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Abstract Background Malaria remains one of the most devastating diseases globally, and the control of mosquitoes as the vector is mainly dependent on chemical insecticides. Elevated temperatures associated with future warmer climates could affect mosquitoes' metabolic enzyme expression and increase insecticide resistance, making vector control difficult. Understanding how mosquito rearing temperatures influence their susceptibility to insecticide and expression of metabolic enzymes could aid in the development of novel tools and strategies to control mosquitoes in a future warmer climate. This study evaluated the effects of temperature on the susceptibility of Anopheles gambiae sensu lato (s.l.) mosquitoes to pyrethroids and their expression of metabolic enzymes. Methods Anopheles gambiae s.l. eggs obtained from laboratory-established colonies were reared under eight temperature regimes (25, 28, 30, 32, 34, 36, 38, and 40 °C). Upon adult emergence, 3- to 5-day-old female non-blood-fed mosquitoes were used for susceptibility tests following the World Health Organization (WHO) bioassay protocol. Batches of 20–25 mosquitoes from each temperature regime (25–34 °C) were exposed to two pyrethroid insecticides (0.75% permethrin and 0.05% deltamethrin). In addition, the levels of four metabolic enzymes (α-esterase, β-esterase, glutathione S-transferase [GST], and mixed-function oxidase [MFO]) were examined in mosquitoes that were not exposed and those that were exposed to pyrethroids. Results Mortality in An. gambiae s.l. mosquitoes exposed to deltamethrin and permethrin decreased at temperatures above 28 °C. In addition, mosquitoes reared at higher temperatures were more resistant and had more elevated enzyme levels than those raised at low temperatures. Overall, mosquitoes that survived after being exposed to pyrethroids had higher levels of metabolic enzymes than those that were not exposed to pyrethroids. Conclusions This study provides evidence that elevated temperatures decreased An. gambiae s.l. mosquitoes' susceptibility to pyrethroids and increased the expression of metabolic enzymes. This evidence suggests that elevated temperatures projected in a future warmer climate could increase mosquitoes' resistance to insecticides and complicate malaria vector control measures. This study therefore provides vital information, and suggests useful areas of future research, on the effects of temperature variability on mosquitoes that could guide vector control measures in a future warmer climate. Graphical Abstract

If femoral blood is not available at autopsy, toxicological analyses, in particular blood ethanol measurements, are carried out on cardiac blood. This is known to be subject to major redistribution. We aimed to determine whether subclavian blood can be equated with a peripheral blood sample and could be used if femoral blood is not available. The study was based on 50 medicolegal autopsies in which we compared ethanol concentrations between subclavian blood, the different heart blood compartments (right and left cardiac blood), and femoral blood. Mechanisms that could lead to variations in concentration, i.e., postmortem redistribution and/or endogenous production, were also taken into account in interpreting the results. Ethanol concentrations were determined by headspace gas chromatography with a flame ionization detector. In each case, we recorded the circumstances of death, resuscitation attempts if any, degree of putrefaction, chest or abdominal trauma, and/or inhalation of gastric fluid in the airways. Ethanol concentrations in subclavian blood were found to be close to those in peripheral blood (p = 0.948) and were not influenced by the degree of putrefaction (r = 0.017, p = 0.904), gastric ethanol concentration (r = -0.011, p = 0.940), inhalation of gastric contents in the airways (p = 0.461), or cardiac resuscitation attempts (p = 0.368). We discuss the possible explanations for these findings and stress the value of sampling subclavian blood when femoral blood is not obtainable at autopsy.

1. The gastroprotective activity of two azomethine prodrugs of (R)-alpha-methylhistamine was examined in lesions induced by absolute ethanol (1 ml/rat intragastrically for 1 h). 2. Pretreatment with (R)-alpha-methylhistamine as well as with the prodrugs (30 and 100 mg/kg intragastrically [IG]) significantly reduced macroscopically visible lesions caused by ethanol, with protection being almost complete at 100 mg/kg. 3. Histologically, in rats pretreated with the three compounds at a dose of 100 mg/kg, the evidence of damage was rare, with the appearance of gastric mucosa being similar in the different groups. 4. Present results are suggestive of a local component in the protective activity of (R)-alpha-methylhistamine.

In biomedical scientific investigations, expositions of findings are conceptually simplest when they comprise comparisons of discrete groups of individuals or involve discrete features or characteristics of individuals. But the descriptive benefits of categorization become outweighed by their limitations in studies involving dose-response relationships, as in many teratogenic and environmental exposure studies. This article addresses a pair of categorization issues concerning the effects of prenatal alcohol exposure that have important public health consequences: the labeling of individuals as fetal alcohol syndrome (FAS) versus fetal alcohol effects (FAE) or alcohol-related neurodevelopmental disorder (ARND), and the categorization of prenatal exposure dose by thresholds. We present data showing that patients with FAS and others with FAE do not have meaningfully different behavioral performance, standardized scores of IQ, arithmetic and adaptive behavior, or secondary disabilities. Similarly overlapping distributions on measures of executive functioning offer a basis for identifying alcohol-affected individuals in a manner that does not simply reflect IQ deficits. At the other end of the teratological continuum, we turn to the reporting of threshold effects in dose-response relationships. Here we illustrate the importance of multivariate analyses using data from the Seattle, Washington, longitudinal prospective study on alcohol and pregnancy. Relationships between many neurobehavioral outcomes and measures of prenatal alcohol exposure are monotone without threshold down to the lowest nonzero levels of exposure, a finding consistent with reports from animal studies. In sum, alcohol effects on the developing human brain appear to be a continuum without threshold when dose and behavioral effects are quantified appropriately.

We evaluated the effects of the seed saponins of Thea sinensis L. on alcohol absorption and metabolism in rats and mice. An ethanolic extract from the seeds of T. sinensis was orally administered to the rats 1 hr before or 0.5 hr after administration of ethanol (2 g/kg), and the blood ethanol assayed 0.5, 1, 2, 3, and 4 hr after ethanol administration. The ethanol level decreased after both pre- and post-administration of the extract. The extract was further purified to obtain a saponin fraction which was orally administered to mice 1 hr before ethanol administration. Blood, liver, and stomach were obtained 0, 1, 3, and 6 hr after ethanol administration, and the ethanol, acetaldehyde, acetate, and acetone concentrations in each specimen were measured by head space gas chromatography. The saponin fraction decreased the ethanol levels in the blood and liver but increased that in the stomach five-fold over the control level, suggesting inhibition of alcohol absorption. The ethanol disappearance time from the blood was shortened, suggesting the promotion of alcohol disappearance. The acetate and acetone levels were unaffected. However, the acetaldehyde level decreased in the blood, liver, and stomach. The decreases in the ethanol and acetaldehyde levels in the liver suggested the protective effects of the seed saponins on the liver. The saponins did not directly inhibit hepatic alcohol dehydrogenase activity. The seed saponins of T. sinensis seem to suppress alcohol absorption by slowing gastric emptying and by inhibiting absorption across the cell membranes of the digestive tract.

Percutaneous transluminal septal myocardial ablation (PTSMA) is a new therapeutic option for patients with hypertrophic obstructive cardiomyopathy (HOCM). In the present study, the acute and follow-up results of PTSMA were evaluated. From August 1997 to March 2003 27 medically refractory patients (New York Heart Association (NYHA) functional class 2.9+/-0.6) with HOCM underwent PTSMA. The target septal branch was determined by probationary ballooning in 3 and by myocardial contrast echocardiography in 24 patients. The mean resting left ventricular outflow tract pressure gradient (PG) was reduced from 70+/-44 to 24+/-22 mmHg (p<0.0001); the peak concentration of creatine kinase was 1545+/-686 IU/L. Although transient trifascicular block was observed in 14 patients, permanent pacemaker implantation was not required. There were no major adverse cardiac events during the hospital stay; the mean clinical follow-up was 2.2+/-1.7 years. Repeated PTSMA was needed in 1 patient; however, symptomatic improvement had been well preserved in all patients (NYHA class 1.2+/-0.4). Follow-up echocardiographic examination showed sustained improvement in PG, septal and left ventricular posterior wall thicknesses, and the grade of systolic anterior movement and regurgitation of the mitral valve. In conclusion, PTSMA is a safe and effective therapeutic option for medically refractory patients with HOCM.

Forty-nine schools (N = 5,680 fifth and sixth grade students) were assigned to pre test/treatment, pretest/no treatment, no pretest/treatment, and no pretest/no treat ment conditions in the context of an alcohol misuse prevention study. At the first posttest, five months after the pretest and two months after the intervention, the effects of the pretest and of the intervention were examined. The analyses showed that failure to correct for the design effect due to clustering within schools resulted in the overestimation of the significance of treatment and pretest effects. After correction for the design effect, a significant treatment effect in the hypothesized direction was found with respect to students' awareness of the content of the curriculum. As hypo thesized, significant treatment effects on the alcohol use and misuse measures had not yet developed but are expected to occur at subsequent posttest occasions. Significant pretest effects were found for indices measuring trouble with peers resulting from students' alcohol use, students' internal health locus of control, and their perceptions of adults as a locus of control for their health. Two of the three pretest effects were in the direction that would be hypothesized if the pretest were providing the same impe tus as the intervention. Implications of these findings for school-based substance abuse prevention programs are discussed.

Abstract An orange and an apple juice each containing 250–385 ppm tin were under suspicion of having caused an outbreak of food poisoning in Kuwait in 1967 but did not cause any toxic signs when fed to pigeons, cats and dogs. One cat out of 11 vomited when fed an orange juice containing 540 ppm tin derived from the container, and with juices containing 1370 ppm tin, 20–30% of the cats vomited but none of the dogs was affected. Fruit juices containing 2000 ppm tin caused vomiting in up to 40% of the cats. Modification of orange juices with a high tin content by addition of nitrate or ethanol or by adjustment of the pH from 3 to 6 did not affect the incidence of vomiting. No toxic signs were produced in rats given fruit juices containing added tin salts up to a level of 995 ppm or in rats and cats given aqueous solutions of tin salts (up to 1200 ppm tin) in citric acid. Solid foods containing tin derived from the containers up to the highest level obtainable (470 ppm) had no toxic effect when fed to dogs and cats. Five human volunteers showed no toxic signs after drinking fruit juices containing 498, 540 or 730 ppm tin derived from the containers, but all five had some gastro-intestinal disturbance after drinking a fruit juice containing 1370 ppm tin. A repeat experiment with the latter juice had no effect in four of the volunteers and only mild symptoms in the fifth. In rats and cats, there was no evidence of tin absorption 24 hr after ingestion of fruit juices containing high levels of tin. No tin was recovered from the urine and in the rats 99% was recovered from the faeces. Only minute amounts of tin could be found in the body, apart from the alimentary tract, of a rat that had been given orange juice with a high tin content ad lib. instead of drinking water for 7 days. It is concluded that toxic signs follow the drinking of tin-containing fruit juices by man and cats only with tin levels of approximately 1400 ppm and above, that there is no evidence from these experiments that toxicity is due to the absorption of tin and that the most likely cause is local irritation of the mucous membrane of the alimentary tract.