Hock Lesions in Dairy Cows in Cubicle Housing Systems in Germany: Prevalence and Risk Factors.

Hock lesions in dairy cows are an important indicator of animal welfare, in particular housing conditions. The aim of this study was to assess the prevalence of hock lesions in dairy cows kept in cubicle housing systems in three structurally different regions of Germany and to derive recommendations from risk factor analyses. Lactating and dry cows kept in cubicle housing systems were assessed for hock lesions (north: 206 farms with 20,792 cows; south: 156 farms with 8050 cows; east: 192 farms with 37,839 cows). Risk factor analyses were conducted using multi-factorial logistic regression models. The median prevalence of hock lesions (hairless patches, wounds, and/or swelling) at farm level was 79.8% (SD: 25.0; north), 66.2% (SD: 31.0; south), and 78.5% (SD: 26.3; east). The mean prevalence of severe hock lesions (wounds and/or swelling) at farm level was 12.5% (SD: 11.3; north), 8.0% (SD: 13.5; south), and 14.4% (SD: 17.9; east). Cows kept in pens with rubber mats or mattresses (with or without a small amount of litter) had a particularly higher chance of hock lesions compared with cows kept in pens with deep-bedded cubicles (OR: north: 3.1 [2.3-4.2]; south: 8.7 [5.9-13.0], east: 2.0 [1.7-2.4]). The study showed that hock lesions are a widespread problem on German dairy farms with cubicle housing systems. Deep-bedded cubicles are likely to reduce hock lesions and increase cows' comfort.

[Herd health problems with a focus on potential involvement of Clostridium botulinum in dairies in Bavaria. - A survey among veterinarians]. / Bestandsprobleme mit möglicher Beteiligung von Clostridium botulinum in bayerischen Milchkuhbetrieben.

OBJECTIVE: To evaluate the perceptions of Bavarian bovine practitioners in regard to ailments that could potentially be associated with chronic Clostridium botulinum infections. MATERIAL AND METHODS: A questionnaire-based survey consisting of two parts was conducted via telephone. The questionnaire contained five main inclusion criteria and seven further criteria for inclusion in the second, special part of the study. The main focus was on diseases suspected to be associated with chronic Clostridium botulinum infections. For the interview in the special part, for each practice, the farm that fulfilled the most of the main criteria was selected. RESULTS: In the general section of the questionnaire, 38 (37%) of the 104 participants stated not to have farms with any of the previously indicated disease patterns in their practice. A total of 532 operations (5% of all managed dairies) were classified as a problem facility that had to deal with the aforementioned main inclusion criteria diseases. The most frequently stated on-farm problems were an increased number of recumbent cows (73 %), lameness or cases of ataxia (70 %), udder problems (69 %), metabolic disorders (68 %), high incidence of chronically ill animals (66 %) and high culling rates (66 %). The housing conditions of dairy cows were assessed to be "mediocre" or "poor" in 49 % of dairies. Feeding management was regarded as "moderately good", "good" or "very good" by 91 % of participants. Testing for Clostridium spp. was performed on 11 farms and positive results were found in seven cases. CONCLUSION: Livestock veterinarians in Bavaria are frequently confronted with an abundance of animal health-related issues on dairy farms. However, even on farms on which there were signs according to the literature of clostridial infection, rather husbandry-related problems were suspec -ted in most cases.

Predicting biopharmaceutical performance of oral drug candidates - Extending the volume to dissolve applied dose concept.

The purpose of the study was to experimentally deduce pH-dependent critical volumes to dissolve applied dose (VDAD) that determine whether a drug candidate can be developed as immediate release (IR) tablet containing crystalline API, or if solubilization technology is needed to allow for sufficient oral bioavailability. pH-dependent VDADs of 22 and 83 compounds were plotted vs. the relative oral bioavailability (AUC solid vs. AUC solution formulation, Frel) in humans and rats, respectively. Furthermore, in order to investigate to what extent Frel rat may predict issues with solubility limited absorption in human, Frel rat was plotted vs. Frel human. Additionally, the impact of bile salts and lecithin on in vitro dissolution of poorly soluble compounds was tested and data compared to Frel rat and human. Respective in vitro - in vivo and in vivo - in vivo correlations were generated and used to build developability criteria. As a result, based on pH-dependent VDAD, Frel rat and in vitro dissolution in simulated intestinal fluid the IR formulation strategy within Pharmaceutical Research and Development organizations can be already set at late stage of drug discovery.

Volume to dissolve applied dose (VDAD) and apparent dissolution rate (ADR): tools to predict in vivo bioavailability from orally applied drug suspensions.

Low solubility of drug candidates generated in research contributes to their elimination during subsequent development due to insufficient oral bioavailability (BA) of crystalline compound. Therefore, the purpose of the study was to identify critical in vitro solubility and dissolution parameter that would predict critical in vivo dissolution by means of in vitro-in vivo correlation. Thermodynamic solubility and apparent dissolution rate (ADR) were determined using the shake-flask method and mini-flow-through-cell, respectively. Oral BA studies in rats and humans were conducted from drug solution and suspension/tablets. Relative BA was calculated using F(rel) [%]=AUC(suspension)/AUC(solution)*100, representing a measure of in vivo dissolution. Roughly, F(rel) rat >50% translates into F(rel) human of >90%. Both, ADR and log volume to dissolve applied dose (VDAD), when plotted against F(rel) rat, revealed certain threshold levels, (ADR, ∼150-200 µg of compound dissolved under respective assay conditions; VDAD, ∼100-500 ml/kg) which translate into F(rel) in rats of >50%. Thus, assuming that F(rel)>50% in rats is indicative of sufficient in vivo dissolution in humans after oral application, drugs should exhibit a VDAD of ∼100-500 ml/kg or less in aqueous media to avoid insufficient or varying drug absorption.