Effects of bile acids on ventricular muscle contraction and electrophysiological properties: studies in rat papillary muscle and isolated ventricular myocytes

Summary The effects of sodium salts of various bile acids on the contractile force and the electrophysiological properties of rat ventricular muscle were studied in vitro. Primary, conjugated, and secondary bile acids were studied in a concentration range of 10^–9–10^–6 mol/l, which corresponds to concentrations found in the plasm of patients with cholestatic jaundice. In general, the bile acid induced a negative inotropic effect which was manifested as a reduction in active tension, maximum rate of tension activation, and maximum rate of tension relaxation. Twitch duration and time to peak tension were unaffected by the bile acids. The negative inotropism was associated with a reduction in ventricular action potential duration. Resting potential, action potential amplitude, and maximum upstroke velocity of phase 0 depolarization were unaffected. Voltage clamp experiments in rat ventricular myocytes demonstrated that sodium taurocholate decreased the slow inward current and slightly increased the outward potassium current. Hence, these effects on the membrane currents are probably responsible for the negative inotropic effect. Send offprint requests to O. Binah at the above address     

Bactericidal/permeability-increasing protein in host defense and its efficacy in the treatment of bacterial sepsis

The 55-kD bactericidal/permeability-increasing protein (BPI) is a neutrophil-derived polypeptide belonging to a family of lipid and endotoxin binding proteins. BPI is composed of two functionally distinct structural domains: a potently antibacterial and antiendotoxin ∼ 20-kD aminoterminal half, and an opsonic carboxy-terminal portion. In multiple animal models, a recombinant amino-terminal fragment of BPI (rBPI₂₁) is nontoxic and protects against gram-negative bacteria and endotoxin. In humans, rBPI₂₁ is also nontoxic and nonimmunogenic and has undergone phase II/III clinical trials with apparent therapeutic benefit.     

Adenocarcinoma arising in a chondroid syringoma of vulva.

Chondroid syringoma of the vulva is an extremely rare tumor. Of the previously reported cases, only one was clinically malignant. The authors describe a case of chondroid syringoma of the right labium majus from which arose a papillary adenocarcinoma. A right inguinal lymph node was replaced with metastatic adenocarcinoma.     

Birth control pills and nonprofessional voice: acoustic analyses.

PURPOSE: Two studies are presented here. Study 1 was aimed at evaluating whether the voice characteristics of women who use birth control pills that contain different progestins differ from the voice characteristics of a control group. Study 2 presents a meta-analysis that combined the results of Study 1 with those from 3 recent studies that compared voices of women who use and do not use birth control pills. METHOD: In Study 1, voice samples from 30 women with no history of voice training, who use pills with different progestins (drospirenone, desogestrel, gestodene), and 10 women who do not use the pill were recorded at specific time points across the menstrual cycle and were analyzed acoustically. In Study 2, results from Study 1 were analyzed jointly with results from three recent studies, which used similar methodologies. RESULTS: Results of Study 1 did not reveal acoustic differences in sustained phonation of vowels across the pill groups and controls. Results of the meta-analysis performed in Study 2 indicated that pill users exhibited lower jitter and shimmer values on sustained vowels, whereas no difference of fundamental frequency was observed among women who use the pill. CONCLUSIONS: These results support findings from previous studies, which suggested that no adverse effect on voice was detected among nonprofessional speakers who use new-generation monophasic birth control pills, for the measures studied. Furthermore, results of the meta-analysis suggested that some acoustic properties of the voice, which are reflected in perturbation measures in sustained vowels, may be improved among women who use the pill.     

Functional and metabolic effects of bupivacaine and lidocaine in the perfused working rat heart

The effects of bupivacaine (2.5, 5, 10, and 12.5 mg/L) and lidocaine (12.5, 25, 40, and 50 mg/L), on spontaneous heart rate, mean pressure development, cardiac output, and coronary flow were compared after 15 minutes' exposure in the isolated perfused working rat heart preparation. In addition, myocardial oxygen consumption, glucose utilization, lactate production, tissue content of glycogen, adenine nucleotides, and creatine phosphate content were measured. The relative potency of bupivacaine to lidocaine, calculated from slopes of regression equations, as indicated by the four mechanical variables and oxygen consumption, was 4.59. When the bupivacaine concentration was "normalized" using this value, bupivacaine and lidocaine showed indistinguishable effects on glucose utilization, lactate production, and tissue glycogen. Neither of the local anesthetics had any influence on energy charge or creatine phosphate content.     

Allicin inhibits SDF-1alpha-induced T cell interactions with fibronectin and endothelial cells by down-regulating cytoskeleton rearrangement, Pyk-2 phosphorylation and VLA-4 expression

Allicin, a major ingredient of fresh garlic extract that is produced during the crushing of garlic cloves, exerts various beneficial biological effects, including a broad spectrum of antimicrobial activity, antihyperlipidaemic and antihypertensive effects. However, how allicin affects the immune system is less well known, and its effect on human T cells has never been studied. Here, we examined the in-vitro effects of allicin on the functioning of T cells related to their entry to inflamed extravascular sites. We found that allicin (20-100 microm) inhibits the SDF-1alpha (CXCL12)-induced T cell migration through fibronectin (FN), and that this inhibition is mediated by the down-regulation of (i) the reorganization of cortical actin and the subsequent T cell polarization, and (ii) T cell adhesion to FN. Moreover, allicin also inhibited T cell adhesion to endothelial cells and transendothelial migration. The mechanisms underlying these inhibitory effects of allicin are associated with its ability to down-regulate the phosphorylation of Pyk2, an intracellular member of the focal adhesion kinases, and to reduce the expression of the VCAM-1- and FN-specific alpha4beta1-integrin (VLA-4). The ability of allicin to down-regulate these chemokine-induced and VLA-4-mediated T cell functions explains its beneficial biological effects in processes where T cells play an important role and suggests that allicin may be used therapeutically with chronic inflammatory diseases.     

Loss-of-function mutations in caspase recruitment domain-containing protein 14 (CARD14) are associated with a severe variant of atopic dermatitis

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