Poly(ADP-ribose) links the DNA damage response to biomineralization

Biomineralization of the extracellular matrix is an essential, regulated process. Inappropriate mineralization of bone and the vasculature has devastating effects on patient health, yet an integrated understanding of the chemical and cell biological processes that lead to mineral nucleation remains elusive. Here, we report that biomineralization of bone and the vasculature is associated with extracellular poly(ADP-ribose) synthesized by poly(ADP-ribose) polymerases in response to oxidative and/or DNA damage. We use ultrastructural methods to show poly(ADP-ribose) can form both calcified spherical particles, reminiscent of those found in vascular calcification, and biomimetically calcified collagen fibrils similar to bone. Importantly, inhibition of poly(ADP-ribose) biosynthesis in vitro and in vivo inhibits biomineralization, suggesting a therapeutic route for the treatment of vascular calcifications. We conclude that poly(ADP-ribose) plays a central chemical role in both pathological and physiological extracellular matrix calcification.Includes BHF and EPSRC funding

Promising cytotoxic activity profile of fermented wheat germ extract (Avemar®) in human cancer cell lines

Fermented wheat germ extract (FWGE) is currently used as nutrition supplement for cancer patients. Limited recent data suggest antiproliferative, antimetastatic and immunological effects which were at least in part exerted by two quinones, 2-methoxy benzoquinone and 2,6-dimethoxybenzquinone as ingredients of FWGE. These activity data prompted us to further evaluate the in vitro antiproliferative activity of FWGE alone or in combination with the commonly used cytotoxic drugs 5-FU, oxaliplatin or irinotecan in a broad spectrum of human tumor cell lines. We used the sulforhodamine B assay to determine dose response relationships and IC50-values were calculated using the Hill equation. Drug interaction of simultaneous and sequential drug exposure was estimated using the model of Drewinko and potential clinical activity was assessed by the model of relative antitumor activity (RAA). Apoptosis was detected by DNA gel electrophoresis

Ophthalmology of clinically normal alpacas ( Vicugna pacos ) in the United Kingdom: a cross-sectional study

Background: Alpacas are being more frequently presented to veterinarians in the UK. It is important to validate whether published normal ocular parameters are consistent with the alpaca population in the UK. Methods: Ophthalmic examinations were performed on healthy alpacas (Vicugna pacos) from three farms in East Anglia, UK. Results: On direct ophthalmoscopy of 35 alpacas, there was a 50 per cent prevalence of opacities within the lens in alpacas older than two years old (n=8/16). There was a 36.8 per cent prevalence of persistent hyaloid arteries in alpacas under two years old (n=7/19). The mean Schirmer tear test-1 value was 20.0 ±6 mm/minute (n=40). The mean intraocular pressure measured by rebound tonometry was 17.2 ±5.5 mmHg (n=46), and applanation tonometry resulted in statistically similar values (P=0.30; n=25). There was a significant variation in intraocular pressure throughout a 24-hour period (n=8). Fluorescein dye was not detected at the nostrils of any of the alpacas which underwent a Jones test to assess nasolacrimal duct patency (n=8). Conclusion: The ophthalmic findings appear largely consistent with previously published values from North America and continental Europe. Variations include the large range of measurements obtained and evidence of diurnal variation in intraocular pressure

Enteritis in weaned cattle: an overview of causes

While calf diarrhoea may receive more attention, enteritis in young adult and mature cattle is common and has a variety of causes. This review provides an overview of such causes and outlines how to approach diagnosis in the weaned animal with diarrhoea. </jats:p

Accuracy and efficiency of pregnancy examinations by means of ultrasound between day 20 and 34 after insemination in dairy cattle and heifers

Titelblatt, Inhalt, Einleitung 2\. Literaturübersicht 3\. Material und Methoden 4\. Ergebnisse 5\. Diskussion 6\. Zusammenfassung, Summary 7\. Literaturverzeichnis 8\. Anhang, Lebenslauf, DankFür milcherzeugende Betriebe ist die Optimierung der Güstzeit von größter Wichtigkeit. Ziel dieser Untersuchung war es, zu zeigen, ab wann die Trächtigkeitsuntersuchung mittels Ultraschall ausreichend genaue Diagnosen liefern kann. Im Falle der Nichtträchtigkeit kann das Tier dann so früh wie möglich wieder besamt werden. Zu diesem Zweck wurden Kühe (n = 579) und Färsen (n = 720) 20 bis 34 Tage nach der künstlichen Besamung mittels Ultraschall auf Trächtigkeit untersucht. Die dabei erhobenen Diagnosen wurden mit den Ergebnissen der Trächtigkeitsuntersuchung mittels manueller Palpation vom Rektum her ab dem 35. Tag nach der Besamung verglichen. Auf diese Weise konnte die Genauigkeit der Trächtigkeitsuntersuchung mittels Ultraschall bestimmt werden. Eine Genauigkeit von 98 % konnte bei Kühen ab dem 29. Tag und bei Färsen ab dem 25. Tag nach der künstlichen Besamung erreicht werden. Für die Rinderpraxis ist für die Trächtigkeitsuntersuchung mittels Ultraschall daher das Zeitintervall von 29 bis 35 Tagen bei Kühen und von 25 bis 31 Tagen bei Färsen bei wöchentlichem Untersuchungsrhythmus empfehlenswert. Durch die Früherkennung nicht-tragender Tiere kann bei konsequentem Eingreifen die Güstzeit, insbesondere in Problemherden verkürzt werden. Durch die Verkürzung der Güstzeit kann die Wirtschaftlichkeit eines milcherzeugenden Betriebes gesteigert werden. Die Wirtschaftlichkeit der Trächtigkeitsuntersuchung mittels Ultraschall ist sowohl aus Sicht des milcherzeugenden Betriebes als auch aus Sicht des Tierarztes von zahlreichen Faktoren abhängig. Eine allgemeingültige Aussage ist nicht möglich. Daher wurden im Rahmen dieser Studie Berechnungsmodelle entwickelt, vorgestellt und diskutiert. In den zugrundeliegenden Tabellen- Kalkulations-Programmen können sämtliche Faktoren variiert werden. Auf diese Weise kann der individuell zu erwartende Gewinn beziehungsweise Verlust für den milcherzeugenden Betrieb ermittelt werden. Der Tierarzt kann durch das Einsetzen seiner individuellen Faktoren errechnen, unter welchen Bedingungen sich die Anschaffung eines Ultraschallgerätes für die Trächtigkeitsuntersuchung mittels Ultraschall für ihn rentiert. Bei dieser Berechnung wurde nur der finanziell messbare Nutzen berücksichtigt. Ideelle Werte, wie Imagegewinn, Marktanteilsicherung oder Ausweitung des Dienstleistungsprofils einer Praxis sollten bei der Entscheidung ebenfalls berücksichtigt werden.Control of days open is of major importance for dairy farms. By implementing regular early pregnancy diagnoses days open can be reduced on a herd level. It was the objective of the study to determine accuracy of pregnancy diagnosis in dairy cows and heifers at different stages of early pregnancy. Dairy cows (n = 579) and heifers (n = 720) were examined by ultrasound 20 to 34 days after artificial insemination. The results of these examinations were compared with the results of pregnancy diagnosis carried out more than 35 days after AI by rectal palpation. Accuracy was determined by crosstabulation. An accuracy of 98 % was achieved at days 29 and 25 in cows and heifers, respectively. Therefore, if farms are visited on a weekly basis, pregnancy diagnosis by ultrasound should be carried out between days 29 and 35 after AI in cows and between days 25 and 31 after AI in dairy heifers. Early detection of non pregnant cows and heifers allows induction of estrus and rebreeding and reduces days open, improving the economic situation of the farm. The cost-benefit analysis of early pregnancy diagnosis by ultrasound depends on a multitude of factors. Therefore a spreadsheet was develoed, presented and discussed in this thesis. All items can be varied in the spreadsheet model. This allows the adjustment of the spreadsheet for the individual situation in a dairy practice or a dairy farm. The model includes only direct economic effects of the implementation of early pregnancy diagnosis by ultrasound on the farm and for the dairy practice. Secondary effects like expansion of the services offered or improved reputation of the practice were not included in the model