Highly selective sigma receptor ligands elevate inositol 1,4,5-trisphosphate production in rat cardiac myocytes

Exposure of cardiac myocytes from adult rat ventricles to the highly selective, high affinity sigma receptor ligands 1S,2 R-cis-N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)-cycloh exylamine (BD-737) (0.1-100 nM) and N-[2-(3,4-dichlorophenyl)ethyl]-N,N',N'-trimethylethylenediamine (BD-1047) (0.01-10 nM), caused potentiation of electrically-evoked amplitudes of contraction and Ca2+ transients, while exposure to 100 nM BD-1047 caused attenuation of these amplitudes. In addition, BD-737 (1-100 nM) and BD-1047 (10-100 nM) caused an increase in the incidence of spontaneous twitches. These effects were inhibited when the incubation with BD-737 was done in the presence of the phospholipase C inhibitor, neomycin, or after pre-incubation with thapsigargin or caffeine which deplete the sarcoplasmic reticulum Ca2+ stores. Inositol 1,4,5-trisphosphate (IP3) production in cardiac myocytes was determined by the IP3 binding protein assay. Both substances caused an increase in the intracellular concentration of IP3. BD-737 caused a rapid transient increase to 3.2-fold in 1 min and stabilization at 2.1-fold of control thereafter. BD-1047 caused a gradual increase reaching 4.4-fold after 5 min. The results suggest that the effects of these sigma receptor ligands on contractility and spontaneous contractions are mediated by activation of phospholipase C and elevation of intracellular IP3 level.     

Reconstructive memory bias in recall of neuropsychological symptomatology

Several hypotheses have been advanced in recent years to understand difficulties in agrammatic patients. Some of them are of a structural kind, as the deficiency is said to lie in some of the linguistic system components. Others are of a functional type, as it is stated that the problem of these patients lies in the loss of processing capacity. Using the existence of a syntactic type of structure in Spanish, that active sentences do not follow the canonical S-V-O order, we will try to prove in this article whether agrammatic patients' problems are due to memory span loss or to one of the syntactic process mechanisms. To this end, the performances of three groups of patients are contrasted. Agrammatic, anomic, and normal Spanish speakers are given several tasks of sentence-picture matching and tests of memory span. Results show that agrammatic patients have specific difficulties processing certain syntactical structures; however, their memory deficiencies are not more pronounced than in other patients. It can be concluded, therefore, that the deficiencies of agrammatic patients are of a structural character rather than due to memory span loss.     

mraY is an essential gene for cell growth in Escherichia coli

The synthesis of the murein precursor lipid I is performed by MraY. We have shown that mraY is an essential gene for cell growth. Cells depleted of MraY first swell and then lyse. The expression of mraY DNA in vitro produces a 40-kDa polypeptide detectable by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.     

Psychopathology in pediatric complex partial and primary generalized epilepsy

Structured psychiatric interviews were administered to 60 children with complex partial seizure disorder (CPS), 40 children with primary generalized epilepsy with absences (PGE), and 48 control children, aged 5 to 16 years. Significantly more patients with epilepsy had psychiatric diagnoses compared with the control children. There were no statistically significant differences, however, in the number of patients with CPS and PGE with psychiatric diagnoses. Other than a schizophrenia-like psychosis found only in the patients with CPS, the two groups of patients had similar psychiatric diagnoses. The presence of psychopathology was related to significantly lower IQ scores and socioeconomic status, but not to seizure-related factors. These findings suggest that the psychopathology of children with CPS and PGE reflects different subtle neuropsychological deficits.     

MDA-MB-453, an androgen-responsive human breast carcinoma cell line with high level androgen receptor expression

The role of androgens and the androgen receptor (AR) in the development and progression of breast cancer is poorly understood. To further define a potential model for androgen action in breast cancer, MDA-MB-453 cells, which express AR in the absence of oestrogen receptors and progesterone receptors, were further characterised in terms of AR expression and androgen responsiveness. High level expression of AR was confirmed by northern blot analysis, radioligand binding and immunocytochemistry, and could not be accounted for by AR gene amplification. Three endogenous androgen-responsive genes (fatty acid synthetase, gross cystic disease fluid protein of 15 kDa and prolactin receptor) and a transfected reporter gene, containing an androgen-responsive element, were induced following androgen administration. A synthetic androgen, mibolerone, induced moderate (27% above control) stimulation of MDA-MB-453 cell proliferation, which was abrogated by the simultaneous administration of the synthetic androgen antagonist, anandron, demonstrating that the effect was AR-mediated. In summary, MDA-MB-453 cells express high levels of functional AR, and thus provide a valuable in vitro model for further studies on androgen regulation of gene expression, and perhaps cell proliferation in breast cancer.     

Inhibition of angiogenesis by thalidomide requires metabolic activation, which is species-dependent

Thalidomide has been shown to be an inhibitor of angiogenesis in a rabbit cornea micropocket model; however, it has failed to demonstrate this activity in other models. These results suggest that the anti-angiogenic effects of thalidomide may only be observed following metabolic activation of the compound. This activation process may be species specific, similar to the teratogenic properties associated with thalidomide. Using a rat aorta model and human aortic endothelial cells, we co-incubated thalidomide in the presence of either human, rabbit, or rat liver microsomes. These experiments demonstrated that thalidomide inhibited microvessel formation from rat aortas and slowed human aortic endothelial cell proliferation in the presence of human or rabbit microsomes, but not in the presence of rat microsomes. In the absence of microsomes, thalidomide had no effect on either microvessel formation or cell proliferation, thus demonstrating that a metabolite of thalidomide is responsible for its anti-angiogenic effects and that this metabolite can be formed in both humans and rabbits, but not in rodents.     

Use of intra-aortic balloon pumping (IABP) in clinical cardiac surgery and management of patients with IABP

One hundred thirty eight patients were reviewed which required IABP assist. Sixty nine (84 per cent) of 82 patients who had been able to come off cardiopulmonary bypass despite increasing pharmacologic support survived operation and 56 patients (68 per cent) discharged hospital. Twenty three (75 per cent) of 31 patients who took for elective coronary artery surgery as extremely high risk because of extensive three vessel coronary artery disease and severely compromised left ventricular function discharged hospital. In summary, hospital death was 35 per cent, late death 12 per cent and long term survivors 54 per cent. Severe complication concerned with inserting balloon catheter occurred in two cases (1.4 per cent) which were abdominal aortic dissection and laceration of iliac artery. At the present time, the primary indication for IABP is in assistance of the open heart surgical patient. Thre are three important factors in successfully managing the patients with IABP. First, begin IABP assist as soon as possible if indicated. Second, keep an adequate circulating volume with mean left atrial pressure being maintained around 20 mmHg and cardiac index at 2.1 L/min./M or greater. Third, improve the peripheral vascular circulation, which might need peripheral vasodilator.