RESUMO
Many cells and their cytokines produce a significant effect on bone metabolism. Bone matrix synthesis is a function of the osteoblast (Fig 1), influenced directly by numerous local and systemic factors (Tables 1 and 2). Locally synthesized factors such as SGF, BMP, and BDGF may be particularly important in stimulating new bone formation at sites of bone resorption or following bony injury. Of the systemic factors, GH; somatomedin C (IGF-1); high concentrations of insulin, testosterone, PDGF and TGF beta; and low concentrations of PGE2 and IL-1 appear to stimulate bone formation in vitro. These latter factors may be more important in maintaining skeletal growth and bone mass. Bone resorption by osteoclasts (Figs 2 and 3) is also controlled by the osteoblast, as this cell produces a leukotriene-dependent polypeptide that stimulates osteoclastic bone resorption. Osteoblasts cover the periosteal and endosteal bone-surfaces and limit exposure of the underlying bone to osteoclasts. PTH, vitamin D, PGE2, and other systemic factors interact directly with the osteoblast, not the osteoclast. Surface receptor binding of PTH increases intracellular cAMP and calcium and results in release of the factor that stimulates osteoclastic bone resorption. PGE2 induces osteoblasts to activate osteoclasts and is a major controlling factor in bone metabolism; the osteoblast produces PGE2, which can then modify osteoblastic function by positive feedback. Although low concentrations of PGE2 stimulate bone formation, higher concentrations promote osteoblast-mediated bone resorption. Furthermore, many of the systemic factors stimulate bone resorption via a PGE2-associated mechanism. Immune cytokines also appear to exert a profound influence on bone metabolism. INF-gamma inhibits osteoclastic resorption, whereas IL-1, TNF, and LT strongly stimulate bone resorption. However, low concentrations of IL-1 paradoxically result in stimulation of bone formation. These cytokines, particularly in various combinations, may prove extremely important in understanding and treating the bone loss associated with malignancies, osteoporosis, and rheumatoid arthritis.
Assuntos
Osso e Ossos/metabolismo , Animais , Fatores Biológicos/fisiologia , Osso e Ossos/citologia , Osso e Ossos/imunologia , Substâncias de Crescimento/fisiologia , Hormônios/fisiologia , Humanos , Linfocinas/fisiologia , Ativação de Macrófagos , Minerais/fisiologia , Monocinas , Prostaglandinas/fisiologiaRESUMO
A blind, placebo-controlled study evaluated the effects of ursodeoxycholic acid (UDCA) given orally, at a dose of 15 mg kg-1 per day for eight weeks, on the physical condition, haematological and serum biochemical profiles, urinalysis, total serum bile acids (TSBA) and hepatic histology of four healthy cats. There were no clinically important significant differences between the groups or within the treatment groups in clinicopathological parameters. TSBA concentrations or histology. A significant lower concentration/proportion of taurochenodeoxycholic acid was observed in the treated cats (P = 0.05). Only one treated cat accumulated measurable quantities of UDCA, and the compound appeared to be non-toxic. It did not increase the concentration of TSBA, and accumulated minimally in the serum. It should be investigated for therapeutic use in cats with hepatobiliary disease.
Assuntos
Ácidos e Sais Biliares/sangue , Fígado/efeitos dos fármacos , Ácido Ursodesoxicólico/farmacologia , Administração Oral , Animais , Gatos , Eletrólitos/sangue , Feminino , Fígado/citologia , Fígado/ultraestrutura , Testes de Função Hepática , Masculino , Valores de Referência , Ácido Ursodesoxicólico/administração & dosagemRESUMO
The efficacy, safety, and metabolic consequences of rapid weight loss in privately owned obese cats by means of a canned weight-reduction diet and the influence of orally administered L-carnitine on rate of weight loss, routine clinical evaluations, hepatic ultrasonography, plasma amino acid profiles, and carnitine analytes were evaluated. A double-blinded placebo-controlled design was used with cats randomly divided into 2 groups: Group 1 (n = 14) received L-carnitine (250 mg PO q24h) in aqueous solution and group 2 (n = 10) received an identical-appearing water placebo. Median obesity (body condition scores and percentage ideal body weight) in each group was 25%. Caloric intake was restricted to 60% of maintenance energy requirements (60 kcal/kg) for targeted ideal weight. The reducing formula was readily accepted by all cats. Significant weight loss was achieved by week 18 in each group without adverse effects (group 1 = 23.7%, group 2 = 19.6%). Cats receiving carnitine lost weight at a significantly faster rate (P < .05). Significant increases in carnitine values developed in each group (P < .02). However, significantly higher concentrations of all carnitine moieties and a greater percentage of acetylcarnitine developed in cats of group 1 (P < .01). The dietary formula and described reducing strategy can safely achieve a 20% weight reduction within 18 weeks in obese cats. An aqueous solution of L-carnitine (250 mg PO q12h) was at least partially absorbed, was nontoxic, and significantly increased plasma carnitine analyte concentrations as well as rate of weight loss.
Assuntos
Carnitina/administração & dosagem , Doenças do Gato/dietoterapia , Dieta Redutora/veterinária , Obesidade/veterinária , Redução de Peso , Ácido 3-Hidroxibutírico/sangue , Abdome/fisiologia , Aminoácidos/sangue , Ração Animal , Animais , Animais Domésticos , Disponibilidade Biológica , Análise Química do Sangue/veterinária , Carnitina/sangue , Carnitina/farmacocinética , Doenças do Gato/metabolismo , Gatos , Suplementos Nutricionais , Método Duplo-Cego , Ingestão de Alimentos , Feminino , Fígado/diagnóstico por imagem , Masculino , Obesidade/dietoterapia , Obesidade/metabolismo , Espectrometria de Massas de Bombardeamento Rápido de Átomos/veterinária , Estatísticas não Paramétricas , UltrassonografiaRESUMO
The effects of human monokines on calcium release from cultured newborn murine calvarium were studied. Highly purified interleukin 1 (IL-1) (17 kDa) and recombinant IL-1 beta in the concentration range 0.2-20 U/ml released significant amounts of calcium. Mean resorption indices (RI) at 0.2 U/ml were 1.28 and 1.49, and at 20 U/ml, were 1.82 and 1.72, respectively. Calcium release was abrogated by the cyclooxygenase inhibitor piroxicam. Thymocyte stimulating activity (TSA) 25-31 kDa alone at 0.14 U/ml released calcium in a prostaglandin dependent manner with a mean RI of 2.13, a significantly greater calcium release than that obtained by 17 kDa IL-1 at 20 U/ml. The 6-9 kDa inhibitor of IL-1 induced thymocyte proliferation alone also released calcium in a prostaglandin dependent manner with a mean RI of 2.29 at 200 inhibitory U/ml. Addition of 6-9 kDa IL-1 inhibitor to the 25-31 kDa material did not significantly change the calcium release, whereas addition of the inhibitor to 17 kDa IL-1 produced a significant increase in calcium release.
Assuntos
Animais Recém-Nascidos/metabolismo , Cálcio/metabolismo , Interleucina-1/farmacologia , Monocinas/farmacologia , Peptídeos/farmacologia , Crânio/citologia , Animais , Radioisótopos de Cálcio , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/farmacologia , Feminino , Interleucina-1/antagonistas & inibidores , Camundongos , Gravidez , Prostaglandinas/fisiologia , Proteínas Recombinantes/farmacologia , Crânio/efeitos dos fármacos , Crânio/metabolismo , Timo/citologia , Timo/efeitos dos fármacos , Timo/metabolismoRESUMO
To determine whether hypocellular MDS differs from normo/hypercellular MDS, we attempted to identify hypocellular MDS cases either by correcting the bone marrow (BM) cellularity by age (28 patients) or by using a single arbitrary value of BM cellularity (25 patients) and compared these two groups of hypocellular cases to the normo/hypercellular MDS cases (72 patients). 18 patients were common to both hypocellular groups. Patients with hypocellular MDS in both of these selected groups have similar features with regard to age and sex distribution, peripheral blood and bone marrow parameters, FAB subtypes, karyotypes, leukaemic transformation, and survival. However, the median age of patients in < 30% BM cellularity group was higher than those patients in the age-corrected group (69 years v 62 years). The selection of < 30% cellularity excluded 10 cases in the age group < 70 years but included another seven patients in the age group of > 70 years. However, correction of BM cellularity by age revealed that those included patients (selected for < 30% cellularity) who had normocellular BM by their age. Therefore we recommend the age-correcting grouping to ensure comparable series for comparison, for response to treatment, and survival. Finally, BM cellularity does not appear to be an important factor on prognosis in MDS, because patients with hypocellular MDS in both selected groups have similar prognosis to those with normo/hypercellular MDS patients.