The effects of cyclosporine on antioxidant enzyme activities and malondialdehyde levels in rabbit hepatic tissues

Possible molecular mechanisms leading to cyclosporine-induced hepatotoxicity has not been cleared yet. Therefore, investigation of antioxidant status of hepatic tissues exposed to cyclosporine A (CsA) and of free radical involvement in the CsA-induced hepatotoxicity seems of importance. For this aim, 20 rabbits were used in the study. In each group (control, CsA, CsA plus vitamin and, vitamin only) there were 5 animals. CsA was given orally (25 mg/kg/day) for 10 days. Vitamins E (100 mg/kg/ day) and C (200 mg/kg/day) combination was injected intramuscularly. After 10th day, animals were killed, and livers were prepared for the enzymatic assays. Activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) and, malondialdehyde (MDA) levels were determined in the supernatant fractions. Lowered SOD, unchanged GSH-Px and, increased CAT activities and MDA levels were detected in hepatic tissues of rabbits treated with CsA as compared with controls. In the CsA plus vitamin group, SOD activity was found to be higher, GSH-Px and CAT activities unchanged and MDA levels lower than the CsA group. In the vitamin-treated group, all of the enzyme activities were higher than the controls but MDA levels were unchanged. Correlation analysis revealed some significant differences between the groups. Results suggest that cyclosporine impairs the antioxidant defense system and thus, leads to oxidant stress and peroxidation in rabbit hepatic tissues. It has been established that this process can be prevented by antioxidant vitamin supplementation.     

Role of G(s) proteins in hypoxic constriction of sheep pulmonary artery rings

The introduction of hypoxia is well known to cause contraction of pulmonary artery rings in vitro. Despite intensive studies, the cellular mechanisms of hypoxic pulmonary vasoconstriction are still not well defined. In this study, we aimed to determine the contribution of G(S) proteins in hypoxia-induced vasoconstriction in large-diameter sheep pulmonary arteries using cholera toxin (CT). Hypoxia caused further contractions in serotonin but not in NaF-precontracted pulmonary artery rings. However, hypoxic vasoconstriction due to lowering of pO(2) from 97 to 5 mm Hg was totally abolished by preincubation with CT in serotonin-precontracted arteries. These preliminary results indicate that signal transduction mediated by G(s) proteins may be an important mechanism in the hypoxic vasoconstriction of isolated pulmonary arteries of sheep.     

Cisplatin induces acute renal failure by impairing antioxidant system in guinea pigs: effects of antioxidant supplementation on the cisplatin nephrotoxicity

This study aims to investigate the role of oxidants in cisplatin-induced nephrotoxicity. Cisplatin was administered intraperitoneally (i.p.) in a single dose (5 mg/kg) and guinea pigs were killed either after 24 h or 7 days. The same experiment was performed using animals treated with vitamins C and E combination and a natural antioxidant extract (SARMEX). The kidneys were then removed to be used in the analyses. Blood samples were also obtained from the animals to be used in routine biochemical assays. Twenty-four hours after treatment there was a significant decrease in the renal activities of total superoxide scavenger activity (TSSA), superoxide dismutase (SOD) and catalase (CAT) accompanied by a rise in malondialdehyde (MDA) levels. After 7 days, the fall in kidney enzymatic activities was far greater, while the increase in blood urea (BUN) and creatinine (CRE) was marked. Treatment with antioxidants causes significant increases in renal TSSA (7 day), non-enzymatic superoxide scavenger activity (NSSA) (24 h and 7 day) and SOD (7 day) activities, does not change glutathione peroxidase (GSH-Px) activity and decreases renal MDA (24 h and 7 day), blood BUN (7 day) and CRE (7 day) levels. Our results suggest that cisplatin treatment impairs both enzymatic and non-enzymatic antioxidant systems and causes peroxidation in the renal tissue, which leads to kidney failure. Antioxidant supplementation strengthens the renal antioxidant system, eliminates oxidation reactions, and prevents cisplatin-induced kidney failure.     

CADASIL and genetics of cerebral ischaemia

Recent advances suggest the existence of several autosomal dominantly inherited forms of cerebrovascular disorders. Mutations in diverse genes may induce direct pathological changes in intracranial vessels to cause cerebral ischaemic or haemorrhagic strokes leading to cognitive impairment and dementia. Similar pathology may also be caused by systemic vascular disease resulting from mutations and polymorphisms in genes that regulate cardiovascular physiology, blood coagulation and metabolic functions. The most common form of familial stroke appears to be CADASIL or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. CADASIL is an arterial disease that has been linked to nucleotide substitutions and deletions in the Notch 3 gene. The pathogenesis of the disorder or how the mutations lead to cerebral infarcts and dementia is not known. However, elucidation of the microvascular pathology associated with such genetic disorders not associated with physiological risk factors for cardiovascular disease or stroke can bear much light on primary vascular mechanisms that lead to ischaemic blood flow and neuronal vulnerability.     

Endovascular treatment of thoracic aortic dissection and its variants

The acute aortic syndrome (AAS) is described. Its pathophysiology is discussed for each of the three entities (penetrating aortic ulcer, intramural hematoma and aortic dissection). The natural history of these three pathologies is reviewed. Diagnostic features and investigation imaging techniques are summarized. The technique of stentgraft-placement is described in detail. The authors report their clinical experience with 127 patients, presenting acute type B aortic dissection or its variants, and treated with an endovascular stent-graft-device. These results are in part compared with a group of control patients with acute type B dissection, submitted to medical non-invasive therapy.     

Clinical and pathologic findings in hereditary spastic paraparesis with spastin mutation

OBJECTIVE: To describe a family with chromosome 2p-linked hereditary spastic paraparesis (HSP) associated with dementia and illustrate the cerebral pathology associated with this disorder. BACKGROUND: HSP comprises a heterogeneous group of inherited disorders in which the main clinical feature is severe, progressive lower limb spasticity. Nongenetic classification relies on characteristics such as mode of inheritance, age at onset, and the presence or absence of additional neurologic features. Several loci have been identified for autosomal dominant pure HSP. The most common form, which links to chromosome 2p (SPG4), has recently been shown to be due to mutations in spastin, the gene encoding a novel AAA-containing protein. RESULTS: The authors report four generations of a British family with autosomal dominant HSP in whom haplotype analysis indicates linkage to chromosome 2p. In addition, a missense mutation has been identified in exon 10 of the spastin gene (A1395G). Dementia was documented clinically in one member of the family, two other affected family members were reported to have had late onset memory loss, and a younger affected individual showed evidence of memory disturbance and learning difficulties. Autopsy of the demented patient confirmed changes in the spinal cord typical of HSP and also demonstrated specific cortical pathology. There was neuronal depletion and tau-immunoreactive neurofibrillary tangles in the hippocampus and tau-immunoreactive balloon cells were seen in the limbic and neocortex. The substantia nigra showed Lewy body formation. The pathologic findings are not typical of known tauopathies. CONCLUSIONS: The authors confirm that chromosome 2p-linked HSP can be associated with dementia and that this phenotype may be associated with a specific and unusual cortical pathology.     

The effect of latanoprost, bimatoprost, and travoprost on intraocular pressure after cataract surgery.

PURPOSE: The aim of this study was to evaluate the effect of preoperative topical latanoprost, bimatoprost, and travoprost administration on postoperative intraocular pressure (IOP) after phacoemulsification and posterior chamber intraocular lens (PC IOL) implantation. METHODS: This prospective, randomized, double-masked study included 120 eyes of 120 consecutive, normotensive, uncomplicated cataract patients having phacoemulsification surgery with PC IOL implantation. They were randomized into 1 of 4 treatment groups, each of which had 30 patients. Two (2) h before the surgery, the patients received 0.005% latanoprost (Group 1), 0.004% bimatoprost (Group 2), 0.03% travoprost (Group 3), or placebo (Group 4, artificial tears). IOP was measured at preoperative, 4, 8, and 24 h postoperative with a Goldmann applanation tonometer. The anterior chamber was examined postoperatively 24 h for levels of cell and flare using slit-lamp biomicroscopy. RESULTS: The preoperative mean IOP was not statistically significant different among the four groups. In Groups 1 and 3, the mean IOP at 4, 8 and 24 h were significantly lower than the control (Group 4; P < 0.05). However, in Group 2, there was no significant difference in IOP during the study period, compared to the control (Group 4; P > 0.05). In addition, the mean postoperative IOP at 24 h in Groups 1 and 3 were significantly lower than the preoperative IOP (P < 0.05). No severe anterior chamber reaction was observed in any group. CONCLUSIONS: Our findings show that a single-dose topical of latanoprost and travoprost can prevent early postoperative IOP elevation after phacoemulsification surgery without any sideeffects.     

Glial cells of the spinal cord and subcortical white matter up-regulate neuronal nitric oxide synthase in sporadic amyotrophic lateral sclerosis

Several studies have suggested that excessive generation of nitric oxide (NO) may contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS). Recently, a selective induction of the neuronal isoform of nitric oxide synthase (nNOS) in glial cells has been reported in an animal model of familial ALS. We therefore examined in postmortem tissue the expression of nNOS in patients with sporadic ALS and patients without any history of neurological disease. Using immunohistochemistry, we found an up-regulation of nNOS in glial cells of the spinal cord and subcortical white matter in ALS patients compared to controls. The enhanced glial nNOS expression seen in ALS patients could conceivably contribute to motoneuronal degeneration through NO-mediated cytotoxic effects.     

Impaired RNA splicing of 5'-regulatory sequences of the astroglial glutamate transporter EAAT2 in human astrocytoma

This case report describes a follow up investigation of a patient with impaired word discrimination due to mitochondrial encephalopathy with lactic acidosis and stroke-like syndrome (MELAS) using proton magnetic resonance spectroscopy ((1)H MRS) and auditory evoked magnetic fields (AEFs). The initial (1)H MRS showed no N-acetyl aspartate (NAA) and marked accumulation of lactate (Lac) in the stroke-like lesion of MELAS, which was silent in neural activity according to AEFs. The follow up investigations, however, demonstrated that NAA reappeared, that the formerly increased Lac signal was significantly reduced, and that the magnitude of AEFs of the lesion was markedly increased. Metabolic and functional changes in (1)H MRS and AEFs reflected the neurological recovery very well. The stroke-like lesion was shown, using AEFs and (1)H MRS, to be able to function properly, although brain tissue of the lesion initially had severe damage due to mitochondrial dysfunction.