Developmental role of adenosine kinase for the expression of sex-dependent neuropsychiatric behavior.

Deficits in social memory, cognition, and aberrant responses to stimulants are common among persons affected by schizophrenia and other conditions with a presumed developmental etiology. We previously found that expression changes in the adenosine metabolizing enzyme adenosine kinase (ADK) in the adult brain are associated with deficits in various cognitive domains. To distinguish between developmental and adult functions of ADK, we used two transgenic mouse lines with widespread disruption of ADK expression in the adult brain, but differences in the onset of ADK deletion. Specifically, we compared Nestin-Cre+/-:ADK-floxfl/fl (ADKΔBrain) mice with global loss of ADK in the whole brain, beginning in mid-gestation and persisting for life, with Gfa2-Cre+/-:ADK-floxfl/fl (ADKΔAstro) mice that have normal ADK expression throughout development, but lose astrocyte-specific ADK-expression in young adulthood. Because ADK-expression in adulthood is generally confined to astrocytes, adult ADKΔAstro mice show a similar expression profile of ADK in key areas of the brain related to neuropsychiatric behavior, compared to adult ADKΔBrain mice. We sought to determine a neurodevelopmental role of ADK on the expression of psychiatric behaviors in adult male and female mice. Adult ADKΔBrain mice showed significant deficits in social memory in males, significant contextual learning impairments in both sexes, and a hyper-responsiveness to amphetamine in males. In contrast, ADKΔAstro mice showed normal social memory and contextual learning but hypo-responsiveness to amphetamine in males. Our results demonstrate a key developmental role of ADK in mediating behaviors in adulthood related to neuropsychiatric disease and support the greater prevalence of these disorders among males.

Novel genes on rat chromosome 10 are linked to body fat mass, preadipocyte number and adipocyte size.

BACKGROUND: The genetic architecture of obesity is multifactorial. We have previously identified a quantitative trait locus (QTL) on rat chromosome 10 in a F2 cross of Wistar Ottawa Karlsburg (WOKW) and Dark Agouti (DA) rats responsible for obesity-related traits. The QTL was confirmed in congenic DA.WOKW10 rats. To pinpoint the region carrying causal genes, we established two new subcongenic lines, L1 and L2, with smaller refined segments of chromosome 10 to identify novel candidate genes. METHODS: All lines were extensively characterized under different diet conditions. We employed transcriptome analysis in visceral adipose tissue (VAT) by RNA-Seq technology to identify potential underlying genes in the segregating regions. Three candidate genes were measured in human paired samples of VAT and subcutaneous (SC) AT (SAT) (N=304) individuals with a wide range of body weight and glucose homeostasis parameters. RESULTS: DA.WOKW and L1 subcongenic lines were protected against body fat gain under high-fat diet (HFD), whereas L2 and DA had significantly more body fat after high-fat feeding. Interestingly, adipocyte size distribution in SAT and epigonadal AT of L1 subcongenic rats did not undergo typical ballooning under HFD and the number of preadipocytes in AT was significantly elevated in L2 compared with L1 and parental rats. Transcriptome analysis identified three candidate genes in VAT on rat chromosome 10. In humans, these candidate genes were differentially expressed between SAT and VAT. Moreover, HID1 mRNA significantly correlates with parameters of obesity and glucose metabolism. CONCLUSIONS: Our data suggest novel candidate genes for obesity that map on rat chromosome 10 in an interval 102.2-104.7 Mb and are strongly associated with body fat mass regulation, preadipocyte number and adipocyte size in rats. Among those genes, AT head involution defective (HID1) mRNA expression may be relevant for human fat distribution and glucose homeostasis.

Treatment of naturally occurring bovine respiratory disease in juvenile calves with a single administration of a florfenicol plus flunixin meglumine formulation.

The efficacy and safety of a florfenicol plus flunixin meglumine formulation in the treatment of respiratory disease was evaluated in calves less than six weeks of age, compared with a positive control group treated with a well-established florfenicol formulation. A total of 210 calves, selected from nine sites in Belgium, France and Spain, showing severe signs of respiratory disease, were randomly assigned to treatment with either florfenicol plus flunixin meglumine (Resflor; MSD Animal Health) or florfenicol (Nuflor; MSD Animal Health), both administered subcutaneously once. Animals were clinically observed daily for 10 days following treatment initiation. The predominant respiratory pathogens were Pasteurella multocida, Mycoplasma bovis, Mannheimia haemolytica and Histophilus somni. All isolates were subject to in vitro sensitivity testing and found susceptible to florfenicol. In both groups, rectal temperature dropped and clinical index (depression and respiratory signs) significantly improved after treatment. Specifically, for the change in rectal temperature from pretreatment to six hours post-treatment, the florfenicol-flunixin formulation was found significantly superior to florfenicol. Moreover, the florfenicol-flunixin formulation alleviated the clinical signs of disease more rapidly, and was demonstrated to be non-inferior to florfenicol on days 4 and 10. The use of the product combining florfenicol and flunixin in calves is safe and efficacious in the treatment of outbreaks of bovine respiratory disease.

The pharmacokinetics of orbifloxacin in the horse following oral and intravenous administration.

The purpose of this study was to determine the pharmacokinetics and physicochemical characteristics of orbifloxacin in the horse. Six healthy adult horses were administered oral and intravenous orbifloxacin at a dose of 2.5 mg/kg. Plasma samples were collected and analyzed by high-pressure liquid chromatography with ultraviolet detection. Plasma protein binding and lipophilicity were determined in vitro. Following i.v. administration, orbifloxacin had a terminal half-life (t1/2) of 5.08 h and a volume of distribution (V(d(SS))) of 1.58 L/kg. Following oral administration, the average maximum plasma concentration (Cmax) was 1.25 microg/mL with a t1/2 of 3.42 h. Systemic bioavailability was 68.35%. Plasma protein binding was 20.64%. The octanol:water partition coefficient (pH 7.4) was 0.2 +/- 0.11. No adverse reactions were noted during this study. Dosage regimens were determined from the pharmacokinetic-pharmacodynamic parameters established for fluoroquinolone antibiotics. For susceptible bacteria, an oral dose of approximately 5 mg/kg once daily will produce plasma concentrations within the suggested range. This dose is suggested for further studies on the clinical efficacy of orbifloxacin for treatment of susceptible bacterial infections in the horse.

Effect of dietary fat on oral bioavailability of tepoxalin in dogs.

A pharmacokinetic study was conducted to compare the oral bioavailability of tepoxalin and its pharmacologically active acid metabolite in fasted dogs and dogs fed either a low-fat or high-fat commercial diet. Using a cross-over design, six beagles were administered tepoxalin (10 mg/kg) intravenously (i.v.) and orally (p.o.) after being fed one of three diets (fasted, low-fat, or high-fat). Thereafter, blood samples were collected at frequent intervals, concentrations of tepoxalin and acid metabolite in plasma were determined by high performance liquid chromatography, and pharmacokinetic parameters were estimated. After i.v. dosing, the mean (+/-SD) half-life of elimination (t(1/2(beta))) was 2.45 +/- 1.47 h. After p.o. administration, plasma concentrations of acid metabolite were consistently higher than corresponding concentrations of the parent tepoxalin, indicating that tepoxalin is subject to a substantial first-pass effect. Mean (+/-SD) peak concentrations of tepoxalin were significantly higher after feeding of low-fat (1.08 +/- 0.37 microg/mL) and high-fat (1.19 +/- 0.29 microg/mL) diets than in fasted dogs (0.53 +/- 0.20 microg/mL), suggesting that feeding improves oral bioavailability.

Ion separation due to magnetic field penetration into a multispecies plasma.

The magnetic field, the electron density, and the ion velocities in a multispecies plasma conducting a high fast-rising current are determined using simultaneous spectroscopic measurements. It is found that ion separation occurs in which a light-ion plasma is pushed ahead while a heavy-ion plasma lags behind the magnetic piston. We show that most of the momentum imparted by the magnetic field pressure is taken by the reflected light ions, and most of the dissipated magnetic field energy is converted into kinetic energy of these ions, even though their mass is only a small part of the total plasma mass. Such species separation with implications to the momenta and energy partitioning is shown to be of a general nature.

Employee effects of an educational program for managers at an insurance company.

BACKGROUND: Possible health effects for employees of efforts to improve the psychosocial competence of managers have not been studied scientifically in the past. OBJECTIVE: To explore how efforts to improve management will change the work environment and health of the employees. METHODS: Managers of the experimental department in a large insurance corporation underwent 2-hour biweekly training sessions for 1 year-altogether, 60 hours. A control group of employees in other departments in the corporation not affected by the modification was followed with the same assessments. Morning blood samples for the assessment of serum cortisol were collected both at baseline and after 1 year in 155 participants in the experimental group and in 147 subjects in the control group. Liver enzymes and lipids were also assessed. In the questionnaire part of the 1-year follow-up study, there were 119 participants in the experimental group and 132 in the control group. RESULTS: When repeated-measures ANOVA was used, a significant interaction effect was found for the level of serum cortisol; serum cortisol levels were decreased in the intervention group and were unchanged in the control group (ANOVA two-way interaction, p =.02; after exclusion of the managers, p =.005). A significant interaction effect was also observed for decision authority, with increased decision authority in the intervention group and, conversely, a decreased level in the control group (p =.001; after exclusion of managers, p =.02). CONCLUSIONS: The study indicates that a moderately intensive psychosocial manager program lasting for 1 year can be beneficial for the employees with regard to both lowered serum cortisol and improved authority over decisions.

Treatment of keratoconjunctivitis sicca in dogs with cyclosporine ophthalmic ointment: a European clinical field trial.

The results are reported of a six-week clinical trial of the efficacy of 0.2 per cent cyclosporine ophthalmic ointment for the treatment of chronic idiopathic keratoconjunctivitis sicca in dogs in the United Kingdom, Germany and France. The 87 dogs were referral cases with a history of chronic unresponsive keratoconjunctivitis sicca of which the aetiology was unknown, and they had to meet stringent criteria before being included in the trial. The clinical response to the therapy was monitored after seven, 21 and 42 days and the results for the right and left eyes were analysed separately. There was a statistically significant increase in lacrimal secretion throughout the study, with most of the increase occurring during the first week of treatment. The percentage of eyes with improved lacrimal secretion was higher in the dogs with initial Schirmer tear test values > or = 2 mm/min than in those with initial values of 0 or 1 mm/min. The observed steady improvement in conjunctival health was not always correlated with an improvement in lacrimal secretion. The incidence of blepharospasm, other signs of discomfort and corneal oedema decreased significantly during the study. No improvement in corneal vascularisation or pigmentation was observed during the six-week trial. Overall, 76 per cent of the left eyes and 87 per cent of the right eyes were considered to have improved at the end of the treatment period. No serious adverse reactions were observed and only mild irritation was noticed by the owners immediately after the application of the ointment. This irritation resulted in the recording of an adverse reaction at the scheduled observations in only three cases.

[Antimalaria campaign in the Middle-east army (1917): the illustrated postcard as a means of information and propaganda by pictures]. / La mission paludéenne de l'Armée d'Orient (1917): La carte postale illustrée, moyen d'information et de propagnande par l'image.

The authors take out from oblivion the series of illustrated post-cards published in 1917 by the French under-secretariat of state for Military Health Service in order to promote the malaria control within the Middle-East French Army. They give some details on how these post-cards were originated, they also illustrate some principles of prevention against malaria made compulsory for the Armed Forces Personnel. The authors also demonstrate how that simple and easy to handle medium, fast vector of sanitary information, was able to support effectively the antimalaria Mission in the Middle-East French Army in its malaria prophylactic action.

Khat-induced hypnagogic hallucinations.

Khat is a plant whose leaves are chewed for their stimulating effect. This effect is attributed to cathinone, an alkaloid identical to dextroamphetamine. Khat chewing is widespread among eastern African and Yemenite populations and is believed to be innocuous. Our experience shows, however, that a substantial number of chronic khat chewers experience persistent hypnagogic hallucinations - a symptom that has not yet been described. Three vignettes illustrates this phenomena, which often interferes with psychiatric diagnosis. Different explanatory models are discussed, among them chronic suppression of REM sleep.

[Highly selective arteriography and embolization in the treatment of angiodysplasias with shunt, in the limbs (author's transl)]. / Place de l'artériographie supersélective et de l'embolisation dans le traitement des angiodysplasies des membres avec shunt.

The authors discuss the role of highly selective arteriography and embolization in the treatment of angiodysplasias with shunt, in the limbs, after analyzing the results in three cases of embolization for congenital arterio-venous fistula of the limbs. They review the arteriographic data necessary for a better understanding of the physiopathology and compare the different therapeutic methods available. The importance of highly selective arteriography in guiding therapy, where embolization is of primary value, is stressed.

[Hepatic arterial embolisation. 35 cases (author's transl)]. / L'embolisation artérielle hépatique. 35 cas.

Thirty five cases of hepatic arterial embolisation are reported. The analgesic effect in association with tumour pathology (27 cases) was virtually constant (80% of cases). Arterial embolisation should thus replace surgical disarterialisation in the management of malignant tumours of the liver. It improves the quality of survival in painful tumours, above all when they are hypervascularised. Two fatal complications as a result of the technique emphasise the absolute need to respect its contraindications: portal thrombosis, even segmental, or hepatic failure. Two cavernous haemangiomas and one angioma with arterioportal fistula complicated by haemobilia were also successfully embolised. Five traumatic vascular lesions, two of which resulted in severe haemobilia, also benefited from superselective embolisation.