Non-hypotensive dose of telmisartan and nimodipine produced synergistic neuroprotective effect in cerebral ischemic model by attenuating brain cytokine levels.

The hypothesis of the present study is that the anti-inflammatory property of telmisartan (TM), an AT1 blocker that may exert neuroprotection through attenuation of excitatory amino acids by controlling cytokines and reactive oxygen species, release during ischemia. The neuroprotective effect of TM and its combination with nimodipine (NM) were studied in rats by using middle cerebral artery occlusion method followed by ischemic reperfusion (IR) after 2 h of occlusion. The drugs were administered 30 min prior to the surgery and continued throughout the study period. After 24 h of IR the neurological deficit was assessed, and the locomotor activity and open field behaviour were assessed on the seventh day. On the ninth day, the brains were isolated for neurochemical and cytokine measurements and histopathological studies. The results have shown that treatment of TM (5 & 10 mg/kg) gradually reduced the glutamate, aspartate and glutamine synthetase levels. It also restored the ATP, Na(+)K(+)ATPase, glutathione and synapse integrity in the different regions of the brain in comparison to ischemic brain. TM ameliorated the pro-inflammatory cytokine (IL-1ß, IL-6, TNF-α), lipid peroxide and nitric oxide levels. Anti-inflammatory cytokine IL-10 level was found to be concurrently increased. Combination therapy of TM with NM (5 mg/kg) has shown additive effects in the above said parameters. Further a positive correlation between glutamate and cytokine release was observed, and it indicated that synaptic clearance of glutamate can be regulated by cytokines. It can be concluded that TM induces neuroprotective activity through amelioration of pro-inflammatory cytokine release during cerebral ischemia. The additive effect of NM on TM neuroprotective effect would be through controlling cytokine release, ATP restoration by cerebrovasodilation, and along with prevention of Ca(2+) dependent glutamate toxicity in neurons. The advantage of TM therapy in ischemic state can be explored clinically due to its dual effect in hypertension.

Elucidation of neuroprotective role of endogenous GABA and energy metabolites middle cerebral artery occluded model in rats.

The excitatory amino acids (EAA) like glutamate, aspartate and inhibitory neurotransmitter GABA (gama amino butyric acid) play an important role in the pathophysiology of cerebral ischemia. The objective of the present study is to elucidate the role of endogenous GABA against EAA release in different regions during ischemia. The transient focal ischemia was induced in rats by using middle cerebral artery occlusion model (MCAo). The results indicate gradual elevation of brain glutamate, aspartate and GABA level at different brain regions and attained peak level at 72 h of ischemic reperfusion (IR). At 168 h of IR the EAA levels declined to base line but GABA level was found to be still elevated. The biochemical analysis shows the depleted brain ATP, Na+K+ATPase content and triphasic response of glutathione activity. It can be concluded that time dependent variation in the EAA and GABA release, endogenous GABA can be neuroprotective and earlier restoration of energy deprivation is essential to prevent further neurodegeneration. To have efficient treatment in ischemic condition, multiple approaches like energy supply, antagonism of EAA, controlling calcium function are essential.

Disseminated infection with Strongyloides stercoralis in a diabetic patient.

A 58-year-old male diabetic who was operated for carcinoma larynx 4 years back was admitted with exertional dyspnoea and bilateral leg swelling for the past 2 years. Over the last 2 months, there was a progressive worsening of symptoms. Echocardiography done 2 years back showed pericardial effusion. Echo done during the current admission also showed pericardial effusion with preserved left ventricular function; cytological examination of the pericardial fluid showed larvae of Strongyloides stercoralis. He was treated with antinematodal drugs. A follow-up echo done at discharge showed no pericardial effusion and the patient was completely asymptomatic. To our knowledge, this is the first reported case of Strongyloides pericardial effusion in a diabetic patient.

Initial results from a randomized trial of cervical visual screening in rural south India.

The impact of a single round of screening of visual inspection with acetic acid (VIA) on cervical cancer incidence and mortality was investigated in a cluster randomized trial in south India. Women 30-59 years of age in 113 clusters in Dindigul District were randomized to VIA screening (57 clusters, 48,225 women) by nurses and to a control group (56 clusters, 30,167 women). 30,577 eligible women were screened between May 2000 and April 2003; 2,939 (9.6%) screen-positive women were investigated with colposcopy by nurses and 2,777 (9.1%) women had biopsy. CIN 1 was diagnosed in 1,778 women, CIN 2-3 lesions were found in 222, and there were 69 screen detected invasive cervical cancers. The detection rates of lesions per 1,000 screened women were 58.2 for CIN 1, 7.3 for CIN 2-3, and 2.3 for invasive cancer. The detection rate of high-grade lesions in our study was 2-3-fold higher than those observed in repeatedly screened populations in developed countries. 71% of women with CIN 1 and 80% of those with CIN 2-3 lesions accepted cryotherapy provided by nurses and surgical treatment by mid-level clinicians. Overall, 97 and 34 incident cervical cancer cases were observed in the intervention and control arms, respectively. The intervention arm accrued 124,144 person years and the control arm accrued 90,172 during the study period. The age standardized cervical cancer incidence rates were 92.4/100,000 person-years in the intervention and 43.1/100,000 in the control arms. In the screened arm, 35.0% of cases were in Stage I as opposed to none in the control arm. The preliminary findings from our study indicate that not only is a VIA-based screening programme feasible, safe and acceptable to a population in rural settings, it also results in early detection of cervical neoplasia.