Pharmacological manipulation of L-carnitine transport into L6 cells with stable overexpression of human OCTN2

The high-affinity Na+-dependent carnitine transporter OCTN2 (SLC22A5) has a high renal expression and reabsorbs most filtered carnitine. To gain more insight into substrate specificity of OCTN2, we overexpressed hOCTN2 in L6 cells and characterized the structural requirements of substances acting as human OCTN2 (hOCTN2) inhibitors. A 1905-bp fragment containing the hOCTN2 complete coding sequence was introduced into the pWpiresGFP vector, and L6 cells were stably transduced using a lentiviral system. The transduced L6 cells revealed increased expression of hOCTN2 on the mRNA, protein and functional levels. Structural requirements for hOCTN2 inhibition were predicted in silico and investigated in vitro. Essential structural requirements for OCTN2 inhibition include a constantly positively charged nitrogen atom and a carboxyl, nitrile or ester group connected by a 2-4-atom linker. Our cell system is suitable for studying in vitro interactions with OCTN2, which can subsequently be investigated in vivo.     

Hepatic effects of <Emphasis Type="Italic">Cimicifuga racemosa</Emphasis> extract <Emphasis Type="Italic">in vivo</Emphasis> and <Emphasis Type="Italic">in vitro</Emphasis>

Extracts of Cimicifuga racemosa are used frequently for menopausal complaints. Cimicifuga is well tolerated but can occasionally cause liver injury. To assess hepatotoxicity of cimicifuga in more detail, ethanolic C. racemosa extract was administered orally to rats, and liver sections were analyzed by electron microscopy. Tests for cytotoxicity, mitochondrial toxicity and apoptosis/necrosis were performed using HepG2 cells. Mitochondrial toxicity was studied using isolated rat liver mitochondria. Microvesicular steatosis was found in rats treated with > 1,000 mg/kg [DOSAGE ERROR CORRECTED] body weight cimicifuga extract. In vitro, cytotoxicity was apparent at concentrations > or =75 microg/mL, and mitochondrial beta-oxidation was impaired at concentrations > or =10 microg/mL. The mitochondrial membrane potential was decreased at concentrations > or =100 microg/mL, and oxidative phosphorylation was impaired at concenq trations > or =300 microg/mL. The mechanism of cell death was predominantly apoptosis. C. racemosa exerts toxicity in vivo and in vitro, eventually resulting in apoptotic cell death. The results are compatible with idiosyncratic hepatotoxicity as observed in patients treated with cimicifuga extracts.     

Peptido-aminobenzophenones--novel latentiated benzo-1,4-diazepines.

It has been shown that cleavage of the N-terminal L-amino acids of a novel series of dipeptide derivatives of 2-aminobenzophenones occurs readily in vivo to give benzo-1,4-diazepines. Such compounds may serve as useful pro-drug forms of minor tranquilizers such as Valium.     

Dose relationships of morning bright white light in seasonal affective disorders (SAD)

Summary Bright white full spectrum light (>2500 lux) can improve depressive symptomatology in a selected group of patients with recurrent autumn and winter depression. This crossover study demonstrates that 0.5-h morning white light is not an effective treatment, whereas 2-h is.     

Dose relationships of morning bright white light in seasonal affective disorders (SAD)

Bright white full spectrum light (greater than 2500 lux) can improve depressive symptomatology in a selected group of patients with recurrent autumn and winter depression. This crossover study demonstrates that 0.5-h morning white light is not an effective treatment, whereas 2-h is.     

Metabolism-weight relationship in 17 humming-bird species at different temperatures during day and night

Summary The mean metabolic rate during day and night of 17 different humming-bird species is considerably higher than the expected value for nonpasserine birds. The weight-metabolism regression exponent for the night-time is in the same range as that reported for other avian orders (and mammals); 0.73.     

Fuzzy Sets and Rough Sets: a Comparison through an Extension of Obtulowicz's Category

<正>This paper is a purely mathematical one dealing with a common possible foundation of Fuzzy Set Theory and Rough Set Theory.It begins with a generalization of Obtulowicz's paper,rough sets and Heyting algebra valued sets,published in Bull.Polish Acad Sc.(math),198.In this paper Obtulowicz proposes a special subcategory of     

Preimplantation mouse embryos cultured in mouse, rat and human sera: differentiation and sister chromatid exchange

Development of 4-cell and of 8-cell mouse embryos and of morulae and blastocysts is inhibited in vitro by mouse serum but not by rat or human sera which also do not influence sister chromatid exchange in cultured morulae and blastocysts.