Background: Tuberculous meningitis (TBM) is a major global health problem, and it is sometimes difficult to perform a differential diagnosis of this disease from other diseases, particularly partiallytreated pyogenic meningitis (PTPM). In an earlier study, we demonstrated the presence of a 30-kD protein antigen in cerebrospinal fluid (CSF) of TBM patients. We have also shown that lymphocytes from CSF of TBM patients respond differently to this antigen than do those from PTPM patients. The purpose of this study was to develop an assay that can discriminate between TBM and PTPM.

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Cyanide is a mitochondrial poison, which is ubiquitously present in the environment. Cyanide-induced oxidative stress is known to play a key role in mediating the neurotoxicity and cell death in rat pheochromocytoma (PC12) cells. PC12 cells are widely used as a model for neurotoxicity assays in vitro. In the present study, we investigated the protective effects of alpha-ketoglutarate (A-KG), a potential cyanide antidote, and N-acetyl cysteine (NAC), an antioxidant against toxicity of cyanide in PC12 cells. Cells were treated with various concentrations (0.625-1.25 mM) of potassium cyanide (KCN) for 4 hours, in the presence or absence of simultaneous treatment of A-KG (0.5 mM) and NAC (0.25 mM). Cyanide caused marked decrease in the levels of cellular antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). Lipid peroxidation indicated by elevated levels of malondialdehyde (MDA) was found to be accompanied by decreased levels of reduced glutathione (GSH) and total antioxidant status (TAS) of the cells. Cyanide-treated cells showed notable increase in caspase-3 activity and induction of apoptotic type of cell death after 24 hours. A-KG and NAC alone were very effective in restoring the levels of GSH and TAS, but together they significantly resolved the effects of cyanide on antioxidant enzymes, MDA levels, and caspase-3 activity. The present study reveals that combination of A-KG and NAC has critical role in abbrogating the oxidative stress-mediated toxicity of cyanide in PC12 cells. The results suggest potential role of A-KG and NAC in cyanide antagonism.

Sulfur mustard (SM; 2,2'-dichloro diethyl sulfide), an alkylating chemical warfare agent, poses a major threat in both military conflict and chemical terrorism situations. 2-chloroethyl ethyl sulfide (CEES) is a monofunctional analogue of SM, frequently used in laboratory settings, therefore increasing chances of its exposure. S-2(ω-aminoalkylamino) alkylaryl sulfide (DRDE-07) is an analogue of amifostine reported to have protective effects against SM but its effect on CEES is largely unexplored. Therefore, this study was planned to explore the effects of DRDE-07 against CEES-induced toxicity. 0.75 LD50 (1068 mg/kg) of CEES was exposed percutaneously in the presence or absence of DRDE-07 (249 mg/kg p.o.) which is given prophylactically (before 30 minute) to male mice. Animals were sacrificed on 24 h, 7th day and 14th day of CEES exposure, and tissues were collected to study oxidative stress and inflammatory markers. CEES exposure depleted intracellular GSH level and activities of GSH-linked enzymes (GR, GPx and GST) which play a major role in GSH metabolism. CEES exposure augmented lipid peroxidation indicating severe oxidative stress. It also initiated inflammation causing an increase in proinflammatory (IL1-α, IL1-β, IL-6, TNF-α and IFN-ϒ) and corresponding decrease in anti-inflammatory cytokines (IL-4 and IL-10). This was also accompanied by neutrophils infiltration indicated by higher than normal myeloperoxidase (MPO) levels. DRDE-07 efficiently reduced the oxidative stress and also facilitated to resolve inflammatory alterations. This study thus evaluated the beneficial role of DRDE-07 in ameliorating the deleterious effects of CEES and can be potentially used against SM/CEES poisoning.

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin associated with drug abuse and causes permanent symptoms of Parkinson's disease (PD) by destroying dopaminergic neurons in the substantia nigra of the brain. In the present study, the neuroprotective effects of two carboxylic acid compounds, viz. alpha-ketoglutarate (A-KG), a Kreb's cycle intermediate and ethyl pyruvate (EP), a lipid-soluble analogue of pyruvate, were evaluated against MPTP intoxication in mice and compared with madopar (MD; combination of levodopa plus benserazide), a standard drug. Animals received oral treatment of A-KG (500 mg/kg), EP (100 mg/kg) or MD (5 mg/kg) daily for 5 days followed by intraperitoneal administration of MPTP (20 mg/kg) and posttreatment (+10 min) of A-KG, EP or MD daily for the remaining 5 days. MPTP caused the inhibition of complex I of electron transport chain accompanied by oxidative stress in the brain. It also caused cytotoxicity in the midbrain region as characterized by histology and immunohistochemistry. Treatments of A-KG and EP were found to resolve the loss of motor coordination, oxidative stress, diminished complex I activity and tyrosine hydroxylase-positive neurons in midbrain. A-KG and EP also regressed the histological damage in the brain and minimized the accumulation of alpha-synuclein in the midbrain region. The data suggest that A-KG and EP which are nontoxic carboxylic acid compounds could be of potential therapeutic value in the treatment of PD.