Bioavailability of phenytoin acid and phenytoin sodium with enteral feedings

In the absence of E1B, the 289-amino acid product of human adenovirus type 5 13S E1A induces p53-independent apoptosis by a mechanism that requires viral E4 gene products (Marcellus, R.C., J.C. Teodoro, T. Wu, D.E. Brough, G. Ketner, G.C. Shore, and P.E. Branton. 1996. J. Virol. 70:6207-6215) and involves a mechanism that includes activation of caspases (Boulakia, C.A., G. Chen, F.W. Ng, J. G. Teodoro, P.E. Branton, D.W. Nicholson, G.G. Poirier, and G.C. Shore. 1996. Oncogene. 12:529-535). Here, we show that one of the E4 products, E4orf4, is highly toxic upon expression in rodent cells regardless of the p53 status, and that this cytotoxicity is significantly overcome by coexpression with either Bcl-2 or Bcl-XL. Conditional expression of E4orf4 induces a cell death process that is characterized by apoptotic hallmark features, such as externalization of phosphatidylserine, loss of mitochondrial membrane potential, cytoplasmic vacuolation, condensation of chromatin, and internucleosomal DNA degradation. However, the wide-spectrum inhibitor of caspases, tetrapeptide zVAD-fmk, does not affect any of these apoptogenic manifestations, and does not alter the kinetics of E4orf4-induced cell death. Moreover, E4orf4 expression does not result in activation of the downstream effector caspase common to most apoptosis-inducing events, caspase-3 (CPP32). We conclude, therefore, that in the absence of E1A, E4orf4 is sufficient by itself to trigger a p53-independent apoptosis pathway that may operate independently of the known zVAD-inhibitable caspases, and that may involve an as yet uncharacterized mechanism.     

Percutaneous transhepatic drainage of the nondilated biliary system

Although reticulocyte counts can be reliably performed for up to 48 h after storage in EDTA, it is unclear whether this is applicable to the pediatric age group. In order to evaluate this, manual reticulocyte counts were performed on 20 specimens from pediatric patients stored at 4 degrees C for up to 24 h post collection. Samples were evaluated at 1-3, 6, 12, 18, and 24 h after storage in EDTA vacutainer tubes at 4 degrees C. The age of the subjects ranged from 1 day to 9 years with a median age of 3 years. Patients' reticulocyte counts ranged from 0 to 27% (5.89 +/- 7.21). No clinically significant changes were evident in the reticulocyte count over 24 h after specimen collection. The mean of the 20 specimens at 1-3 h was 5.50 and at 24 h was 5.40 (P > .05). The standard deviation of the mean values ranged from 7.03 to 7.26 (P > .05). The results indicate that reticulocyte counts may be performed on previously drawn blood held at 4 degrees C for up to 24 h post collection in a pediatric population without significant difference from baseline values.     

Cytotoxicity of polycyclic aromatic hydrocarbon o-quinones in rat and human hepatoma cells

A novel pathway of polycyclic aromatic hydrocarbon (PAH) metabolism involves the oxidation of non-K-region trans-dihydrodiols by dihydrodiol dehydrogenase (DD) to yield PAH o-quinones whose cytotoxicity and genotoxicity are unknown. The cytotoxicity of several PAH o-quinones derived from this reaction [naphthalene-1,2-dione (NPQ), benzo[a]pyrene-7,8-dione (BPQ), and 7,12-dimethylbenz[a]anthracene-3,4-dione (DMBAQ)] was examined in rat (H-4IIe) and human (Hep-G2) hepatoma cells which are known to express DD. 2-Methylnaphthalene-1,4-dione (menadione), a known cytotoxic p-quinone, was used as a positive control. Hepatoma cells (1 x 10(6) cells/mL) were exposed to PAH o-quinones (1-100 microM) for 0-4 h, and cell viability and survival were measured and related to O2.- production and changes in redox potential [GSSG/GSH and NAD(P)+/NAD(P)H]. Three different modes of cytotoxicity were observed: (1) NPQ (no bay region) and DMBAQ (methylated bay region) were as cytotoxic as menadione in reducing cell survival but had less effect on cell viability. These o-quinones adversely affected GSH levels and the redox state of the cell and caused an increase in the production of O2.- in cell suspensions. This cytotoxicity was not enhanced by dicoumarol (10 microM), a DT-diaphorase inhibitor, implying that this enzyme is unable to prevent these PAH o-quinones from entering one-electron redox-cycles. (2) BPQ (bay region only) was the least cytotoxic of the PAH o-quinones studied. BPQ decreased cell viability (< 40% at 20 microM) but did not adversely affect cell survival or the redox state of the cell.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rat and human pancreatic islet cells contain a calcium ion independent phospholipase A2 activity selective for hydrolysis of arachidonate which is stimulated by adenosine triphosphate and is specifically localized to islet beta-cells

The recent demonstration that myocardial Ca(2+)-independent phospholipase A2 exists as a complex of catalytic and regulatory polypeptides that is modulated by ATP has suggested a novel mechanisms through which alterations in glycolytic flux can be coupled to the generation of eicosanoids which facilitate insulin secretion. To determine the potential relevance of this mechanism, we examined the kinetic characteristics, substrate specificities, and cellular locus of phospholipase A2 activity in pancreatic islets. Rat pancreatic islets contain a Ca(2+)-independent phospholipase A2 activity which is optimal at physiologic pH, preferentially hydrolyzes phospholipid substrates containing a vinyl ether linkage at the sn-1 position, and prefers arachidonic acid compared to oleic acid in the sn-2 position. Rat islet Ca(2+)-independent phospholipase A2 activity is inhibited by the mechanism-based inhibitor (E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one and is stimulated by ATP. Purification of beta-cells from dispersed pancreatic islet cells by fluorescence-activated cell sorting demonstrated that beta-cells (but not non-beta-cells) contain Ca(2+)-independent, ATP-stimulated phospholipase A2 activity. Remarkably, clonal RIN-m5f insulinoma cells, which possess a defect in glucose-induced insulin secretion, contain a Ca(2+)-independent phospholipase A2 which is not modulated by alterations in ATP concentration. Collectively, these results and those of an accompanying paper [Ramanadham et al. (1993) Biochemistry (following paper in this issue)] implicate Ca(2+)-independent phospholipase A2 as a putative glucose sensor which can couple alterations in glycolytic metabolism to the generation of biologically active eicosanoids and thereby facilitate glucose-induced insulin secretion.     

Adolescents in stepfamilies: Developmental family interventions.

Discusses issues and interventions for working with adolescents who live in stepfamilies. A developmental perspective, using psychoeducation and brief strategic intervention approaches, is proposed for working with stepfamilies. Six major issues for adolescents in stepfamilies are discussed: developmental issues, sexuality issues, parent–child relationships, parenting in stepfamilies, nonresidential parent–child issues, and changes in visitation and custody. Case illustrations and suggested interventions are presented for each of these areas. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Benefits to 0+ fishes of connecting man‐made waterbodies to the lower River Trent,England

Floodplain waterbodies are reputed to enhance recruitment of riverine fish populations via provision of spawning and nursery habitat, refuge from floods, and increased availability of planktonic food resources compared with main river channels. Notwithstanding, there have been few parallel studies of fishes and their food resources at both main river and floodplain sites. Thus, this study investigated the 0+ fishes, zooplankton and phytoplankton (chlorophyll a) at four main river and four (man‐made) floodplain sites on the lower River Trent, England, between May 1999 and October 2004 inclusive. All sites shared the same key fish species, and there were no consistent differences in the densities, growth or condition of 0+ fishes from main river and floodplain sites. Similarly, all sites shared the same key zooplankton taxa. However, zooplankton densities, notably of large‐bodied cladocerans, and chlorophyll a concentrations, were significantly higher at floodplain sites than at main river sites. Thus, connection of man‐made waterbodies has the potential to enhance recruitment of riverine fish populations via provision of important spawning and nursery habitat, and superior feeding opportunities for 0+ fishes compared with main river channels. Copyright © 2007 John Wiley & Sons, Ltd.     

A behavioral probe of the growth of intake potential during the inter-meal interval in the rat.

The rat's willingness to ingest glucose after an initial intraoral intake test was probed by beginning a 2nd intraoral intake test at variable durations (1–220 min). In Exp 1, after an initial meal of 12.5% glucose solution averaging 26.9?±?1.7 ml, the size of the 2nd (probe) meal of the same stimulus increased linearly from 4.0?±?0.9 ml after a 1-min delay to 15.4?±?2.7 ml after a 120-min delay. In Exp 2, intraoral intake of a more concentrated (37.5%) glucose solution rose more slowly as a function of delay from 2.4?±?2.7 ml to 4.9?±?0.6 ml. For each glucose concentration, the linear recovery function and a slope that depends on stimulus concentration are consistent with a role for gastric emptying during the delay in intake recovery. In Exp 3, rats ingested 12.5% or 37.5% glucose to satiety in an initial test and received, after a variable delay, either the same or the other concentration as the probe stimulus. The same volumes were ingested at each delay whether the glucose concentration of the probe stimulus was the same or was switched from that presented in the initial test. This result shows that the taste and caloric properties of the probe stimulus played no role in determining how much of it would be ingested… (PsycINFO Database Record (c) 2010 APA, all rights reserved)