Because of intrinsic differences between humans and mice, no single mouse model can represent all features of a complex human trait such as alcoholism. It is therefore necessary to develop partial ...models. One important feature is drinking to the point where blood ethanol concentration (BEC) reaches levels that have measurable affects on physiology and/or behavior (>1.0 mg ethanol/ml blood). Most models currently in use examine relative oral self-administration from a bottle containing alcohol versus one containing water (two-bottle preference drinking), or oral operant self-administration. In these procedures, it is not clear when or if the animals drink to pharmacologically significant levels because the drinking is episodic and often occurs over a 24-h period. The aim of this study was to identify the optimal parameters and evaluate the reliability of a very simple procedure, taking advantage of a mouse genotype (C57BL/6J) that is known to drink large quantities of ethanol. We exchanged for the water bottle a solution containing ethanol in tap water for a limited period, early in the dark cycle, in the home cage. Mice regularly drank sufficient ethanol to achieve BEC>1.0 mg ethanol/ml blood. The concentration of ethanol offered (10%, 20% or 30%) did not affect consumption in g ethanol/kg body weight. The highest average BEC (∼1.6 mg/ml) occurred when the water-to-ethanol switch occurred 3 h into the dark cycle, and when the ethanol was offered for 4 rather than 2 h. Ethanol consumption was consistent within individual mice, and reliably predicted BEC after the period of ethanol access. C57BL/6J mice from three sources provided equivalent data, while DBA/2J mice drank much less than C57BL/6J in this test. We discuss advantages of the model for high-throughput screening assays where the goal is to find other genotypes of mice that drink excessively, or to screen drugs for their efficacy in blocking excessive drinking.
Much evidence from studies in humans and animals supports the hypothesis that alcohol addiction is a complex disease with both hereditary and environmental influences. Molecular determinants of ...excessive alcohol consumption are difficult to study in humans. However, several rodent models show a high or low degree of alcohol preference, which provides a unique opportunity to approach the molecular complexities underlying the genetic predisposition to drink alcohol. Microarray analyses of brain gene expression in three selected lines, and six isogenic strains of mice known to differ markedly in voluntary alcohol consumption provided >4.5 million data points for a meta-analysis. A total of 107 arrays were obtained and arranged into six experimental data sets, allowing the identification of 3,800 unique genes significantly and consistently changed between all models of high or low amounts of alcohol consumption. Several functional groups, including mitogen-activated protein kinase signaling and transcription regulation pathways, were found to be significantly overrepresented and may play an important role in establishing a high level of voluntary alcohol drinking in these mouse models. Data from the general meta-analysis was further filtered by a congenic strain microarray set, from which cis-regulated candidate genes for an alcohol preference quantitative trait locus on chromosome 9 were identified: Arhgefl2, Carml, Cryab, Cox5a, Dlat, Fxyd6, Limd1, Nicn1, Nmnat3, Pknox2, Rbp1, Sc5d, Scn4b, Tcf12, Vps11, and Zfp291 and four ESTs. The present study demonstrates the use of (i) a microarray meta-analysis to analyze a behavioral phenotype (in this case, alcohol preference) and (ii) a congenic strain for identification of cis regulation.
Summary
Reasons for performing study: There is increasing evidence of involvement of inflammatory cells in acute laminitis.
Objective: To immunolocalise monocytes/macrophages and B and T lymphocytes ...in the laminar tissue of normal horses and those with black walnut extract (BWE)‐induced laminitis.
Methods: Immunohistochemistry was used in archived laminar tissue samples from 20 horses divided equally into 4 groups: control animals (CON), and those administered BWE at 1.5 h (1.5H DTP group), at the onset of leucopenia (3H DTP group) and at the onset of lameness (LAM group). Antibodies against CD3, CD20 and CD163 were used to recognise lymphocytes (T and B) and monocytes/macrophages, respectively.
Results: Mononuclear cells were present in laminar tissue of normal horses. The majority of CD3‐ and CD20‐positive lymphocytes were localised around the deep dermal vessels but were also evident around vessels of the primary dermal laminae. CD163‐positive macrophages were primarily perivascular in deep dermis or in dermal laminae. No changes in the number of laminar B or T lymphocytes occurred at any time point post BWE administration. However, increases (P = 0.0016) in laminar CD163‐positive cells occurred in the secondary dermal laminae (SDL) in the 1.5H DTP and 3H DTP groups, returning to basal values in LAM group.
Conclusions: Lymphocyte and macrophage populations are present in the laminar tissue of clinically normal horses and BWE administration induces an increase in CD163‐positive macrophages in SDL.
Potential relevance: Both the host tissue population of mononuclear cells and the influx of monocytes may play an important role in the pathophysiological changes leading to laminar injury.
Rituximab has been associated with hepatitis B virus reactivation (HBV-R). However, the characteristics and scope of this association remain largely undefined.
We completed a comprehensive literature ...search of all published rituximab-associated HBV-R cases and from the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) MedWatch database. Literature and FDA cases were compared for completeness, and a meta-analysis was completed.
One hundred and eighty-three unique cases of rituximab-associated HBV-R were identified from the literature (n = 27 case reports, n = 156 case series). The time from last rituximab to reactivation was 3 months (range 0–12), although 29% occurred >6 months after last rituximab. Within FDA data (n = 118 cases), there was a strong signal for rituximab-associated HBV-R proportional reporting ratio = 28.5, 95% confidence interval (CI) 23.9–34.1; Empiric Bayes Geometric Mean = 26.4, 95% CI 21.4–31.1. However, the completeness of data in FDA reports was significantly inferior compared with literature cases (P < 0.0001). Among HBV core antibody (HBcAb(+)) series, the pooled effect of rituximab-based therapy showed a significantly increased risk of HBV-R compared with nonrituximab-treated patients (odds ratio 5.73, 95% CI 2.01–16.33; Z = 3.33, P = 0.0009) without heterogeneity (χ2 = 2.12, P = 0.5473).
The FDA AERS provided strong HBV-R safety signals; however, literature-based cases provided a significantly more complete description. Furthermore, meta-analysis of HBcAb(+) series identified a more than fivefold increased rate of rituximab-associated HBV-R.
Objective— To describe in horses and ponies a laparoscopic ovariectomy technique facilitated by electrosurgical instrumentation.
Study Design— Elective ovariectomy was performed in 23 mares using ...laparoscopic electrosurgical instrumentation.
Animals or Sample Population— Twenty‐three mares (13 horses, 10 ponies), aged from 2 to 21 years and weighing 90 to 545 kg.
Methods— Food was withheld for a minimum of 12 hours. Mares were sedated with detomidine hydrochloride (0.02 to 0.03 mg/kg) or xylazine hydrochloride (0.5 to 1.0 mg/kg). Excluding the pony mares, all other mares were restrained in stocks. Portal sites in the paralumbar fossa region were desensitized with 2% mepivacaine. Abdominal insufflation was achieved through a teat cannula positioned in the ventral abdomen or a Verres‐type needle placed through the paralumbar fossa. After trocar and laparoscope insertion, the ipsilateral ovary and mesovarium were identified, and the mesovarium, tubal membrane, and proper ligament were infiltrated with 2% mepivacaine. The mesovarium was coagulated using bipolar or monopolar electrosurgical forceps and transected sequentially from cranial to caudal until the ovary was completely freed and then removed. The contralateral ovary was removed in a similar fashion through the opposite paralumbar fossa.
Results— Bipolar and monopolar electrosurgical forceps were easy to use and provided adequate coagulation of vessels within the mesovarium. Two mares were euthanatized after the procedure for unrelated reasons. One mare had mild signs of colic 24 hours after ovariectomy. In 1 pony mare, the incision used to remove one ovary dehisced on the 5th postoperative day and was allowed to heal by second‐intention. No long‐term complications had occurred in 11 horses and 10 ponies, 6 to 24 months after surgery.
Conclusion— Laparoscopic ovariectomy and hemostasis of the mesovarium can be easily accomplished using electrosurgical instrumentation.
Clinical Relevance— Standing laparoscopic ovariectomy, using electrosurgical instrumentation, is an effective and safe technique to provide hemostasis of the mesovarium in mares.
While prolonged access to ethanol (EtOH), or deprivations, or their combination have occasionally been shown to yield high levels of voluntary self-administration, in almost all cases, rodents do not ...self-administer alcohol to the degree that they will develop substantial, intoxicating blood alcohol levels and then continue to self-administer at these levels.
The purpose of the present series of experiments was to modify a fluid restriction procedure to demonstrate consistent, high EtOH consumption.
Male and female mice from an alcohol preferring inbred strain (C57BL/6J; B6) as well as from a genetically heterogeneous strain (WSC) were given varying periods of access to fluid, ranging from 90 min to 10 h per day, for 12-21 days. Every 3rd or 4th day, separate groups of mice were offered a 5, 7 or 10% EtOH solution for either 10 min or 30 min, followed by water for the remainder of the time.
In all studies, stable high EtOH doses were consumed by both B6 and WSC mice across the EtOH sessions, exceeding 2 g/kg in a 30-min session. Mean blood EtOH concentration exceeded 1 mg/ml (i.e. 100 mg%), with values in individual animals ranging from 0.6 mg/ml to 3.4 mg/ml. Notably, mice receiving 10 h of fluid/day continued to consume 2 g/kg doses of EtOH. While this procedure did not produce subsequent preference for EtOH in WSC mice, consumption remained high in some animals.
These data indicate that scheduling fluid intake produces high, stable EtOH consumption and BEC in male and female B6 and WSC mice.
The objective of this study was to investigate the accumulation of selenium in lakes downstream of a uranium mine operation in northern Saskatchewan, Canada. Selenium concentrations in sediment and ...biota were elevated in exposure areas even though water concentrations were low (<5
μg/L). The pattern (from smallest to largest) of selenium accumulation was: periphyton
<
plankton and filterer invertebrates
<
detritivore and predator invertebrates
<
small bodied (forage) fish and predatory fish. Biomagnification of selenium resulted in an approximately 1.5–6 fold increase in the selenium content between plankton, invertebrates and forage fish. However, no biomagnification was observed between forage fish and predatory fish. Selenium content in organisms from exposure areas exceeded the proposed 3–11
μg/g (dry weight) dietary toxicity threshold for fish, suggesting that the selenium released into these aquatic systems has the potential to bioaccumulate and reach levels that could impair fish reproduction.
Selenium bioaccumulation patterns in a north temperate, cold water aquatic ecosystem were similar to those reported from warm water systems.
Abstract The cross section for Higgs boson production in pp collisions is studied using the H arrow right W+W- decay mode, followed by leptonic decays of the W bosons to an oppositely charged ...electron-muon pair in the final state. The measurements are performed using data collected by the CMS experiment at the LHC at a centre-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 19.4 fb -1. The Higgs boson transverse momentum (p T) is reconstructed using the lepton pair p T and missing p T. The differential cross section times branching fraction is measured as a function of the Higgs boson p T in a fiducial phase space defined to match the experimental acceptance in terms of the lepton kinematics and event topology. The production cross section times branching fraction in the fiducial phase space is measured to be 39 ± 8 (stat) ± 9 (syst) fb. The measurements are found to agree, within experimental uncertainties, with theoretical calculations based on the standard model. Figure not available: see fulltext.
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