Effects of alcohol exposure during early life on neuron numbers in the rat hippocampus. I. Hilus neurons and granule cells

We previously showed that 16-day-old rats exposed to a relatively high dose of ethanol at 10-15 postnatal days of age have fewer neurons in the hilus region of the hippocampus compared with controls. Dentate gyrus granule cell numbers, however, showed no statistically significant changes attributable to the ethanol treatment. It is possible that some of the changes in brain morphology, brought about as a result of the exposure to ethanol during early life, may not be manifested until later in life. This question has been further addressed in an extension to our previous study. Wistar rats were exposed to a relatively high daily dose of ethanol on postnatal days 10-15 by placement in a chamber containing ethanol vapour, for 3 h/day. The blood ethanol concentration was found to be similar to430 mg/dl at the end of the period of exposure. Groups of ethanol-treated (ET), separation control (SC), and mother-reared control (MRC) rats were anaesthetised and killed either at 16 or 30 days of age by perfusion with phosphate-buffered 2.5% glutaraldehyde. The Cavalieri principle and the physical disector methods were used to estimate, respectively, the regional volumes and neuron cell numerical densities in the hilus and granule cell regions of the dentate gyrus. The total numbers of neurons in the hilus region and granule cell layer were computed from these estimates. It was found that 16-day-old animals had 398,000-441,000 granule cells, irrespective of group. The numbers of granule cells increased such that by 30 days of age, rats had 487,000-525,500 granule cells. However, there were no significant differences between ethanol-treated rats and their age-matched controls in granule cell numbers. In contrast, ethanol-treated rats had slightly but significantly fewer neurons in the hilus region than did control animals at 16 days of age, but not at 30 days of age. Therefore, it appears that a short period of ethanol exposure during early life can have effects on neuron numbers of some hippocampal neurons, but not others. The effects on hilar neuron numbers, observed as a result of such short periods of ethanol treatment, appeared to be transitory. (C) 2003 Wiley-Liss, Inc.

Molecular and cellular biology of pre-malignancy in the gastrointestinal tract

Important pathogenic alterations within established cancers are acquired during the premalignant stage. These genetic alterations can be grouped into specific neoplastic pathways that differ within and between anatomical sites. By understanding the mechanisms that determine the initiation and progression of each pathway, it will be possible to develop novel approaches to the diagnosis, prevention and treatment of cancer. This chapter outlines the principles underlying the molecular characterization of pre-malignant lesions, taking colorectal neoplasia as the main model.

Functional beta(1)- and beta(2)-adrenoceptors in the left and right atrium of pre-hypertensive rats

There is a small increase in the functional beta(2)-adrenoceptor response on the spontaneously hypertensive rat (SHR) left atrium in the early stages of hypertension. In the present study, the functional beta(1)- and beta(2)-adrenoceptors of the left and right atrium in SHR pre-hypertension and age-matched (5-week-old) Wistar Kyoto (WKY) rats were characterized. Contractility methods with isoprenaline, T-0509 (a selective beta(1)-adrenoceptor agonist) and procaterol (a selective beta(2)-adrenoceptor agonist) were used. At 5 weeks, the SHRs were pre-hypertensive. Isoprenaline was more potent on the left atrium of 5-week-old SHRs than WKY rats. Bisoprolol, a selective beta(1)-adrenoceptor antagonist, was more potent against isoprenaline and T-0509 on the SHR than WKY rat left atrium. ICI 118,551, a selective beta(2)-adrenoceptor antagonist, was more potent against procaterol and T-0509 on the SHR than WKY rat left atrium. The results with bisoprolol and ICI 118,551 suggest that there are more functional beta(1)- and beta(2)-adrenoceptors on the left atrium of 5-week-old SHRs than WKY rats. Isoprenaline, T-0509 and procaterol were equipotent on the right atrium of 5-week-old WKY rats and SHRs. Bisoprolol was more potent against isoprenaline, T-0509 and procaterol on the SHR than WKY rat right atrium. ICI 118,551 was more potent against T-0509, but not isoprenaline and procaterol, on the SHR than WKY rat left atrium. This suggests there are more functional beta(1)-adrenoceptors, and probably more functional beta(2)-adrenoceptors, on the right atrium of 5-week-old SHRs than WKY rats. These functional differences in beta(1)-and beta(2)-adrenoceptor-mediated responses of the left and right atria of pre-hypertensive SHRs cannot be caused by hypertension, and may be associated with the onset of hypertension.

Systematic review of the role of pre-oxygenation for tracheal suctioning in ventilated newborn infants

Pre-oxygenation for endotracheal suctioning for mechanically ventilated infants is routine practice in many neonatal intensive care units. In the present systematic review the evidence to support its use is discussed and the authors conclude that no confident recommendations can be made from the results of this review.

Environmental conditions and variation in levels of sun exposure among children in child care

Sun exposure in childhood is I of the risk factors for developing skin cancer, yet little is known about levels of exposure at this age. This is particularly important in countries with high levels of ultraviolet radiation. (UVR) such as Australia. Among 49 children 3 to 5 years of age attending child care centers, UVR exposure was studied under 4 conditions in a repeated measures design; sunny days, cloudy days, teacher's instruction to stay in the shade, and a health professionals instruction to apply sunscreen. Three different data collection methods were employed: (a) completion of questionnaire or diary by parents and researcher, (b) polysulphone dosimeter readings, and (c) observational audits (video recording). Results of this study indicated that more than half the children had been sunburnt (pink or red) and more than a third had experienced painful sunburn (sore or tender) in the last summer. Most wore short sleeve shirts, short skirts or shorts and cap, that do not provide optimal levels of skin protection. However, sunscreen was applied to all exposed parts before the children went out to the playground. Over the period of I hr (9-10 a.m.) the average amount of time children spent in full sun was 22 min. On sunny days there was more variation across children in the amount of sun exposure received. While the potential amount of UVR exposure for young children during the hour they were outside on a sunny day was 1.45 MED (Minimum Erythemal Dose), they received on average 0.35 MED, which is an insufficient amount to result in an erythemal response on fair skin even without the use of sunscreen.

Lysine requirements of pre-lay broiler breeder pullets: Determination by indicator amino acid oxidation

The indicator amino acid oxidation (IAAO) method allows the determination of amino acid requirements under conditions of low growth rate as found in pre-laying broiler breeder pullets. Cobb 500 breeder pullets (20 wk old; 2290 +/- 280 g, n = 4) were adapted (6 d) to a pelleted, purified control diet containing all nutrients at greater than or equal to 110% of NRC recommendations. After recovery from surgery for implantation of a jugular catheter, each bird was fed, in random order, test diets containing one of nine levels of lysine (0.48, 0.96, 1.92, 2.88, 3.84, 4.80, 7.68, 9.60 and 14.40 g/kg of diet). Indicator oxidation was determined during 4-h primed (74 kBq/kg body), constant infusions (44 kBq (.) h(-1) (.) kg body(-1)) of L-[1-C-14]phenylalanine. Using the breakpoint of a one-slope broken-line model, the lysine requirement was determined to be 4.88 +/- 0.96 g/kg of diet or 366 +/- 72 mg (.) hen(-1) (.) d(-1) with an upper 95% Cl of 6.40 g/kg of diet or 480 mg (.) hen(-1) (.) d(-1). IAAO allows determination of individual bird amino acid requirements for specific ages and types of birds over short periods of time and enables more accurate broiler breeder pullet diet formulation.

A comparison of the efficacy and safety of olanzapine versus haloperidol during transition from intramuscular to oral therapy

Background: Acutely agitated patients with schizophrenia who receive intramuscular (IM) medications typically are switched to oral (PO) antipsychotic maintenance therapy Objective: The goal of this study was to assess the efficacy and safety of olanzapine versus those of haloperidol during transition from IM to PO therapy We used additional data from a previously reported trial to test the hypothesis that the reduction in agitation achieved by IM olanzapine 10 mg or IM haloperidol 7.5 mg would be maintained following transition to 4 days of PO olanzapine or PO haloperidol (5-20 mg/d for both). We also hypothesized that olanzapine would maintain its more favorable extrapyramidal symptom (EPS) safety profile. Methods: This was a multinational (hospitals in 13 countries), double-blind, randomized, controlled trial. Acutely agitated inpatients with schizophrenia were treated with 1 to 3 IM injections of olanzapine 10 mg or haloperidol 7.5 mg over 24 hours and were entered into a 4-day PO treatment period with the same medication (5-20 mg/d for both). The primary efficacy measurement was reduction in agitation, as measured by the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) score. Adverse events and scores on EPS rating scales were assessed. Results: A total of 311 patients (204 men, 107 women; mean [SD] age, 38.2 [11.6] years) were enrolled (131, 126, and 54 patients in the olanzapine, haloperidol, and placebo groups, respectively). In all, 93.1% (122/131) of olanzapine-treated patients and 92.1% (116/126) of haloperidol-treated patients completed the IM period and entered the PO period; 85.5% (112/131) of olanzapine-treated patients and 84.1% (106/126) of haloperidol-treated patients completed the PO period. IM olanzapine and IM haloperidol effectively reduced agitation over 24 hours (mean [SD] PANSS-EC change, -7.1 [4.8] vs -6.7 [4.3], respectively). Reductions in agitation were sustained throughout the PO period with both study drugs (mean [SD] change from PO period baseline, -0.6 [4.8] vs -1.3 [4.4], respectively). During PO treatment, haloperidol-treated patients spontaneously reported significantly more acute dystonia than olanzapine-treated patients (4.3% [5/116] vs 0% [0/122], respectively; P = 0.026) and akathisia (5.2% [6/116] vs 0% [0/122], respectively; P = 0.013). Significantly more haloperidol-treated patients than olanzapine-treated patients met categorical criteria for treatment-emergent akathisia (18.5% [17/92] vs 6.5% [7/107], respectively; P = 0.015). Conclusions: In the acutely agitated patients with schizophrenia in this study, both IM olanzapine 10 mg and IM haloperidol 7.5 mg effectively reduced agitation over 24 hours. This alleviation of agitation was sustained following transition from IM therapy to 4 days of PO treatment (5-20 mg/d for both). During the 4 days of PO treatment, olanzapine-treated patients did not spontaneously report any incidences of acute dystonia, and olanzapine had a superior EPS safety profile to that of haloperidol. The combination of IM and PO olanzapine may help improve the treatment of acutely agitated patients with schizophrenia. Copyright (C) 2003 Excerpta Medica, Inc.