Prenatal exposure to valproic acid reduces synaptic δ-catenin levels and disrupts ultrasonic vocalization in neonates.

Valproic acid (VPA) is an effective and commonly prescribed drug for epilepsy and bipolar disorder. However, children born from mothers treated with VPA during pregnancy exhibit an increased incidence of autism spectrum disorder (ASD). Although VPA may impair brain development at the cellular level, the mechanism of VPA-induced ASD has not been completely addressed.

Prenatal exposure to valproic acid reduces synaptic δ-catenin levels and disrupts ultrasonic vocalization in neonates.

Unlabelled: Valproic acid (VPA) is an effective and commonly prescribed drug for epilepsy and bipolar disorder. However, children born from mothers treated with VPA during pregnancy exhibit an increased incidence of autism spectrum disorder (ASD). Although VPA may impair brain development at the cellular level, the mechanism of VPA-induced ASD has not been completely addressed.

EMG Activity With Use of a Hands-Free Single Crutch vs a Knee Scooter.

Background: Foot and ankle injuries frequently require a period of nonweightbearing, resulting in muscle atrophy. Our previous study compared a hands-free single crutch (HFSC) to standard axillary crutches and found increased muscle recruitment and intensity while using the HFSC. Knee scooters are another commonly prescribed nonweightbearing device.

Sex Offenses Perpetrated Against Older Adults: A Multivariate Analysis of Crime Scene Behaviors.

The aim of this study was to thematically explore the relationship between crime scene behaviors and background characteristics of offenders who commit sexual offenses against female victims aged 60 years or more. Research and understanding of offense behaviors in this area is extremely limited; therefore, the study sought to provide a preliminary understanding and multivariate model of offense behaviors in cases where older female adults were sexually abused. Twenty-seven crime scene behaviors from 143 rape or attempted rape cases of an older adult victim were analyzed; frequency data were computed to provide base rate information, and Smallest Space Analysis provided a visual representation of the co-occurrence of crime scene behaviors.

General anaesthesia in a patient with Brugada syndrome.

The successful administration of a combined general and epidural anaesthetic to a patient with Brugada syndrome is reported. A review of the literature is presented.

Incidence of student exposures to blood and body fluids and postexposure management protocols in dental hygiene programs.

Purpose: The purpose of this study was to determine the incidence of occupational exposures to blood or body fluids reported in dental hygiene students from 1996 to 1998 as well as postexposure management protocols used in dental hygiene programs.

Methods: A 23-item, self-designed questionnaire was sent to the 214 dental hygiene programs that were accredited in 1996. Sixty-seven percent (143) of the sample completed the questionnaire.

Pulmonary blood flow measured by inspiratory inert gas concentration forcing oscillations.

The aim of this study was to discover if the forced inspired inert gas sinewave technique could be used to measure pulmonary blood flow, using nitrous oxide as the indicator gas, following inotropic stimulation of the heart by dobutamine, in the presence of a constant alveolar ventilation. Cardiac output (range 1-4.5 L min(-1)) was measured in six dogs by thermodilution and by calculation from the sinusoidal expired partial pressures of argon and nitrous oxide using: (i) analytical equations and a conventional continuous ventilation three-compartment lung model, which did not include recirculation; and (ii) a digital simulation tidal ventilation lung model (Gavaghan and Hahn, 1996.

A reconciliation of continuous and tidal ventilation gas exchange models.

Continuous-ventilation mathematical gas exchange models are widely used since their analytical equations are amenable to physiological interpretation. They describe qualitatively the respiratory system's response to changing physiological conditions, but do not calculate accurate values for respiratory parameters when experimental tidal ventilation expired gas data are inserted into their analytical expressions. A simple mathematical expression is presented to reconcile continuous and tidal ventilation gas exchange models.

Characterization of novel indenoindoles. Part I. Structure-activity relationships in different model systems of lipid peroxidation.

Structure-activity relationships are presented for some representative compounds from a novel series of potent inhibitors of lipid peroxidation. The compounds are indenoindole derivatives with oxidation potentials in organic solvents of between 0.2 and 1.

Molecular modeling parameters predict antioxidant efficacy of 3-indolyl compounds.

Many dietary constituents, such as indole-3-carbinol, are chemoprotective in toxicity and carcinogenicity bioassays. Indole-3-carbinol and related congeners appear to protect partly via radical and electrophile scavenging. To develop better chemoprotective indoles with lower intrinsic toxicity, we performed molecular graphic and quantum-mechanical analyses of model indolyl compounds to ascertain the determinant molecular features for antioxidant activity.

Response of [Ah] battery genes to compounds that protect against menadione toxicity.

We have studied the response of genes in the dioxin-inducible [Ah] battery to three compounds that protect mouse hepatoma cells (Hepa-1c7c7 wild-type, wt) against menadione toxicity. Pretreatment of wt cells with 25 microM 5,10-dihydroindenol[1,2-b]indole (DHII), 25 microM tert-butylhydroquinone (tBHO) or 10 microM menadione itself, generated substantial protection against toxicity produced by subsequent menadione exposure. The gene response was examined in wt cells, and three mutant lines: CYP1A1 metabolism-deficient (c37 or P1-); nuclear translocation-impaired (c4 or nt-); and AHR-deficient (c2 or r-, containing < 10% of normal functional receptor levels).

Retardation of benzo[a]pyrene-induced epidermal tumor formation by the potent antioxidant 4b,5,9b,10-tetrahydroindeno[1,2-b]indole.

The ability of the potent antioxidant, 4b,5,9b,10-tetrahydroindeno[1,2-b]indole (THII), to inhibit tumor formation by topically-applied benzo[a]pyrene was evaluated using a complete carcinogenicity mouse skin bioassay. THII was administered by direct application to the skin, in the food or through the drinking water. In each case, THII increased the average time until the appearance of tumors by 4 weeks, and also decreased the total number of tumors compared with benzo[a]pyrene alone.

Regulation of [Ah] gene battery enzymes and glutathione levels by 5,10-dihydroindeno[1,2-b]indole in mouse hepatoma cell lines.

The murine aromatic hydrocarbon ([Ah]) gene battery consists of at least six genes that code for two functionalizing (Phase I) enzymes and four non-functionalizing (Phase II) enzymes. These enzymes are induced by compounds such as aromatic hydrocarbons and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) that bind to the cytosolic Ah receptor protein. Studies in rodents indicate that certain enzymes of this battery, namely cytochrome P4501A1 (CYP1A1), UDP-glucuronosyltransferase (UGT1*06) and NAD(P)H: quinone acceptor oxidoreductase (NMO1) are induced by the synthetic antioxidant 5,10-dihydroindeno[1,2-b]indole (DHII).

Assessment of cardiorespiratory function using oscillating inert gas forcing signals.

A theoretical model (Hahn et al. J. Appl.

Measurement of dead-space in a model lung using an oscillating inspired argon signal.

In a model lung, airways dead-space can be accurately measured using a forced inspired oscillating argon signal, which varies sinusoidally about a mean concentration of 6% v/v with an amplitude of +/- 4% v/v. With sinusoid forcing periods longer than 120 seconds, and at a breathing rate of 13.4 breaths minute-1, the mean airways dead-space can be measured with a standard error of less than 5%.

Mechanisms of protection from menadione toxicity by 5,10-dihydroindeno[1,2,-b]indole in a sensitive and resistant mouse hepatocyte line.

Established cell lines derived from newborn livers of c14CoS/c14CoS and cch/cch mice have been shown to be genetically resistant (14CoS/14CoS cells) or susceptible (ch/ch cells) to menadione toxicity. These differences are due in part to relatively higher levels of reduced glutathione (GSH) and NAD(P)H:menadione oxidoreductase (NMO1) activity in the 14CoS/14CoS cells. The indolic membrane-stabilizing antioxidant 5,10-dihydroindeno[1,2-b]indole (DHII) was shown previously to protect against various hepatotoxicants in vivo and in primary rat hepatocytes.

Development of a concentric water-displacement model lung.

Simulation of lung ventilation using a model lung can provide a means of evaluating lung function tests, mathematical models and computer algorithms. We describe a new water-displacement lung model, which can simulate lung volumes up to 3.8 l and tidal volumes up to 1 l.

Menadione-mediated membrane fluidity alterations and oxidative damage in rat hepatocytes.

Menadione toxicity in isolated rat hepatocytes was mitigated by the antioxidant 4b,5,9b,10-tetrahydroindeno[1,2-b]indole at low concentrations (less than 100 microM), but not at high concentrations (greater than 200 microM) of menadione. When hepatocytes were incubated with menadione, there was a time-dependent and concentration-dependent inhibition of lipid peroxidation in intact cells, as well as an increase in the antioxidative potency of acetone extracts, suggesting that metabolites of menadione could inhibit oxidative stress, and that at high menadione concentrations a different mechanism was involved in cytotoxicity. A possible mechanism was suggested by the ability of acetone extracts from hepatocytes that had been incubated with menadione to increase osmotic fragility in red blood cells.

Chemoprotective and hepatic enzyme induction properties of indole and indenoindole antioxidants in rats.

Three indole antioxidants were compared for their efficacy to inhibit lipid peroxidation, prevent chemical hepatotoxicity and induce enzyme systems involved in the biotransformation of xenobiotics. The dietary indolyl compound indole-3-carbinol (I-3-C), and the synthetic compounds 5,10-dihydroindeno[1,2-b]-indole (DHII) and 4b,5,9b,10-tetrahydroindeno[1,2-b]indole (THII) inhibited carbon tetrachloride (CCl4)-initiated lipid peroxidation in rat-liver microsomes, with the order of efficacy THII greater than DHII = butylated hydroxytoluene (BHT) much greater than I-3-C. Each of the indole compounds protected isolated rat hepatocytes against toxicity by CCl4, N-methyl-N'-nitro-N-nitrosoguanidine and methylmethanesulphonate (THII congruent to DHII much greater than I-3-C).

Intrinsic acute toxicity and hepatic enzyme inducing properties of the chemoprotectants indole-3-carbinol and 5,10-dihydroindeno[1,2-b]indole in mice.

Indole-3-carbinol (I-3-C) and 5,10-dihydroindeno[1,2-b]indole (DHII) have been shown to be protective against carbon tetrachloride and other chemicals that cause hepatic toxicity. In part, this protection appears to be afforded by the ability of these compounds to act as antioxidants, with DHII having much the greater efficacy. In order to understand the mechanisms of chemoprotection, as well as the potential for therapeutic and pharmaceutical use in humans, the antioxidants I-3-C and DHII were examined for their intrinsic acute toxicity, and their hepatic enzyme inducing properties in mice.

Mechanisms of chemical mediated cytotoxicity and chemoprotection in isolated rat hepatocytes.

Although N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and methylmethanesulfonate (MMS) cause injury and malondialdehyde formation in rat hepatocytes, MNNG toxicity is much more sensitive to inhibition by antioxidants. In order to quantify the relationship between toxicity and antioxidation potential, we compared 14 antioxidants that protected against MNNG and MMS toxicity. Chemoprotection was quantified as the concentration that delayed by 1 h the decline in trypan blue exclusion to less than or equal to 50%.