Prevalence of radiographic changes in forelimb digits and metacarpophalangeal joints of South African endurance racehorses.

Background: If the number of events alone is considered, endurance riding is the fastest growing and the second-most popular Fédération Equestre Internationale (FEI) discipline. Lameness is the most common cause of elimination from endurance races worldwide. To the authors' knowledge, no studies have been published investigating the prevalence of radiographic changes in the forelimb digits and metacarpophalangeal joints (MCP) of endurance racehorses in South Africa. Objective: Investigate the prevalence of radiographic changes in the forelimb digits and MCP joints of South African endurance racehorses. Method: One hundred endurance racehorses registered with ERASA were volunteered by their owners to partake in the current study. Radiographs were obtained from horses competing in endurance races during the 2018-2019 endurance racing season. Radiographs included seven standard views of each distal forelimb. Radiographic images were independently evaluated by three observers, point prevalence and inter-rater reliability (IRR) was calculated. Results: Data analysis of the forelimb digits revealed a large proportion of horses with bilateral signs of dorsopalmar hoof imbalance (95%); a diversion from a straight digital axis (91%), with an extended (broken back) proximal interphalangeal joint (67%) being the most common abnormality. Osteoarthritis of the proximal (16%) and distal (7%) interphalangeal joints was only observed in a low percentage of horses. Interestingly, the hoof-distal-phalanx-ratio of the majority (86%) of horses was more than 25% but none of these horses showed any other signs of chronic laminitis, indicating that hoof-distal-phalanx-ratio might not be a reliable indicator of chronic laminitis in this population of horses. Ossification of the ungular cartilages was observed in the majority (69%) of horses, either affecting one or both distal phalanges. Descriptive data analysis of the MCP joints showed that a large proportion of horses displayed radiological signs of MCP joint osteoarthritis (28%), with 10% being bilateral. Conclusions and clinical relevance: The current study provides insight into radiographic changes and their prevalence in the distal front limbs of South African endurance racehorses. Knowledge about the prevalence of specific radiographic changes would enable equine practitioners to better evaluate and manage horses that are affected. Although no correlations were made with age, speed or number of competitive kilometres competed, the current study may serve as a basis for future research.

Glycogen synthase kinase-3ß is a crucial mediator of signal-induced RelB degradation.

The immediate early transcription factor nuclear factor (IκBs) kappa B (NF-κB) is crucially involved in the regulation of numerous physiological or pathophysiological processes such as inflammation and tumourigenesis. Therefore, the control of NF-κB activity, which is mainly regulated by signal-induced degradation of cytoplasmic inhibitors of NF-κB (IκBs), is of high relevance. One known alternative pathway of NF-κB regulation is the stimulus-induced proteasomal degradation of RelB, a component of the NF-κB dimer. Here, we identified the serine/threonine protein kinase glycogen synthase kinase-3ß (GSK-3ß) as a critical signalling component leading to RelB degradation. In Jurkat leukaemic T cells as well as in primary human T cells, tetradecanoylphorbolacetate/ionomycin- and CD3/CD28-induced RelB degradation were impaired by a GSK-3ß-specific pharmacological inhibitor, an ectopically expressed dominant-negative GSK-3ß mutant and by small-interfering RNA-mediated silencing of GSK-3ß expression. Furthermore, a physical interaction between RelB and GSK-3ß was shown by co-immunoprecipitation, which was already notable in unstimulated cells. Most importantly, as demonstrated by in vitro kinase assays, human RelB is inducibly phosphorylated by GSK-3ß, indicating a direct substrate-enzyme relationship. The serine residue 552 is a target of GSK-3ß-mediated phosphorylation in vitro and in vivo. We conclude that GSK-3ß is a crucial regulator of RelB degradation, stressing the relevant linkage between the NF-κB system and GSK-3ß.

Desenvolvimento pós-natal e potencial teratogênico da prole de ratos Wistar no estudo da toxicidade reprodutiva de duas preparações fitoterápicas contendo soja Glycine max (L) Merr / Neonatal development and teratogenic potential of Wistar rats offspring in the study of reproductive toxicity of two commercial phytotherapic preparations with soy Glycine max (L) Merr

Avaliou-se o efeito de duas preparações fitoterápicas comerciais que continham soja sobre o desenvolvimento geral e sexual da progênie de ratos Wistar e sobre o potencial teratogênico das preparações fitoterápicas durante um estudo de toxicidade reprodutiva. Para tanto, observaram-se, diariamente, as características de desenvolvimento dos filhotes e analisou-se o comportamento em campo aberto, e, para avaliar o potencial teratogênico, realizou-se diafanização dos fetos removidos por cesariana. Inferiu-se que o tratamento dos pais não comprometeu o desenvolvimento de sua progênie e também não determinou efeitos teratogênicos aos fetos de ratos Wistar.

The effect of two commercial phytotherapic preparations containing soy was evaluated on the general and sexual development of Wistar rats offspring and on the teratogenic potential during a reproductive toxicity study. For this, the offspring development characteristics were daily observed, and the behavior in open field was studied. To assess the teratogenic potential, diaphanization of the fetuses removed by caesarean section was done. It was concluded that the treatment of the parents did not compromise the development of their progeny and also did not determine the teratogenic effects in the fetuses.

Rapid and sensitive determination of catecholamines and the metabolite 3-methoxy-4-hydroxyphen-ethyleneglycol using HPLC following novel extraction procedures.

In the present study assays were improved for the determination of free catecholamines and 3-methoxy-4-hydroxyphenethyleneglycol (MHPG), the major metabolite of peripheral and central noradrenaline. The compounds were extracted by a fluid phase extraction: a diphenyl boric acid method for the purification of catecholamines and an ethyl acetate extraction for MHPG were used, respectively. High-performance liquid chromatography with electrochemical detection was employed for quantitative analysis. In previous studies, significant differences between plasma concentrations of these substances in normal volunteers and hospital patients were demonstrated. Therefore, we established valid reference values for a hospital population. Blood and urine samples of 59 patients without disorders and medication affecting catecholamine synthesis and metabolism or the activity of the sympatho-adrenal system were collected and analyzed for free and total (free plus conjugated) MHPG, noradrenaline (NA), adrenaline (A) and dopamine (DA); total MHPG was assayed after enzymatic hydrolysis of conjugates. Our data clearly demonstrate that these methods are sensitive, specific, rapid, and can easily be standardized. The intra- and inter-assay precision were high (CV 2.6-5.3% and 4.3-6.9% for plasma, CV 3.8-4.9% and 5.1-8.2% for urine, respectively). For plasma, the mean concentrations +/- SD were determined to be 20.82+/-4.70 pmol/ml for free MHPG, 68.43+/-16.21 pmol/ml for total MHPG, 2.11+/-0.24 pmol/ml for NA and 0.31+/-0.08 pmol/ml for A. For 24h-urine the mean concentrations +/-SD were determined to be 0.44+/-0.13 mmol/24h for free MHPG, 8.79+/-2.13 mmol/24h for total MHPG, 169.8+/-58.25 nmol/24h for NA, 62.19+/-21.79 nmol/24h for A and 757.2+/-382.6 nmol/24h for DA. In summary, these novel and rapid methods can clearly be employed in a routine clinical setting.

Confirmation of an association between a polymorphism in exon 3 of the low-density lipoprotein receptor-related protein gene and Alzheimer's disease.

C766T, a polymorphism in exon 3 of the gene for the low-density lipoprotein receptor-related protein (LRP), was found to be associated with late-onset Alzheimer's disease (AD). We developed a PCR-restriction enzyme-based assay to analyze this allele in 234 AD patients and 103 controls. We confirmed that the LRP C766T polymorphism was in disequilibrium with AD--the C/C genotype was present in 76% of AD patients and 60% of controls (p < 0.01); however, the LRP polymorphism did not influence age at onset of AD.

Analysis of liver tissue for olestra following long-term feeding to rats and monkeys.

The potential for olestra to be absorbed and to accumulate in tissues was investigated by analysing liver tissue from rats and monkeys in long-term feeding studies using sensitive chromatographic methods. Studies with intravenously administered olestra indicated that absorbed olestra is predominantly taken up by the liver. In monkeys, 74% of the injected dose was detected in the liver, as intact olestra, 48 hr after dosing. In rats, 58-96% of the injected dose was found in the liver, as intact olestra, within 24 hr. No olestra was detected (limit, 34 micrograms/g) in the livers of 14 monkeys fed olestra at 8% of the diet for 29 months. Also, no olestra was found in samples of liver, heart, kidney, spleen, lymph nodes and adipose tissues from 26 monkeys fed olestra at 0, 2, 4 or 6% of the diet, in random order, for consecutive 2-month periods. No olestra was detected in the livers of 47 out of 50 rats fed olestra at levels of up to 9% of the diet for up to 2 years. The amounts (2-4 micrograms/g) detected in the other three rats were near the detection limit of the chromatographic method (1.6 micrograms/g). The results show that accumulation of olestra in the liver, the primary target organ for absorbed olestra, was less than 3 x 10(-6)% of the total amount eaten by rats over 24 months and less than 4 x 10(-5)% of the amount eaten by monkeys over 29 months. These results are consistent with previous studies which showed that olestra is essentially not absorbed from the gastro-intestinal tract.

Isomeric fatty acids and tumorigenesis: a commentary on recent work.

This article critically reviews the existing, although limited, literature concerning trans fatty acids and tumorigenesis. Neither epidemiological nor experimental studies published to date have demonstrated any valid association between trans fatty acid ingestion and tumorigenesis. A recent study showed that under controlled conditions, a fat with a high content of trans fatty acids did not promote the development of mammary tumors induced in rats by 7,12-dimethylbenz[a]anthracene to any greater extent than did a comparable fat with a high content of cis fatty acids. In addition, in this study a high trans fat was less tumor promoting than was a blend of fats that simulated the dietary fat composition of the United States and had a lower level of trans fatty acids. Another study using comparable cis and trans fats demonstrated that the high trans fat did not affect the growth and metastasis of implanted mammary tumors in mice relative to the high cis fat. Also, two recent studies reported no significant difference in the development of induced colon tumors in rats fed diets high in cis or trans fatty acids. The results of these and other studies are consistent with the conclusion that trans fatty acids are not uniquely related to tumor development.

Sucrose polyester and covert caloric dilution.

Total daily caloric intake was measured in 10 obese subjects when sucrose polyester (SPE), a nonabsorbable synthetic fat, covertly replaced conventional fats in a single crossover study consisting of three periods: a period of 7 to 14 days to determine baseline caloric intake and two 20-day study periods. An average of 60 g SPE/day replaced conventional fat in one of the two study periods. During both study periods, 60% of the base line caloric intake was "required intake" at mealtime; an additional 60% of base line caloric intake was allowed as "free choice" foods at a specified snacktime. It was thus possible during both study periods to consume more than 100% of the base line caloric intake. In the SPE study period, 40 g SPE replaced 40 g conventional fat for every 1200 kcal of required intake, resulting in a 30% reduction in mealtime caloric intake. Mean total caloric intake (meal and snack) fell 23% during the SPE period (p less than 0.05), despite an average daily weight loss of 0.18 kg. Snack caloric intake did not increase significantly to compensate for caloric dilution of the meals during the SPE period. These results indicate that the obese may not detect or may not compensate for covert dilution of fat calories with SPE. In addition, during the SPE period, there was a 10% reduction in total plasma cholesterol, a 14% reduction in low-density lipoprotein cholesterol, and a 10% reduction in triglyceride concentration. Thus, fat replacement with SPE may benefit weight reduction regimens in obese subjects by facilitating decreased caloric intake and by improving the circulating lipoprotein profile as well.

The effect of a non-absorbable fat, sucrose polyester, on the metabolism of vitamin A by the rat.

Sucrose polyester (SPE) is a fat-like material that is not absorbed. The effect of this material on vitamin A metabolism was determined by measuring the amount of the vitamin that was stored in the liver of rats following the ingestion of a known amount of vitamin A. In one study, the vitamin A was administered as an oral dose in a vehicle consisting of various proportions of cottonseed oil and SPE. Each 1% replacement of cottonseed oil by SPE resulted in a 0.26% decrease in the amount of vitamin A found in the liver. In the second study, the vitamin A was incorporated into diets in which the fat component consisted of various proportions of cottonseed oil and SPE. When these diets were consumed for 1 week, each 1% replacement of cottonseed oil by SPE resulted in a 0.84% decrease in the storage of vitamin A by the liver. It is proposed that in the lumen of the intestine vitamin A distributes between the customary micellar phase and the unhydrolyzed oil phase of SPE. The vitamin A in this latter phase is eliminated in the feces.

Effect of hydrogenated fat on the plasma cholesterol and triglyceride levels of man.

A group of 33 adult males was fed for 21 days a formula diet that supplied 38 per cent of their calories as fat. The fatty acid composition of the diet was 25 per cent saturates, 16 per cent polyunsaturates and 58 per cent monounsaturates. All of the unsaturated acids were in the cis configuration. The subjects were then divided into two groups. One group of 17 men continued on the same diet. In the diet of the remaining subjects, 80 per cent of the dietary fat was replaced with a hydrogenated fat. Over 60 per cent of the monounstaurated acids and approximately one-half of the polyunsaturated acids of the diet of this latter group were in the trans configuration. Except for the presence or absence of trans acids, the fatty acid intakes of the two groups were the same. Over the 4-week period that the two diets were consumed, the group receiving the hydrogenated fat showed no change in plasma cholesterol or triglyceride levels relative to the subjects consuming the unhydrogenated fat. It is concluded that the effect of a hydrogenated fat on blood lipid level is determined by its fatty acid composition and this effect is not altered by the isomeric form of the unsaturated acids.