307 research outputs found

    Enzyme replacement therapy treatment from birth increases therapeutic efficacy and generates tolerance to enzyme in canine mucopolysaccharidosis type I

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    Mucopolysaccharidosis I is a lysosomal storage disease where the lack of alpha-L-iduronidase leads to lysosomal accumulation of heparan and dermatan sulfates. This storage results in varying degrees of cardiac, skeletal, respiratory, corneal, and neural disease. Few treatments are available to patients with limited results, especially in treatment of cardiac and skeletal complications. We treated neonatal mucopolysaccharidosis I dogs with intravenous recombinant enzyme replacement therapy at the conventional 0.58 mg/kg or a higher 1.57 mg/kg weekly dose. Higher dosage led to complete normalization of lysosomal storage in liver, spleen, lung, kidney, synovium and myocardium, as well as normalization of storage in the hard-to-treat mitral valve. There was normalization of all biochemical and functional cardiac disease and striking improvements in clinical and radiographic signs of skeletal disease. In addition to somatic improvements, high and intrathecal enzyme treatment led to decreased secondary storage burden of gangliosides in the cerebral gray matter. Importantly, all animals failed to mount an antibody response to enzyme therapy, consistent with neonatal tolerization. Taken together, these findings using the canine model advocate neonatal testing and early treatment of mucopolysaccharidosis I to more completely treat cardiac and skeletal manifestations of human mucopolysaccharidosis I disease

    The interplay between voluntary food intake, dietary carbohydrate-lipid ratio and nutrient metabolism in an amphibian, (Xenopus laevis)

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    Digestion of food and metabolism of frogs are little studied at the moment, and such processes could be very particular in the case of amphibians, given their ectothermic and carnivorous nature which may lead them to use nutrients through specific biochemical pathways. In the present study, 24 adult Xenopus laevis (six replicates with two frogs per treatment) were randomly assigned to two diets with different carbohydrate:fat ratio (4.5:1 and 2.1:1), changing the dietary glucogenic and lipogenic proportions. Food intake (FI) per unit metabolic body weight (MBW) as well as macronutrient digestibility were calculated, and circulating blood acylcarnitines and amino acids measured, in order to evaluate the effect of the diet treatments. Results demonstrated that food intake regulated most of the changes in the parameters evaluated; significant differences were obtained in crude protein and fat digestibilities through the effect of FI/MBW (p<0.05), whereas diet treatment had a significant effect on the levels of malonyl-CoA. Food intake also significantly impacted malonyl, isovaleryl, hydroxyisovaleryl and long chain fatty acid concentrations; significant (p<0.05) interactions between those metabolites were detected owing to diet. The findings obtained suggest that food intake was the main factor controlling digestion and metabolism in X. laevis, with frogs preferring to utilise protein and fat as primary sources for energy production in the citric acid cycle, reflecting characteristics of a strict carnivore physiological model

    Gaining insights in the nutritional metabolism of amphibians : analyzing body nutrient profiles of the African clawed frog, Xenopus laevis

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    Whole bodies of Xenopus laevis (n = 19) were analysed for chemical composition and morphometrics. The nutrient profile (macronutrients, amino acids, fatty acids and minerals) was evaluated by sex; interactions among variables with body weights and lengths, and comparisons made with different species of marine and fresh water fish. Significant differences were found in morphometric measurements, water content, several minerals and fatty acids between sexes of X. laevis. Amino acid profiles differed in methionine, proline and cysteine, which could underlie different metabolic pathways in frogs when compared to fish. In addition, fatty acid profiles revealed more monounsaturated and n - 6 polyunsaturated fatty acids in frogs than in fish, more similar to values reported for terrestrial than aquatic vertebrates. Important interactions were also found between body measurements and fat, calcium, and phosphorus, as well as between essential and non-essential amino acids. The results indicate that frogs might have particular biochemical pathways for several nutrients, dependent on sex and linked to body weight, which ultimately could reflect specific nutrient needs

    Evaluation of three popular diets fed to pet sugar gliders (Petaurus breviceps): intake, digestion and nutrient balance

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    Three diets fed to 12 pair-housed sugar gliders, Petaurus breviceps, were evaluated through 5-day intake and digestion trials following 10-day transitions. Diets 1 and 2 comprised liquid formula mixes with added vegetables and fruit, and Diet 3 comprised extruded pellets and a liquid formula. Diets eaten contained 16 —19% crude protein, 3%–15% crude fat, 10%–11% neutral detergent fibre, 4%–20% starch and 8%–49% sugar (dry basis). Calculated individual dry matter intakes (DMI) ranged from 3.9 to 5.1 g/day, representing 58.2–78.4 kJ/day. DMI was greater for Diet 2 (7.2% BW) vs. Diet 1 (5.6; p = .006) and Diet 3 (4.2% BW; p = .003). Although these differences were no longer detectable on a MBW basis, animals were shown to have gained BW (+14.2 g; p = .03) on Diet 2. In addition to nutrient composition differing widely among diets, DM digestibility (DMD) was higher in Diet 1 (91.2%) compared to Diet 2 (87.3%; p = .03), but DMD for Diet 3 (88.9%) did not differ from other diets. Gliders demonstrated ability to digest a variety of energy substrates, including simple sugars (96%–99%), fats (81%–96%) and starches (79%–98%), as well as substantial insoluble dietary fibre (58%–75%), with significant difference among diets demonstrated for some nutrients. Animals displayed selective feeding behaviours, rejecting insoluble fibre in produce and preferring the lipid-coated exterior of pellets. The diets used appeared to be balanced with respect to energy, protein and macromineral content, but may predispose to iron excess, other mineral imbalances (especially Ca deficiency) and obesity—clinical health issues described for pet gliders. Future focus on concentrations, types and utilization of dietary fibre in natural and captive diets, vitamin D metabolism and trace mineral interactions in sugar gliders would assist diet optimization for this highly gummivorous species

    Trialling nutrient recommendations for slow lorises (Nycticebus spp.) based on wild feeding ecology

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    Slow loris (Nycticebus spp.) captive diets have been based on routine and anecdotes rather than scientific fact. The growing body of evidence contradicts the high fruit diet supported by such anecdotes. Non-human primate nutrient requirements are grouped into new (based on the common marmoset Callithrix jacchus) or old world (based on rhesus macaques Macaca mulatta) primates. Slow lorises are known to suffer from many health ailments in captivity such as dental disease, obesity, wasting and kidney issues all of which have been linked to diet. This study aimed to estimate nutrient intake from free-ranging slow lorises and to determine whether this intake can be used as nutrient recommendations. We collected data of nutrient intake, food passage rate and digestibility of captive slow lorises on three diet treatments 1: current captive type diet which is mostly fruits, 2: wild-type diet made only of food items from their natural diet, 3: new diet made to reflect wild slow loris nutrient intake. In order to validate our nutrient recommendations, diets 2 and 3 would have to be significantly different to Diet 1 in terms of nutrients, but not different from each other. Captive diets were significantly higher in soluble carbohydrates and lower in minerals and fibre fractions than both diets 2 and 3. Diets 2 and 3 led to a significantly increased food passage time and to more effective fibre and calcium digestion compared to Diet 1. We also observed obese individuals lost weight and underweight individuals gained weight. Our nutrient recommendations have been validated by our trials, and new or old world monkey nutrient recommendations are not consistent with our results. Diets should be high in protein and fibre and low in soluble carbohydrates and fats
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