Phenolic antioxidants attenuate hippocampal neuronal cell damage against kainic acid induced excitotoxicity.

Increasing evidence supports the role of excitotoxicity in neuronal cell injury. Thus, it is extremely important to explore methods to retard or reverse excitotoxic neuronal injury. In this regard, certain dietary compounds are beginning to receive increased attention, in particular those involving phytochemicals found in medicinal plants in alleviating neuronal injury. In the present study, we examined whether medicinal plant extracts protect neurons against excitotoxic lesions induced by kainic acid (KA) in female Swiss albino mice. Mice were anesthetized with ketamine and xylazine (200 mg and 2 mg/kg body wt. respectively) and KA (0.25 microg in a volume of 0.5 microl) was administered to mice by intra hippocampal injections. The results showed an impairment of the hippocampus region of brain after KA injection. The lipid peroxidation and protein carbonyl content were significantly (P < 0.05) increased in comparison to controls. Glutathione peroxidase (GPx) activity (EC 1.11.1.9) and reduced glutathione (GSH) content declined after appearance of excitotoxic lesions. As GPx and GSH represent a major pathway in the cell for metabolizing hydrogen peroxide (H2O2), their depletion would be expected to allow H2O2 to accumulate to toxic levels. Dried ethanolic plant extracts of Withania somnifera (WS), Convolvulus pleuricauas (CP) and Aloe vera (AV) dissolved in distilled water were tested for their total antioxidant activity. The diet was prepared in terms of total antioxidant activity of plant extracts. The iron (Fe3+) reducing activity of plant extracts was also tested and it was found that WS and AV were potent reductants of Fe3+ at pH 5 5. CP had lower Fe3+ reducing activity in comparison to WS and AV. Plant extracts given singly and in combination 3 weeks prior to KA injections resulted in a decrease in neurotoxicity. Measures of lipid peroxidation and protein carbonyl declined. GPx activity and GSH content were elevated in hippocampus supplemented with WS and combination of WS + CP + AV. However, when CP and AV were given alone, the changes in the GPx activity and GSH content were not significant. Although the major factors involved in these properties of phytochemicals remain to be specified, the finding of this study has suggested that phytochemicals present in plant extracts mitigate the effects of excitotoxicity and oxidative damage in hippocampus and this might be accomplished by their antioxidative properties.

Reactive oxygen species and oxidative DNA damage.

Reactive oxygen species (ROS) such as the superoxide anion radical (O2.-) hydrogen peroxide (H2O2) and hydroxyl radical (.OH) have been implicated in the pathophysiology of various states, including ischemia reperfusion injury, haemorrhagic shock, atherosclerosis, heart failure, acute hypertension and cancer. The free radicals, nitric oxide (NO) and O2.- react to form peroxynitrite (ONOO-), a potent cytotoxic oxidant. A potential mechanism of oxidative damage is the nitration of tyrosine residues of protein, peroxidation of lipids, degradation of DNA and oligonucleosomal fragments. Several mechanisms are responsible for the protection of the cells from potential cytotoxic damage caused by free radicals. Cells have developed various enzymatic and nonenzymatic defense systems to control excited oxygen species, however, a certain fraction escapes the cellular defense and may cause permanent or transient damage to nucleic acids within the cells, leading to such events as DNA strand breakage and disruption of Ca2+ metabolism. There is currently great interest in the possible role of ROS in causing DNA damage that leads to cancer and spontaneous mutations. A high rate of oxidative damage to mammalian DNA has been demonstrated by measuring oxidized DNA bases excreted in urine after DNA repair. The rate of oxidative DNA damage is directly related to the metabolic rate and inversely related to life span of the organism.

Clinical dysautonomia in diabetes mellitus--a study with seven autonomic reflex function tests.

Thirty-eight patients of NIDDM, 12 of IDDM and 10 healthy age matched controls were subjected to seven standardised autonomic reflex function tests. A scoring criteria was utilised for diagnosing and grading the severity of dysautonomia. Eight patients of IDDM and 24 of NIDDM had dysautonomia. One-third of the patients in each group had grade IV autonomic dysfunction. Severity of autonomic dysfunction was directly related to the duration of disease in NIDDM whereas in IDDM this relation was not seen. Peripheral neuropathy was almost always associated with dysautonomia in NIDDM. On the contrary, in IDDM dysautonomia was independent of peripheral neuropathy. Charcot's arthopathy, dysphagia, constipation and nocturnal diarrhea were always associated with evidence of dysautonomia. Other symptoms viz. gustatory sweating, postural dizziness and impotence did not necessarily indicate dysautonomia.

The role of skeletal sonography in limb lengthening procedures.

Eleven patients (8 males, 3 females) undergoing limb-lengthening procedures were subjected to weekly conventional radiography along with fortnightly skeletal sonography of the distraction site, to assess the rate of new bone production and complications. The radiographs were assessed for: (i) distance between the distracted bone ends, (ii) presence of new bone formation at the distraction site, (iii) regeneration of the cortical outline and (iv) overlaying soft tissue abnormality. The sonographs were assessed for: (i) distance between the distracted bone ends, (ii) rate of new bone formation, (iii) density of the new bone produced, (iv) integrity and continuity of the cortical outline and (v) overlaying soft tissue abnormality. Our results indicate the superiority of sonography over conventional radiographs in: (i) detecting early new bone formation, (ii) establishing cortical and medullary canal remodelling, (iii) detecting soft tissue complications at the distraction site and (iv) determining the presence of fluid collection at the distraction site, in patients with delayed consolidation. Conventional radiographs were more accurate in determining the distance between the two distracted bone ends, and thus the degree of distraction achieved. Ideal assessments of events at the distraction site can be achieved by a combined assessment of conventional radiotherapy and skeletal sonography.

Cardiovascular response to dynamic treadmill exercise in patients with essential hypertension before and after therapy with atenolol or captopril.

Thirty eight patients with essential hypertension and 20 healthy volunteers were subjected to treadmill exercise test. The hypertensives were then controlled with atenolol or captopril by randomly forming two groups of 19 patients each, and treadmill evaluation was repeated. The resting rate-pressure product (RPP) and myocardial oxygen consumption (MVO2), as well as peak RPP and MVO2 and recovery time, were increased and exercise duration decreased significantly in uncontrolled hypertensives (p less than 0.001). Control of hypertension resulted in significant improvement of exercise performance in both the groups. Atenolol, when compared to captopril, resulted in better exercise conditioning with considerable lowering of resting and peak RPP and MVO2 (p less than 0.001), though the difference in exercise duration, maximum work load and recovery time were not significant (p greater than 0.05). Thus, where myocardial oxygen consumption is an important consideration while treating hypertension, atenolol offers a better choice.