Efficacy of Chondroprotective Food Supplements Based on Collagen Hydrolysate and Compounds Isolated from Marine Organisms

Osteoarthritis belongs to the most common joint diseases in humans and animals and shows increased incidence in older patients. The bioactivities of collagen hydrolysates, sulfated glucosamine and a special fatty acid enriched dog-food were tested in a dog patient study of 52 dogs as potential therapeutic treatment options in early osteoarthritis. Biophysical, biochemical, cell biological and molecular modeling methods support that these well-defined substances may act as effective nutraceuticals. Importantly, the applied collagen hydrolysates as well as sulfated glucosamine residues from marine organisms were strongly supported by both an animal model and molecular modeling of intermolecular interactions. Molecular modeling of predicted interaction dynamics was evaluated for the receptor proteins MMP-3 and ADAMTS-5. These proteins play a prominent role in the maintenance of cartilage health as well as innate and adapted immunity. Nutraceutical data were generated in a veterinary clinical study focusing on mobility and agility. Specifically, key clinical parameter (MMP-3 and TIMP-1) were obtained from blood probes of German shepherd dogs with early osteoarthritis symptoms fed with collagen hydrolysates. Collagen hydrolysate, a chondroprotective food supplement was examined by high resolution NMR experiments. Molecular modeling simulations were used to further characterize the interaction potency of collagen fragments and glucosamines with protein receptor structures. Potential beneficial effects of collagen hydrolysates, sulfated glycans (i.e., sulfated glucosamine from crabs and mussels) and lipids, especially, eicosapentaenoic acid (extracted from fish oil) on biochemical and physiological processes are discussed here in the context of human and veterinary medicine.     

Acute myelogenous leukaemia in a mare

SUMMARY: A 5-year-old Thoroughbred mare presented with a 4 week history of weight loss, fever and leukopenia. Rectally, a large active foetus, thickened spleen and an abdominal mass were palpated. Leukopenia, mild anaemia, marked thrombocytopenia and hyperfibrinogenaemia were found. Cytology and cytochemical staining of a bone marrow aspirate supported a diagnosis of acute myelogenous leukaemia. The mare deteriorated despite medical therapy and was humanely euthanased.     

Regulation of uterine estrogen receptors (ER) by beta-adrenergic stimulation in immature rats

The effects of a 3-day intramuscular (i.m.) administration of clenbuterol (25 μ.g/ Kg), propranolol (12 mg/kg), clenbuterol (25 μg/kg) plus propranolol (12 mg/ Kg) and estradiol (0.5 μg) upon the female reproductive system were investigated in immature Sprague-Dawley rats. Clenbuterol and estradiol treatments induced a significant increase in uterus weight and in relative uterus weight, whereas in the groups treated with propranolol and clenbuterol plus propranolol no differences were detected versus controls. The uterine estrogen receptor levels were significantly increased by clenbuterol administration. In the rats dosed with propranolol and clenbuterol plus propranolol, no modifications occurred in estrogen receptor concentrations when compared with control values. Uterine progesterone receptors were never significantly affected by any of the considered treatments. Data obtained indicate that clenbuterol treatment induces an increase in uterus weight and in estrogen receptor levels and that these effects are regulated by acute beta-adrenergic stimulation, as the contemporaneous administration of high doses of a beta-blocker inhibit such effects.     

The so-called "fox tapeworm"

The so-called "fox tapeworm" (Echinococcus multilocularis), the causative agent of a severe disease in man (alveolar echinococcosis), is presently under public discussion in Switzerland. Therefore, actual information is provided on the life cycle of the parasite, epidemiology, disease in humans, symptomatology, diagnosis, therapy and prophylaxis. It is recommended that in endemic regions hunters handling foxes should wear protective gloves, dead foxes should be transported in plastic bags and wild fruits, berries and vegetables should be carefully washed and--if possible--heated to more than 70 degrees C for some minutes prior to consumption. After contact with foxes or other final hosts (dogs, cats) infected with E. multilocularis, persons should be monitored with the highly sensitive and specific Em2-ELISA for serum antibodies aiming at an early diagnosis and treatment of a potential infection.     

The mechanism of fungistatic action of sec-butylamine: II. The effect of sec-butylamine on pyruvate oxidation by mitochondria of Penicillium digitatum and on the pyruvate dehydrogenase complex

sec-Butylamine at 5 mM inhibited the oxidation of pyruvate by mitochondria isolated from hyphae of Penicillium digitalum, but had little effect on the oxidation of citrate, isocitrate, succinate, malate, acetyl-coenzyme A, or reduced nicotinamide adenine dinucleotide. sec-Butylamine did not interfere with oxidative phosphorylation, as evidenced by similar $\text{P}\text{O}$ ratios in treated and control mitochondria. The pyruvate dehydrogenase complex (EC 1.2.4.1) isolated from young hyphae of P. digitatum was inhibited strongly by 20 mM sec-butylamine, whereas other tricarboxylic acid cycle enzymes were only slightly affected at most. Inhibition of the pyruvate dehydrogenase complex by sec-butylamine was competitive with respect to pyruvate. The K_i for sec-butylamine in the reaction was 1.38 × 10^?2M, and the K_m for pyruvate was 2.28 × 10^?4M. These observations and other evidence derived from studies with intact hyphae support the hypothesis that the pyruvate dehydrogenase complex is the primary site of the fungistatic action of sec-butylamine.     

Pharmacokinetics of intravenous ceftiofur sodium and concentration in body fluids of foals

The objectives of this study were to determine pharmacokinetics of intravenous (i.v.) ceftiofur in foals, to compare ultra-high performance liquid chromatography tandem mass spectometry (UPLC-MS/MS) and microbiologic assay for the measurement of ceftiofur concentrations, and to determine the minimum inhibitory concentration ( MIC ) of ceftiofur against common equine bacterial pathogens. In a cross-over design, ceftiofur sodium was administered i.v. to six foals (1–2 days-of-age and 4–5 weeks-of-age) at dosages of 5 and 10 mg/kg. Subsequently, five doses of ceftiofur were administered i.v. to six additional foals between 1 and 5 days of age at a dose of 5 mg/kg q 12 h. Concentrations of desfuroylceftiofur acetamide (DCA), the acetamide derivative of ceftiofur and desfuroylceftiofur-related metabolites were measured in plasma, synovial fluid, urine, and CSF by use of UPLC-MS/MS. A microbiologic assay was used to measure ceftiofur activity for a subset of plasma samples. Following i.v. administration of ceftiofur at a dose of 5 mg/kg to 1–2 day-old foals, DCA had a t _½ of 7.8 ± 0.1 h, a body clearance of 74.4 ± 8.4 mL/h/kg, and an apparent volume of distribution of 0.83 ± 0.09 L/kg. After multiple i.v. doses at 5 mg/kg, DCA concentrations in CSF were significantly lower than concurrent plasma concentrations. Ceftiofur activity using a microbiologic assay significantly underestimated plasma concentrations of DCA. The MIC of ceftiofur required to inhibit growth of 90% of isolates of Escherichia coli , Pasteurella spp, Klebsiella spp, and β-hemolytic streptococci was <0.5 μg/mL. Intravenous administration of ceftiofur sodium at the rate of 5 mg/kg every 12 h would provide sufficient coverage for the treatment of susceptible bacterial isolates.     

Haycocknema-like nematodes in muscle fibres of a horse

A 14-year-old horse (imported to Switzerland from Ireland 8 years earlier) showed signs of chewing muscle atrophy. A severe chronic myositis, caused by numerous immature and mature female nematodes, was diagnosed in muscle samples obtained by biopsy and subsequently at necropsy. Most of the nematodes had invaded muscle fibres of the masseter, root of the tongue and anterior breast, only a few were found in the intermuscular interstitium. Isolated nematodes and parasite sections were clearly different from muscle larvae of Trichinella spp. but showed morphological similarities to Haycocknema perplexum, a nematode species (order Enoplida, family Robertdollfusidae) recently found in the musculature of a human patient in Australia. However, our material did not allow the precise identification of the nematode genus nor the unequivocal differentiation from Halicephalobus gingivalis. This species infects horses and humans and can cause severe granuloma formation in muscles and many other organ systems, but has never been observed to invade individual muscle fibres. Our findings show that nematodes of another genus than Trichinella may invade muscle fibres of the horse and cause myositis. These nematodes are provisionally regarded as Haycocknema-like.