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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.

The interconversion of the ethanolate, hydrate and amorphous form of TMC114 ((3-[(4-amino-benzenesulfonyl)-isobutyl-amino]-1-benzyl-2-hydroxypropyl)-carbamic acid hexahydrofuro-[2,3-b]furan-3-yl ester) in open conditions was characterized. TMC114 hydrate and ethanolate form isostructural channel solvates. The crystal structure of TMC114 was obtained from single crystal X-ray diffraction, confirming that it is a channel solvate. Ethanol and water can exchange with one another. TMC114 ethanolate converts into TMC114 hydrate at moderate or high relative humidity (RH) at 25 degrees C, and it converts back into the ethanolate in ethanol atmosphere. The hydration level of the hydrate is determined by the environmental humidity. TMC114 hydrate collapses to the amorphous product when water is removed by drying at low RH or increasing temperature. TMC114 ethanolate becomes amorphous at elevated temperature in a dry environment below the desolvation temperature. Amorphous TMC114 obtained by dehydrating the hydrate during storage at room temperature/<5% RH, by increasing the temperature, or via desolvating the ethanolate by heating, converts into the hydrate at moderate or high RH at ambient conditions, and into TMC114 ethanolate in an ethanol atmosphere. Under ambient conditions, TMC114 ethanolate may convert into the hydrate, whereas the opposite will not occur under these conditions. The amorphous form, prepared by melting-quenching shows a limited water uptake. Whereas TMC114 ethanolate is stable in the commercialized drug product, special conditions can trigger its conversion.

AbstractObjectiveTo assess the epidemiological evidence on the joint effects of climate variability and socioecological factors on dengue transmission.MethodsFollowing PRISMA guidelines, a detailed literature search was conducted in PubMed, Web of Science and Scopus. Peer‐reviewed, freely available and full‐text articles, considering both climate and socioecological factors in relation to dengue, published in English from January 1993 to October 2015 were included in this review.ResultsTwenty studies have met the inclusion criteria and assessed the impact of both climatic and socioecological factors on dengue dynamics. Among those, four studies have further investigated the relative importance of climate variability and socioecological factors on dengue transmission. A few studies also developed predictive models including both climatic and socioecological factors.ConclusionsDue to insufficient data, methodological issues and contextual variability of the studies, it is hard to draw conclusion on the joint effects of climate variability and socioecological factors on dengue transmission. Future research should take into account socioecological factors in combination with climate variables for a better understanding of the complex nature of dengue transmission as well as for improving the predictive capability of dengue forecasting models, to develop effective and reliable early warning systems.

C57BL/6J mice showed dose dependent devreases in locomotor activity with increasing IP doses of ethanol (0.0, 0.75, 1.50 and 2.25 g/kg), while BALB/cJ mice showed dose dependent increases in activity; both strains were equally active with saline. Whether this finding represents decreased CNS responsivity in C57BL mice to ethanol's excitatory effect or increased response to its depressant action at sub-hypnotic doses is unclear, since anesthetic doses produce anesthesia of far shorter duration in the C57BL strain than in the BALB strain. It is possible that the biphasic action of alcohol is under the control of separate and distinct mechanisms, rather than a common one, and that these two mechanisms are differentially affected by alcohol. Endogenous as well as ethanol-induced neurochemical differences in biogenic amines may also be correlated with the gentic variation in CNS responsivity towards alcohol.

The developmental and behavioral effects of prenatal exposure to cocaine and/or ethanol were examined in rats. Pregnant rats received ethanol (E; 2 g/kg, b.i.d.) orally, cocaine (C; 6 mg/kg/day, IV), or both (C/E) on gestational days 8-20. Controls consisted of pair-fed (PF) and untreated (UNT) groups. Offspring were weighed and examined for developmental markers beginning postnatal day one (PD1). On PD21 pups were individually observed in an open-field following either an injection of cocaine (10 mg/kg, IP), an injection of saline, or no treatment. Drug-treated and PF dams ate less food and gained less weight than the UNT dams. C and E litters had slightly increased mortality rates. Pups from both the C and E groups appeared less sensitive to the locomotor stimulant effect of cocaine. Pups from the E group engaged in significantly less spontaneous stereotypic locomotion than UNT and PF pups, while male pups from the C group exhibited a decrease in spontaneous exploratory behavior. Thus, prenatal exposure to C or E altered spontaneous and/or cocaine-induced behavior in weanling-aged rats, while the C/E combination did not augment either effect.

Serum lipoproteins have received considerable notoriety as risk factors for atherosclerotic disease, yet the kinetic factors that determine serum concentrations are often unappreciated. Simple compartmental models for lipoprotein kinetics are herein presented which integrate key features of lipoprotein metabolism and allow prediction of very low-density lipoprotein and low-density lipoprotein levels in a wide variety of clinical circumstances. Possible changes in kinetic parameters responsible for hyperlipidemia in obesity, insulin resistance, diabetes, carbohydrate (sugar)-induced hypertriglyceridemia, alcoholic type V hyperlipemia, polyunsaturated fat diets, and several pharmacological interventions are discussed. Key features of lipoprotein metabolism are briefly reviewed.

Heatwaves have potential health and safety implications for many workers, and heatwaves are predicted to increase in frequency and intensity with climate change. There is currently a lack of comparative evidence for the effects of heatwaves on workers' health and safety in different climates (sub-tropical and temperate). This study examined the relationship between heatwave severity (as defined by the Excess Heat Factor) and workers' compensation claims, to define impacts and identify workers at higher risk.Workers' compensation claims data from Australian cities with temperate (Melbourne and Perth) and subtropical (Brisbane) climates for the years 2006-2016 were analysed in relation to heatwave severity categories (low and moderate/high severity) using time-stratified case-crossover models.Consistent impacts of heatwaves were observed in each city with either a protective or null effect during heatwaves of low-intensity while claims increased during moderate/high-severity heatwaves compared with non-heatwave days. The highest effect during moderate/high-severity heatwaves was in Brisbane (RR 1.45, 95% CI: 1.42-1.48). Vulnerable worker subgroups identified across the three cities included: males, workers aged under 34 years, apprentice/trainee workers, labour hire workers, those employed in medium and heavy strength occupations, and workers from outdoor and indoor industrial sectors.These findings show that work-related injuries and illnesses increase during moderate/high-severity heatwaves in both sub-tropical and temperate climates. Heatwave forecasts should signal the need for heightened heat awareness and preventive measures to minimise the risks to workers.

Proton nuclear magnetic resonance (NMR) spectroscopy was used to follow glucose metabolism in Crithidia luciliae. Parasites were grown aerobically and anaerobically in culture, with glucose as the major carbon source and 1H NMR spectra were acquired for the cell free medium. The 1H NMR resonances of metabolites utilised and produced during cell growth were identified by difference spectroscopy, and quantitated from standard curves using 3-trimethylsilyl propionate-2,2,3,3-d4 sodium salt as an internal standard. The major metabolites produced by C. luciliae grown aerobically on 8 mM glucose were succinate, pyruvate, acetate and ethanol, in final concentrations in the media when the cells entered stationary phase of 8.5 +/- 0.5, 5.0 +/- 0.3, 2.1 +/- 0.2 and 2.5 +/- 0.6 mM, respectively. The production of succinate and pyruvate, but not acetate and ethanol, followed closely the growth curve of the parasites. Succinate was also measured enzymically and glucose using an autoanalyser. In both cases the results correlated well with the NMR data. The amounts of end products formed were greater than could be accounted for by the utilisation of glucose or any other metabolite observable in the 1H NMR spectra. There was approximately one extra atom of carbon for each molecule of succinate formed, supporting the view that succinate is produced via phosphoenolpyruvate carboxykinase and carbon dioxide fixation. Anaerobically the same major metabolites were produced, but with a decreased ratio of succinate to acetate and ethanol. The formation of glycerol from glucose was not observed under these conditions.