Anticonvulsant drug concentrations in epileptic patients

Using Wistar stain male rats, it has been shown that 2 atmospheric pressures associated with oxygen saturation, together or singly for 90 minutes daily for successive 46 days, resulted in no significant change on the ratio of testes to body weight. No significant change was observed in the incorporation of 3H-thymidine into testes and pituitary glands between the pressure-treated groups and the control group.     

Depressed writing: Cognitive distortions in the works of depressed and nondepressed poets and writers.

Previous research has consistently found that poets and writers suffer from higher rates of psychological disturbance than the general population; what is lacking in the research is analysis of the works themselves. This study examined cognitive distortions, a known indicator of depression, in writing samples of 36 eminent depressed authors and 36 eminent nondepressed authors. Results indicate that depressed authors have more cognitive distortions in their writings than nondepressed authors. However, greater significance was found between poets and prose writers, with poets having substantially more cognitive distortions in their works. An interaction effect was found between study group (depressed or control) and medium (poetry or prose) indicating that nondepressed prose writers had significantly fewer cognitive distortions than nondepressed poets, depressed poets, and depressed writers. Differences in gender and time period are explored as well. Findings suggest a general acceptance of depressive thinking and writing for poets that is not present for prose writers. Implications for the effectiveness of writing as a form of psychotherapy are also discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modeling study of the effects of overlapping Ca2+ microdomains on neurotransmitter release

Although single-channel Ca2+ microdomains are capable of gating neurotransmitter release in some instances, it is likely that in many cases the microdomains from several open channels overlap to activate vesicle fusion. We describe a mathematical model in which transmitter release is gated by single or overlapping Ca2+ microdomains produced by the opening of nearby Ca2+ channels. This model accounts for the presence of a mobile Ca2+ buffer, provided either that the buffer is unsaturable or that it is saturated near an open channel with Ca2+ binding kinetics that are rapid relative to Ca2+ diffusion. We show that the release time course is unaffected by the location of the channels (at least for distances up to 50 nm), but paired-pulse facilitation is greater when the channels are farther from the release sites. We then develop formulas relating the fractional release following selective or random channel blockage to the cooperative relationship between release and the presynaptic Ca2+ current. These formulas are used with the transmitter release model to study the dependence of this form of cooperativity, which we call Ca2+ current cooperativity, on mobile buffers and on the local geometry of Ca2+ channels. We find that Ca2+ current cooperativity increases with the number of channels per release site, but is considerably less than the number of channels, the theoretical upper bound. In the presence of a saturating mobile buffer the Ca2+ current cooperativity is greater, and it increases more rapidly with the number of channels. Finally, Ca2+ current cooperativity is an increasing function of channel distance, particularly in the presence of saturating mobile buffer.     

Minimal graphics

Photorealistic rendering of graphical models continues to be a topic of considerable research effort in the computer graphics community. However, photorealism isn't the only criterion for judging an image's value. In visualization, where rendering is the conduit through which abstract, nonrealistic forms (such as isosurfaces or streamtubes) become perceivable to users, photorealism may neither be the most useful nor appropriate property. This article describes our long-term research vision in an area that, in our view, should gain a lot of importance in the future     

Detailed active site configuration of a new crystal form of methanol dehydrogenase from Methylophilus W3A1 at 1.9 A resolution

The three-dimensional structure of a new crystal form of methanol dehydrogenase from Methylophilus W3A1 has been obtained in the presence of substrate using data recorded at a synchrotron. The structure of this approximately 140 kDa heterotetramer, refined at 1. 9 A resolution, reveals the detailed configuration of its redox cofactor, pyrroloquinoline quinone (PQQ). C4, one of the oxygen-bearing atoms of this orthoquinone is in a planar configuration while C5, which bears the other quinone oxygen, is tetrahedral, suggesting that the PQQ is in the semiquinone redox state. The substrate binding site has been identified close to PQQ and to the side chain of Asp297, the putative active site base. The proximity of the hydroxyl of methanol to C5 of PQQ compared to the greater separation of the substrate methyl group from C5 supports the addition-elimination reaction mechanism involving a hemiketal intermediate.     

A longitudinal study of the relationships between haemostatic, lipid, and oestradiol changes during normal human pregnancy

BACKGROUND: Chronic leukemia is a disease characterized by the malignant proliferation of immunologically incompetent lymphocytes. The knowledge of open heart surgery in patients with this disorder is limited. METHODS: Twelve patients with chronic lymphocytic leukemia underwent open heart surgery (nine coronary artery bypass grafting (CABG), two aortic valve replacement (AVR), one CABG and AVR) from September 1991 to September 1996. There were nine males and three females with a mean age of 68 years (41-81 years). Staging was assigned according to the Rai Classification. There were seven Stage 0, two Stage I, zero Stage II, one Stage III and two Stage IV patients. Cardiopulmonary bypass (CPB) was performed using standard techniques of cannulation, moderate hypothermia and antegrade/retrograde cardioplegia. RESULTS: Hospital mortality occurred in two (17%) patients. Both patients died of sepsis. Hospital morbidity occurred in seven (58%) patients. The most common complications were infections. Five patients were found to have other malignancies (basal cell, laryngeal, prostate, bladder and breast cancers). Transfusion of blood products was required in eight (67%) patients. The average length of stay was 15 days (7-50 days). Follow-up was complete. Late mortality occurred in four patients at a mean of 7 months (1-18 months). All deaths were non-cardiac related (ruptured AAA, kidney failure, respiratory failure and sepsis). Six patients remain alive at a mean of 25 months (1-48 months). CONCLUSION: Hospital mortality and morbidity in patients with chronic lymphocytic leukemia undergoing open heart surgery are high. Infection is the leading cause of hospital death, as well as the most common complication. The majority of patients receive blood products during the course of their hospitalization. Late mortality is high and non-cardiac related. Based on these findings, a re-definition of the aims, goals and expectations of open heart surgery in patients with chronic leukemia is necessary. Suggestions in management are presented.     

Amifostine protects normal tissues from paclitaxel toxicity while cytotoxicity against tumour cells is maintained

The objectives of this study were to evaluate the protective effects of amifostine against paclitaxel-induced toxicity to normal and malignant human tissues. Haematopoietic progenitor colony assays were used to establish the number of CFU-GEMM and BFU-E colonies after incubation with WR-1065 alone, Amifostine alone, paclitaxel (2.5 or 5 microM) +/- WR-1065 or amifostine. MTT and alkaline elution assays evaluated the in vitro growth inhibitory and DNA damaging effects, respectively, of paclitaxel with or without amifostine against normal human fibroblasts and human non-small cell lung cancer (NSCLC) cells. This combination was also evaluated in vivo using severe combined immune deficient (scid) mouse models of early (non-palpable tumours) and advanced (palpable tumours) human ovarian cancer. Human 2780 ovarian cancer cells were inoculated subcutaneously while paclitaxel and amifostine were administered intraperitoneally. A brief exposure (15 min) to amifostine not only protected human haematopoietic progenitor colonies from paclitaxel toxicity, but stimulated the growth of CFU-GEMM and BFU-E beyond control values. Amifostine protected normal human lung fibroblasts from paclitaxel-induced cytotoxicity and DNA single-strand breaks. However, paclitaxel cytotoxicity and DNA single-strand breaks were actually enhanced by pretreatment with amifostine in the NSCLC model. Importantly, amifostine did not interfere with paclitaxel antitumour activity even with prolonged exposure (24.5 h) of the lung cancer cells to high concentrations (1.2 mM) in vitro or following five repetitive high doses (200 mg/kg) given to scid mice with human ovarian cancer xenografts. Indeed, under certain circumstances, amifostine resulted in sensitisation of tumour cells to paclitaxel. Our results confirm previous reports of the ability of amifostine to protect normal tissues from the toxic effects of chemotherapy drugs and now extend these observations to paclitaxel.