RESUMEN
The objective of this study was to illuminate the changes in serum NEFA concentrations during a combined glucose-insulin test (CGIT) and basal serum triacylglycerides (TGs) with increasing BW in Shetland ponies and warmblood horses. Therefore, basal blood samples were taken during fasting and a CGIT was performed in 19 healthy equines (10 Shetland ponies, 9 warmblood horses) (t0). After one (t1) and two (t2) year(s) of receiving 200% of their maintenance metabolizable energy requirement, procedures were repeated in the same equines. Sixteen of 19 equines had no signs of insulin dysregulation confirmed by CGIT. Basal plasma glucose concentrations increased in ponies (P = 0.001) when comparing t0 and t2, and basal serum insulin concentrations increased in ponies (P = 0.009) and horses (P = 0.024) from t0 to t2. Basal serum NEFA concentrations increased in ponies comparing t0 and t2 (P = 0.01). During CGIT, NEFA levels dropped until reaching a nadir and subsequently recovered until reaching basal concentrations. The minimum serum NEFA value did not change over time in ponies or horses. However, a strong correlation between basal serum NEFA concentrations and the percentage drop to minimum NEFA levels was found in ponies. Two of three equines (one horse and one pony) graded as insulin-dysregulated suffered from laminitis at t2. The serum NEFA concentrations of these animals had a delay in recovery of the minimum NEFA levels. Basal serum TG levels did not change with BW gain, and no breed differences were observed. In conclusion, serum NEFA concentrations are useful parameters during CGIT to detect insulin dysregulation in equines. Thus, further investigation should be focused on lipid metabolism during insulin dysregulation.
Asunto(s)
Enfermedades de los Caballos/metabolismo , Insulina/metabolismo , Metabolismo de los Lípidos/fisiología , Obesidad/veterinaria , Animales , Glucemia , Ácidos Grasos no Esterificados/sangre , Ácidos Grasos no Esterificados/metabolismo , Glucosa/administración & dosificación , Glucosa/metabolismo , Caballos , Masculino , Obesidad/metabolismoRESUMEN
BACKGROUND: Mesenchymal stromal cells (MSC) have shown promising results in the treatment of tendinopathy in equine medicine, making this therapeutic approach seem favorable for translation to human medicine. Having demonstrated that MSC engraft within the tendon lesions after local injection in an equine model, we hypothesized that they would improve tendon healing superior to serum injection alone. METHODS: Quadrilateral tendon lesions were induced in six horses by mechanical tissue disruption combined with collagenase application 3 weeks before treatment. Adipose-derived MSC suspended in serum or serum alone were then injected intralesionally. Clinical examinations, ultrasound and magnetic resonance imaging were performed over 24 weeks. Tendon biopsies for histological assessment were taken from the hindlimbs 3 weeks after treatment. Horses were sacrificed after 24 weeks and forelimb tendons were subjected to macroscopic and histological examination as well as analysis of musculoskeletal marker expression. RESULTS: Tendons injected with MSC showed a transient increase in inflammation and lesion size, as indicated by clinical and imaging parameters between week 3 and 6 (p < 0.05). Thereafter, symptoms decreased in both groups and, except that in MSC-treated tendons, mean lesion signal intensity as seen in T2w magnetic resonance imaging and cellularity as seen in the histology (p < 0.05) were lower, no major differences could be found at week 24. CONCLUSIONS: These data suggest that MSC have influenced the inflammatory reaction in a way not described in tendinopathy studies before. However, at the endpoint of the current study, 24 weeks after treatment, no distinct improvement was observed in MSC-treated tendons compared to the serum-injected controls. Future studies are necessary to elucidate whether and under which conditions MSC are beneficial for tendon healing before translation into human medicine.
Asunto(s)
Modelos Animales de Enfermedad , Trasplante de Células Madre Mesenquimatosas/métodos , Suero , Tendinopatía/diagnóstico por imagen , Tendinopatía/terapia , Animales , Células Cultivadas , Femenino , Estudios de Seguimiento , Caballos , Masculino , Trasplante de Células Madre Mesenquimatosas/tendenciasRESUMEN
Stem cells play an important role in veterinary medicine in different ways. Currently several stem cell therapies for animal patients are being developed and some, like the treatment of equine tendinopathies with mesenchymal stem cells (MSCs), have already successfully entered the market. Moreover, animal models are widely used to study the properties and potential of stem cells for possible future applications in human medicine. Therefore, in the young and emerging field of stem cell research, human and veterinary medicine are intrinsically tied to one another. Many of the pioneering innovations in the field of stem cell research are achieved by cooperating teams of human and veterinary medical scientists.Embryonic stem (ES) cell research, for instance, is mainly performed in animals. Key feature of ES cells is their potential to contribute to any tissue type of the body (Reed and Johnson, J Cell Physiol 215:329-336, 2008). ES cells are capable of self-renewal and thus have the inherent potential for exceptionally prolonged culture (up to 1-2 years). So far, ES cells have been recovered and maintained from non-human primate, mouse (Fortier, Vet Surg 34:415-423, 2005) and horse blastocysts (Guest and Allen, Stem Cells Dev 16:789-796, 2007). In addition, bovine ES cells have been grown in primary culture and there are several reports of ES cells derived from mink, rat, rabbit, chicken and pigs (Fortier, Vet Surg 34:415-423, 2005). However, clinical applications of ES cells are not possible yet, due to their in vivo teratogenic degeneration. The potential to form a teratoma consisting of tissues from all three germ lines even serves as a definitive in vivo test for ES cells.Stem cells obtained from any postnatal organism are defined as adult stem cells. Adult haematopoietic and MSCs, which can easily be recovered from extra embryonic or adult tissues, possess a more limited plasticity than their embryonic counterparts (Reed and Johnson, J Cell Physiol 215:329-336, 2008). It is believed that these stem cells serve as cell source to maintain tissue and organ mass during normal cell turnover in adult individuals. Therefore, the focus of attention in veterinary science is currently drawn to adult stem cells and their potential in regenerative medicine. Also experience gained from the treatment of animal patients provides valuable information for human medicine and serves as precursor to future stem cell use in human medicine.Compared to human medicine, haematopoietic stem cells only play a minor role in veterinary medicine because medical conditions requiring myeloablative chemotherapy followed by haematopoietic stem cell induced recovery of the immune system are relatively rare and usually not being treated for monetary as well as animal welfare reasons.In contrast, regenerative medicine utilising MSCs for the treatment of acute injuries as well as chronic disorders is gradually turning into clinical routine. Therefore, MSCs from either extra embryonic or adult tissues are in the focus of attention in veterinary medicine and research. Hence the purpose of this chapter is to offer an overview on basic science and clinical application of MSCs in veterinary medicine.
Asunto(s)
Enfermedades de los Animales/patología , Enfermedades de los Animales/cirugía , Trasplante de Células Madre/métodos , Trasplante de Células Madre/veterinaria , Células Madre/citología , Células Madre/fisiología , Ingeniería de Tejidos/métodos , Animales , Técnicas de Cultivo de Célula/métodos , Diferenciación Celular/fisiología , Proliferación Celular , Células Cultivadas , HumanosRESUMEN
N-terminal chain extension of unprotected amino acid amides and peptides with dipeptide amides using Cathepsin C (dipeptidyl aminopeptidase I, EC 3.4.14.1)-mediated reverse proteolysis in water was studied. Taking Pro-X-NH2 as the acyl donor, the sensitivity of the kinetically controlled peptide, coupling to pH value, temperature, acetonitrile addition, and nucleophile type were investigated. Basic or hydrophobic amino acids as the alpha-amino-N-nucleophile proved to be much more prone to catalyzed bond formation than their neutral, hydrophilic, or negatively charged analogues. In a preparative run a pentapeptide was obtained with 83% yield by directed and regioselective coupling of ProTrpNH2 with LysLeuPheNH2 catalyzed by Cathepsin C in aqueous buffer.