalase (CAT) activities were determined. There was a slight decrease, but not significant, in the SOD activity in UE group compared to TE and TR groups. Activity of GSH-Px decreased in the UE group compared to UR, TR and TE groups. Acute exhaustive exercise did not affect testicular tissue GSH-Px activity in trained rats. Testicular tissue GST activity of the UE group was similar to TE group, but lower than UR and TR groups. In UE group, testicular tissue AOP values were lower than UR, TR and TE groups. The oxidative effects of acute exhaustive exercise on the rat testis decreased with endurance training. Endurance training prevents oxidative injuries by eliminating oxygen radicals and inhibiting lipid peroxidation via preventing decreases in antioxidant enzyme activities.     

Host defense mechanisms in urinary tract infections

The host response to urinary tract infections is directed against both bacterial surface antigens, as well as bacterial products. The local response is perhaps the most important, with prevention of binding and tissue invasion as the hallmarks. Once an infection is established, the humoral immune system is most active in curtailing the damage and clearing the infecting organism. The prostate has a specialized complex of defenses that serves to reduce the incidence of infections in males.     

The role of a free radical mechanisms in intestinal obstruction during peritonitis and its repair]

In 53 patients with diffuse peritonitis in a toxical phase there was investigated the dynamics of the gut functional impassability regress after the operation. There were adduced the grounds for application of the preparations with antihypoxical and antioxidant properties in complex therapy of such patients. The method of selective spectral peripheric electrogastroenterography was introduced as a noninvasive method of computeric monitoring of the gut functional state.     

The role of oxygen free radical and free radical scavenger in septic and hemorrhagic shock

The roles of oxygen free radical (O2-), lipoperoxide (LPO) and free radical scavenger were clinically and experimentally studied in septic and hemorrhagic shock. The reduction of hepatic tissue blood flow (TBF) were equalized in two groups (40-55% of normal level) and rats were subdivided into 3 groups: untreated, normal saline (NS) continuous IV and superoxide dismutase: SOD + catalase (S/c) continuous IV as free radical scavenger. The change of TBF, destruction of mitochondrial structure and elevation of LPO were prevented by S/c in Et shock. No significant effect by S/c was observed in hemorrhagic shock. The neutrophil derived O2- was markedly elevated in Et shock animals as well as septic shock patients but no significant change was noted in hemorrhagic shock animals or non septic shock patient. SOD and catalase were effective for neutrophil derived O2- in septic shock whereas little beneficial effect was noted in hemorrhagic or non septic shock.