No abstract

Diabetes is associated with severe secondary complications, largely caused by poor glycemic control. Treatment with exogenous insulin fails to prevent these complications completely, leading to significant morbidity and mortality. We previously demonstrated that it is possible to generate a “glucose sensor” in skeletal muscle through coexpression of glucokinase and insulin, increasing glucose uptake and correcting hyperglycemia in diabetic mice. Here, we demonstrate long-term efficacy of this approach in a large animal model of diabetes. A one-time intramuscular administration of adeno-associated viral vectors of serotype 1 encoding for glucokinase and insulin in diabetic dogs resulted in normalization of fasting glycemia, accelerated disposal of glucose after oral challenge, and no episodes of hypoglycemia during exercise for >4 years after gene transfer. This was associated with recovery of body weight, reduced glycosylated plasma proteins levels, and long-term survival without secondary complications. Conversely, exogenous insulin or gene transfer for insulin or glucokinase alone failed to achieve complete correction of diabetes, indicating that the synergistic action of insulin and glucokinase is needed for full therapeutic effect. This study provides the first proof-of-concept in a large animal model for a gene transfer approach to treat diabetes.

No abstract

Male growing pigs were fed a diet containing 250 g/kg of native corn starch (CS; 26% amylose, 74% amylopectin) or 250 g/kg of raw potato starch (RPS), as examples of digestible starch and resistant starch (Type II), respectively. Whole-tract digestibilities of organic matter, crude protein and starch were greater in pigs fed CS than in those fed RPS through at least d 23 of the study. However, the values progressively increased in the RPS-fed pigs up to d 38, at which time the groups did not differ in organic matter and starch digestibility. The digestive tract and colonic digesta were heavier and colon length longer in pigs fed the RPS diet. Digestibility of starch in the ileum on d 38 was significantly lower in RPS-fed pigs, but rose from ileum to rectum; most starch was extensively fermented in the cecum and proximal colon. Purine base (PB) and short-chain fatty acid (SCFA) concentrations in feces initially increased and then decreased beginning on d 4 for PB and on d 21 for SCFA. PB concentration in feces was greater in pigs fed RPS than in those fed CS. In the large bowel digesta, PB and SCFA concentrations increased from the ileum to the cecum and proximal colon and then fell in the distal colon. Pigs fed the RPS diet had a higher PB concentration in the middle colonic digesta and a greater SCFA concentration in the proximal colonic digesta than the CS-fed group. Adaptation of growing pigs to supplementary RPS required 5 wk, as reflected by whole-tract digestibility and PB and SCFA fecal excretion data.

Hypoferremia is a sensitive marker of systemic inflammation in dogs. In this study, the increase in iron concentrations during the hospitalization period of SIRS/septic dogs was associated with a better prognosis, suggesting that plasma iron in combination with CRP and albumin concentrations might be used to monitor dogs with inflammatory disease processes.

The “One world, one health” initiative emphasizes the need for new strategies to control human and animal tuberculosis (TB) based on their shared interface. A good example would be the development of novel universal vaccines against Mycobacterium tuberculosis complex (MTBC) infection. This study uses the goat model, a natural TB host, to assess the protective effectiveness of a new vaccine candidate in combination with Bacillus Calmette-Guerin (BCG) vaccine.Thirty-three goat kids were divided in three groups: Group 1) vaccinated with BCG (week 0), Group 2) vaccinated with BCG and boosted 8 weeks later with a recombinant adenovirus expressing the MTBC antigens Ag85A, TB10.4, TB9.8 and Acr2 (AdTBF), and Group 3) unvaccinated controls. Later on, an endobronchial challenge with a low dose of M. caprae was performed (week 15). After necropsy (week 28), the pulmonary gross pathology was quantified using high resolution Computed Tomography. Small granulomatous pulmonary lesions (< 0.5 cm diameter) were also evaluated through a comprehensive qualitative histopathological analysis. M. caprae CFU were counted from pulmonary lymph nodes.The AdTBF improved the effects of BCG reducing gross lesion volume and bacterial load, as well as increasing weight gain. The number of Ag85A-specific gamma interferon-producing memory T-cells was identified as a predictor of vaccine efficacy. Specific cellular and humoral responses were measured throughout the 13-week post-challenge period, and correlated with the severity of lesions.Unvaccinated goats exhibited the typical pathological features of active TB in humans and domestic ruminants, while vaccinated goats showed only very small lesions. The data presented in this study indicate that multi-antigenic adenoviral vectored vaccines boosts protection conferred by vaccination with BCG.

The purpose of this randomised trial was to compare the effects of alfaxalone and propofol on tear production (STT-1), intraocular pressure (IOP) and globe position (GP) in healthy dogs. Fourteen Beagles were randomly divided into two groups; dogs in one group received alfaxalone (3 mg/kg) (n=7) and dogs in the other group received propofol (6 mg/kg) (n=7), both administered intravenously. IOP and GP were evaluated at basal time (Tb) and T2,5,10,15,20,25&30 (minutes after complete drug administration). STT-1 was evaluated at Tb and T10,20&30. STT-1 and IOP results were analysed using analysis of variance and GP was analysed using the likelihood ratio χ(2) test. Dogs in the alfaxalone group showed a significant reduction in STT-1 at T10&20 (P<0.05), while the propofol group did not show statistically significant differences in this parameter over time. Both anaesthetic drugs produced a transient elevation of IOP at T2 (P>0.05), which then decreased (P<0.01). While alfaxalone caused a ventral globe deviation that lasted from T2 to T10 (P<0.05) and was fully recovered at T30, propofol induced a ventral globe deviation from T2 to T5 (P<0.05), being restored at T20. These results suggest that both alfaxalone and propofol can be safely used for intraocular surgery, as they significantly reduce IOP. Furthermore, anaesthetic induction with propofol would be especially recommended for dogs with tear deficiencies.

No abstract