Training-Induced Mitochondrial Adaptation: Role of PGC-1?, NF?B and ?-Blockade.

Training-induced Mitochondrial Adaptation: Role of PGC-1?, NF?B and ?-Blockade.

Filed under: Drug and Alcohol Rehabilitation

Exp Physiol. 2012 Oct 26;
Feng H, Kang C, Dickman J, Koenig R, Awoyinka I, Zhang Y, Ji LL

Aim Interaction of peroxisome proliferator-activated receptor ? co-activator 1? (PGC-1?) with other cellular signaling pathways plays an important role in the training-induced mitochondrial adaptations. The purpose of this study is to examine whether pyrolidine dithiocarbamate (PDTC), a nuclear factor ?B (NF?B) inhibitor and antioxidant, and ?-adrenergic blocker propranolol (PROP) would affect PGC-1?-induced mitochondrial transcription factors, enzymes and proteins involved in energy metabolism and antioxidant defense in response to endurance training. Methods Female Sprague-Dawley rats (age 8 wks) were randomly divided into two groups (N=24): subjected to 8-wk treadmill training or remained sedentary. Each group of rats was injected (i.p.) daily with either PDTC (50 mg/kg body wt), PROP (30 mg/kg) or saline as control 1 h before daily exercise session. Results Sedentary PDTC rats showed 75% higher PGC-1? content (P<0.01) but lower mitochondrial transcription factor A (Tfam) and phosphorylated cAMP-responsive element binding protein (p-CREB) than control rats. Training increased PGC-1? by 57% (P<0.01), cytochrome c oxidase 4 (COXIV) by 30% (P<0.05) and p-CREB by 13% (P<0.05), whereas mitochondrial mitofusin-2 (Mfn2) level was decreased 24% (P<0.01). PDTC treatment decreased PGC-1? and p-CREB content by 34 and 53% (P<0.05), respectively, in trained rats and abolished training effects on COXIV and Mfn2. None of the training effects was abolished by PROP treatment. Mitochondrial superoxide dismutase activity was decreased with PDTC whereas training-induced glutathione peroxidase activity was unaltered by either drug. Conclusion NF?B-inhibitory and antioxidant properties of PDTC can attenuate PGC-1? mediated mitochondrial adaptation to endurance training, whereas the ?-adrenergic pathway has little adverse effect. HubMed – drug

 

Does the integration of TB medical services in the general hospital improve the quality of TB care? Evidence from a case study in China.

Filed under: Drug and Alcohol Rehabilitation

J Public Health (Oxf). 2012 Oct 26;
Sun Q, Yin J, Yin X, Zou G, Liang M, Zhong J, Walley J, Wei X

BACKGROUND: Moving the clinical services from tuberculosis (TB) dispensary to the integrated county hospital (called integrated approach) has been practiced in China; however, it is unknown the quality of TB care in the integrated approach and in the dispensary approach. METHODS: A total of 202 new TB patients were investigated using structured questionnaires in three counties implementing the integrated approach and one county implementing the dispensary approach. The quality of TB care is measured based on success rate of treatment, medical expenditure, health system delay and second-line drug use. RESULTS: The integrated approach showed a high success treatment rate. The medical expenditure in the integrated approach was USD 432, significantly lower than that in the dispensary approach (Z = -5.771, P < 0.001). The integrated approach had a shorter health system delay (5 days) than the dispensary approach (32 days). Twenty-six percent of patients in integrated hospitals were prescribed with second-line TB drugs, significantly lower than that in the TB dispensary (47%, ?(2) = 7.452, P = 0.006). However, the medical expenditure, use of second-line anti-TB drug and liver-protection drugs indeed varied greatly across the three integrated hospitals. CONCLUSIONS: The integrated approach showed better quality of TB care, but the performance of the integrated hospitals varied greatly. A method to standardize TB treatment and management of this approach is urgent. HubMed – drug

 

SPSens: A software package for stochastic parameter sensitivity analysis of biochemical reaction networks.

Filed under: Drug and Alcohol Rehabilitation

Bioinformatics. 2012 Oct 25;
Sheppard PW, Rathinam M, Khammash M

SUMMARY: SPSens is a software package for the efficient computation of stochastic parameter sensitivities of biochemical reaction networks. Parameter sensitivity analysis is a valuable tool that can be used to study robustness properties, for drug targeting, and many other purposes. However its application to stochastic models has been limited when Monte Carlo methods are required due to extremely high computational costs. SPSens provides efficient, state of the art sensitivity analysis algorithms in a single software package so that sensitivity analysis can be easily performed on stochastic models of biochemical reaction networks. SPSens implements the algorithms in C and estimates sensitivities with respect to both infinitesimal and finite perturbations to system parameters, in many cases reducing variance by orders of magnitude compared to basic methods. Included among the features of SPSens are serial and parallel command line versions, an interface with Matlab, and several example problems. AVAILABILITY: SPSens is distributed freely under GPL version 3 and can be downloaded from http://sourceforge.net/projects/spsens/. The software can be run on Linux, Mac OS X, and Windows platforms. CONTACT: mustafa.khammash@bsse.ethz.ch SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
HubMed – drug

 

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