We studied the pharmacokinetics of dichloroacetate (DCA) in naive rats and rats depleted of glutathione S-transferase-zeta (GST-zeta), at doses approaching human daily exposure levels. We also compared in vitro metabolism of DCA by rat and human liver cytosol. Jugular vein-cannulated male Fischer-344 rats received graded doses of DCA ranging from 0.05 to 20 mg/kg (intravenously or by gavage), a...

The endogenous bile acid metabolite 1β-hydroxy-deoxycholic acid (1β-OH-DCA) excreted in human urine may be used as a sensitive CYP3A biomarker in drug development reflecting in vivo CYP3A activity. An efficient and stereospecific enzymatic synthesis of 1β-OH-DCA was developed using a Bacillus megaterium (BM3) cytochrome P450 (P450) mutant, and its structure was confirmed by nuclear magnetic res...

Impairment of gut barrier is associated with a fat-rich diet, but mechanisms are unknown. We have earlier shown that dietary fat modifies fecal bile acids in mice, decreasing the proportion of ursodeoxycholic acid (UDCA) vs. deoxycholic acid (DCA). To clarify the potential role of bile acids in fat-induced barrier dysfunction, we here investigated how physiological concentrations of DCA and UDC...

The aim of this study was to investigate the effects of deoxycholic acid (DCA) on the contractions of rat proximal colonic smooth muscle (PCSM) in vitro. The contractile response of rat PCSM strips was tested using a polyphysio-graph. The whole cell patch-clamp technique was also used in rat colonic smooth muscle cells (SMCs) isolated by an enzymatic procedure to record the L-type calcium curre...

Even in the presence of oxygen most cancer cells convert glucose to lactate via pyruvate instead of performing oxidative phosphorylation (aerobic glycolysis-Warburg effect). Thus, it has been considered to shift pyruvate - the metabolite of aerobic glycolysis - to acetylCoA by activation of pyruvate dehydrogenase (PDH). AcetylCoA will then be metabolized by oxidative phosphorylation. Therefore,...

Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase, has anti-tumor properties in various carcinoma models. Diisopropylamine dichloroacetate (DADA), an over-the-counter drug for chronic liver disease, is a derivative of DCA. To date, few studies have evaluated the anticancer potential of DADA in breast cancer. In this study, MDA-MB-231 cells, a breast adenocarcinoma cell line, ...

BACKGROUND Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis responds to immunnotherapy, and approximately 80% of patients with this disorder fully recover or have only minor sequelae. Brain magnetic resonance imaging (MRI) does not show a specific abnormality, but some patients have progressive cerebral atrophy. The cerebral atrophy can become reversible after clinical improvement. ...

Previous research has shown an inconsistent effect of hypoxia on dynamic cerebral autoregulation (dCA), which may be explained by concurrent CO2 control. To test the hypothesis that hypoxic dCA is mediated by CO2, we assessed dCA (transcranial Doppler) during and following acute normobaric isocapnic and poikilocapnic hypoxic exposures. On 2 separate days, the squat-stand maneuver was used to de...

Ansamycin antibiotics that target heat shock protein 90 function are being developed as anticancer agents but are also known to be dose limiting in patients due to hepatotoxicity. Herein, to better understand how the normal tissue toxicity of geldanamycins could be ameliorated to improve the therapeutic index of these agents, we examined the interactions of 17-allylamino-17-demethoxygeldanamyci...

In this paper a multi-channel MAC protocol with dynamic channel allocation (MMAC-DCA) in CDMA Ad Hoc networks is proposed. Under MMAC-DCA, the service sub-channels are dynamically allocated by the RTS/CTS dialogue on the common sub-channel, only when a node has a packet to transmit. In addition, a Markov mode is presented to analyze the performance of MMAC-DCA. key words: Ad Hoc networks, dynam...