Expression of c-fos, fos B, and egr-1 in the medial preoptic area and bed nucleus of the stria terminalis during maternal behavior in rats

The spatial and temporal pattern of expression of the protein products of immediate early genes (IEGs) c-fos, fos B, and egr-1 were mapped in medial preoptic area (MPOA) and ventral bed nucleus of stria terminalis (VBST) during maternal behavior in rats. Immunocytochemical analysis indicated significant increases in the number of cells expressing c-Fos after 2 h of pup exposure, while Fos B levels showed a delayed response, reaching maximal levels after 6 h.     

Enhanced Fluid Removal Guided by Blood Volume Monitoring During Chronic Hemodialysis

Fluid overload predisposes chronic hemodialysis patients to cardiovascular disease, a significant cause of morbidity and mortality in these patients. We evaluated the efficacy of monitoring changes in blood volume during routine hemodialysis to detect fluid overload. Intradialytic changes in blood volume were monitored by continuously measuring hematocrit in all 56 patients in a single dialysis unit over 7 weeks. After Week 1, patients were categorized into 2 separate groups depending on their maximum intradialytic decreases in blood volume. In Group 1, 46 of 56 or 82% had greater than a 5% decrease in blood volume while in Group 2, 10 of 56 or 18% had less than a 5% decrease in blood volume. During Weeks 2–7, dialytic fluid removal was intentionally increased in Group 2 patients by 0.80 ± 0.62 L (mean ± SD) or 47 ± 43%. This intervention resulted in a larger (p < 0.02) intradialytic decrease in body weight (2.7 ± 0.9 kg versus 2.0 ± 0.8 kg) and a larger (p < 0.02) intradialytic decrease in blood volume (15 ± 5% versus 4 ± 1%) than experienced during Week 1 with a low incidence of symptoms. We conclude that there is a significant percentage of chronic hemodialysis patients who can tolerate additional fluid removal without hypovolemic symptoms even though they are considered to be at dry weight by routine physical examination and that the identification of these patients can be facilitated by intradialytic blood volume monitoring.     

Ischemia-reperfusion-induced muscle damage: Protective effect of corticosteroids and antioxidants in rabbits

We examined the potential protective effect of pretreatment with corticosteroids or antioxidants (ascorbic acid or allopurinol) in rabbits with reper-fusion-induced damage to skeletal muscle after ischemia.

4 hours of limb ischemia induced by a pneumatic tourniquet, followed by reperfusion for 1 hour, caused a considerable amount of ultrastructural damage to the anterior tibialis muscles accompanied by a rise in circulating creatine kinase activity. Pretreatment of animals with depomedrone by a single 8 mg bolus injection led to a preservation of the anterior tibialis structure on both light and electron microscopy. High-dose continuous intravenous infusion with ascorbic acid (80 mg/hr) throughout the period of ischemia and reperfusion also preserved skeletal muscle structure, although allopurinol in various doses had no protective effect.

These data are fully compatible with a mechanism of ischemia/reperfusion-induced injury to skeletal muscle, involving generation of oxygen radicals and neutrophil sequestration and activation. They also indicate that damage to human skeletal muscle caused by prolonged use of a tourniquet is likely to be reduced by simple pharmacological interventions.     

Past exposure and the dynamics of lymphatic filariasis infection in young children.

This study utilizes parallel, longitudinal entomological and parasitological data collected during a 5-year vector control programme in Pondicherry, South India, to quantify Wuchereria bancrofti transmission from the vector to the human population. A simple mathematical model, derived from the standard catalytic model, is used to examine the hypothesis that current infection prevalence in young children is a dynamical function of their cumulative past exposure to infective bites. Maximum likelihood fits of the model to the observed data indicate a constant child infection rate with age, above a threshold representing the pre-patent period, or equivalently, the cumulative biting intensity required to produce patent infections. Extrapolation of the model allows the crude estimation of the equilibrium microfilaria age-prevalence curve due to control. The results suggest that vector control alone may have little impact on the overall age-prevalence of infection even when sustained for long periods. These observations are discussed in terms of the likely impact of density dependent mechanisms, such as acquired immunity, on model predictions.     

Surface treatment of indirect resin composite surfaces before cementation

Statement of problem. Controversy surrounds the use of hydrofluoric acid to prepare precementation surfaces of indirect composites.Purpose. This study was conducted to compare effects of combining hydrofluoric or orthophosphoric acid with microetching as precementation treatments.Material and methods. Nine specimens of three composite materials were prepared to simulate heat-cured indirect restorations. The specimen surfaces were prepared with one of three treatments. Adhesive Bond II and Twinlook cements were used to bond a phosphoric acid-etched disk of P50 to the treated surface. Analysis of variance and Scheffé tests were used to assess the bond strength data. Scanning electron microscopy and microscopic analysis of the fractured and treated surfaces were also performed.Results. Bond strengths for all surface treatments did not significantly differ. Hybrids had a higher bond strength with etching than microfills, and mechanical roughening produced the greatest bond strengths with microfills. Microetching with orthophosphoric acid produced higher bond strengths than microetching with hydrofluoric acid on hybrids.Conclusions. Acid etching alone is not sufficient to produce effective bond strengths, and hydrofluoric acid treatments are detrimental to the resin composite. (J Prosthet Dent 1997;77:568-72.)     

Clinical importance,statistical significance and the assessment of economic and quality-of-life outcomes

The assessment of economic and quality-of-life outcomes of health care interventions is moving into a new era, with such assessments increasingly being made within the context of controlled clinical trials. Traditionally the measurement of many variables in economic evaluations, particularly costs, has been deterministic. In the context of clinical trials the measurement of variables is stochastic, with the standard principles of statistical inference being applied to analyse differences between treatments in terms of effectiveness. Economists participating in clinical research are therefore being called upon to specify the sample size for the economic component of the evaluation and to undertake statistical tests for differences in cost or cost-effectiveness. This paper discusses the current methodological issues surrounding stochastic measurement in clinical trials, discusses the additional issues raised by the assessment of economic and quality-of-life outcomes and specifies the challenges facing economists if they are to answer the questions now being posed about economic analysis by statisticians and clinical researchers. It is concluded that application of the standard principles of statistical inference to economic data is not straightforward and will require value judgements to be made about statistical significance and economic importance, which may differ from those already made in purely clinical studies.     

Synthesis and Antitumour Activity of New Derivatives of Flavone-8-acetic Acid (FAA). Part 1: 6-Methyl Derivatives

A range of 17 derivatives of flavone-8-acetic acid (FAA) with a 6-methyl substituent have been prepared and their anti-tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A. While many of the compounds show activity comparable to FAA in vitro, this essentially disappears in vivo, possibly due to degradation before the compounds can reach the tumour site.     

New Potent Azomethine Prodrugs of the Histamine H3-Receptor Agonist (R)-α-Methylhistamine Containing a Heteroarylphenyl Partial Structure

The therapeutic value of histamine H₃-receptor ligands is under current investigation. On the basis of recently described diaryl imine prodrugs of the histamine H₃-receptor agonist (R)-α-methyl-histamine ( 1 ) a series of new azomethine prodrugs containing five- and six-membered heterocycles were synthesized and tested for their in vitro hydrolysis rates and in vitro activity after oral application. It was found that electron-deficient six-membered heterocycles drastically destabilized the imine double bond so that these prodrugs decomposed unsuitably fast. On the contrary, prodrugs containing five-membered heterocycles appeared to be highly effective for the CNS delivery of 1 , and a remarkable correlation between chemical structure and pharmacokinetic profile was observed. Particularly (R)-4-fluoro-2-[[N-[1-(1H-imidazol-4-yl)-2-propyl]imino](1H-pyrrol-2-yl)methyl]phenol ( 8c ), the 2-furanyl analogue 8d , and its 3-furanyl isomer 8e proved to be equipotent to the most potent of recently described halogenated diaryl imine prodrugs of 1. However, in contrast to any other azomethine prodrug, 8c exhibited an incomparably long lasting delivery of 1 in the CNS and can thus be regarded as a ‘retard’ prodrug. Assuming that a therapeutic indication of histamine H₃-receptor agonists will soon be established, these highly potent heteroarylphenyl azomethine prodrugs, which already serve as valuable pharmacological tools, may also become potential drugs in clinical use.