Miracle-dz/UniFAR-FTUs huggingface dataset:
Dabigatran

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. Subscribers to The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I. X. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service or The F.I. X. , call The Formulary at 800-322-4349. The March 2011 monograph topics are on fentanyl sublingual tablet, brentuximab vedotin, rilpivirine hydrochloride, denufosol, abiraterone acetate. The DUE/MUE is on dabigatran etexilate mesylate.
Intestinal morphology, brush border and digesta enzyme activities of broilers fed on a diet containing Cu2+-loaded montmorillonite

1. A total of 320 1-d-old Arbor Acres broiler chicks were used to investigate the effect of Cu2+-loaded montmorillonite (CM) on the growth performance, intestinal morphology and activities of brush border enzyme in the intestinal mucosa and digestive enzyme in the intestinal digesta of broilers. 2. The chicks were assigned randomly into 4 groups with 80 chicks per treatment. The 4 dietary treatments were: basal diet only (control group), basal diet + 2 g montmorillonite/kg, basal diet + 1 g CM/kg, and basal diet + 2 g CM/kg. The chicks were raised in cages and feed and water were provided ad libitum for a period of 42 d. 3. The addition of CM to the diet of broilers significantly increased body weight and feed efficiency. Similarly, birds receiving montmorillonite had higher feed efficiency than the control after 42 d of feeding. 4. Data on villus height and crypt depth for duodenum, jejunum and ileum indicated that treating the diet of broilers with either CM or montmorillonite improved the mucosal morphology of the small intestine. 5. The presence of CM in the diet of broilers significantly increased the activities of maltase, aminopeptidase N and alkaline phosphatase in small intestinal mucosa. However, the activities of protease, trypsin, chymotrypsin, amylase and lipase in small intestinal digesta of broilers fed on the CM-supplemented diet were slightly higher than control values.
Epigallocatechin-3-gallate supplementation can improve antioxidant status in stressed quail

1. Heat stress causes oxidative stress, which decreases plasma antioxidants in poultry. Epigallocatechin gallate (EGCG), the most abundant polyphenol in green tea, is a powerful antioxidant against lipid peroxidation. This experiment was conducted to evaluate the effects of dietary EGCG supplementation on performance, carcase characteristics, concentrations of malondialdehyde, lipid peroxidation indicator, vitamins C, E, A, cholesterol, triglyceride, and glucose in Japanese quail (Coturnix coturnix japonica) exposed to a high ambient temperature of 34°C. 2. One hundred and eighty Japanese quails (10 d old) were assigned at random to 6 treatment groups consisting of 10 replicates of three birds. Birds were kept in cages in a temperature-controlled room at either 22°C (thermo-neutral) or 34°C (heat stress) for 8 h/d. Birds were fed either a basal diet or the diet supplemented with 200 or 400 mg of EGCG/kg of diet. 3. EGCG supplementation linearly increased feed intake, live weight gain, feed efficiency, cold carcase weight and yield under heat stress conditions but did not show the same effect at thermoneutral conditions. Serum vitamin C, E, and A concentrations increased in birds reared at high temperature while non-significant changes occurred in thermo-neutral groups. Malondialdehyde concentrations in serum and liver decreased in all birds of both thermo-neutral and heat stressed groups as dietary EGCG supplementation increased. Heat stress-induced increase in serum cholesterol, triglycerides and glucose concentrations were linearly reversed by EGCG supplementation. 4. The results indicate that EGCG supplementation improved the live performance and antioxidant status of heat-stressed Japanese quail.
Quantifying genetic (co)variation and effects of genetic selection on tibial bone morphology and quality in 37 lines of broiler, layer and traditional chickens

1. Tibial bone morphology and quality was assessed at 6, 8 and 10 weeks of age in 12 broiler, 12 layer and 13 traditional lines of chickens. 2. High intraclass correlations (0·65–0·96) were estimated for tibial weight, length, width, strength, stiffness, stress radiodensity, plateau angle but not for cortical width and tibial torsion at 6 and 10 weeks of age and for weight, length, width, strength radiodensity and plateau angle at 8 weeks of age. Lower intraclass correlations (0·4–0·8) were estimated within category (broiler, layer and traditional) for weight, length, width at 6, 8 and 10 weeks, and for stiffness, stress and radiodensity at 6 and 10 weeks, and were lower (<0·33) at 8 weeks of age. Intraclass correlations for tibial torsion angles were low (≤0·4) at all ages. 3. Tibia from layers and traditional lines were similar suggesting that intensive genetic selection for high rates of egg laying has not changed bone size, shape or quality. Tibia from broilers, as expected, were heavier and larger and the differences were greatest at 6 weeks of age suggesting that the broilers were earlier maturing than layers and traditional lines. Broiler tibiae were more radiodense, stronger and stiffer and had lower stress values than bones from layers and traditional lines. Plateau angles were higher in broilers and torsion angles had higher external rotation compared with layers and traditional lines.
Effects of structure and xylanase treatment of brewers’ spent grain on performance and nutrient availability in broiler chickens

1. A factorial (2 × 3) feeding trial was set up to investigate the effects of coarse or finely ground brewers’ spent grain (BSG) and xylanase treatment, either with no xylanase, top-dressed with xylanase or pre-treated with xylanase. 2. The experimental diets shared the same basal formulation and were fed to male broiler chickens (Ross 308) housed in individual cages from 12 to 29 d of age. 3. Xylanase pre-treatment reduced the dietary concentration of arabinoxylan by 15–30%. Pellet durability increased when BSG was ground. 4. Feed utilisation was significantly higher (6%) when the birds were given coarse BSG rather than ground BSG, whereas there was no significant effect of enzyme treatment. Apparent metabolisable energy was unaffected by the dietary treatments. 5. The overall starch digestibility was high (99%), with no dietary differences, whereas ileal protein digestibility was low (57%). Xylanase top-dressing tended to improve ileal protein digestibility but, in general, xylanase treatment had no major effect on overall performance in male broilers given diets with BSG.
HIV Drug Resistance at Patients on HAART and Transmitted HIV Drug Resistance (tHIVDR) in Treatment Naive Patients in Belarus

Of the 59 patients (adults) who have been identified to have a virus with a high level resistance to HAART drugs, in 38 (64.4%) patients mutation M184V/I was identified. In 27 (45.8%) patients (13 female and 14 male) K103N mutation was detected. In 20 (33.9%) patients (16 male and 4 female) we found G190G/S/A mutation. Of the 18 childrenpatients, born to HIV-infected mothers, in 15 (83.3%) cases (9 girls and 6 boys) we detected HIV resistance mutation M184V. In 10 (55.6%) and 2 (11.1%) cases mutations in position G190S and K103S were found, respectively. Of 82 samples collected from newly diagnosed HIV-infected antiretroviral naive patients only 6 samples (7.3%) had other resistance mutations which can be classified as 'minor' or 'other' according to HIVDR database of Stanford University: L10V - PI minor mutation associated with resistance to most PIs when present with other mutations; L33F - PI minor mutation selected by FPV/r, DRV/r, LPV/r, ATV/r, and TPV/r, and contributes decreased susceptibility to these PIs; V118I - accessory mutation usually occurred with multiple TAMs and contributes some resistance to each of the NRTIs including 3TC and FTC; T74S is ‘other’ mutation associated with reduced NFV susceptibility; and V108I - accessory mutation, causes low-level resistance to NVP and EFV.
Isolation, identification and antimicrobial susceptibility of Bacteroides fragilis group strains recovered from broiler faeces

1. The objective was to evaluate the occurrence of cultivable components of the Bacteroides fragilis group in faeces of broiler chickens and their antimicrobial susceptibility patterns. 2. Faecal samples of 36 × 45-d-old Cobb broilers of both sexes from 15 different flocks on one farm were diluted 10-fold and plated on to Bacteroides-bile-esculin agar for colony count and isolation. Identification was by molecular methods and antimicrobial susceptibility in the agar dilution assay. 3. A total of 236 isolates was recovered from a mean population of 3·32 × 107 colony-forming units/g of faeces. B. fragilis was shown to be the predominant Bacteroides species (45·3%), followed by B. distasonis (35·6%), B. vulgatus (8·9%), B. ovatus (2·5%) and B. stercoris (1·3%). 4. Among 204 bacterial isolates tested, high resistance to ampicillin (98·5%), norfloxacin (95·1%) and tetracycline (88·2%) were observed. High (89·7%) multi-drug resistance was observed to 3–7 of the tested drugs. 5. Components of the B. fragilis group were sub-dominant in broiler faecal microbiota, with a different species pattern compared with human and high antimicrobial multi-drug resistance.
PRECLINICAL STUDY: Pentylenetetrazole‐induced status epilepticus following training does not impair expression of morphine‐induced conditioned place preference

Learning and memory play an important role in morphine addiction. Status epilepticus (SE) can impair the spatial and emotional learning and memory. However, little is known about the effects of SE on morphine‐induced conditioned place preference (CPP). The present study was designed to investigate the effects of SE on morphine CPP, with food CPP being used as a control. The effects of SE on spatial memory in the Morris water maze (MWM) and Y‐maze were investigated. SE was induced in adult mice using intraperitoneal injection of pentylenetetrazole; control mice received saline. The data indicated that SE had no effects on the formation of morphine CPP; however, the formation of food CPP was blocked by SE. Meanwhile, spatial memory assayed in the MWM and Y‐maze was impaired by SE. In addition, the data demonstrated that SE did not cause a lasting disturbance of motor activity nor a change in the mice's appetite. These results suggested that although SE had no effects on morphine CPP, there was impaired food CPP and spatial memory in both the MWM and the Y‐maze. The mechanisms underlying memory process of morphine CPP may be different from other types of memory.
PRECLINICAL STUDY: Mifepristone and spironolactone differently alter cocaine intravenous self‐administration and cocaine‐induced locomotion in C57BL/6J mice

Corticosterone, the main glucorticoid hormone in rodents, facilitates behavioral responses to cocaine. Corticosterone is proposed to modulate cocaine intravenous self‐administration (SA) and cocaine‐induced locomotion through distinct receptors, the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR), respectively. However, this remains debatable. On one hand, modulation of both responses by the GR was tested in different experimental conditions, i.e. light versus dark nycthemeral phase and naïve versus cocaine‐experienced animals. On the other hand, modulation of both responses by the MR was never tested directly but only inferred based on the ability of low plasma corticosterone levels (those for which corticosterone almost exclusively binds the MR) to compensate the effects of adrenalectomy. Our goal here was to test the involvement of the GR and the MR in cocaine‐induced locomotor and reinforcing effects in the same experimental conditions. C57Bl/6J mice were trained for cocaine (1 mg/kg/infusion) intravenous SA over 40 SA sessions. The animals were then administered with mifepristone (30 mg/kg i.p.), a GR antagonist, or with spironolactone (20 mg/kg/i.p.), an MR antagonist, 2 hours before either cocaine intravenous SA or cocaine‐induced locomotion. In a comparable nycthemeral period and in similarly cocaine‐experienced animals, a blockade of the GR decreased cocaine‐induced reinforcing effects but not cocaine‐induced locomotion. A blockade of the MR decreased both cocaine‐induced reinforcing (but to a much lesser extent than the GR blockade) and locomotor effects. Altogether, our results comforted the hypothesis that the GR modulates cocaine‐related operant conditioning, while the MR would modulate cocaine‐related unconditioned effects. The present data also reveal mifepristone as an interesting tool for manipulating the impact of corticosterone on cocaine‐induced reinforcing effects in mice.
Interventions to Promote Physical Activity in Chronically Ill Adults

OVERVIEW: The importance of promoting physical activity in adults with chronic illness cannot be overstated. Although numerous studies have evaluated interventions developed to increase physical activity in this population, it can be difficult to interpret the results without the benefit of a statistical analysis across studies. A 2008 meta-analysis synthesized the findings of 163 reports on such studies. This article discusses the implications of those findings, describing the strategies and practices commonly used to promote physical activity in chronic illness and identifying those that are most effective.
Bioavailability and pharmacokinetic profile of levofloxacin following intravenous, intramuscular and oral administration in turkeys

Abstract 1. The pharmacokinetics and bioavailability of levofloxacin in turkeys were investigated after a single intravenous (IV), intramuscular (IM) and oral (PO) administration of 10 mg/kg body weight. 2. The concentrations of levofloxacin in plasma samples were assayed using a microbiological assay method and pharmacokinetic parameters were calculated by non-compartmental analysis. 3. Following IV administration, the elimination half-life (t0.5(β)), volume of distribution at steady state (Vdss) and total body clearance (Cl) were 4.49 h, 1.31 l/kg and 0.23 l/h/kg, respectively. 4. After single IM and PO administrations at the same dose, levofloxacin was rapidly absorbed as indicated by an absorption half-life (t0.5ab) of 1.02 and 0.76 h, respectively; maximum plasma concentrations (Cmax) of 5.59 and 5.15 μg/ml were obtained at a maximum time (Tmax) of 2 h for both routes and levofloxacin bioavailability (F) was 96.5 h and 79.9% respectively after IM and PO administration. In vitro plasma protein binding of levofloxacin was 24.3%. 5. Based on these pharmacokinetic parameters, a dose of 10 mg/kg body weight given intramuscularly or orally every 24 h in turkeys can maintain effective plasma concentrations with bacterial infections with (minimum inhibitory concentration) MIC90 > 0.1 μg/ml.
Wichtige Signifikanztests

Zum statistischen Nachweis von Unterschieden oder Effekten werden in der medizinischen Forschung häufig Signifikanztests [6] verwendet. Die Grundprinzipien statistischer Tests, die von Lange und Bender [6] am Beispiel des ungepaarten t-Tests erläutert werden, gelten auch für andere Testverfahren. Der t-Test kommt für viele Testsituationen der medizinischen Forschung in Frage, er deckt aber nicht alle Anwendungsgebiete ab. Je nach Fragestellung und Datensituation benötigt man andere statistische Testmethoden. Die für medizinische Anwendungen wichtigsten statistischen Tests für die einfachen Standardsituationen werden in dieser Arbeit kurz und übersichtlich zusammengefasst.
Depletion of florfenicol and florfenicol amine residues in chicken eggs

Abstract 1. The aim of this study was to develop a suitable method for the analysis of florfenicol (FF) and its metabolite florfenicol amine (FFA) in chicken eggs and to determine FF and FFA residue depletion in eggs of laying hens. 2. The analytes were extracted from yolk, albumen and whole egg by phosphate buffer and ethyl acetate. Following purification, samples were analysed by high-performance liquid chromatography. 3. Fifty laying hens were divided into 5 groups, and each hen received doses of 20 mg/kg FF: Group 1 (received a single oral dose by gavage); Group 2 (a single intramuscular dose); Group 3 (a single subcutaneous dose); Group 4 (multiple oral doses for 3 d) and Group 5 (multiple oral doses for 5 d). 4. Limits of detection and of quantitation values were 1.94 and 6.45 g/109 g (ppb) for FF, respectively, and 0.48 and 1.58 ppb for FFA, respectively. Relative standard deviation values of intra-day and inter-day variation below 11% also confirmed the usefulness of the method for analysing FF and FFA in eggs. 5. From the first day of both oral and parenteral administration, FF and FFA were detected at 0.1% and 0.08% of dosage, respectively, and 57% of the drugs were eliminated from the egg yolk. Elimination time of FF was 8 d in Groups 1, 2 and 3; 9 d in Group 4 and 10 d in Group 5.
Binge‐like ethanol consumption increases corticosterone levels and neurodegneration whereas occupancy of type II glucocorticoid receptors with mifepristone is neuroprotective

Excessive ethanol (EtOH) use leads to impaired memory and cognition. Using a rat model of binge‐like intoxication, we tested whether elevated corticosterone (Cort) levels contribute to the neurotoxic consequences of EtOH exposure. Rats were adrenalectomized (Adx) and implanted with cholesterol pellets, or cholesterol pellets containing Cort in order to achieve basal, medium, or high blood concentrations of Cort. Intragastric EtOH or an isocaloric control solution was given three times daily for 4 days to achieve blood alcohol levels ranging between 200 and 350 mg/dl. Mean 24‐hour plasma levels of Cort were ∼110 and ∼40 ng/ml in intact EtOH‐treated and intact control animals, respectively. Basal Cort replacement concentrations in EtOH‐treated Adx animals did not exacerbate alcohol‐induced neurodegeneration in the hippocampal dentate gyrus (DG) or the entorhinal cortex (EC) as observed by amino‐cupric silver staining. In contrast, Cort replacement pellets resulting in plasma Cort levels twofold higher (medium) than normal, or greater than twofold higher (high) in Adx‐Cort‐EtOH animals increased neurodegeneration. In separate experiments, pharmacological blockade of the Type II glucocorticoid (GC) receptor was initiated with mifepristone (RU38486; 0, 5, 15 mg/kg/day, i.p.). At the higher dose, mifepristone decreased the number of degenerating hippocampal DG cells in binge‐EtOH–treated intact animals, whereas, only a trend for reduction was observed in 15 mg/kg/day mifepristone‐treated animals in the EC, as determined by fluoro‐jade B staining. These results suggest that elevated circulating Cort in part mediates EtOH‐induced neurotoxicity in the brain through activation of Type II GC receptors.
Advances in the therapy of rheumatoid arthritis with biological agents

Rheumatoid arthritis (RA) is the most common chronic systemic autoimmune inflammatory disease. The physiology of inflammation has been systemically studied and this has provided specific therapeutic targets for its modulation. The classical treatments of the disease, such as myocrisin and sulphasalazine, are not always effective at controlling the disease. This has necessitated the development of novel agents for treating RA, most of which are biological in nature and are targeted at specific sites of the inflammatory cascades. Advances in molecular biology have heralded the advent of bio-drugs (recombinant proteins) and gene therapy in which specific genes are introduced to locally enhance in vivo gene expression or suppress gene(s) of interest with a view to downregulating inflammation. Some bio-drugs, such as antitumour necrosis factor-α (TNF-α) antibodies and interleukin-1 receptor antagonists (IL-1Ra) have been tested, shown to be effective, and are licensed for clinical use. The clinical effects that have been observed are transient, necessitating repeated treatments and increasing the risk of vaccination effects. Anti-inflammatory cytokines, such as IL-4, IL-10, transforming growth factor-β (TGF-β) and interferon-β (IFN-β) are undergoing clinical trials. Many of these agents have to be administered parenterally and production costs are very high. Consequently, chemical entities which can be taken orally need to be developed. Since the immune system is very complex with pleiotropic cytokines and redundancy in some of the regulatory networks, it may be necessary to use multiple agents targeting different specific sites of the inflammatory cascade or different agents that could be given at different stages of the disease, in order to induce disease remission and maintain the response to it. Cytokines and other mediators play important physiological roles in the host’s defence systems against infections and malignancy. The chronic inhibition, exogenous administration or constitutive overexpression of some cytokines may therefore lead to the development of side effects. Thus, carefully controlled long-term studies will be required to assess the safety of selective targeting of processes involved in the physiology of inflammation. This review summarises the important developments in the biotherapy of RA.
Cloning of the growth hormone receptor and its muscle-specific mRNA expression in black Muscovy duck (Cairina moschata)

Abstract The cDNA sequence of the growth hormone receptor (GHR) from the black Muscovy duck was obtained and compared to the mRNA expression of growth hormone (GH) in the breast and leg muscles during 2–13 weeks of age using quantitative RT-PCR. The cDNA sequence of the Muscovy duck GHR gene is 1903 bp in length, with an 1830 bp coding region that encodes 609 amino acids. It exhibits > 92.9% homology with the poultry GHR cDNA and amino acid sequences. Overall, GHR mRNA expression was the highest at 2 weeks and the lowest at 13 weeks of age, exhibiting different profiles in different muscles. In the breast muscles, the GHR mRNA level declined sharply at 2–4 weeks, maintained at a plateau at 4–10 weeks and decreased slightly at 10–13 weeks. In the leg muscles, a gradual and slow decrease was observed during the whole period of 2–13 weeks. Robust extra-pituitary GH mRNA expression was detected in the muscles and the expression profile was highly correlated with that of GHR mRNA, in contrast to the inverse correlation between the pituitary GH and tissue GHR levels shown previously. These data suggest that the locally synthesised GH in the muscles, rather than the pituitary GH, is more closely associated with GHR and may be more critical for the regulation of muscle growth and contribute to the tissue-specific effects of GH.