16α-Bromoepiandrosterone as a new candidate for experimental diabetes-tuberculosis co-morbidity treatment.

Tuberculosis (TB) is the leading cause of death from a single bacterial infectious agent and is one of the most relevant issues of public health. Another pandemic disease is type II diabetes mellitus (T2D) that is estimated to affect half a billion people in the world. T2D is directly associated with obesity and a sedentary lifestyle and is frequently associated with immunosuppression. Immune dysfunction induced by hyperglycemia increases infection frequency and severity. Thus, in developing countries the T2D/TB co-morbidity is frequent and represents one of the most significant challenges for the health-care systems. Several immunoendocrine abnormalities are occurring during the chronic phase of both diseases, such as high extra-adrenal production of active glucocorticoids (GCs) by the activity of 11-ß-hydroxysteroid dehydrogenase type 1 (11-ßHSD1). 11-ßHSD1 catalyzes the conversion of inactive cortisone to active cortisol or corticosterone in lungs and liver, while 11-ß-hydroxysteroid dehydrogenase type 2 (11-ßHSD2) has the opposite effect. Active GCs have been related to insulin resistance and suppression of Th1 responses, which are deleterious factors in both T2D and TB. The anabolic adrenal hormone dehydroepiandrosterone (DHEA) exerts antagonistic effects on GC signaling in immune cells and metabolic tissues; however, its anabolic effects prohibit its use to treat immunoendocrine diseases. 16α-bromoepiandrosterone (BEA) is a water miscible synthetic sterol related to DHEA that lacks an anabolic effect while amplifying the immune and metabolic properties with important potential therapeutic uses. In this work, we compared the expression of 11-ßHSD1 and the therapeutic efficacy of BEA in diabetic mice infected with tuberculosis (TB) (T2D/TB) with respect to non-diabetic TB-infected mice (TB). T2D was induced by feeding mice with a high-fat diet and administering a single low-dose of streptozotocin. After 4 weeks of T2D establishment, mice were infected intratracheally with a high-dose of Mycobacterium tuberculosis strain H37Rv. Then, mice were treated with BEA three times a week by subcutaneous and intratracheal routes. Infection with TB increased the expression of 11-ßHSD1 and corticosterone in the lungs and liver of both T2D/TB and TB mice; however, T2D/TB mice developed a more severe lung disease than TB mice. In comparison with untreated animals, BEA decreased GC and 11-ßHSD1 expression while increasing 11-ßHSD2 expression. These molecular effects of BEA were associated with a reduction in hyperglycemia and liver steatosis, lower lung bacillary loads and pneumonia. These results uphold BEA as a promising effective therapy for the T2D/TB co-morbidity.

Effects of slow-release urea on in vitro rumen fermentation parameters, growth performance, nutrient digestibility and serum metabolites of beef cattle / Efeitos da uréia de liberação lenta nos parâmetros de fermentaçãono do rúmen em vitro, desempenho de crescimento, digestibilidade dos nutrientes e metabolitos séricos de gado de corte

Two experiments were conducted to investigate the effects of slow-release urea (SRU) on in vitro rumen fermentation parameters, growth performances, nutrient digestibility, and serum metabolites of beef cattle. The single factor design was applied in both experiments. Three diets with different nitrogen sources including soybean meal (Control group), slow-release urea (SRU group), and common urea (Urea group) was designed (concentrate to forage ratio was 4:6). The diets were formulated to be isoenergetic and isonitrogenous, 75% of the soybean meal in the control diet was replaced by 1.41% SRU and 1.15% urea in SRU group and Urea group, respectively. In experiment 1, five healthy Jinjiang cattle (average body weight (BW) was 380 ± 17.1 kg) with permanent rumen fistulas were used in in vitro ruminal fermentation experiment. The results showed that supplementing SRU increased the dry matter degradation rate (DMD), digestible organic matter (DOM) and propionic acid concentration in cultivated fluid, and SRU supplementation decreased pH, NH3 -N, total volatile fatty acid (TVFA), acetic acid, butyric acid concentration and microbial growth efficiency (MOEFF) in cultivated fluid. In experiment 2, eighteen Simmental crossbred cattle BW= 315 ± 5.2 kg) were stratified by BW and then assigned to the three groups to have equal BW among groups. The results showed that supplementing SRU reduced the average dry matter intake (ADMI), apparent digestibility of ether extract (EE), the activity of glutathione peroxidase (GSH-Px), the levels of IgG and IgA, and the production of thiiodothronine (T3) in serum, SRU supplementation increased the apparent digestibility of dry matter and organic matter (OM) and alanine aminotransferase (ALT) concentration in serum. These results indicated that some soybean meal could be replaced by SRU and urea in the production of beef cattle. In addition, compared with urea, SRU had a good sustained-release effect. The replacement of some soybean meal by SRU in the diet had no adverse impact on rumen fermentation, growth performance, and serum metabolites of beef cattle.(AU)

Os dois experimentos foram conduzidos para investigar os efeitos da uréia de liberação lenta nos parâmetros de fermentaçãono do rúmen em vitro, desempenho de crescimento, digestibilidade dos nutrientes e metabolitos séricos de gado de corte. O design de fator único foi aplicado em ambos os experimentos. As três dietas com diferentes fontes de nitrogênio, incluindo farelo de soja (Grupo de controle), uréia de liberação lenta (Grupo de uréia de liberação lenta) e uréia comum (Grupo de uréia) foi designado (concentre-se em relação forrageira foi de 4: 6). As dietas foram formuladas para serem isoenergéticas e isonitrógenas, 75% da farinha de soja na dieta controle foi substituída por 1,41% de uréia de liberação lenta e 1,15% de uréia no Grupo uréia de liberação lenta e Grupo uréia, respectivamente. No experimento 1, cinco gados Jinjiang saudáveis (peso corporal médio (PC) de 380 ± 17,1 kg) com fístulas ruminais permanentes foram utilizadas no experimento de fermentação do rúmen em vitro. Os resultados mostraram que a suplementação de uréia de liberação lenta aumentou a taxa de degradação da substância seca, substância orgânica digestível e concentração de ácido propiônico no líquido cultivado, e a suplementação de SRU diminuiu o pH, NH3-N, ácido graxo volátil total, ácido acético, concentração de ácido butírico e eficiência de crescimento microbiano no fluido cultivado. No experimento 2, dezoito gados mestiços Simmental (PC = 315 ± 5,2 kg) foram estratificados por PC e, em seguida, atribuído aos três grupos para ter PC igual entre os grupos. Os resultados mostraram que a suplementação de uréia de liberação lenta reduziu a ingestão média da substância seca, digestibilidade aparente do extrato etéreo, a atividade da glutationa peroxidase, os níveis de IgG e IgA, e a produção de tiiodotronina (T3) no soro, a suplementação de uréia de liberação lenta aumentou a digestibilidade aparente da concentração de substância seca e substância orgânica e concentração de alanina aminotransferase no soro. Esses resultados indicaram que algum farelo de soja pode ser substituída por uréia de liberação lenta e uréia na produção de gado de corte. Além disso, comparado com a uréia, uréia de liberação lenta teve um bom efeito de liberação sustentada. A substituição de algum farelo de soja por uréia de liberação lenta na dieta não teve impacto adverso na fermentação ruminal, desempenho de crescimento e metabolitos séricos de gados de corte.(AU)