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1.
Bulletin of Alexandria Faculty of Medicine. 2009; 45 (1): 149-155
in English | IMEMR | ID: emr-100746

ABSTRACT

Focal cerebral ischemia [st, oke] is a leading cause of death and disability among adult population. Many pathological events including inflammation and oxidative stress during the acute period contribute to the secondary neuronal death. Peroxisome prohferator-activated receptors [PPARs] are ligand-activated transcription factors known to upstream to many inflammatory and antioxidant genes. The present study was carried out to evaluate the physiological role of PPAR-gamma and possible neuroprotective effects of its agonist, rosiglitazone, in experimentally induced focal cerebral ischemia in rats. The current study was conducted on 30 male albino rats [180-220 gm], they were divided into 3 groups: Group 1: included 10 normal healthy control rats that were sham operated. Group 2: included 10 rats that were subjected to middle cerebral artery occlusion [MCAO] induced focal cerebral ischemia for 2 h followed by reperfusion for 22 h. Group 3: included 10 rats that were pretreated with rosiglitazone 3mg/kg body weight orally for 7 days followed by MCAO induced focal cerebral ischemia. The following parameters were assessed in all rats of the studied groups: Serum levels of both tumor necrosis-alpha [TNF-alpha] and interleukin-6 [IL-6] and cerebral cortex tissue levels of glutathione reductase [GR], reduced glutathi one [GSH] and glutathi one peroxidase [GPx] The present study revealed that the induced focal cerebral ischemia in rats of group2 was associated with a statistical sign ifi cant increase in serum levels of both TNF-alpha and IL-6 as compared to normal controls. Pretreatment of rats with rosiglitazone in group3 resulted in a statistical significant reduction of the TNF-alpha and IL-6 levels as compared to group2 [This reflects that the ischemic neuronal injury is associated with massive inflammatory processes that lead to brain damage]. And treatment with rosiglitazone could have an anti-inflammatory neuroprotective role. Considering the brain tissue levels of GR, GSH and GPx, which are tissue oxidant defense mechanisms, the present study showed that focal cerebral ischemia in rats of group2 led to a statistical signfi cant reduction in their levels as compared to control group indicating that cerebral ischemia and reperfusion are responsible for oxidative stress by generation of free radicals which culminate to serious damaging effect and overproduction of free radicals takes the upper hand and predominates the detoxication and scavenging capacity of cellular antioxidant enzymes. Treatment of rats with rosiglitazone before induction of focal cerebral ischemia led to a statistical significant increase in the brain tissue levels of defense antioxidant enzymes as GR and GPx as well as GSH assuming its potential neuroprotective role which could be due to its ability to increase the natural defense mechanisms in case of ischemic oxidative stress. PPAR-gamma agonist [rosiglitzone] could be the drug of use in stroke therapy due to its potential to influence multiple molecular mechanisms by its ability to minimize both the inflammation and oxidative stress and at the same time promotes the antioxidant defense mechanisms and protein chaperones


Subject(s)
Male , Animals, Laboratory , Infarction, Middle Cerebral Artery , Protective Agents , PPAR gamma/blood , Tumor Necrosis Factors/blood , Interleukin-6/blood , Glutathione , Glutathione Peroxidase , Rats
2.
Bulletin of Alexandria Faculty of Medicine. 2005; 41 (3): 475-486
in English | IMEMR | ID: emr-70168

ABSTRACT

Pulmonary fibrosis is the end stage of a heterogeneous group of disorders of known and unknown etiology. One of the clinically important causative agents in pulmonary fibrosis is bleomycin [BLM]. Silymarin is an old herbal remedy known to protect a cell membrane against xenobiotic injury principally due to its antioxidant potential. Melatonin, which is the chief secretory product of the pineal gland, was recently found to be a potent free radical scavenger and antioxidant. The antioxidant, N-acetylcysteine [NAC], has shown beneficial effects in diseases in which reactive oxygen species appear to be involved. The aim of the present study was to assess and compare the protective effect of orally administered silymarin, melatonin, or N-acetylcysteine on lung injury induced in rat model by endotracheal instillation of BLM. Fifty six animals were divided into: group I [control group] [n=24] which were equally subdivided into IA [vehicle and intratracheal saline]; IB [silymarin and intratracheal saline]; IC [melatonin and intratracheal saline]; ID [NAC and intratracheal saline]. Group II [treatment group] [n=32]: which were equally subdivided into IIA [vehicle and intratracheal BLM]; IIB [silymarin and intratracheal BLM]; IIC [melatonin and intratracheal BLM]; IID [NAC and intratracheal BLM]. silymarin was taken in a dose of 50 mg/kg/day suspended in 2% gum acacia mucilage. Melatonin was administered in a dose of 10 mg/kg/day. NAC was given in a dose of 486.6 mg/kg/ day. Treatments were administered orally for 14 days after the day of BLM or saline instillation. Animals received endotracheally a single dose of BLM hydrochloride [5 mg/kg body weight] to produce pulmonary fibrosis. Bronchoalveolar lavage fluid [BALF] was used to measure total protein concentration, lactate dehydrogenase [LDH] activity, and total glutathione levels. Lung tissue homogenates were used to measure myeloperoxidase [MPO] activity, lipid peroxide [LPO] content, and total lung collagen. The body weight of rats not exposed to BLM increased with time. Rats in group IIA failed to gain weight during the first week; thereafter weight gain paralleled that observed in rats not exposed to BLM. A similar but less marked trend was noticed for treated rats. Bleomycin produced a significant increase in lung weight. Treatment with silymarin, melatonin, or NAC decreased lung weight but statistical significance was not reached. The lung hydroxyproline levels were increased in BLM-instilled rats [group IIA] but significantly deceased on treatment with silymarin, melatonin, or NAC. The total cell count and neutrophil cell count in BALF were significantly increased in BLM-exposed rat group. On the contrary of melatonin and NAC, treatment with silymarin significantly decreased these elevated cell counts. The elevated protein concentration in BALF due to the effect of BLM instillation was not reduced by treatment with any of the drugs used. Treatment with silymarin, melatonin, or NAC significantly attenuated the increased LDH activity following BLM instillation. Bleomycin was shown to reduce glutathione levels in the lung. Treatment with silymarin, melatonin, or NAC resulted in a significant increase of glutathione in BALF. Silymarin, but not melatonin or NAC significantly attenuated the increase in lung MPO activity following BLM instillation. The lipid peroxide content in the lung was significantly increased in BLM instilled rats. Treatment with silymarin, melatonin, or NAC attenuated this elevated peroxidation. We conclude that treatment with silymarin inhibit lung fibrotic progression induced by BLM. The decreased neutrophil recruitment to the lung, attenuation of cell damage and the antioxidant properties of silymarin may be involved in its protective mechanism against pulmonary fibrosis. Melatonin also exerts protection against BLM- induced pulmonary fibrosis, probably by suppressing oxidative stress. Treatment with oral NAC is partially effective against lung fibrosis which may be due to replenishment of lung glutathione or reduction of damage to lung structure in the early stage of the disease


Subject(s)
Male , Animals, Laboratory , Lung , Protective Agents , Silymarin , Melatonin , Acetylcysteine , Oxidative Stress , Glutathione Reductase , Lipid Peroxidation , Lactate Dehydrogenases , Peroxidase , Antioxidants , Rats
3.
Bulletin of Alexandria Faculty of Medicine. 2005; 41 (4): 747-754
in English | IMEMR | ID: emr-70197

ABSTRACT

A common side effect to cytotoxic antibiotic bleomycin [BLM] is interstitial pneumonitis with progressive pulmonary fibrosis. At the same time, some of the angiotensin renin system [RAS] inhibitors are reported to have anti-inflammatory in addition to their antihypertensive effects. This study investigated the potential anti-inflammatory effect of angiotensin converting enzyme inhibitors captopril and enalapril and angiotensin receptor blockers losartan and candesartan on experimental BLM-induced acute lung injury in rats. BLM-induced lung injury was assessed by the total white cell count, neutrophil count and interleukin-8 [IL-8] in bronchoalveolar lavage [BAL] fluid and serum level of tumor necrosis factor-alpha [TNF- alpha]. In addition, oxidative stress in lung tissue was measured by tissue contents of malondialdehyde [MDA] and reduced glutathione [GSH], enzymatic activity of superoxide dismutase [SOD] and catalase [CAT] in lung homogenate. A single intravenous dose of BLM was given on day 14[th] of the study. The four investigated RAS inhibitors [Captopril, enalapril, losartan and candesartan] were examined in two different regimens. The first regimen [a] was to start the RAS inhibitor on day 14[th] of the study with BLM and to continue for one week after BLM. In the second regimen [b], the RAS was started 2 weeks prior to BLM and continued for one week thereafter. Administration of candesartan was accompanied with significant decrease in the total white cell and neutrophil counts. Further, significantly lower counts were found when the drug was started two weeks prior to induction of BLM-lung injury [regimen b] compared to its introduction with BLM on day 14[th] [regimen a] [p<0.001]. The associated lower level of IL-8 in BAL in all RAS inhibitors groups failed to reach level of statistical significance compared to BLM control injury [p>0.05]. However, the level of TNF-alpha in serum was decreased significantly in all RAS inhibitors-treated groups. Significant higher lung tissue content of GSH with all RAS treated groups - especially with captopril, there was a significant difference between regimen a and b- compared to BLM-injury control group. There was a significant lower activation of SOD and CAT and less MDA content with all RAS inhibitors treated groups than BLM-injury control group [p<0.001]. All the investigated drugs exhibited significant anti-inflammatory and antioxidant effect especially the prophylactic regimen with captopril. Candesartan was the only drug that affects the macrophage mobility and its chemotactic activity


Subject(s)
Animals, Laboratory , Protective Agents , Angiotensin-Converting Enzyme Inhibitors , Receptors, Angiotensin , Bronchoalveolar Lavage Fluid , Tumor Necrosis Factor-alpha , Malondialdehyde , Superoxide Dismutase , Interleukin-8 , Catalase , Antioxidants , Anti-Inflammatory Agents , Rats
4.
EMHJ-Eastern Mediterranean Health Journal. 2002; 8 (1): 6-17
in English | IMEMR | ID: emr-158034

ABSTRACT

A study of 113 blind people in Mansoura, Egypt highlighted the causes and risk factors for blindness, and health and social care needs of the blind. In two-thirds of cases, blindness occurred before 10 years of age. Risk factors for blindness were reported by more than half the study population. Congenital causes accounted for almost half the cases. The commonest causes of bilateral blindness were corneal opacities, cataract and glaucoma. Almost three-quarters of causes were avoidable. Health and social care for this group was inadequate and more than half would benefit from further management. Legislation for keratoplasty, a registry of blind people, and a nationwide community survey on the epidemiology of blindness are needed urgently


Subject(s)
Adolescent , Adult , Child , Humans , Activities of Daily Living , Age Distribution , Causality , Child, Preschool , Corneal Transplantation/legislation & jurisprudence , Health Care Surveys , Schools/organization & administration , Sex Distribution
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