Search

The aim of this study was to investigate the effects of onion (Allium cepa) extracts (ACE) on doxorubicin (DOX)-induced apoptosis in aortic endothelial cells. The rats in the ACE-pretreated group were given a daily dose of 1 ml ACE for 14 days. To induce aortic endothelial cell apoptosis, DOX (30 mg kg(-1) body weight) was injected intraperitoneally by a single dose and the rats were sacrificed after 48 h. To date, no such studies have been performed on antiapoptotic potential of ACE on DOX-induced apoptosis in aortic endothelial cells. Our data indicate a significant reduction in the activity of in situ identification of apoptosis using terminal dUTP nick end-labeling in aortic endothelial cells of the DOX-treated group with ACE therapy. DOX-treated with ACE groups showed a significant decrease in malondialdehyde levels and increased levels of glutathione in comparison with the DOX-treated group. Data from our study show that prevention of endothelial cell apoptosis by ACE may contribute to the restoration of aortic endothelial dysfunction that is associated with DOX treatment., (Copyright © 2011 John Wiley & Sons, Ltd.)

Scrotal hyperthermia has been known as a cause of male infertility but the exact mechanism leading to impaired spermatogenesis is unknown. This work was aimed to investigate the role of scrotal hyperthermia on cell proliferation and apoptosis in testes. The rats were randomly allotted into one of the four experimental groups: A (control), B (1 day after scrotal hyperthermia), C (14 days after scrotal hyperthermia), and D (35 days after scrotal hyperthermia); each group comprised 7 animals. Scrotal hyperthermia was carried out in a thermostatically controlled water bath at 43°C for 30 min once daily for 6 consecutive days. Control rats were treated in the same way, except the testes were immersed in a water bath maintained at 22°C. Hyperthermia-exposed rats were killed under 50 mg/kg ketamine anaesthesia and tissue samples were obtained for biochemical and histopathological investigations. Hyperthermia treatment significantly decreased the testicular antioxidant system, including decreases in the glutathione level, superoxide dismutase, and glutathione peroxidase activities. Moreover, exposure to hyperthermia resulted in lipid peroxidation increase in testes. Our data indicate a significant reduction in the expression of proliferating cell nuclear antigen and an enhancement in the activity of terminal deoxynucleotidyl transferase dUTP nick end labelling after scrotal hyperthermia. In scrotal hyperthermia, the mitochondrial degeneration, dilatation of smooth endoplasmic reticulum, and enlarged intercellular spaces were observed in both Sertoli and spermatid cells. Scrotal hyperthermia is one of the major factors that impair spermatogenesis in testis. This heat stress is shown to be closely associated with oxidative stress, followed by apoptosis of germ cells.

Objectives: To evaluate whether consumption of the low-glycemic index (GI) carbohydrate sucromalt improves healthy adults' perceptions of mental and physical energy and fatigue compared to dextrose (glucose), a high GI control., Methods: In this double-blind, randomized, cross-over study, subjects (n = 44 healthy adults) consumed a standardized dinner, and following an overnight fast, ingested 75 g of either sucromalt or glucose in solution at 7:30 AM the next day. Subjects completed validated questionnaires that assessed mental and physical energy, and fatigue, hunger, and sleepiness at baseline and hourly until 12:30 PM for a total of five post-consumption time points. Within-subject differences adjusted for baseline for individual questions and composite scores (Mental Energy State, Mental Fatigue State, Physical Energy State, and Physical Fatigue State) were analyzed using repeated measures analysis of variance., Results: Mental Energy State, Physical Energy State, and Physical Fatigue State results favored sucromalt compared to glucose, with significant differences emerging particularly after 4-5 hours (P < 0.050). A trend toward a delay in Mental Fatigue State was also observed with sucromalt compared to glucose (P < 0.100). Minimal differences in ratings of hunger and sleepiness were observed between the beverages., Discussion: Sucromalt may help attenuate the perceived decline in mental and physical energy and rise in mental and physical fatigue that can occur 4-5 hours after ingestion of a high GI beverage. Trials examining effects of sucromalt on cognitive and physical performance are of future interest.

The aim of this study was to investigate the antioxidant and anti-apoptotic effects of onion (Allium cepa) extracts (ACE) on doxorubicin (DOX)-induced cardiotoxicity. The rats in the ACE-pretreated group were given a daily dose of 1 ml ACE for 14 days. To induce cardiotoxicity, DOX (30 mg kg(-1) body weight) was injected intraperitoneally by a single dose and the rats were sacrificed after 48 h. To date, no such studies have been performed on the cardioprotective and anti-apoptotic potential of ACE on DOX-induced cardiotoxicity. Our data indicate a significant reduction in the activity of in situ identification of apoptosis using terminal dUTP nick end-labeling in cardiomyocytes of the DOX-treated group with ACE therapy. The DOX-treated with ACE groups showed a significant decrease in malondialdehyde levels, and increased activities of superoxide dismutase, glutathione and glutathione peroxidase in comparison with the DOX-treated group. Creatine kinase, creatine kinase MB, lactate dehydrogenase activities and cardiac troponin I levels were significantly decreased in the DOX + ACE group in comparison with the DOX group. These biochemical and histological disturbances were effectively attenuated on pretreatment with ACE. The present study showed that ACE may be a suitable cardioprotector against toxic effects of DOX., (Copyright © 2011 John Wiley & Sons, Ltd.)

The present study was designed to determine the role of topical treatment with curcumin (Cur) on burn wound healing in rats. The Wistar-albino rats were randomly allotted into one of three experimental groups: 4th, 8th and 12th day (post burn) and all groups include subgroups which Burn and Burn + Cur. Each group contains 12 animals. Burn wounds were made on the back of rat and Cur was administered topically. At the end of the study, all animals were sacrificed and the wound tissues removed for analyse to biochemical and histopathological changes. There was a significant increase in the hydroxyproline levels in the skin of the Cur groups. Cur treated wounds were found to heal much faster as indicated by improved rates of inflammatory cells, collagen deposition, angiogenesis, granulation tissue formation and epithelialization which were also confirmed by histopathological and biochemical examinations. Our data also indicate that there is a rise in the expression of proliferating cell nuclear antigen in skin tissues of Cur-treated rats in the Burn group. The results clearly substantiate the beneficial effects of the topical application of Cur in the acceleration of wound healing.

The uterosacral ligaments are an important part of the pelvic support system. The objective of this study was to compare the expression of collagen type I and collagen type III in the uterosacral ligament biopsies from women with and without pelvic organ prolapse (POP). The uterosacral ligament biopsies were obtained from women with POP (n = 29) and non-POP subjects (n = 35). Immunohistochemistry for collagen type I and collagen type III was performed on formalin-fixed and paraffin-embedded sections. The two groups were matched for age, body mass index, parity and postmenopausal status. The expression of collagen type I (p < 0.001) and collagen type III (p < 0.0001) differed between women with POP and non-POP subjects. There was decreased expression of collagen type I and increased expression of collagen type III in uterosacral ligaments of women with POP compared with non-POP subjects. This difference indicates a possible relationship between POP and the immunohistochemical expression of collagen type I and collagen type III in uterosacral ligaments.

Aim: The aim of this study is to determine the structural changes of electromagnetic waves in the frontal cortex, brain stem and cerebellum., Material and Methods: 24 Wistar Albino adult male rats were randomly divided into four groups: group I consisted of control rats, and groups II-IV comprised electromagnetically irradiated (EMR) with 900, 1800 and 2450 MHz. The heads of the rats were exposed to 900, 1800 and 2450 MHz microwaves irradiation for 1h per day for 2 months., Results: While the histopathological changes in the frontal cortex and brain stem were normal in the control group, there were severe degenerative changes, shrunken cytoplasm and extensively dark pyknotic nuclei in the EMR groups. Biochemical analysis demonstrated that the Total Antioxidative Capacity level was significantly decreased in the EMR groups and also Total Oxidative Capacity and Oxidative Stress Index levels were significantly increased in the frontal cortex, brain stem and cerebellum. IL-1β level was significantly increased in the EMR groups in the brain stem., Conclusion: EMR causes to structural changes in the frontal cortex, brain stem and cerebellum and impair the oxidative stress and inflammatory cytokine system. This deterioration can cause to disease including loss of these areas function and cancer development.

Renal ischemia-reperfusion (I/R) injury may occur after renal transplantation, thoracoabdominal aortic surgery, and renal artery interventions. This study was designed to investigate the effect of Urtica dioica L. (UD), in I/R induced renal injury. A total of 32 male Sprague-Dawley rats were divided into four groups: control, UD alone, I/R and I/R + UD; each group contain 8 animals. A rat model of renal I/R injury was induced by 45-min occlusion of the bilateral renal pedicles and 24-h reperfusion. In the UD group, 3 days before I/R, UD (2 ml/kg/day intraperitoneal) was administered by gastric gavage. All animals were sacrificed at the end of reperfusion and kidney tissues samples were obtained for histopathological investigation in all groups. To date, no more histopathological changes on intestinal I/R injury in rats by UD treatment have been reported. Renal I/R caused severe histopathological injury including tubular damage, atrophy dilatation, loss of brush border and hydropic epithelial cell degenerations, renal corpuscle atrophy, glomerular shrinkage, markedly focal mononuclear cell infiltrations in the kidney. UD treatment significantly attenuated the severity of intestinal I/R injury and significantly lowered tubulointerstitial damage score than the I/R group. The number of PCNA and TUNEL positive cells in the control and UD alone groups was negligible. When kidney sections were PCNA and TUNEL stained, there was a clear increase in the number of positive cells in the I/R group rats in the renal cortical tissues. However, there is a significant reduction in the activity of PCNA and TUNEL in kidney tissue of renal injury induced by renal I/R with UD therapy. Our results suggest that administration of UD attenuates renal I/R injury. These results suggest that UD treatment has a protective effect against renal damage induced by renal I/R. This protective effect is possibly due to its ability to inhibit I/R induced renal damage, apoptosis and cell proliferation.

The aim of this study was to investigate the possible protective effects of infliximab on oxidative stress, cell proliferation and apoptosis in the rat intestinal mucosa after ischemia/reperfusion (I/R). A total of 30 male Wistar albino rats were divided into three groups: sham, I/R and I/R+ infliximab; each group comprised 10 animals. Sham group animals underwent laparotomy without I/R injury. I/R groups after undergoing laparotomy, 1 hour of superior mesenteric artery ligation occurred, which was followed by 1 hour of reperfusion. In the infliximab group, 3 days before I/R, infliximab (3 mg/kg) was administered intravenously. All animals were killed at the end of reperfusion and intestinal tissues samples were obtained for biochemical and histopathological investigation in all groups. To date, no biochemical and histopathological changes have been reported regarding intestinal I/R injury in rats due to infliximab treatment. Infliximab treatment significantly decreased the elevated tissue malondialdehyde levels and increased reduced superoxide dismutase and glutathione peroxidase enzyme activities in intestinal tissues samples. I/R caused severe histopathological injury including mucosal erosions, inflammatory cell infiltration, necrosis, hemorrhage, and villous congestion. Infliximab treatment significantly attenuated the severity of intestinal I/R injury, inhibiting I/R-induced apoptosis, and cell proliferation. Because of its anti-inflammatory and antioxidant effects, infliximab pretreatment may have protective effects on the experimental intestinal I/R model of rats.

Background: Little is known about whether health information technology (HIT) affects patient experiences with health care., Objective: To develop HIT questions that assess patients care experiences not evaluated by existing ambulatory Consumer Assessment of Health Plans and Systems (CAHPS) measures., Research Design: We reviewed published articles and conducted focus groups and cognitive testing to develop survey questions. We collected data, using mail and the internet, from patients of 69 physicians receiving care at an academic medical center and 2 regional integrated delivery systems in late 2009 and 2010. We evaluated questions and scales about HIT using factor analysis, item-scale correlations, and reliability (internal consistency and physician-level) estimates., Results: We found support for 3 HIT composites: doctor use of computer (2 items), e-mail (2 items), and helpfulness of provider's website (4 items). Corrected item-scale correlations were 0.37 for the 2 doctor use of computer items and 0.71 for the 2 e-mail items, and ranged from 0.50 to 0.60 for the provider's website items. Cronbach α was high for e-mail (0.83) and provider's website (0.75), but only 0.54 for doctor use of computer. As few as 50 responses per physician would yield reliability of 0.70 for e-mail and provider's website. Two HIT composites, doctor use of computer (P<0.001) and provider's website (P=0.02), were independent predictors of overall ratings of doctors., Conclusions: New CAHPS HIT items were identified that measure aspects of patient experiences not assessed by the CAHPS C&G 1.0 survey.

The aim of this study was to evaluate the antiapoptotic and proliferative activity of curcumin (Cur) on the ovarian follicles in mice exposed to whole body ionizing radiation (Rd). The mice were exposed to 8.3 gray whole body Rd, and Cur groups were given as a daily dose of 100 mg/kg of Cur for 10 days (10 days before Rd). The ovaries were collected 3 and 12 h after irradiation. To date, no such studies have been performed on antiapoptotic and proliferative activity of Cur on the ovarian follicles in mice exposed to whole body Rd. Analysis of mice ovary after exposure to Rd by terminal-deoxynucleotidyl-transferase-mediated dUTP nick end labeling showed that there were apoptotic cells both in the follicular wall and the antrum, and that the number of follicles showing early atresic features was high 3 h after Rd. On the other hand, analysis of mice ovary 12 h after exposure to Rd showed that the number of follicles containing apoptotic cells with advanced atresic features was significantly higher when compared to the 3-h Rd exposure group. The proliferating cell nuclear antigen -positive granulosa cells were decreased in association with follicular atresia. The groups given treatment were observed to have some benefit from Cur against the damage caused by Rd. The results of this study demonstrate that Cur prevents follicular atresia in Rd-induced apoptosis in ovarian follicles.

The aim of this study was to evaluate the possible protective effects of quercetin (QE) on liver injury caused by chronic toluene exposure in rats. The rats were randomly allotted into one of three experimental groups: control, toluene treated and toluene treated with QE; each group contained 10 animals. The control group received 1 ml physiologic serum, and toluene treatment was performed by inhalation of 3000 ppm toluene, for 8 h/day and 6 days/week for 12 weeks. The rats in the QE-treated groups were given QE (15 mg/kg, intraperitoneal) once a day for 12 weeks starting just after toluene exposure. Tissue samples were obtained for histopathological investigation. To date, no histopathological changes in the liver of rats after chronic toluene exposure by QE treatment have been reported. Light microscopic evaluation of liver tissue samples of toluene-exposed rats revealed enlarged sinusoids filled with blood. In addition, some of the hepatocytes showed loss of cytoplasm, and some had a hyperchromatic nucleus. QE treatment attenuated alterations in liver histology. The alpha smooth muscle actin, transforming growth factor beta-positive cells and the activity of terminal deoxynucleotidyl transferase dUTP nick end labeling in the toluene-treated group were observed to be reduced with QE treatment. The data indicate that QE attenuates toluene-induced liver injury, but further investigation is still absolutely necessary.

The purpose of this study was to investigate the role of infliximab on acute lung injury induced by intestinal ischemia/reperfusion (I/R). A total of 30 male Wistar albino rats were divided into three groups: sham, I/R and I/R+ infliximab; each group contain 10 animals. Sham group animals underwent laparotomy without I/R injury. After I/R groups animals underwent laparotomy, 1 h of superior mesenteric artery ligation were followed by 1 h of reperfusion. In the infliximab group, 3 days before I/R, infliximab (3 mg/kg) was administered by intravenously. All animals were sacrificed at the end of reperfusion and lung tissues samples were obtained for biochemical and histopathological investigation in all groups. To date, no more biochemical and histopathological changes on intestinal I/R injury in rats by infliximab treatment have been reported. Infliximab treatment significantly decreased the elevated tissue malondialdehyde levels and increased of reduced superoxide dismutase, and glutathione peroxidase enzyme activities in lung tissues samples. Intestinal I/R caused severe histopathological injury including edema, hemorrhage, increased thickness of the alveolar wall and a great number of inflammatory cells that infiltrated the interstitium and alveoli. Infliximab treatment significantly attenuated the severity of intestinal I/R injury. Furthermore, there is a significant reduction in the activity of inducible nitric oxide synthase and arise in the expression of surfactant protein D in lung tissue of acute lung injury induced by intestinal I/R with infliximab therapy. It was concluded that infliximab treatment might be beneficial in acute lung injury, therefore, shows potential for clinical use. Because of its anti-inflammatory and antioxidant effects, infliximab pretreatment may have protective effects in acute lung injury induced by intestinal I/R.

Ziprasidone has been rarely associated with QT prolongation especially in patients (1) with no underlying cardiac or metabolic disorders, (2) who are receiving no concomitant medications known to prolong the QT interval, and (3) whom therapy is being initiated at a low dose. We report a 47-year-old patient who was agitated with suicidal ideation. He had a history of cocaine use, the last time being 72 hours before emergency department (ED) presentation. His electrocardiogram (ECG) on arrival in the ED showed a QT of 484 milliseconds and a QTc of 475 milliseconds with a pulse of 58 beats per minute. The patient was given 20 mg intramuscular (IM) ziprasidone for agitation. He reported feeling palpitations and weakness 45 minutes after receiving ziprasidone. His QT interval was prolonged on ECG and returned to baseline after 72 hours. Clinicians should consider obtaining an ECG before ziprasidone administration.

Myoglobinuric acute renal failure (ARF) is a uremic syndrome caused by traumatic or non-traumatic skeletal muscle breakdown and intracellular elements that are released into the bloodstream. We hypothesized that hyperbaric oxygen (HBO) therapy could be beneficial in the treatment of myoglobinuric ARF caused by rhabdomyolysis. A total of 32 rats were used in the study. The rats were divided into four groups: control, control+hyperbaric oxygen (control+HBO), ARF, and ARF+hyperbaric oxygen (ARF+HBO). Glycerol (8 ml/kg) was injected into the hind legs of each of the rats in ARF and ARF+HBO groups. 2.5 atmospheric absolute HBO was applied to the rats in the control+HBO and ARF+HBO groups for 90 min on two consecutive days. Plasma urea, creatinine, sodium, potassium, calcium, aspartate aminotransferase, alanine aminotransferase, lactic dehydrogenase, creatinine kinase and urine creatinine and sodium were examined. Creatinine clearance and fractional sodium excretion could then be calculated. Superoxide dismutase, catalase, glutathione and malondialdehyde (MDA) levels were assessed in renal tissue. Tissue samples were evaluated by Hematoxylin-eosin, PCNA and TUNEL staining histopathologically. MDA levels were found to be significantly decreased whereas SOD and CAT were twofold higher in the ARF+HBO group compared to the ARF group. Renal function tests were ameliorated by HBO therapy. Semiquantitative evaluation of histopathological findings indicated that necrosis and cast formation was decreased by HBO therapy and TUNEL staining showed that apoptosis was inhibited. PCNA staining showed that HBO therapy did not increase regeneration. Ultimately, we conclude that, in accordance with our hypothesis, HBO could be beneficial in the treatment of myoglobinuric ARF.

The aim of this study was to examine the preventive and therapeutic effects of thymoquinone (TQ) against cholestatic oxidative stress and liver damage in common bile duct ligated rats. A total of 24 male Sprague-Dawley rats were divided into three groups: control, bile duct ligation (BDL) and BDL + received TQ; each group contain 8 animals. The rats in TQ treated groups were given TQ (50 mg/kg body weight) once a day orally for 2 weeks starting 3 days prior to BDL operation. To date, no more biochemical and histopathological changes on common bile duct ligated rats by TQ treatment have been reported. The application of BDL clearly increased the tissue hydroxyproline (HP) content, malondialdehyde (MDA) levels and decreased the antioxidant enzyme [superoxide dismutase (SOD), glutathione peroxidase (GPx)] activities. TQ treatment significantly decreased the elevated tissue HP content, and MDA levels and raised the reduced of SOD, and GPx enzymes in the tissues. The changes demonstrating the bile duct proliferation and fibrosis in expanded portal tracts include the extension of proliferated bile ducts into lobules, mononuclear cells, and neutrophil infiltration into the widened portal areas were observed in BDL group. Treatment of BDL with TQ attenuated alterations in liver histology. The immunopositivity of alpha smooth muscle actin and proliferating cell nuclear antigen in BDL were observed to be reduced with the TQ treatment. The present study demonstrates that oral administration of TQ in bile duct ligated rats maintained antioxidant defenses and reduces liver oxidative damage and ductular proliferation. This effect of TQ may be useful in the preservation of liver function in cholestasis.

Cadmium (Cd) is one of the environmental pollutants affecting various tissues and organs including testis. The aim of this study was to investigate the anti-apoptotic effects of curcumin (Cur) on Cd-induced apoptosis in rat testes. The rats were randomly allotted into one of three experimental groups: control, Cd treated and Cd treated with Cur; each group contained 10 animals. The control group received 2 ml/day of dimethyl sulfoxide (DMSO). To induce toxicity, Cd (1 mg/kg body weight) was dissolved in normal saline and subcutaneously injected into rats for 4 weeks. The rats in Cur-treated group was given a daily dose of 100 mg/kg of Cur for 4 weeks. To date, no examinations of the anti-apoptotic properties of Cur on Cd-induced apoptosis in rat testes have been reported. The mean seminiferous tubule diameter, mean testicular biopsy score values and serum testosterone levels were significantly decreased in Cd-treated groups were compared to the control group. Furthermore, the Cur-treated animals showed an improved histological appearance and serum testosterone levels in Cd-treated group. Our data indicate a significant reduction in the activity of in situ identification of apoptosis using terminal dUTP nick end-labeling in testis tissues of the Cd-treated group with Cur therapy. The present study showed that Cur treatment protected testes against toxic effects of Cd. We believe that further preclinical research into the utility of Cur may indicate its usefulness as a potential treatment on the spermatogenesis after testicular injury caused by Cd-treated rats.

The aim of this study was to investigate the protective effect of quercetin (QE) on oxidative stress, apoptosis, and cell proliferation in the rat testis after streptozotocin (STZ)-induced diabetes. Diabetes was induced by a single intraperitoneal injection of STZ (50 mg/kg). The rats in the QE-treated group were given QE (15 mg/kg) once a day intraperitoneally for 8 weeks starting 3 days prior to STZ injection. At the end of the study, all animals were sacrificed. Testis tissues and blood samples were collected for histopathologic and biochemical analysis. QE treatment significantly decreased the elevated tissue malondialdehyde (MDA) levels and increased the reduced superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzyme activities in testis tissues samples. The QE-treated rats in the diabetic group showed an improved histologic appearance and serum testosterone levels. Our data indicate a significant reduction in the activity of in situ identification of apoptosis using terminal dUTP nick end-labeling (TUNEL) and there was a rise in the expression of proliferating cell nuclear antigen (PCNA) in testis tissues of QE-treated rats in the diabetic group. These results suggest that administration of QE is a potentially beneficial agent to reduce testicular damage in diabetic rats by decreasing oxidative stress., (Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.)

The elderly are particularly sensitive to delirium-inducing medications. We report a case of a 93-year-old woman who developed anticholinergic delirium from subcutaneous diphenhydramine that she received in the emergency department. This patient was reportedly allergic to “caine” anesthetic agents, and thus, subcutaneous diphenhydramine was administered as an alternative local anesthetic, as recommended in emergency medicine textbooks. Within 20 minutes of administration, the patient developed agitation, tachycardia, dilated pupils, and dry skin, consistent with a classic anticholinergic toxidrome. Diphenhydramine use is associated with a high incidence of anticholinergic adverse effects, especially in the elderly. Clinicians should carefully consider using diphenhydramine in this vulnerable population.

The aim of this study was to evaluate the therapeutic efficacy of caffeic acid phenethyl ester (CAPE) with an experimental traumatic brain injury (TBI) model in rats. Twenty-four adult male Sprague-Dawley rats were randomly divided into three groups of 8 rats each: control, TBI, and TBI + CAPE treatment. In TBI and TBI + CAPE treatment groups, a cranial impact was delivered to the skull from a height of 7 cm at a point just in front of the coronal suture and over the right hemisphere. Rats were sacrificed at 4 h after the onset of injury. Brain tissues were removed for biochemical and histopathological investigation. To date, no biochemical and histopathological changes of neurodegeneration in the frontal cortex after TBI in rats by CAPE treatment have been reported. The TBI significantly increased tissue malondialdehyde (MDA) levels, and significantly decreased tissue superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, but not tissue catalase (CAT) activity, when compared with controls. The administration of a single dose of CAPE (10 μmol/kg) 15 min after the trauma has shown protective effect via decreasing significantly the elevated MDA levels and also significantly increasing the reduced antioxidant enzyme (SOD and GPx) activities, except CAT activity. In the TBI group, severe degenerative changes, shrunken cytoplasma and extensively dark picnotic nuclei in neurons, as well as vacuolization indicating tissue edema formation. The morphology of neurons in the CAPE treatment group was well protected. The number of neurons in the trauma alone group was significantly less than that of both the control and TBI +CAPE treatment groups. The caspase 3 immunopositivity was increased in degenerating neurons of the traumatic brain tissue. Treatment of CAPE markedly reduced the immunoreactivity of degenerating neurons. TBI caused severe degenerative changes, shrunken cytoplasma, severely dilated cisternae of endoplasmic reticulum, markedly swollen mitochondria with degenerated cristae and nuclear membrane breakdown with chromatin disorganization in neurons of the frontal cortex. In conclusion, the CAPE treatment might be beneficial in preventing trauma-induced oxidative brain tissue damage, thus showing potential for clinical implications. We believe that further preclinical research into the utility of CAPE may indicate its usefulness as a potential treatment on neurodegeneration after TBI in rats.

The aim of this study was to demonstrate the role of curcumin on oxidative stress, cell proliferation and apoptosis in the rat intestinal mucosa after ischemia/reperfusion (I/R). A total of 30 male Wistar albino rats were divided into three groups: sham, I/R and I/R+ curcumin; each group contain 10 animals. Sham group animals underwent laparotomy without I/R injury. After I/R groups animals underwent laparotomy, 1 h of superior mesenteric artery ligation were followed by 1 h of reperfusion. In the curcumin group, 3 days before I/R, curcumin (100 mg/kg) was administered by gastric gavage. All animals were sacrificed at the end of reperfusion and intestinal tissues samples were obtained for biochemical and histopathological investigation in all groups. Curcumin treatment significantly decreased the elevated tissue malondialdehyde levels and increased of reduced superoxide dismutase, and glutathione peroxidase enzyme activities in intestinal tissues samples. I/R caused severe histopathological injury including mucosal erosions and villous congestion and hemorrhage. Curcumin treatment significantly attenuated the severity of intestinal I/R injury, with inhibiting of I/R-induced apoptosis and cell proliferation. These results suggest that curcumin treatment has a protective effect against intestinal damage induced by intestinal I/R. This protective effect is possibly due to its ability to inhibit I/R-induced oxidative stress, apoptosis and cell proliferation.

The aim of this study was to investigate the protective effect of Ginkgo biloba (EGb 761) on testicular torsion/detorsion induced ischemia-reperfusion (I/R) injury. A total of 24 male Wistar albino rats were divided into three groups: control, I/R and I/R treated with EGb 761; each group contains 8 animals. Testicular torsion was created by rotating the left testis 720° in a clockwise direction. The ischemia period was 5 h and orchiectomy was performed after 5 h of detorsion. EGb 761 (50 mg/kg, orally) was administrated only once, 40 min prior to detorsion. To date, no more histopathological changes on testicular torsion/detorsion induced ischemia-reperfusion (I/R) injury in rats by EGb 761 treatment have been reported. Spermatogenesis and mean seminiferous tubule diameter (MSTD) were significantly decreased in I/R groups were compared to the control group. Furthermore, EGb 761 treated animals showed an improved histological appearance in I/R group. Our data indicate a significant reduction in the activity of TUNEL and endothelial nitric oxide synthase (eNOS) in testes tissue of I/R treated with EGb 761 therapy. Electron microscopy of the testes of rats demonstrated that EGb 761 pretreatment was particularly effective in preventing the mitochondrial degeneration, dilatation of SER and enlarged intercellular spaces in both Sertoli and spermatid cells in I/R treated animals. We believe that further preclinical research into the utility of EGb 761 may indicate its usefulness as a potential treatment on testes injury after I/R in rats., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate the possible protective effects of caffeic acid phenethyl ester (CAPE) against cholestatic oxidative stress and liver damage in the common bile duct ligated rats. A total of 18 male Sprague-Dawley rats were divided into three groups: control, bile duct ligation (BDL) and BDL + received CAPE; each group contain 6 animals. The rats in CAPE treated groups were given CAPE (10 μmol/kg) once a day intraperitoneally (i.p) for 2 weeks starting just after BDL operation. The changes demonstrating the bile duct proliferation and fibrosis in expanded portal tracts include the extension of proliferated bile ducts into lobules, inflammatory cell infiltration into the widened portal areas were observed in BDL group. Treatment of BDL with CAPE attenuated alterations in liver histology. The proliferating cell nuclear antigen and the activity of TUNEL in the BDL were observed to be reduced with the QE treatment. The application of BDL clearly increased the tissue hydroxyproline (HP) content, malondialdehyde (MDA) levels and decreased the antioxidant enzyme (superoxide dismutase (SOD), glutathione peroxidase (GPx)) activities. CAPE treatment significantly decreased the elevated tissue HP content, and MDA levels and raised the reduced of SOD, and GPx enzymes in the tissues. The data indicate that CAPE attenuates BDL-induced cholestatic liver injury, bile duct proliferation, and fibrosis. The hepatoprotective effect of CAPE is associated with antioxidative potential.

We have studied whether hyperbaric oxygen (HBO) prevents different pulmonary aspiration materials-induced lung injury in rats. The experiments were designed in 60 Sprague-Dawley rats, ranging in weight from 250 to 300 g, randomly allotted into one of six groups (n = 10): saline control, Biosorb Energy Plus (BIO), hydrochloric acid (HCl), saline + HBO treated, BIO + HBO treated, and HCl + HBO treated. Saline, BIO, HCl were injected into the lungs in a volume of 2 ml/kg. A total of seven HBO sessions were performed at 2,4 atm 100% oxygen for 90 min at 6-h intervals. Seven days later, rats were sacrificed, and both lungs in all groups were examined biochemically and histopathologically. Our findings show that HBO inhibits the inflammatory response reducing significantly (P < 0.05) peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar edema, alveolar exudate, alveolar histiocytes, interstitial fibrosis, granuloma, and necrosis formation in different pulmonary aspiration models. Pulmonar aspiration significantly increased the tissue HP content, malondialdehyde (MDA) levels and decreased (P < 0.05) the antioxidant enzyme (SOD, GSH-Px) activities. HBO treatment significantly (P < 0.05) decreased the elevated tissue HP content, and MDA levels and prevented inhibition of SOD, and GSH-Px (P < 0.05) enzymes in the tissues. Furthermore, there is a significant reduction in the activity of inducible nitric oxide synthase, TUNEL and arise in the expression of surfactant protein D in lung tissue of different pulmonary aspiration models with HBO therapy. It was concluded that HBO treatment might be beneficial in lung injury, therefore, shows potential for clinical use.

This study evaluated the possible effects of flaxseed oil on renal damage associated with hyperlipidaemic rats. Wistar albino male rats were divided into three groups. Group I was fed with a pellet chow. Group II was fed with a high cholesterol diet (HCD) consisting of 5% cholesterol and 0.35% cholic acid added to the pellet chow. Group III was fed with the same HCD, but were orally treated with a dose of 15 mg/kg body wt/day flaxseed oil. Flaxseed oil treatment started 1 week before and continued throughout the 22 weeks of the HCD. At the end of the experiment, renal tissue and blood samples were collected. The biochemical and histopathological findings confirmed renal damage in hypercholesterolaemia conditions. Flaxseed oil reduced the hypercholesterolaemia-induced increase in the serum levels of total cholesterol, LDL and urea. Oil red O stain revealed that lowered serum lipid was accompanied by a decreased deposition of neutral lipid. Flaxseed oil effectively reversed these abnormalities, verifying the protective effects of flaxseed oil in ameliorating renal injuries associated with hypercholesterolaemia., (Copyright © 2010 John Wiley & Sons, Ltd.)

The aim of this study was designed to evaluate the possible protective effects of thymoquinone (TQ) on the lung injury in rats after chronic toluene exposure. The rats were randomly allotted into one of three experimental groups: control, toluene-treated and toluene-treated with TQ; each group contain 10 animals. Control group received 1 mL serum physiologic and toluene treatment was performed by inhalation of 3000 parts per million (ppm) toluene, in an 8-hr/day and 6 day/week order for 12 weeks. The rats in TQ treated group was given TQ (50 mg/kg body weight) once a day orally for 12 weeks starting just after toluene exposure. Tissue samples were obtained for histopathological investigation. To date, no histopathological changes of lung in rats after chronic toluene exposure by TQ treatment have been reported. Our study showed that TQ treatment inhibits the inflammatory pulmonary responses reducing significantly peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar edema, alveolar exudate, interstitial fibrosis and necrosis formation in toluene-treated rats. Our data indicate a significant reduction in the activity of in situ identification of apoptosis using terminal dUTP nick end-labeling (TUNEL), inducible nitric oxide synthase (iNOS) and a rise in the expression of surfactant protein D in lung tissue of toluene-treated with TQ therapy. We believe that further preclinical research into the utility of TQ may indicate its usefulness as a potential treatment on lung injury after chronic toluene exposure in rats.

The aim of this study was designed to evaluate the possible protective effects of thymoquinone (TQ) on the spermatogenesis after testicular injury caused by chronic toluene exposure in rats. The rats were randomly allotted into one of three experimental groups: control, toluene-treated and toluene treated with TQ; each group contained 10 animals. Control group received 1 mL serum physiologic and toluene treatment was performed by inhalation of 3000 ppm toluene, in an 8-hour/day and 6-day/week order for 12 weeks. The rats in TQ-treated group was given TQ (50 mg/kg body weight) once a day orally for 12 weeks starting just after toluene exposure. Tissue samples were obtained for histopathological investigation. To date, no histopathological changes of testis in rats after chronic toluene exposure by TQ treatment have been reported. Spermatogenesis and mean seminiferous tubule diameter (MSTD) were significantly decreased in toluene treated groups when compared to the control group. Furthermore, the TQ-treated animals showed an improved histological appearance in toluene-treated group. Our data indicate a significant reduction in the activity of in situ identification of apoptosis using terminal dUTP nick end-labeling (TUNEL), endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and there was a rise in the expression of proliferating cell nuclear antigen (PCNA) in testis tissues of the toluene-treated group with TQ therapy. Electron microscopy of the testes of the rats demonstrated that pretreatment with TQ was particularly effective in preventing the mitochondrial degeneration, dilatation of smooth endoplasmic reticulum (SER) and enlarged intercellular spaces in both Sertoli and spermatid cells in the toluene-treated animals. We believe that further preclinical research into the utility of TQ may indicate its usefulness as a potential treatment on the spermatogenesis after testicular injury caused by chronic toluene exposure in rats.

The aim of this study was designed to evaluate the possible protective effects of thymoquinone (TQ) on the neuronal injury in the frontal cortex after chronic toluene exposure in rats. The rats were randomly allotted into one of three experimental groups: A (control), B (toluene treated) and C (toluene treated with TQ); each group contain 10 animals. Control group received 1 ml normal saline solution and toluene treatment was performed by inhalation of 3,000 ppm toluene, in a 8 h/day and 6 day/week order for 12 weeks. The rats in TQ treated group was given TQ (50 mg/kg body weight) once a day orally for 12 weeks starting just after toluene exposure. Tissue samples were obtained for histopathological investigation. To date, no histopathological changes of neurodegeneration in the frontal cortex after chronic toluene exposure in rats by TQ treatment have been reported. In this study, the morphology of neurons in the TQ treatment group was well protected. Chronic toluene exposure caused severe degenerative changes, shrunken cytoplasma, severely dilated cisternae of endoplasmic reticulum, markedly swollen mitochondria with degenerated cristae and nuclear membrane breakdown with chromatin disorganization in neurons of the frontal cortex. We conclude that TQ therapy causes morphologic improvement on neurodegeneration in frontal cortex after chronic toluene exposure in rats. We believe that further preclinical research into the utility of TQ may indicate its usefulness as a potential treatment on neurodegeneration after chronic toluene exposure in rats.

Background: The present study was performed to determine the effect of amifostine in the prevention of radiation-induced acute and late period morphologic damages in rat kidney via light and electron microscopic examinations., Materials and Methods: Control rats (n=6) received saline solution 30 min before sham irradiation; the radiotherapy alone group (n=12) received saline solution 30 min before irradiation (a single dose of 15 Gy, applied unilaterally to the kidney) and a final radiotherapy +amifostine group (n=12) received 200 mg/kg amifostine 30 min prior to irradiation., Results: Microscopic examinations of irradiated kidneys revealed presence of glomerular tuft capsular adhesion, fusion of the foot processes and ballon-like cellular degeneration and loss of luminal brush border in tubules as early as eight weeks after irradiation. By 24 weeks post-irradiation, these changes were advanced and associated with focal mesangiolysis, segmental sclerosis and focal tubular atrophy. In addition, local irradiation caused interstitial fibrotic lesions in the kidney. Pretreatment of amifostine markedly prevented these glomerular and tubular changes, and interstitial fibrotic lesions., Conclusion: This study suggests that amifostine pretreatment may contribute to prevention of radiation-induced acute and late nephrotoxicity.

The aim of this study was to evaluate the possible protective effects of quercetin (QE) against cholestatic oxidative stress and liver damage in the common bile duct ligated rats. A total of 24 male Wistar albino rats were divided into three groups: control, bile duct ligation (BDL) and BDL + received QE; each group contain 8 animals. The rats in QE treated groups were given QE (15 mg/kg) once a day intraperitoneally for 4 weeks starting 3 days prior to BDL operation. The changes demonstrating the bile duct proliferation and fibrosis in expanded portal tracts include the extension of proliferated bile ducts into lobules, mononuclear cells, and neutrophil infiltration into the widened portal areas were observed in BDL group. Treatment of BDL with QE attenuated alterations in liver histology. The alpha smooth muscle actin (α-SMA), transforming growth factor beta (TGF-β1) positive cells and the activity of TUNEL in the BDL were observed to be reduced with the QE treatment. The data indicate that QE attenuates BDL-induced cholestatic liver injury, bile duct proliferation, and fibrosis. The hepatoprotective effect of QE is associated with antioxidative potential.

Testicular torsion causes an enhanced formation of reactive oxygen species, which contributes to the pathophysiology of tissue damage. The aim of this study was to investigate the protective effect of melatonin on testicular torsion/detorsion-induced ischemia-reperfusion (I/R) injury. A total of 24 male Wistar albino rats were divided into three groups of 8 animals each: control, I/R, and I/R treated with melatonin. The ischemia period was 5 h and orchiectomy was performed after 5 h of detorsion. Melatonin (10 mg/kg, intraperitoneally [i.p.]) was administrated only once, 40 min prior to detorsion. Spermatogenesis and mean seminiferous tubule diameter (MSTD) were significantly decreased in the I/R groups were compared to the control group. Furthermore, the melatonin treated animals showed an improved histological appearance in the I/R group. Our data indicate a significant reduction in the activity of TUNEL; there was a rise in the expression of proliferating cell nuclear antigen (PCNA) and testosterone in testes tissue of the I/R group treated with melatonin therapy. Electron microscopy of the testes of the rats demonstrated that pretreatment with melatonin was particularly effective in preventing mitochondrial degeneration, dilatation of SER, and enlarged intercellular spaces in both Sertoli and spermatid cells in the I/R treated animals. We believe that further preclinical research into the utility of melatonin may indicate its usefulness as a potential treatment on testes injury after I/R in rats., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The aim of this study was to investigate the protective effect of quercetin (QE) on testicular torsion/detorsion-induced ischaemia-reperfusion (I/R) injury. A total of 24 male Wistar albino rats were divided into three groups: control, I/R and I/R treated with QE; each group contain eight animals. Testicular torsion was created by rotating the left testis 720° in a clockwise direction. The ischaemia period was 5 h and orchiectomy was performed after 5 h of detorsion. QE (15 mg kg(-1) , i.p.) was administered only once, 40 min prior to detorsion. Left orchiectomy was performed in all I/R groups. To date, no histopathological changes on testicular torsion/detorsion-induced I/R injury in rats by QE treatment have been reported. Spermatogenesis and mean seminiferous tubule diameter were significantly decreased in I/R groups were compared with the control group. Furthermore, QE treated animals showed an improved histological appearance in I/R group. Our data indicate a significant reduction in the activity of TUNEL, endothelial nitric oxide synthase and a rise in the expression of testosterone in testes tissue of I/R treated with QE therapy. We believe that further preclinical research into the utility of QE may indicate its usefulness as a potential treatment on testes injury after I/R in rats., (© 2010 Blackwell Verlag GmbH.)

The aims of the study were to investigate the effects of immunization against GnRH using OL protein (Ovalbumin-LHRH-7) on feedlot performance, carcass, meat quality and some reproductive traits in Kıvırcık ram lambs. Ram lambs in the immunization (I, n=7) group were immunized against GnRH using OL protein and boosted 2 weeks later. Control (C, n=7) group was not treated. The animals were kept at pasture for 6 weeks after the first immunization, subjected to a 70 day fattening program, and then slaughtered. Growth performance, various carcass and meat quality characteristics were not affected from the immunization. GnRH immunization induced GnRH antibody production, suppressed testosterone production and testicular growth (P<0.01). Testicular structure was negatively affected from the immunization, but not pituitary. These results suggest that immunization against GnRH with OL could be an alternative castration technique in ram lambs without negatively affecting carcass and meat quality characteristics., (Copyright © 2010 The American Meat Science Association. Published by Elsevier Ltd. All rights reserved.)

In 2007, Kaiser Permanente's (KP) Southern California Region designed and implemented a systematic in-reach program, the Proactive Office Encounter (POE), to address the growing needs of its three million patients for preventive care and management of chronic disease. The program sought staff from both primary and specialty care departments to proactively identify gaps in care and to assist physicians in closing those gaps. The POE engaged the entire health team in a proactive patient-care experience, creating standard work flows and using information technology to identify gaps in patient care. The goals were to improve consistency of preventive care and improve quality of care for chronic conditions and to improve reliability of staff support for physicians. The POE has been implemented in all outpatient settings in KP's Southern California Region's 13 medical centers and 148 medical office buildings. The program has contributed to significant improvements in key clinical quality metrics, including cancer screenings, blood pressure control, and tobacco cessation. It is now being extended into the inpatient setting and is being shared with other KP Regions.

The aim of this study was designed to investigate the possible beneficial effects of the angiotensin (ang) II T(1) (AT(1)) receptor blocker, irbesartan (Irb), and the alpha lipoic acid (ALA) in streptozotocin (STZ)-induced diabetic nephropathy (DNP) in rats. The rats were randomly allotted into one of five experimental groups: A, control; B, diabetic untreated; C, diabetic treated with Irb; D, diabetic treated with ALA; and E, diabetic treated with Irb + ALA; each group contains 10 animals. B, C, D, and E groups received STZ. Diabetes was induced in four groups by a single intraperitoneal injection of STZ (50 mg/kg, freshly dissolved in 5 mmol/L citrate buffer, pH 4.5). The rats in Irb-, ALA-, and Irb + ALA-treated groups were given Irb (5 mg/kg), ALA (in a dose of 3 mg/kg), and Irb + ALA (in a dose of 2.5 + 1.5 mg/kg) once a day orally by using intragastric intubation for 12 weeks starting 2 days after STZ injection, respectively. Treatment with ALA and especially Irb reduced the glomerular size; thickening of capsular, glomerular, and tubular basement membranes; increased amounts of mesangial matrix and tubular dilatation as compared with diabetic-untreated rats. Notably, the better effects were obtained when Irb and ALA were given together. We conclude that Irb, ALA, and especially Irb + ALA therapy causes renal morphologic improvement after STZ-induced diabetes in rats. We believe that further preclinical research into the utility of Irb and ALA treatment, alone or its combination, may indicate its usefulness as a potential treatment in DNP.

The aim of this study was to evaluate the effects of methylene blue against cholestatic oxidative stress and liver damage after ligation of the common bile duct in male Wistar rats. Eight animals were included in each of the following five groups: untreated control, methylene blue control, sham-operated, bile-duct ligation, and bile-duct ligation plus methylene blue. Methylene blue was administered intraperitoneally for 14 days at a daily dose of 2mg/kg per day. All rats were sacrificed 2 weeks following the experimental treatment and the livers of all groups were examined biochemically and histopathologically. The severity of cholestasis and hepatic injury were determined by changes in the plasma, including enzymatic activities: aspartate aminotransferase, alanine aminotransferase, gamma glutamine transferase, and also bilirubin levels. Malondialdehyde, nitric oxide and superoxide dismutase were measured to indicate the oxidative status in the liver tissue. Myeloperoxidase activity and levels of tissue hydroxyproline were determined as measures of neutrophil activation and collagen accumulation, respectively. Liver damage was significantly prevented in the bile-duct ligated rats treated with methylene blue compared with the control bile-duct ligated rats without methylene blue. Treatment with methylene blue markedly reduced activities of serum transaminase, gamma glutamine transferase and bilirubin levels as compared to bile-duct ligated rats without methylene blue. Positive immunolabelling for alpha-smooth muscle actin (alpha-SMA) was increased, especially in vascular smooth muscle cells, fibrotic septa and also around the proliferated bile ducts, after bile-duct ligation. Only weak alpha-SMA immunolabelling was seen in livers of rats treated with methylene blue. These results indicate that methylene blue can attenuate hepatic damage in extrahepatic cholestasis by reducing oxidative stress and inflammatory processes., (2008 Elsevier GmbH. All rights reserved.)

We evaluated the effects of L-carnitine on apoptosis of germ cells in the rat testis following irradiation. Male Wistar rats were divided into three groups. Control group received sham irradiation plus physiological saline. Radiotherapy group received scrotal gamma-irradiation of 10 Gy as a single dose plus physiological saline. Radiotherapy + L-carnitine group received scrotal irradiation plus 200 mg/kg intraperitoneally L-carnitine. Twenty-four hours post-irradiation, the rats were sacrificed and testes were harvested. Testicular damage was examined by light and electron microscopy, and germ cell apoptosis was determined by terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate in situ nick end-labeling (TUNEL) technique. Morphologically, examination of irradiated testis revealed presence of disorganization and desquamation of germinal cells and the reduction in sperm count in seminiferous tubule lumen. Under electron microscopy, the morphological signs of apoptosis were frequently detected in spermatogonia. Apoptotic spermatogonia showed the marginal condensation of chromatin onto the nuclear lamina, nucleus and cytoplasm shrinkage and still functioning cell organelles. TUNEL-positive cells were significantly more numerous in irradiated rats than in control rats. L-carnitine treatment significantly attenuated the radiation-induced morphological changes and germ cell apoptosis in the irradiated rat testis. In conclusion, these results suggested that L-carnitine supplementation during the radiotherapy may be beneficial for spermatogenesis following testicular irradiation by decreasing germ cell apoptosis.

It is well known that formaldehyde (FA) is cytotoxic and potentially carcinogenic. Although the individual effects of this reactant on cells has been investigated, the cytotoxicity exerted by the coexistence of FA is poorly understood. The aim of this study was to investigate the effects of FA on the liver in rats, by light and electron microscopic level. We used 18 Wistar albino rats divided into three groups, exposed to 0 (control), 19.7 ppm FA gas for a total of 4 weeks, 8 h/day, 5 days a week (subacute) and 20.3 parts per million (ppm) FA gas for a total of 13 weeks, 8 h/day, 5 days a week (subchronic). After the completion of the exposure period, they were sacrificed by decapitation and their liver tissue samples were taken in order to be processed for light and electron microscopic studies. Light microscopic evaluation of liver tissue samples of FA-exposed rats revealed enlarged sinusoids filled with blood and mononuclear cell infiltration in the portal areas and around the central veins. In addition, some of the hepatocytes showed loss of cytoplasm, and some had a hyperchromatic nucleus. The cells of FA-exposed livers, on the other hand, showed an electron-lucent ground-cytoplasm and a hypertrophy of the smooth-surfaced endoplasmic reticulum. In conclusion, we observed that exposure FA caused diverse histopathological changes indicating the destruction in the liver tissue and this destruction has direct relationship with the length of the exposure period.

Our objective was to investigate the endothelial nitric oxide synthase (eNOS) immuno-reactivity and the ultrastructure of endothelial cells of a human umbilical artery in both normal and preeclamptic pregnancies. The umbilical cords from normal and preeclamptic pregnancies were collected immediately after vaginal and abdominal deliveries. Umbilical arteries were isolated and fixed in 10% neutral formaline solution, embedded in paraffin, and then stained with hematoxylin and eosin (H&E) for the histologic investigation, and eNOS activation were examined in samples by streptavidine-biotine immunohistochemical methods. The arterial sections were also fixed in phosphate-buffered 2.5% glutaraldehyde solution (pH 7.2) for 3 h and post-fixed with 1% osmium tetroxide at 4°C for 2 h for the investigation of the ultrastructural examination. In the umbilical artery of preeclamptic pregnancies, endothelial cells were oval, triangular, or polygonal, and were disorganized. Some endothelial cells were separated by enlarged intercellular spaces. A dilated endoplasmic reticulum, swollen mitochondria, and vanished mitochondrial cristae were observed. The nuclei of some endothelial cells displayed deep invaginations and irregular outlines. Most endothelial cells had a high number of cytoplasmic vacuoles. In preeclampsia, eNOS immunoreactivity increased considerably in endothelial cells when compared to normal pregnancies. We believe that preeclampsia plays an important role in the pathogenesis of endothelial cell dysfunction and activation in the umbilical artery. However, the disturbance mechanism of endothelial cells is not known, and further studies are necessary to clarify the exact mechanism.

The aim of this study was to evaluate the possible protective effects of the volatile oil of Nigella sativa (NS) seeds on insulin immunoreactivity and ultrastructural changes of pancreatic beta-cells in STZ-induced diabetic rats. STZ was injected intraperitoneally at a single dose of 50 mg/kg to induce diabetes. The rats in NS treated groups were given NS (0.2 ml/kg) once a day orally for 4 weeks starting 3 days prior to STZ injection. To date, no ultrastructural changes of pancreatic beta-cells in STZ induced diabetic rats by NS treatment have been reported. Islet cell degeneration and weak insulin immunohistochemical staining was observed in rats with STZ-induced diabetes. Increased intensity of staining for insulin, and preservation of beta-cell numbers were apparent in the NS-treated diabetic rats. The protective effect of NS on STZ-diabetic rats was evident by a moderate increase in the lowered secretory vesicles with granules and also slight destruction with loss of cristae within the mitochondria of beta-cell when compared to control rats. These findings suggest that NS treatment exerts a therapeutic protective effect in diabetes by decreasing morphological changes and preserving pancreatic beta-cell integrity. Consequently, NS may be clinically useful for protecting beta-cells against oxidative stress.

The present study, we hypothesized that L-carnitine can minimize germ-cell depletion and morphological features of late cell damage in the rat testis following gamma (gamma)-irradiation. Wistar albino male rats were divided into three groups. Control group received physiological saline 0.2 ml intraperitoneally (i.p.), as placebo. Radiation group received scrotal gamma-irradiation of 10 Gy as a single dose plus physiological saline. Radiation + L-carnitine group received scrotal gamma-irradiation plus 200 mg/kg i.p. L-carnitine. L-carnitine starting 1 day before irradiation and 21 days (three times per week) after irradiation. Testis samples of the all groups were taken at day 21, 44 and 70 post-irradiation. All samples were processed at the light and electron microscopic levels. Morphologically, examination of gamma-irradiated testis revealed presence of marked disorganization and depletion of germ cells, arrest of spermatogenesis, formation of multinucleated giant cells, and vacuolization in the germinal epithelium. The type and extent of these changes varied at different post-treatment intervals. The damage was evident at the 21st day and reached maximum level by the 44th day. By day 44 post-irradiation, the changes were most advanced, and were associated with atrophied seminiferous tubules without germ cells, the increase in the number and size of vacuolizations in germinal epithelium, and the absent multinucleated giant cells due to spermatids had completely disappeared. The increase in nucleus invaginations, the dilatation of smooth endoplasmic reticulum cysternas and the increase in the number and size of lipid droplets in the Sertoli cells were determined at the electron microscopic level. In conclusion, L-carnitine supplementation during the radiotherapy would be effective in protecting against radiation-induced damages in rat testis, and thereby may improve the quality of patient's life after the therapy.

The major objective of this study was to test curcumin as a potential radioprotectant for the ileum goblet cells of the rat. Wistar albino rats were used in the study. Group A was the control group and group B was the single dose radiation group. Group C was the two dose radiation group (4 days interval). The rats in groups D and E were given a daily dose of 100 mg/kg of curcumin for 14 and 18 days, respectively. During the curcumin administration period, the rats in group D were exposed to abdominal area gamma (gamma)-ray dose of 5 Gy on the 10th day and group E was exposed to same dose radiation on the 10th and 14th day. Irradiation and treatment groups were decapitated on the 4th day after exposure to single or two-dose irradiation and ileum tissues were removed for light and electron microscopic investigation. Single or two dose 5 Gy gamma-irradiation caused a marked intestinal mucosal injury in rats on the 4th day. Radiation produced increases in the number of goblet cells. Curcumin appears to have protective effects against radiation-induced damage, suggesting that clinical transfer is feasible.

The aim of this study was designed to investigate the possible beneficial effects of the thymoquinone (TQ) in streptozotocine (STZ)-induced diabetes in rats. The rats were randomly allotted into one of three experimental groups: A (control), B (diabetic untreated), and C (diabetic treated with TQ); each group contain ten animals. B and C groups received STZ. Diabetes was induced in two groups by a single intra-peritoneal (i.p) injection of STZ (50 mg/kg, freshly dissolved in 5 mmol/l citrate buffer, pH 4.5). Two days after STZ treatment, development of diabetes in two experimental groups was confirmed by measuring blood glucose levels in a tail vein blood samples. Rats with blood glucose levels of 250 mg/dl or higher were considered to be diabetic. The rats in TQ treated groups were given TQ (50 mg/kg body weight) once a day orally by using intra gastric intubation for 12 weeks starting 2 days after STZ injection. Treatment of TQ reduced the glomerular size, thickening of capsular, glomerular and tubular basement membranes, increased amounts of mesangial matrix and tubular dilatation and renal function as compared with diabetics untreated. We conclude that TQ therapy causes renal morphologic and functional improvement after STZ-induced diabetes in rats. We believe that further preclinical research into the utility of TQ treatment may indicate its usefulness as a potential treatment in diabetic nephropathy.

We have previously demonstrated that scrotal hyperthermia induce Leydig cell (LC) damage in short-term. The objectives of this pilot study were to investigate morphological changes and regulation of steroidogenesis on LC in long-term and the time of observation were extended to investigate whether the LC would eventually make a recovery after scrotal hyperthermia. The rats were randomly allotted into one of four groups: A (control), B (70 days after scrotal hyperthermia), C (105 days after scrotal hyperthermia), D (140 days after scrotal hyperthermia); each group contain seven animals. Scrotal hyperthermia was carried out in a thermostatically controlled water bath at 43 degrees C for 30 min once daily for six consecutive days. Control rats were treated in the same way, except the testes were immersed in a water bath maintained at 22 degrees C. Hyperthermia applied rats were sacrificed under 50 mg/kg ketamine anaesthesia after 70, 105 and 140 days, and biopsy materials of testes were obtained for light and electron microscopic examinations. Morphologically normal and the number of testosterone positive LC was significantly higher in 140 days after last heat than all other heat treatment groups. In heat treated groups, a dilated smooth endoplasmic reticulum, swollen mitochondria, and vanished mitochondrial cristae were observed. In the 140 days after scrotal hyperthermia, the severities of degenerative changes of LC were less than that observed in the other heat treated groups. We conclude that, scrotal hyperthermia cause morphological damaging and impaired steroidogenesis in LC and recovery of these findings were noted first time in 140 days after the last heat treatment.

The goal of this study was to evaluate the possible protective effects of sphingosylphosphorylcholine (SPC) against cholestatic oxidative stress and liver damage in the common bile duct ligated rats. Fifty-six animals were included in each of the following 7 groups: control, SPC control, phosphate-buffered solution control, sham operated, bile duct ligation (BDL), BDL plus phosphate-buffered solution, and BDL plus SPC. Sphingosylphosphorylcholine was administered 14 days at a daily dose of 2 microm/mL intraperitoneally. The severity of cholestasis and hepatic injury was determined by changes in the plasma enzyme activities of aspartate aminotransferase, alanine aminotransferase, gama glutamin transferase, and levels of total bilirubin and direct bilirubin. Malondialdehyde, nitric oxide, and superoxide dismutase were determined to evaluate the oxidative status in the liver tissue. Myeloperoxidase activity and levels of tissue hydroxyproline were determined to assess neutrophil activation and collagen accumulation, respectively. Treatment with SPC markedly reduced serum transaminase activities as compared to BDL rats. Sphingosylphosphorylcholine also inhibited the increase in liver malondialdehyde; nitric oxide levels significantly and also attenuated the depletion of superoxide dismutase in the liver after BDL. Similarly, the increase in tissue myeloperoxidase activity and hydroxyproline owing to BDL was also attenuated by the SPC treatment. These data were supported by histopathologic findings. The alpha-smooth muscle actin-positive cells in the BDL were observed to be reduced with the SPC treatment. In conclusion, these findings suggested that SPC can attenuate hepatic damage in extrahepatic cholestasis by prevention of oxidative stress, and inflammatory process. All these findings suggest that SPC may be a promising new therapeutic agent for cholestatic liver injury.

Objectives: Early oesophagoscopy is usually recommended in children after caustic ingestion to assess the severity of the initial digestive lesions. An oesophagoscopic procedure in children always demands to be performed under sedation and bears a certain risk of iatrogenic injury. The purpose of the study is to determine the value and sensitivity of Tc-99m pyrophosphate (99mTc-PYP) scintigraphy for the detection of caustic oesophageal injury., Methods: The caustic oesophageal burns were created with 25% NaOH in an experimental rat model. Seventeen rats were divided into two groups. The BURN group (n=9) included caustic oesophageal burning rats. Non-BURN group (n=8) included sham-operated rats. All animals underwent 99mTc-PYP scintigraphy 72 h after the burning experiment. Anterior static and single-photon emission computed tomography images were obtained using a low-energy all-purpose collimator, 2.55 zoom factor, 3h after intravenous injection of 10 mCi 99mTc-PYP. After the imaging, all the oesophagi were explored for external determination of the injury sites and macroautoradiographic scintigraphy as well. Rectangular region of interest were placed in the visually determined lesion of oesophagus (O) as well as non-lesion area (N), and an ON ratio was created. The severity and extension of oesophageal burn were assessed 3 days after burning by histopathologic evaluation. The injuries were graded according to the ulcer depth, ulcer width, thrombus formation, and the development of perivascular fibrinoid necrosis., Results: The oesophageal burning areas were demonstrated by visual evaluation of the Tc-99m PYP scintigraphy on all animals. The mean ON ratio of 99mTc-PYP was 21.61+/-7.01 in the BURN group and in the non-BURN group, was 2.25+/-0.24 (p<0.001). The best cut-off point of the ON ratio for caustic oesophageal injury was 5.45, with sensitivity and specificity of 100%. PYP scan findings were also confirmed by histological evidence of ulcer depth, ulcer width, thrombus formation, and perivascular fibrinoid necrosis in the same areas., Conclusions: The caustic oesophageal injuries have been demonstrated by 99mTc-PYP scintigraphy in burning experiment. 99mTc-PYP scintigraphy is sensitive for detection of caustic oesophageal injury. This new imaging tool is found to be sensitive and specific for the detection of caustic oesophageal injury in the rats.