The underlying mode of action for lung tumors in a tiered approach to the assessment of inhaled cobalt compounds.

A mode of action (MOA) for cobalt substances based on the "International Programme on Chemical Safety Conceptual Framework for Evaluating a MOA for Chemical Carcinogenesis" is presented. The data recorded therein were generated in a tiered testing program described in the preceding papers of this special issue, as well as data from the public domain. The following parameters were included in the evaluation: solubility of cobalt substances in artificial lung fluids (bioelution), in vitro biomarkers for cytotoxicity, reactive oxygen species and hypoxia mimicry, inhalation toxicity following acute exposure and repeated dose inhalation effects.

Bioelution, Bioavailability, and Toxicity of Cobalt Compounds Correlate.

Based on the wide use of cobalt substances in a range of important technologies, it has become important to predict the toxicological properties of new or lesser-studied substances as accurately as possible. We studied a group of 6 cobalt substances with inorganic ligands, which were tested for their bioaccessibility (surrogate measure of bioavailability) through in vitro bioelution in simulated gastric and intestinal fluids. Representatives of the group also underwent in vivo blood kinetics and mass balance tests, and both oral acute and repeated dose toxicity (RDT) testing.

1,25-Dihydroxyvitamin D3-induced aortic calcifications in experimental uremia: up-regulation of osteoblast markers, calcium-transporting proteins and osterix.

Background And Objective: Whether treatment with vitamin D receptor activators contributes to cardiovascular disease in patients with chronic kidney disease is a matter of debate. We studied mechanisms involved in vitamin D-related vascular calcifications in vivo and in vitro.

Methods: Aortic calcifications were induced in subtotally nephrectomized (SNX) rats by treatment with a high dose (0.

Ultrastructural analysis of vascular calcifications in uremia.

Accelerated intimal and medial calcification and sclerosis accompany the increased cardiovascular mortality of dialysis patients, but the pathomechanisms initiating microcalcifications of the media are largely unknown. In this study, we systematically investigated the ultrastructural properties of medial calcifications from patients with uremia. We collected iliac artery segments from 30 dialysis patients before kidney transplantation and studied them by radiography, microcomputed tomography, light microscopy, and transmission electron microscopy including electron energy loss spectrometry, energy dispersive spectroscopy, and electron diffraction.

Sampling techniques for oviductal and uterine luminal fluid in cattle.

Analysis of luminal fluid microenvironments in the reproductive tract is pivotal to elucidate embryo-maternal signaling mechanisms responsible for successful reproduction in mammals, including cattle. Besides facilitating production of an optimized medium for in vitro fertilization and embryo culture in assisted reproductive technologies, screening of luminal fluid constituents in the oviduct and uterus could also provide critical information for elucidation of mechanisms underlying developmental programming. A key issue in this type of research is the sampling of luminal fluids.

Hepatocellular transport and gastrointestinal absorption of lanthanum in chronic renal failure.

Lanthanum carbonate is a new phosphate binder that is poorly absorbed from the gastrointestinal tract and eliminated largely by the liver. After oral treatment, we and others had noticed 2-3 fold higher lanthanum levels in the livers of rats with chronic renal failure compared to rats with normal renal function. Here we studied the kinetics and tissue distribution, absorption, and subcellular localization of lanthanum in the liver using transmission electron microscopy, electron energy loss spectrometry, and X-ray fluorescence.

Uremia-related vascular calcification: more than apatite deposition.

In the present study, we characterized and compared the mineral phase deposited in the aortic wall of two different frequently used chronic renal failure rat models of vascular calcification. Vascular calcification was induced in rats by either a 4-week adenine treatment followed by a 10-week high-phosphate diet or 5/6 nephrectomy followed by 6 weeks of 0.25 microg/kg/day calcitriol treatment and a high-phosphate diet.

Low dose insemination in cattle with the Ghent device.

A new artificial insemination device for semen deposition near the uterotubal junction (UTJ) in cattle (Ghent device) was developed at Ghent University (Belgium). In this study, UTJ insemination of dairy cows with the Ghent device was compared with the conventional insemination technique to evaluate the effect on pregnancy rates after insemination with different doses of semen. In each of three field trials, the cows (n=795, 659, 360) and heifers (n=253, 182, 231) were randomly assigned to receive 12 million sperm deposited in the uterine body using conventional techniques (control) or a reduced sperm dose (RSD) deposited in the same manner as the control or bilateral deposition near the uterotubal junction using the Ghent device (Ghent).

Localization of lanthanum in bone of chronic renal failure rats after oral dosing with lanthanum carbonate.

Background: Lanthanum carbonate has been shown to be a safe, effective phosphate-binding agent. We have shown that an impaired mineralization in chronic renal failure rats treated with high doses of lanthanum carbonate develops secondary to phosphate depletion and is therefore pharmacologically mediated rather than a direct effect of lanthanum on bone. Although bulk bone lanthanum concentrations are low, it is important to consider the localization within a given tissue.

Use of a homologous radioimmunoassay (RIA) to evaluate the effect of maternal and foetal parameters on pregnancy-associated glycoprotein (PAG) concentrations in sheep.

Early pregnancy detection and prediction of the number of lambs would be profitable for sheep breeders because it enables them to adjust nourishment of pregnant ewes according to the individual needs in order to prevent health problems around parturition. The concentration of ovPAG has previously been reported to be related with maternal parameters (farm, breed and age) as well as foetal parameters (number of lambs, their sex and birth weight), but contradictory results were obtained in different small-scale studies. This large-scale study evaluates the effect of these parameters on the ovPAG concentration, determined by a homologous radioimmunoassay (RIA), and it further investigates the possibility to predict the number of lambs by means of homologous ovPAG determination.

Time-evolution and reversibility of strontium-induced osteomalacia in chronic renal failure rats.

Background: Patients with impaired renal function can accumulate strontium in the bone, which has been associated with the development of osteomalacia. A causal role for strontium in the development of the disease was presented in chronic renal failure (CRF) rats. Strontium-ranelate has been put forward as a therapeutic agent in the treatment of osteoporosis.

First established pregnancies in Mediterranean Italian buffaloes (Bubalus bubalis) following deposition of sexed spermatozoa near the utero tubal junction.

At the time of AI following Ovsynch protocol, a total of 51 buffaloes were randomly divided in a first group (n = 30) subjected to conventional AI into the uterine body with 20 million non-sex sorted frozen-thawed spermatozoa, while a second group (n = 21) was inseminated near the utero-tubal junction (UTJ) ipsilateral to the ovary carrying the preovulatory follicle with 2.5 million live (4 million total) sex-sorted frozen-thawed spermatozoa. The semen used for flowcytometric sorting was collected and processed on a farm in Italy, and then shipped to a laboratory in Germany.

Comparison of three diluents for the storage of fresh bovine semen.

In New Zealand, 95% of the semen used for artificial insemination in cattle is processed as liquid semen. Storage of liquid semen for up to 3 days in Caprogen) diluent enables a 10-fold reduction of the insemination dose, compared to frozen-thawed semen, without a reduction in fertility. In this Caprogen) diluent spermatozoa are stored under N2 gas in the presence of catalase.

Storage of fresh bovine semen in a diluent based on the ionic composition of cauda epididymal plasma.

For artificial insemination (AI) in cattle, much lower insemination doses can be applied when fresh semen is used instead of frozen-thawed semen. However, a particular disadvantage of fresh semen is its limited shelf life. As bovine spermatozoa can be stored for several weeks in the cauda epididymis without negative effects on their fertilizing capacity, it is an interesting organ to serve as a model in order to prolong the shelf life of fresh semen.

Effects of strontium on the physicochemical characteristics of hydroxyapatite.

In a previous experimental study using a chronic renal failure rat model, a dose-related multiphasic effect of strontium (Sr) on bone formation was found that could be reproduced in an in vitro set-up using primary rat osteoblasts. The results from the latter study allowed us to distinguish between a reduced nodule formation in the presence of an intact mineralization at low Sr-doses (1 microg/ml) and an interference of the element with the hydroxyapatite (HA) formation at high doses (20-100 microg/ml). To further investigate the latter effect of Sr on physicochemical bone mineral properties, an in vitro study was set up in which the UMR-106 rat osteosarcoma cell line was exposed to Sr, added to the cell culture medium in a concentration range varying between 0-100 microg/ml.

[Deep intrauterine insemination in cattle].

Introduction: Most of the artificial inseminations in cattle nowadays are being performed in the uterine body with a rigid insemination device. Uterotubal junction insemination can only be performed in cattle with a device which is rigid enough to pass the cervix and flexible enough to follow the curvature of the uterine horns. At the Faculty of Veterinary Medicine in Ghent, a new insemination device has been developed for semen deposition near the utero-tubal junction in cattle and other animals.

Lanthanum carbonate: a new phosphate binder.

Purpose Of Review: Hyperphosphatemia remains an important aspect in the management of end-stage renal disease patients. Consequently, there is a need for new, efficient and well-tolerated phosphate binders. In this review, a new phosphate-binding drug, lanthanum carbonate, with an attractive preclinical efficacy profile compared with existing binders, is discussed.

Intra-uterine insemination in farm animals and humans.

Artificial insemination (AI) is the oldest and currently most common technique in the assisted reproduction of animals and humans. The introduction of AI in farm animals was forced by sanitary reasons and the first large-scale applications with a commercial goal were performed in cattle in the late 1930s of last century. After the Second World War, cryopreservation of semen facilitated distribution and AI was mainly performed for economic reasons, especially in dairy cattle industry.

Effect of blood admixture on in vitro survival of chilled and frozen-thawed canine spermatozoa.

Hematospermia in the dog usually occurs secondary to benign prostatic hypertrophy or trauma of the penis or prepuce during semen collection. Regarding the difficulty of removing blood cells from a hematospermic sample, the present study was performed to determine whether blood contaminated ejaculates can still be chilled (4 degrees C) or frozen (-196 degrees C) without an additional decrease in sperm quality. In the first experiment, blood additions of up to 10% exerted no negative effects on the functional characteristics of canine spermatozoa cooled (4 degrees C) and stored for 4 days in an egg-yolk-Tris extender.

Assessment of a new utero-tubal junction insemination device in dairy cattle.

A new artificial insemination device for semen deposition near the utero-tubal junction in cattle (Ghent device) has been developed at the Ghent University (Belgium). In this study, the effect of the new insemination device on sperm quality was evaluated. Moreover, in a field trial 4064 dairy cows were inseminated by 12 inseminators to examine the efficacy of the device under field conditions.

Effect of whole blood and serum on bovine sperm quality and in vitro fertilization capacity.

Under physiologic conditions, low concentrations of blood may be present in the uterine fluid of the estrous cow at the moment of insemination. To decrease the insemination dose and to obtain good insemination results with less fertile semen, more invasive insemination methods such as utero tubal junction (UTJ) insemination can be used. More invasive insemination methods increase the risk of damaging the hyperemic endometrium, with blood in the uterine fluid as result.

Dose-dependent effects of strontium on osteoblast function and mineralization.

Background: Strontium-ranelate is now being used in the treatment of osteoporosis in elderly patients. As the majority of these patients already have a decreased renal function they are at an increased risk for accumulation of the element. Recent findings from epidemiologic studies in dialysis patients and experimental data obtained in a chronic renal failure (CRF) rat model established a dose-related multiphasic effect of strontium (Sr) on bone formation.