New drug development in India

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Glutaredoxin is essential for maintenance of brain mitochondrial complex I: studies with MPTP

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Aneurysmal bone cyst in proximal phalanx treated without bone grafting

Aneurysmal bone cyst involving the hand are a rare occurrence especially in the proximal phalanx. We report a case of 5 years old female child with proximal phalanx aneurysmal bone cyst treated without bone grafting. Magnetic resonance imaging may show fluid filled spaces but definite diagnosis can only be obtained histologically. It is a benign lesion still it can involve growth plate hence intervention is necessary. The treatment includes curettage with or without bone grafting

Schiff’s base Fufural Phenylhydrazone as a Potential Corrosion Inhibitor for Mild Steel in Hydrochloric Acid Solution

Heterocyclic Schiff base furfural phenylhydrazone [FPH] was prepared and formulated as a corrosion inhibitor for mild steel in 2M hydrochloric acid solution. Mass change measurement and electrochemical methods adapted to study the effectiveness of the FPH during the corrosion process. FPH inhibitor protected 94.53 % corrosion of mild steel at optimum inhibitor strength of 0.0007 M at 303 ±1 K. Route of corrosion protection was interpreted through adsorption of FPH molecules on specimen surfaces in acid solution. Nature of the adsorption was established via Langmuir adsorption isotherm. Stability of the inhibitor was investigated with higher temperatures. Tafel polarization curves revealed, FPH molecules exhibit mixed nature of inhibitor. SEM and AFM images suggested that corroded specimen surface was severely affected in free acid comparatively in presence of FPH inhibitor. FT-IR analysis proved that, chemical interaction takes place between specimen surface atoms with FPH molecules and established chemical bond between them

Estrogen and neuroprotection: higher constitutive expression of glutaredoxin in female mice offers protection against MPTP-mediated neurodegeneration

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Thioltransferase (glutaredoxin) mediates recovery of motor neurons from excitotoxic mitochondrial injury

Mitochondrial dysfunction involving electron transport components is implicated in the pathogenesis of several neurodegenerative disorders and is a critical event in excitotoxicity. Excitatory amino acid L-β-N-oxalylamino-L-alanine (L-BOAA), causes progressive corticospinal neurodegeneration in humans. In mice, L-BOAA triggers glutathione loss and protein thiol oxidation that disrupts mitochondrial complex I selectively in motor cortex and lumbosacral cord, the regions affected in humans. We examined the factors regulating postinjury recovery of complex I in CNS regions after a single dose of L-BOAA. The expression of thioltransferase (glutaredoxin), a protein disulfide oxidoreductase regulated through AP1 transcription factor was upregulated within 30 min of L-BOAA administration, providing the first evidence for functional regulation of thioltransferase during restoration of mitochondrial function. Regeneration of complex I activity in motor cortex was concurrent with increase in thioltransferase protein and activity, 1 hr after the excitotoxic insult. Pretreatment with α-lipoic acid, a thiol delivery agent that protects motor neurons from L-BOAA-mediated toxicity prevented the upregulation of thioltransferase and AP1 activation, presumably by maintaining thiol homeostasis. Downregulation of thioltransferase using antisense oligonucleotides prevented the recovery of complex I in motor cortex and exacerbated the mitochondrial dysfunction in lumbosacral cord, providing support for the critical role for thioltransferase in maintenance of mitochondrial function in the CNS

Down-regulation of glutaredoxin by estrogen receptor antagonist renders female mice susceptible to excitatory amino acid mediated complex I inhibition in CNS

β-N-oxalyl-amino-L-alanine, (L-BOAA), an excitatory amino acid, acts as an agonist of the AMPA subtype of glutamate receptors. It inhibits mitochondrial complex I in motor cortex and lumbosacral cord of male mice through oxidation of critical thiol groups, and glutaredoxin, a thiol disulfide oxido-reductase, helps maintain integrity of complex I. Since incidence of neurolathyrism is less common in women, we examined the mechanisms underlying the gender-related effects. Inhibition of complex I activity by L-BOAA was seen in male but not female mice. Pretreatment of female mice with estrogen receptor antagonist ICI 182,780 or tamoxifen sensitizes them to L-BOAA toxicity, indicating that the neuroprotection is mediated by estrogen receptors. L-BOAA triggers glutathione (GSH) loss in male mice but not in female mice, and only a small but significant increase in oxidized glutathione (GSSG) was seen in females. As a consequence, up-regulation of γ-glutamyl cysteinyl synthase (the rate-limiting enzyme in glutathione synthesis) was seen only in male mouse CNS but not in females. Both glutathione reductase and glutaredoxin that reduce oxidized glutathione and protein glutathione mixed disulfides, respectively, were constitutively expressed at higher levels in females. Furthermore, glutaredoxin activity in female mice was down-regulated by estrogen antagonist indicating its regulation by estrogen receptor. The higher constitutive expression of glutathione reductase and glutaredoxin could potentially confer neuroprotection to female mice

Aeroelastic testing of LCA wing models - Model fabrication - Ground testing - Wind tunnel testing and Data analysis

Aeroelastic Testing Programme of Scaled Aeroelastic model of LCA half wing with rigid fuselage