Gabapentin: pharmacokinetics, efficacy, and safety

Gabapentin is a new antiepileptic drug (AED) with an attractive pharmacokinetic profile. It is absorbed by an active and saturable transport system, and has a high volume of distribution. Gabapentin is not bound to plasma proteins, does not induce hepatic enzymes and is not metabolized. At steady state, it has a half-life of 6-8 h, and is eliminated unchanged by renal route with a plasma clearance proportional to the creatinine clearance. It is devoid of significant drug-drug interactions when administered with the established AEDs or with oral contraceptives. Gabapentin used as an add-on AED significantly reduced the frequency of partial seizures and secondarily generalized tonic-clonic seizures in three large double-blind, placebo-controlled, parallel-group clinical trails. It is well tolerated, with transient somnolence and dizziness being the most frequent adverse effects. Although the mechanism of action of gabapentin is not fully established, there is strong evidence to suggest a novel mechanism of action. Gabapentin is a unique and promising drug that could improve the quality of life of patients with epilepsy and is a welcome addition to the armamentarium of currently available AEDs for the treatment of patients with seizures of partial onset.     

Ammonia transport by the urinary bladder of Bufo marinus

Among cyanobacteria, the heterocystous, N2-fixing Anabaena variabilis and the unicellular Anacystis nidulans have recently been shown to possess an NAD+-dependent, bidirectional hydrogenase. A 5.0 kb DNA segment of the A. nidulans genome is now identified to harbor the structural genes hoxUYH coding for three subunits of the bidirectional hydrogenase. The gene arrangement in A. nidulans and in A. variabilis is remarkably dissimilar. In A. nidulans, but not in A. variabilis, the four accessory genes hoxW, hypA, hypB and hypF could be identified downstream of hoxH. An insertional homozygous mutant in hoxH from A. nidulans was completely inactive in performing Na2S204-dependent H2 evolution but could utilize the gas with almost 50% of the activity of the wild type. These findings with the first defined hydrogenase mutant in any photosynthetic, 02-evolving microorganism indicate that the unicellular cyanobacterium A. nidulans possesses both an uptake and a bidirectional hydrogenase. The physiological role(s) of the two hydrogenases in unicellular non-N2-fixing cyanobacteria is not yet understood.     

Abdominal assessment in the home: from A to Zzz

Conducting a through abdominal assessment in the home setting is an important part of the home care nurse's role. By using every letter of the alphabet, the tool presented in this article helps the nurse conduct a thorough health history in a concise manner. In addition, reviewing the procedure outlined in the article and using the documentation form presented, the nurse can conduct a through abdominal assessment in the home in a cost-effective manner.     

IL-10 regulates thrombus-induced vein wall inflammation and thrombosis

Vein wall inflammation associated with venous thrombosis is mediated by an imbalance in proinflammatory as compared with antiinflammatory molecules. We hypothesize that IL-10 is an important antiinflammatory cytokine that influences vein wall inflammation and thrombus propagation during venous thrombosis. To test this hypothesis a model of inferior vena caval thrombosis was used. Studies were performed at sacrifice 2 days after thrombus induction and included leukocyte morphometrics, myeloperoxidase activity, vein wall permeability, thrombus weight, and IL-10 ELISA analysis from the vein wall. IL-10 was elevated in the vein wall during venous thrombosis. Neutralization of IL-10 increased inflammation, while supplementation with rIL-10 demonstrated a dose- and time-dependent decrease in inflammation. Interestingly, a low 2.5-microg rIL-10 dose given at time of initiation of thrombosis most significantly decreased inflammation. Thrombus weight was importantly diminished by reconstitution of IL-10. These studies support an important role for IL-10 in the regulation of thrombus-associated inflammation and thrombosis and suggest that IL-10 could be used as a therapeutic agent in the treatment of venous thrombosis.     

Answer changing: a meta-analysis of the prevalence and patterns

In order to determine the prevalence and patterns of answer-changing behavior, a meta-analysis of 61 studies was conducted. The findings of the individual primary studies were supported, which increased confidence in the conclusion that most students will change answers and this behavior will likely improve test scores. Moreover, neither age, gender, academic ability, personality traits, beliefs about answer changing, nor item characteristics systematically influenced answer-changing behavior. Practitioners of continuing nursing education need to know the effect of answer changing on test scores so that they may appropriately advise nurses who are preparing for objective tests.     

Linkage of antisocial alcoholism to the serotonin 5-HT1B receptor gene in 2 populations

We examined the effects of repeated administration of (S)-alpha-fluoromethylhistidine (FMH), a specific inhibitor of histidine decarboxylase (HDC), on radial maze performance and brain contents of histamine and amino acids in rats. By daily subcutaneous (s.c.) administration of FMH (100 mg/kg), rats showed significant enhancement of a radial maze performance without changes in locomotion. Six days after FMH treatment, the histamine levels both in the cerebral cortex and diencephalon decreased significantly. However, the glutamate and glycine levels significantly increased in the cerebral cortex and hippocampus. These results suggest that FMH enhances the acquisition phase of radial maze study with the increases in glutamate and glycine levels in the cerebral cortex and hippocampus of rats.     

Biotransformation of tirilazad in human: 3. tirilazad A-ring reduction by human liver microsomal 5alpha-reductase type 1 and type 2

Connexin 43, a member of the highly conserved connexin family of gap junction proteins, is expressed in the pig ovary. In other species, ovarian connexin 43 expression and phosphorylation are hormonally regulated. We characterized connexin 43 expression and phosphorylation in the ovaries of mature pigs during the estrous cycle and in prepubertal gilts during follicular development induced by eCG (750 IU)/hCG (500 IU; 72 h later). Ovarian connexin 43 protein expression and phosphorylation were examined by immunoblot analysis. Connexin 43 was localized to specific follicular cell types during development by immunofluorescence. While no change in total connexin 43 protein expression was seen during the cycle, connexin 43 phosphorylation was significantly higher (p < 0.05) during the late follicular stage of the cycle than during the early luteal and early to mid-follicular stages. In ovaries of eCG/hCG-primed prepubertal pigs, connexin 43 protein levels remained steady, while phosphorylation of the protein increased significantly at 72 h and 84 h after eCG treatment (p < 0.05), then declined to pretreatment levels by 96 h (24 h post-hCG administration). Immunoreactive connexin 43 was localized predominantly to granulosa cells of cyclic pigs and eCG/hCG-primed prepubertal gilts. Follicular connexin 43 was highest between 60 h and 84 h after eCG and declined after hCG administration. Connexin 43 was not detected in morphologically atretic follicles, stroma, or vascular tissue of the ovary. This is the first evidence that porcine ovarian connexin 43 phosphorylation is differentially regulated during follicular development. The results suggest that hormonally induced changes in connexin 43 phosphorylation may play a coordinating role in porcine follicular development.     

Variation in growth form and precocity at birth in eutherian mammals

Using the flexible Chapman-Richards model for describing the growth curves from birth to adulthood of 69 species of eutherian mammals, we demonstrate that growth form differs among eutherian mammals. Thereby the commonly used Gompertz model can no longer be considered as the general model for describing mammalian growth. Precocial mammals have their peak growth rate earlier in the growth process than altricial mammals. However, the position on the altricial-precocial continuum accounts for most growth-form differences only between mammalian lineages. Within mammalian genera differences in growth form are not related to precocity at birth. This indicates that growth form may have been associated with precocity at birth early in mammalian evolution, when broad patterns of body development radiated. We discuss four non-exclusive interpretations to account for the role of precocity at birth on the observed variation in growth form among mammals. Precocial and altricial mammals could differ according to (i) the distribution of energy output by the mother, (ii) the ability of the young to assimilate the milk yield, (iii) the allocation of energy by the young between competing functions and (iv) the position of birth between conception and attainment of physical maturity.     

Antibody isotypes, including IgG subclasses, in Ecuadorian patients with pulmonary paragonimiasis

An ELISA test was developed to detect Paragonimus-specific antibodies, including IgG subclasses, using P. mexicanus crude water-soluble antigens. The test was standardized to detect antibodies in sera of Ecuadorian patients with pulmonary paragonimiasis and negative controls from the endemic area. The detected mean levels of IgG (0.753, SEM: 0.074) and IgM (0.303, SEM: 0.033) were significantly elevated (P < 0.05). Within the IgG subclasses, IgG4 showed the highest detected mean level (0.365, SEM: 0.116) and the other three subclasses showed considerably lower mean levels (IgG1, 0.186 SEM: 0.06; IgG2, 0.046 SEM: 0.01; IgG3, 0.123 SEM: 0.047). The number of P. mexicanus eggs found in sputum of infected individuals showed a positive correlation with the level of antibodies detected for IgM, IgG and its subclasses (P < 0.001). The relevance of these findings in Ecuadorian patients suffering from pulmonary paragonimiasis is discussed.