Molecular Targets Related Drug Resistance Mechanisms in MDR-, XDR-, and TDR-Mycobacterium tuberculosis Strains.

Tuberculosis (TB) is a formidable infectious disease that remains a major cause of death worldwide today. Escalating application of genomic techniques has expedited the identification of increasing number of mutations associated with drug resistance in Mycobacterium tuberculosis. Unfortunately the prevalence of bacillary resistance becomes alarming in many parts of the world, with the daunting scenarios of multidrug-resistant tuberculosis (MDR-TB), extensively drug-resistant tuberculosis (XDR-TB) and total drug-resistant tuberculosis (TDR-TB), due to number of resistance pathways, alongside some apparently obscure ones. Recent advances in the understanding of the molecular/ genetic basis of drug targets and drug resistance mechanisms have been steadily made. Intriguing findings through whole genome sequencing and other molecular approaches facilitate the further understanding of biology and pathology of M. tuberculosis for the development of new therapeutics to meet the immense challenge of global health.

Enteral supplements of a carbon monoxide donor CORM-A1 protect against cerebrovascular dysfunction caused by neonatal seizures.

Cerebral blood flow dysregulation caused by oxidative stress contributes to adverse neurologic outcome of seizures. A carbon monoxide (CO) donor CORM-A1 has antioxidant and cytoprotective properties. We investigated whether enteral supplements of CORM-A1 can improve cerebrovascular outcome of bicuculline-induced seizures in newborn piglets. CORM-A1 (2 mg/kg) was given to piglets via an oral gastric tube 10 minutes before or 20 minutes after seizure onset. Enteral CORM-A1 elevated CO in periarachnoid cerebrospinal fluid and produced a dilation of pial arterioles. Postictal cerebral vascular responses to endothelium-, astrocyte-, and vascular smooth muscle-dependent vasodilators were tested 48 hours after seizures by intravital microscopy. The postictal responses of pial arterioles to bradykinin, glutamate, the AMPA receptor agonist quisqualic acid, ADP, and heme were greatly reduced, suggesting that seizures cause injury to endothelial and astrocyte components of the neurovascular unit. In contrast, in the two groups of piglets receiving enteral CORM-A1, the postictal cerebral vascular responsiveness to these dilators was improved. Overall, enteral supplements of CORM-A1 before or during seizures offer a novel effective therapeutic option to deliver cytoprotective mediator CO to the brain, reduce injury to endothelial and astrocyte components of cerebral blood flow regulation and to improve the cerebrovascular outcome of neonatal seizures.

[Comparative study on the content of chlorogenic acid in Solanum torvum from different origin, different harvest time and different part].

OBJECTIVE: To develop a HPLC method for determination of chlorogenic acid in Solanum torvum and provide a scientific basis for evaluating the quality and reasonable utilization of the herb. METHODS: HPLC was used to quantitatively determine the chlorogenic acid content in Solanum torvum from different origin, different harvest time and different part. The assay was performed on a Agela Promosil C18 (4.6 mm x 250 mm, 5 microm) column and eluted with a mobile phase consisted of acetonitrile -0.1% phosphoric acid solution at a flow rate of 1.0 ml/min. The column temperature was set at 35 degrees C. The detection wavelength was 327 nm. RESULTS: The calibration curve was linear within the range of 0.1000 - 200.0 microg/mL (r = 0.9999). The average recoveries were 99.8% (RSD = 0.71%). The contents of chlorogenic acid in Solanum torvum were different from different origin, different harvest time and different part. CONCLUSION: The method is reliable, accurate and specific. It can be used for quality control of Solanum torvum and reasonable utilization of the herb.