Anti-oxidative effect of resveratrol on aluminum induced toxicity in rat cerebral tissue.

INTRODUCTION: The direct protective effects of resveratrol against oxidative stress have been demonstrated in neuroglial cells, the mechanisms of these effects are not fully understood. The aim of this research was to study the effect of resveratrol on AL induced cerebral injury in rat. METHODS: We divided the groups as follows with 10 animals each: a) Group I - served as control receiving normal drinking water and diet ad libitum. b) Group II - animals were administered aluminum at a dose level of 100 mg/kg body weight for a period of 6 weeks daily through oral gavage. c) Group III - animals were administered aluminum at a dose level of 100 mg/kg body weight and resveratrol at a dose of 10 mg/kg body weight intraperitoneally for a period of 6 weeks daily. After 6 weeks rats were anesthetized and decapitated. Brains were removed immediately and frozen in liquid nitrogenRESULTS: The levels of SOD and GPx antioxidant enzymes were decreased in all of the groups receiving aluminium, but it was less severe in resveratrol treated group. SOD and GPx levels in aluminium + resveratrol group were higher than in the aluminum group (p < 0.05). MDA level, as an index of lipid peroxidation, increased significantly in all of the groups receiving aluminium. MDA level was lower in aluminium + resveratrol group compared to aluminum group and the difference was significant (p < 0.05). CONCLUSIONS: This study suggests that resveratrol is effective in preventing AL induced toxicity by reducing MDA production in cerebral tissue. Resveratrol also attenuated SOD and GPx suppression in cerebral tissue significantly. Our findings provide the rationale for further studies directed to understanding the mechanism of resveratrol in preventing neurodeterioration (Tab. 1, Ref. 35).

Combination effect of melatonin and dexamethasone on liver ischemia/reperfusion injury.

OBJECTIVE: Liver failure following ischemia-reperfusion (I/R) injury is a major concern in liver surgery. The purpose of this study was to evaluate combination pretreatment with melatonin (MEL) and dexamethasone (DEX) on liver I/R model. Male Wistar rats (n = 60) were assigned to 5 groups of 12 animals each: (1) Sham: laparotomy without I/R; (2) I/R: hepatic I/R; (3) I/R+MEL: hepatic I/R+melatonin injected intraperitoneally (20 mg/kg); (4) I/R+DEX: hepatic I/R+ dexamethasone injected intravenously (10 mg/kg); (5) I/R+MEL+DEX: hepatic I/R+ melatonin injected intraperitoneally+dexamethasone injected intravenously. The liver was subjected to ischemia by clamping the portal triad for 30 minutes and then reperfused for 6 hours after ischemia by removing the clamps. RESULTS: The levels of glutathione peroxidase (GPx) and superoxide dismutase (SOD) decreased after hepatic I/R in all groups. Levels of GPx and SOD were higher in I/R+MEL+DEX group compared to I/R, I/R+MEL and I/R+DEX groups and they were significantly higher in I/R+MEL group compared to I/R and I/R+DEX groups (p < 0.05). Levels of ALT, AST, TNF-α, hepatic tissue malondialdehyde (MDA), liver injury index, and apoptotic index increased after hepatic I/R. Levels of ALT, AST, tissue MDA, tissue injury index and apoptotic index were lower in I/R+MEL+DEX group compared to those in I/R, I/R+MEL and I/R+DEX groups, and in I/R+MEL they were significantly lower than in I/R+DEX group (p < 0.05). TNF-α level was lower in I/R+MEL+DEX group compared to other groups and it was significantly lower in I/R+DEX group than in I/R+MEL and I/R groups (p < 0.05). CONCLUSION: Combination therapy with melatonin and dexamethasone had better results in decreasing the liver injury compared to when each of them was administered alone (Tab. 3, Ref. 58).

Phenytoin accelerates tendon healing in a rat model of Achilles tendon rupture.

INTRODUCTION: Tendons are vulnerable to various types of acute or chronic injures. Different methods have been investigated to achieve better healing. Phenytoin is a drug which could stimulate fibroblasts to produce collagen. This experimental study was performed to assess the effect of phenytoin on tendon healing in a rat model of tendon rupture. METHODS: Thirty healthy rats were divided into 3 groups, 1) Sham group; 2) Tendon rupture; 3) Tendon rupture+phenytoin (100 mg/kg intraperitoneally) for 21 days. On 21st day after tendon injury, the rats were anesthetized and tendon tissue was sampled for studying by light and electron microscopy. RESULTS: Qualitative and quantitative microscopic comparisons of the repair tissues of both groups were made on the 21st day. The results obtained from light and electron microscopy studies showed that tendon tissue healing was significantly better in phenytoin group compared to the control group (p < 0.05). CONCLUSIONS: Systemic administration of phenytoin may have a positive effect on tendon healing by increasing fibroblast quantity, fibrillar collagen synthesis, vascularity, and suppressing inflammation (Tab. 2, Ref. 25).

Lipoic acid prevents hepatic and intestinal damage induced by obstruction of the common bile duct in rats.

INTRODUCTION: Cholestatic liver diseases are characterized by impaired hepatocellular secretion of bile, resulting in intracellular accumulation of bile acids which result in a shift in the oxidant/prooxidant balance in favor of increased free radical activity and injury of different tissues including liver and intestine. The aim of this research was to study protective effect of lipoic acid (LA) as a potent antioxidant in cholestsis induced hepatic and intestinal injury in rats. MATERIALS AND METHODS: Forty five adult male Wistar rats were randomly assigned to four groups each containing fifteen rats as follows: sham operation (SO) (control), bile duct ligating (BDL), and BDL+LA (25 mg/kg). After fourteen days hepatic and intestinal tissue sampled and blood serum sampled for pathologic and biochemical studies. RESULTS: Levels of SOD and GPx antioxidant enzymes were higher in BDL+LA group comparing to BDL group, levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltranspeptidase (GGT), and pathologic scores in liver and intestine were lower in BDL+LA group comparing to BDL group significantly, but there is no significant difference in concentrations of total bilirubin between groups. CONCLUSIONS: Our results showed the protective potential of LA with liver and intestine damage. Despite improvements in operative technique and the development of potent, broad-spectrum antibiotics, biliary tract surgery in patients with obstructive jaundice is still associated with high morbidity and mortality rates In summary, our results show that BDL induced hepatic and intestinal injury were significantly attenuated by LA administration and the administration of LA could effectively diminish this damage.

Protective effect of pentoxyfilline in renal toxicity after methotrexate administration.

INTRODUCTION: Nephrotoxicity is an important side-effect of treatment with Methotrexate (MTX). Pentoxifylline (PTX) is an anti-inflmmatory and anti-oxidant agent. We hypothesized that pentoxifylline may affords renal protection by downregulating TNF-alpha as well as by improving cellular anti-oxidant activity. MATERIALS AND METHODS: Forty five male Wistar rats were assigned to 3 groups of 15 animals each: Group 1: control group (0.9% saline). Group 2: MTX; injected with 20 mg/kg MTX intraperitoneally (i.p.). Group 3: MTX + PTX injected i.p. MTX (20 mg/kg) + PTX (50 mg/kg) i.p. PTX was administered since 3 days before MTX administration and continued for 6 days. After 6 days rats were anesthetized and serum sampled and renal tissue removed for biochemical and histological evaluation. RESULTS: Data showed that glutathione peroxidase (GPx), superoxide dismutase (SOD) activities were lower in PTX + MTX group comparing to MTX group significantly (p < 0.05). Renal tissue injury index and percent of TUNEL positive cells, renal tissue malondialdehyde (MDA) levels, serum BUN (Blood Urea Nitrogen), creatinine (Cr) and TNF-alpha levels were higher in MTX group comparing to MTX+PTX group significantly (p < 0.05). CONCLUSIONS: In this study, the increased level of tissue MDA and serum TNF-alpha level together may be suggested that the underlying mechanism is related to direct toxicity of MTX rather than blockage in folate synthesis in kidneys. PTX administration also attenuated renal tissue injury and number of apoptic cells and suppressed the elevation of BUN and Cr levels. However, further studies are essential to elucidate the exact mechanisms of MTX-induced renal toxicity, and protection and the effect of PTX.

Simvastatin attenuates intestinal ischemia/reperfusion induced injury in rat.

Ischaemia/reperfusion (I/R) injury is commonly seen in the field of intestine surgical interventions, shock, trauma, and many other clinical conditions. Simvastatin is known to have antioxidant and anti-inflammatory properties. This study investigated the effect of simvastatin administration in a warm intestinal I/R model on TNF-alpha, antioxidant enzymes and intestinal tissue morphology. Thirty-six male wistar rats underwent laparotomy under general anaesthesia. Simvastatin was administered from four days before ischaemia induction. The rats were divided in to three groups (n = 12): the sham group, the I/R group, and the I/R + simvastatin group. Intestinal ischaemia was induced by superior mesenteric artery ligation with microvascular clamps for 60 minutes, and after ischaemia, blood perfusion was released into the tissue and a reperfusion phase was started, which lasted for 3 hours. After 3 hours, the animals were sacrificed and serum and tissue obtained for biochemical and histological study. In the simvastatin treated group, intestinal tissue injury, TNF-alpha level, and tissue malondealdehyde levels were significantly lower than in the I/R group (p < 0.05). Glutathion peroxidase and superoxide dismutase levels were significantly higher in the simvastatin treated group than in the I/R group (p < 0.05). Simvastatin pretreatment reduced intestinal I/R injury and was associated with down- -regulation of serum TNF-alpha and tissue malondealdehyde level, and simvastatin administration maintained cellular antioxidant enzyme contents compared to the I/R group after 3 hours reperfusion time.

Simvastatin decreases hepatic ischaemia/reperfusion-induced liver and lung injury in rats.

Liver failure is still a significant clinical problem after transplantation surgery, tissue resections (the Pringle manoeuvre) and haemorrhagic shock. The restoration of blood flow to an ischaemic region leads to tissue injury at a greater rate than the original ischaemic insult, an event termed "ischaemia-reperfusion injury" (I/R). Despite advances in surgical techniques, I/R still poses a problem of clinical importance. In this research, we studied the effect of simvastatin pretreatment on liver and lung injury induced by hepatic I/R. Rats were subjected to 30 min of ischaemia followed by 24 h of reperfusion. Simvastatin (10 mg/kg) was administered orally from three days before the operation. After the reperfusion time, serum ALT, AST, LDH and TNF a levels were studied and liver and lung tissues were stained with haematoxylin and eosin and TUNEL to detect apoptotic cells. Serum aminotransferase activity and LDH and TNFalpha levels were increased markedly by hepatic I/R, and these were suppressed significantly by simvastatin. The tissue injury index and the number of apoptotic cells via TUNEL staining in the liver and lungs were higher in the I/R group than in the I/R + simvastatin group. These results suggest that simvastatin ameliorates I/R-induced liver and lung tissue damage by inhibiting the level of inflammation and the apoptotic pathways. Simvastatin administration may therefore provide protection against the adverse effects of I/R injury in liver transplantation.

Scalpel blade changer.

Surgical knife has been extensively used in surgery for a number of years and is the most widely used surgical instrument in the world at present. Manual removal of the blade can be difficult, particularly when the scalpel is wet. Percutaneous injuries during changing the scalpel blade may lead to serious and potentially fatal infections from blood borne pathogens such as hepatitis B virus (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV) and others including cytomegalovirus, herpes simplex virus and parvovirus B19. In addition to the risk of illness and death after an exposure, psychological trauma and long-term disability are of great concern. Many devices have been developed in an effort to facilitate the removal of the blade from the scalpel, and to render the removal procedure less dangerous. But there is no device to both remove and install the blade at the same time. In particular, the present invention relates to a scalpel blade changer that enables a blade to be removed from a scalpel and retained in the remover and at the same time to install the blade on to the scalpel handle.

Comparison of 5 IU and 10 IU tuberculin test results in patients on chronic dialysis.

Immunocompromised patients such as those with end-stage kidney failure under-going hemodialysis (HD) are at increased risk of developing tuberculosis (TB). For this reason, routine TB screening of HD patients with tuberculin test has been recommended. The Center for Disease Control and Prevention (CDC) has recommended that patients with chronic renal failure should undergo annual skin testing for TB with tuberculin [purified protein derivative (PPD)], with an induration of ≥10 mm at 48 h depicting a positive reaction. The aim of this study was to compare the results of two different doses of PPD in dialysis patients. This descriptive and comparative multicenter study was performed on 255 patients on chronic dialysis in Tabriz, Iran. These patients did not have the PPD test done within the preceding one year. Patients were divided into two groups randomly and conventional or double-dose tuberculin test was performed using the Mantoux technique with 5 IU (group 1) and 10 IU (group 2) of PPD. Results were interpreted 48-72 h after injection. Patients were divided into those with less than 10 mm and those with ≥10 mm duration. Mean age was 44.6 ± 15 years (M/F = 1.5/1). The mean duration on dialysis was 39 ± 7 months. There was no significant difference regarding the age, gender, dura-tion on dialysis, causes of chronic kidney disease, erythrocyte sedimentation rate, C-reactive protein and serum albumin between the two groups. The mean induration was 4.6 mm and 7.7 mm in groups 1 and 2, respectively. There was induration ≥10 mm in 19.6% and 25.5% of group 1 and 2, respectively, which showed a significant difference (P <0.05). In conclusion, because of the high frequency of TB in dialysis patients, an annual tuberculin test may be recommended. Our study showed that the double-dose tuberculin test may be a better substitute to the conventional test in dialysis patients.

Evaluation of Copper, Zinc, Cu/Zn, and VEGF in Patients with AML in Iran.

BACKGROUND: Copper and zinc are the elements with numerous physiological activities. Copper (Cu) has an important role in angiogenesis and acts by increasing Vascular Endothelial Growth Factor (VEGF). Serum levels of copper will be increased in cancer incidence, progression and recurrence. The aim of this study was to measure blood levels of copper, zinc, and the ratio of Cu /Zn, as well as VEGF levels before and after treatment of acute myeloid leukemia. METHODS: Thirty patients who were recently diagnosed with Acute Myeloblastic Leukemia (AML) in Shahid Ghazi Tabatabai oncology hospital enrolled in this clinical trial. On the first day, blood samples were taken for copper, zinc, and VEGF assay and flowcytometry. Treatment protocol was (7×3) regimen. Blood samples were collected for evaluation of copper, zinc, and VEGF. They were sent to Biochemistry Laboratory in medicine faculty for analysis. RESULTS: Amongst 30 AML patients, 14 (46.7%) were female and 16 (53.3%) were male. Patients of various ages ranged from 16 to 53 years, with a median age of 9.1±9.35 years. The mean serum level of copper, zinc, and mean Cu/Zn ratio before and after treatment showed significant difference (p<0.05) There was also significant difference between the mean VEGF level before and after treatment (p<0.05). CONCLUSION: This study reveals that there is no significant relationship between copper, zinc serum levels, their ratio, and VEGF in AML patients. We hypothesize that increased serum copper is associated with increase of VEGF levels which can indicate the impact of copper in malignancies including AML.

Pioglitazone attenuates ischemia/reperfusion-induced liver injury in rats.

INTRODUCTION: Hepatic ischemia/reperfusion (I/R) injury leads to free radical generation and acute inflammatory responses that cause liver damage, an important problem for liver transplantation. Pioglitazone is known to protect I/R injury in various tissues; however, the mechanism of cytoprotection is not well understood. This study investigated the effects of pioglitazone administration in a warm hepatic I/R model on tumor necrosis factor (TNF)-alpha level, tissue injury, and antioxidant enzyme activity. MATERIALS AND METHODS: Eighty wistar strain rats were divided into 4 groups (n = 20): Group 1 sham hosts; Group 2 hepatic I/R; Group 3 hepatic I/R + pioglitazone (10 mg/kg); and Group 4 hepatic I/R + vehicle. Rat livers were subjected to 30 minutes of ischemia followed by 6 hours of reperfusion. After reperfusion rats were humanely killed to obtain liver tissue to study glutathione peroxidase (GPx), superoxide dysmutase (SOD), malondialdehyde (MDA) levels and for histopathologic assessment. TNF-alpha, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured in serum. RESULTS: Pioglitazone pretreatment significantly reduced liver enzyme content (ALT, 176.80 +/- 13.75 vs 235.28 +/- 31.92 and AST, 748.20 +/- 79.29 vs 944.85 +/- 101.87) and TNF-alpha level (9:8.60 +/- 8.67 vs 138.28 +/- 9.99) after I/R compared with the control group. MDA level (3.02 +/- 0.37 vs 4.36 +/- 0.38) and hepatocytic degeneration were reduced in the pioglitazone-treated group. GPx (2.40 +/- 0.25 vs 1.36 +/- 0.31) and SOD activity (2.22 +/- 0.30 vs 1.40 +/- 0.35) were significantly higher in the pioglitazone-treated group compared with the control group. CONCLUSION: The present study showed that pioglitazone administration improved hepatic I/R injury that was associated with enhanced antioxidant enzyme activities and suppression of TNF-alpha, ALT, and AST levels. Because peroxisome proliferator-activated receptor-gamma agonists are widely used to treat diabetic patients, it may be relatively easy to expand their clinical indication. However, further investigations will be required to delineate protective mechanisms by which pioglitazone attenuates hepatic tissue injury after I/R.