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BackgroundAlcohol abuse is a risk factor for bone damage and fracture‐related complications. Through precise β‐catenin signaling, canonical Wnt signaling plays a key role in fracture repair by promoting the differentiation of new bone and cartilage cells. In this study, we examined the effects of alcohol on the Wnt pathway in injured bone using a murine model of alcohol‐induced impaired fracture healing.MethodsMale C57Bl/6 or T cell factor (TCF)‐transgenic mice were administered 3 daily intraperitoneal doses of alcohol or saline. One hour following the final injection, mice were subjected to a stabilized, mid‐shaft tibial fracture. Injured and contralateral tibias were harvested at 6, 9, or 14 days post‐fracture for the analysis of biomechanical strength, callus tissue composition, and Wnt/β‐catenin signaling.ResultsAcute alcohol treatment was associated with a significant decrease in fracture callus volume, diameter, and biomechanical strength at day 14 post‐fracture. Histology revealed an alcohol‐related reduction in cartilage and bone formation at the fracture site, and that alcohol inhibited normal cartilage maturation. Acute alcohol exposure caused a significant 2.3‐fold increase in total β‐catenin protein at day 6 and a significant decrease of 53 and 56% at days 9 and 14, respectively. lacZ staining in β‐galactosidase‐expressing TCF‐transgenic mice revealed spatial and quantitative differences in Wnt‐specific transcriptional activation at day 6 in the alcohol group. Days 9 and 14 post‐fracture showed that acute alcohol exposure decreased Wnt transcriptional activation, which correlates with the modulation of total β‐catenin protein levels observed at these time points.ConclusionsAcute alcohol exposure resulted in significant impairment of fracture callus tissue formation, perturbation of the key Wnt pathway protein β‐catenin, and disruption of normal Wnt‐mediated transcription. These data suggest that the canonical Wnt pathway is a target for alcohol in bone and may partially explain why impaired fracture healing is observed in alcohol‐abusing individuals.

Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security.

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.

AbstractThe brief exposure of recently ovulated mouse oocytes to a dilute solution of ethanol in vitro for 1, 3, or 5 min induced a uniform high incidence of parthenogenetic activation. The majority of parthenogenones developed a single haploid pronucleus after the extrusion of a second polar body. The proportionate incidence of this parthenogenetic class was significantly reduced as the duration of ethanol exposure increased from 1 min to 5 min. There was a concomitant increase in the incidence of parthenogenones that developed two haploid pronuclei following failure of extrusion of the second polar body. Cytogenetic analysis of the ethanol‐induced single‐pronuclear haploid parthenogenones at metaphase of the first cleavage division clearly demonstrated that a significant proportion were aneuploid. The incidence of aneuploidy observed was directly related to the duration of ethanol exposure. G‐band analysis of the aneuploid metaphases revealed that the chromosomes were not randomly involved in the malsegregation events. This observation may be a reflection of the relationship of particular chromosomes to the meiotic spindle apparatus rather than on any specific property of the agent to which they were exposed. It is believed that ethanol disrupts the organisation of cytoskeletal elements and, in particular, interferes with the processes of chromosome segregation at the second meiotic division.

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 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.