Evaluation of the protective effect of Paeonia emodi Wall on rat model of Parkinson’s disease induced by 6 hydroxy dopamine

Background: Generation of reactive oxygen species together with paucity of antioxidant defense is considered as an important cause for dopaminergic neuronal death. Review of literature indicates that none of the drugs so far studied for preventing the PD were found to be promising for use. Therefore, the present study was planned to evaluate the neuroprotective effect of Paeonia emodi Wall (PEW) in 6-hydroxy dopamine induced Parkinson’s disease (PD) model.Methods: The study was conducted on Wistar rats where Parkinson’s disease was induced by producing the striatal 6-hydroxy dopamine lesions. The test animals received ethanolic extract of PEW at dose of 200 and 300mg/kg for 28 days. Circling behavior, spontaneous locomotor activity, muscular coordination and akinesia were studied. Antioxidant levels were assessed by biochemical estimation and histopathology was carried out for dopaminergic neuronal loss.Results: PEW ethanolic extract showed significant dose dependent recovery in number of circlings, line crossing, muscular coordination and akinesia. A significant increase in MDA levels and decreased GSH level in PEW treated groups was observed in test groups as compared to control group (p<0.05). Normal architecture was retained only in PEW 300mg/Kg (p<0.05). L-Dopa did not showed effect on biochemical and histological parameters.Conclusions: The ethanolic extract of PEW showed neuroprotective activity against 6-hydroxy dopamine induced Parkinson’s disease in rats in both 200 and 300mg/kg doses. The protective action of PEW in PD can be because of its ability to reduce the oxidative stress

Endocytic uptake, transport and macromolecular interactions of anionic PAMAM dendrimers within lung tissue

Purpose: Polyamidoamine (PAMAM) dendrimers are a promising class of nanocarrier with applications in both small and large molecule drug delivery. Here we report a comprehensive evaluation of the uptake and transport pathways that contribute to the lung disposition of dendrimers. Methods: Anionic PAMAM dendrimers and control dextran probes were applied to an isolated perfused rat lung (IPRL) model and lung epithelial monolayers. Endocytosis pathways were examined in primary alveolar epithelial cultures by confocal microscopy. Molecular interactions of dendrimers with protein and lipid lung fluid components were studied using small angle neutron scattering (SANS). Results: Dendrimers were absorbed across the intact lung via a passive, size-dependent transport pathway at rates slower than dextrans of similar molecular sizes. SANS investigations of concentration-dependent PAMAM transport in the IPRL confirmed no aggregation of PAMAMs with either albumin or dipalmitoylphosphatidylcholine lung lining fluid components. Distinct endocytic compartments were identified within primary alveolar epithelial cells and their functionality in the rapid uptake of fluorescent dendrimers and model macromolecular probes was confirmed by co-localisation studies. Conclusions: PAMAM dendrimers display favourable lung biocompatibility but modest lung to blood absorption kinetics. These data support the investigation of dendrimer-based carriers for controlled-release drug delivery to the deep lung

Utility of electroencephalogram in altered states of consciousness in intensive care unit patients

BACKGROUND: EEG is an investigative tool for assessing cerebral activity. Although certain EEG patterns may have a specific diagnostic or prognostic inference, they may not be precise for any sole etiology in majority of cases and may need clinical correlation. OBJECTIVE: Aim of this study was to assess the severity and prognosis of cerebral dysfunction in patients admitted to Intensive Care Unit (ICU) and to evaluate the incidence of non-convulsive status epilepticus (NCSE). DESIGN: A prospective study, wherein we analyzed EEG characteristics in a series of 70 patients. SETTING: A tertiary care hospital in Mumbai, India. PATIENTS: EEG characteristics of 70 patients admitted in ICU over a period of 9 months were comprehensively analyzed. These patients were clinically examined and a questionnaire was completed without knowledge of the EEG findings. EEGs were requested for by neurologist or intensivist and our inclusion criteria were (i) patients with altered sensorium of varying etiology, (ii) unconscious patients at risk for non-convulsive status epilepticus (those with a history of epilepsy), and (iii) unconscious patients with involuntary jerky eye movements. RESULTS: Of the various clinical presentations on ICU admission, there were 20 patients with seizures, 15 with metabolic disorders, 13 with infective causes, 9 with hypoxia, 9 with cerebro-vascular accident on presentation, 1 patient with alcohol/drug overdose, 2 with intra-cerebral space occupying lesion and 1 with ambiguous etiology on admission (there being an overlap among the presentation). Mean duration from presentation to performing EEG was 13 hours. 64 (91.42%) patients had abnormal EEGs. 32(50%) patients had EEG slowing and 4(6.25%) patient had electro cerebral inactivity. Eleven (21.87%) patients had epileptiform activity on the EEG of which seven did not have overt seizures (NCSE). Follow-up EEGs of these patients showed resolution of the epileptiform activity. CONCLUSIONS: EEG is useful in patients admitted to ICU in diagnosing NCSE and various other conditions. Emergent EEG study in obtunded patients provides valuable diagnostic and prognostic information

An audit of decompressive craniectomies

Background: The management of acute intracranial hypertension refractory, to the medical management, remains a challenging endeavour. Mortality and morbidity rates remain high despite optimal medical management. Decompressive craniectomy has been proposed as an effective treatment for patients who have raised intracranial pressure (ICP) refractory, to the medical management. This study examined the outcome of patients who underwent this procedure. Aim: To assess the outcome of patients who underwent decompressive craniectomy. Materials and Methods: We conducted a prospective audit of consecutive patients of one neurosurgical unit, who underwent decompressive craniectomy at a tertiary care centre between 01/01/2004 to 31/03/2005. A complete neurological assessment, including Glasgow coma scale (GCS) and pupils was done and recorded at the time of admission, deterioration, post-op one wk and post-op three wks. End points were Glasgow outcome score (GOS) and Karnofsky score at 30 days, at discharge and at 6 months. Results: We studied 12 patients who were aged 30 to 69 yrs (Mean = 47 yrs). Unlike most interventions in critical care, survival is not an acceptable single end point. Good recovery ( Karnofsky score ≥80 / GOS≥4) was seen in five patients. Three patients were alive with severe disability ( Karnofsky score 1-70 / GOS 2-3), at follow up. Four patients died (Karnofsky score 0 / GOS 1). Conclusion: Eight patients who underwent decompressive craniectomy survived. Five of these patients had a good recovery. The other three survived with severe disability

The Swansong of the Galactic Center Source X7: An Extreme Example of Tidal Evolution near the Supermassive Black Hole

We present two decades of new high-angular-resolution near-infrared data from the W. M. Keck Observatory that reveal extreme evolution in X7, an elongated dust and gas feature, presently located half an arcsecond from the Galactic Center supermassive black hole. With both spectro-imaging observations of Br- γ line emission and Lp (3.8 μ m) imaging data, we provide the first estimate of its orbital parameters and quantitative characterization of the evolution of its morphology and mass. We find that the leading edge of X7 appears to be on a mildly eccentric ( e ∼ 0.3), relatively short-period (170 yr) orbit and is headed toward periapse passage, estimated to occur in ∼2036. Furthermore, our kinematic measurements rule out the earlier suggestion that X7 is associated with the stellar source S0-73 or with any other point source that has overlapped with X7 during our monitoring period. Over the course of our observations, X7 has (1) become more elongated, with a current length-to-width ratio of 9, (2) maintained a very consistent long-axis orientation (position angle of 50°), (3) inverted its radial velocity differential from tip to tail from −50 to +80 km s ^−1 , and (4) sustained its total brightness (12.8 Lp magnitudes at the leading edge) and color temperature (425 K), which suggest a constant mass of ∼50 M _Earth . We present a simple model showing that these results are compatible with the expected effect of tidal forces exerted on it by the central black hole, and we propose that X7 is the gas and dust recently ejected from a grazing collision in a binary system