Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response

In innate immune responses, activation of Toll-like receptors (TLRs) triggers direct antimicrobial activity against intracellular bacteria, which in murine, but not human, monocytes and macrophages is mediated principally by nitric oxide. We report here that TLR activation of human macrophages up-regulated expression of the vitamin D receptor and the vitamin D-1-hydroxylase genes, leading to induction of the antimicrobial peptide cathelicidin and killing of intracellular Mycobacterium tuberculosis. We also observed that sera from African-American individuals, known to have increased susceptibility to tuberculosis, had low 25-hydroxyvitamin D and were inefficient in supporting cathelicidin messenger RNA induction. These data support a link between TLRs and vitamin D-mediated innate immunity and suggest that differences in ability of human populations to produce vitamin D may contribute to susceptibility to microbial infection.     

Hf-W Isotopic Evidence for Rapid Accretion and Differentiation in the Early Solar System

The time scales over which inner solar system objects accreted and differentiated are unclear because the isotopic systems of many meteorites are disturbed. 182Hf decays to 182W with a half-life of 9 million years and is a particularly useful chronometer because both elements are highly refractory and immobile. Tungsten isotopic data for IIA, IIIA, IVA, and anomalous iron meteorites and H, L, and LL chondrites indicate that their parent bodies accreted rapidly and segregated metal within just a few million years.     

Snake bites recorded by veterinary practices in Australia

Objective To determine the extent of the snake bite problem in domestic animals, its regional significance and the effects of antivenom treatment.
Design A questionnaire was designed seeking information on the number and type of domestic animals referred, whether treated or untreated, type of snakes and management of the bite.
Procedure The survey form was sent to 10% of veterinary surgeons, selected at random throughout Australia.
Results The response of 106 veterinary surgeons revealed that snake bite in domestic animals is frequent, with an estimated 6200 cases reported annually. Bites were more prominent in rural (78%) than urban areas (22%) with brown, tiger and black snakes accounting for 76%, 13% and 6% of cases, respectively. Cats and dogs were the most frequently reported victims. Ninety-one percent of cats and 75% of dogs survived following the administration of antivenom whereas 66% of cats and 31% of dogs survived without antivenom. Overall, in 33% of cases antivenom was not used, and venom detection kits were used in only 1% of cases. A number of drugs were used in various combinations with or without antivenom and intravenous fluids in the treatment of animals with snake bite, but their role in reducing the severity of envenomations was not assessed.
Clinical implications Antivenom significantly improves the chances of survival of domestic animals bitten by snakes.     

Protein kinase C overactivity impairs prefrontal cortical regulation of working memory

The prefrontal cortex is a higher brain region that regulates thought, behavior, and emotion using representational knowledge, operations often referred to as working memory. We tested the influence of protein kinase C (PKC) intracellular signaling on prefrontal cortical cognitive function and showed that high levels of PKC activity in prefrontal cortex, as seen for example during stress exposure, markedly impair behavioral and electrophysiological measures of working memory. These data suggest that excessive PKC activation can disrupt prefrontal cortical regulation of behavior and thought, possibly contributing to signs of prefrontal cortical dysfunction such as distractibility, impaired judgment, impulsivity, and thought disorder.     

Evaluation of the effect of ketoprofen on experimentally induced ephemeral fever in dairy heifers

Objective To evaluate ketoprofen for the therapy of ephemeral fever.
Design A blind controlled clinical trial.
Animals Sixteen cattle (one immature Holstein bull, eight Holstein and seven Jersey heifers).
Procedure Ephemeral fever was induced by the intravenous injection of blood leucocyte layer from a clinical case. Ketoprofen solution or a coded placebo was injected intramuscularly at the rate of 3 mg/kg daily for three days.
Results Ketoprofen reversed locomotor dysfunctions significantly compared with controls, but did not have any effect on rectal temperatures, leucocyte counts, plasma fibrinogen concentrations, ionised Ca-concentrations or the presence of dyspnoea.
Conclusion Ketoprofen is a safe and effective drug for the treatment of locomotor symptoms of milk fever, but has no effect on the duration of clinical respiratory abnormalities.     

Gold-induced immune thrombocytopenia in the dog

In two seven-year studies with gold compounds in dogs of both sexes, thrombocytopenia was observed after 45 to 72 months of dosing in three of 14 and two of 14 dogs in high-dose groups that received 2.4 to 3.6 mg/kg of auranofin per day orally or 0.5 to 2.0 mg/kg of gold sodium thiomalate intramuscularly once every three days, respectively. An immune basis for the disorder was suggested by the apparent consumptive nature of the thrombocytopenia (increased bone marrow megakaryocytes and large peripheral blood platelets), the response to corticosteroid therapy and the demonstration of increased platelet-associated immunoglobulin. The latter was demonstrated with a solid phase radioimmunoassay and by electron microscopy using a staphylococcal protein A-colloidal gold conjugate. Platelet-associated immunoglobulin decreased as the platelet counts rose, and in one dog monitored over periods of steroid-induced remissions and subsequent relapses, the amount of platelet-associated immunoglobulin G correlated inversely with the platelet count (r = 0.82). These findings suggest that the long-term administration of gold compounds in dogs is associated with a dose-dependent incidence of thrombocytopenia, which is immune-mediated and similar to that associated with parenteral chrysotherapy in man. The application of tests for platelet-associated immunoglobulin to canine patients with immune thrombocytopenia should be useful in the diagnosis of the disorder in clinical practice.