Solid dispersions with hydrogenated castor oil increase solubility, dissolution rate and intestinal absorption of praziquantel

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats

Background: It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle.Methods: To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein):pregnant (N), tumor-bearing (WN), pair-fed rats (Np). Three other pregnant groups were fed a diet supplemented with 3% leucine (15% protein plus 3% leucine):leucine (L), tumor-bearing (WL) and pair-fed with leucine (Lp). Non pregnant rats (C), which received a normal protein diet, were used as a control group. After 20 days, the animals were submitted to intestinal perfusion to measure leucine, methionine and glucose absorption.Results: Tumor-bearing pregnant rats showed impairment in food intake, body weight gain and muscle protein content, which were less accentuated in WL than in WN rats. These metabolic changes led to reduction in both fetal and tumor development. Leucine absorption slightly increased in WN group. In spite of having a significant decrease in leucine and methionine absorption compared to L, the WL group has shown a higher absorption rate of methionine than WN group, probably due to the ingestion of the leucine supplemented diet inducing this amino acid uptake. Glucose absorption was reduced in both tumor-bearing groups.Conclusions: Leucine supplementation during pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the availability of the amino acid for neoplasic cells and, mainly, for fetus and host utilization. This may have contributed to the better preservation of body weight gain, food intake and muscle protein observed in the supplemented rats in relation to the non-supplemented ones.

Development of praziquantel-loaded PLGA nanoparticles and evaluation of intestinal permeation by the everted gut Sac model

Praziquantel has been shown to be highly effective against all known species of Schistosoma infecting humans. Spherical nanoparticles made of poly(D,L-lactide-co-glycolide) acid with controlled size were designed as drug carriers. Praziquantel, a hydrophobic drug, was entrapped into the polymeric nanoparticles with 30% (w/w) of theoretical loading. The nanoparticles size was approximately of 350 nm with 66% of encapsulation efficiency. The everted gut sac model shows to be efficient to evaluate the drug permeation through the intestinal membrane. The results show that free praziquantel presents 4-fold times more permeation than praziquantel-loaded PLGA nanoparticles and physical mixture. For this drug, in special, this result can be interesting, since the nanoparticulate system can behave as a drug reservoir and/or to have a more localized effect in intestinal membrane for a prolonged period of time, since great amounts of parasites can be usually found in the mesenteric veins.

Apparent absorption of zinc from supplemental inorganic and organic sources to Nile tilapia Oreochromis niloticus juveniles

Nile tilapia Oreochromis niloticus fingerlings were fed with purified or practical diets, supplemented with 150 Ing Zn/kg, from different sources. Dry matter (DM), crude protein (CP), ether extract (EE), and gross energy (GE) apparent digestibility coefficients (ADC), as well as zinc, copper, calcium, and phosphorus apparent absorption coefficients (AAC) were determined by the addition of 0.1% chromic oxide to the diets. The supplemental zinc sources utilized were commercial grade zinc sulfate monohydrate (ZnSO 4), zinc oxide (ZnO) and a zinc amino acid complex (Zn-AA). Analytical grade zinc sulfate heptahydrate was also utilized as a standard reference zinc source. There was a significant difference between purified (74.9%) and practical (41.3%) zinc AAC for the ZnO supplemented diets (P < 0.05). The supplemental zinc sources presented similar AAC when purified diets were utilized. However, ZnSO 4 was the best supplemental zinc source when practical type diets were used. There were no significant differences between supplemental zinc AAC from ZnS0 4 (68.9%), and supplemental zinc AAC from Zn-AA (61.3%) in practical diets, but Zn-AA diet showed a statistically lower zinc AAC when compared with the standard zinc source diet (75.6%). The practical diet supplemented with ZnO had the worst supplemental zinc AAC (41.3%). Dietary copper (74.21%), calcium (70.9%), and phosphorus (71.9%) AAC of the practical diets supplemented with ZnO were statistically lower (P < 0.05) than the respective AAC of the practical ZnSO 4 supplemented diets (83.6%, 84.1%, 87.1%).The ADC of the practical ZnO supplemented diet for DM (76.3%), CP (88.6%), EE (82.4%), and GE (81.6%) were statiscally lower than the respective ADC of the ZnSO 4 practical diet (86.0, 92.7, 93.6, 89.6%, respectively) and those ADC of the Zn-AA practical diet (84.7, 92.7, 93.7, 88.2%, respectively) (P < 0.05). Hence, these results indicate that ZnSO 4 and Zn-AA have equivalent intestinal absorption as supplemental zinc sources for Nile tilapia juveniles and both are superior to ZnO. © Copyright by the World Aquaculture Society 2005.

Estudo da capacidade de absorção intestinal de ferro e zinco em indivíduos com obesidade grave, antes e após cirurgia bariátrica

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Old beagle dogs have lower faecal concentrations of some fermentation products and lower peripheral lymphocyte counts than young adult beagles

The effects of age on microbiota composition, gut fermentation end-product formation and peripheral lymphocyte numbers were compared between old and young adult Beagle dogs fed four kibble diets differing in yeast cell wall contents. The experiment had a double 4 x 4 Latin square design, one with four mature dogs (4 years old) and the other with four old dogs (10 years old), with four replicates (diets) per dog. In each period a 15d adaptation period preceded a 5d total collection of faeces for the digestibility trial. on day 21, fresh faecal samples were collected for the determination of bacterial enumeration, pH, biogenic amine and short-chain fatty acid. Flow cytometry was used for immunophenotypic evaluation. Dogs were fed four kibble diets with similar composition with 0, 0.15, 0.30 and 0.45% of yeast cell wall (as-fed), respectively. Data were evaluated using general linear models of Statistical Analysis Systems statistical software (P<0.05). No evidence of a difference in faecal bacteria counts between ages was found (total aerobes, total anaerobes, Bifidobacterium, Lactobacillus, Clostridium and Escherichia coli: P. 0.15). Faecal concentrations of butyrate, histamine, agmatine and spermine were lower (P <= 0.05) and faecal pH was higher (P=0.03) in older dogs than in mature adult dogs, suggesting an alteration in bacterial metabolic activity, or in the rate of intestinal absorption of these compounds. Concentrations of T-lymphocytes, T-cytotoxic lymphocytes and B-lymphocytes were also lower (P <= 0.01) in older dogs than in mature adult dogs. The study confirmed alterations in peripheral lymphocytes and revealed a reduced concentration of some fermentation end products in the colon of old dogs.

Disponibilidade e absorção de aminoácidos em bovinos alimentados com diferentes fontes de compostos nitrogenados

Objetivou-se estudar o fluxo e a absorção de aminoácidos em bovinos alimentados com dietas isoprotéicas formuladas com diferentes fontes nitrogenadas. As dietas foram fornecidas a bezerros holandeses canulados no abomaso, com 8 meses de idade e peso médio de 187 kg, em um total de 21 animais escolhidos aleatoriamente para formar o grupo que constituiu as repetições experimentais (sete por tratamento). As dietas experimentais foram constituídas de 40% de volumoso e 60% de concentrado. Como volumoso, utilizou-se feno de capim-de-rhodes e, no concentrado, utilizaram-se milho, farelo de algodão, levedura, uréia, melaço e minerais. As dietas diferiram apenas quanto à fonte nitrogenada (farelo de algodão, levedura ou uréia). As quantidades (g/dia) de aminoácidos no abomaso e a composição em aminoácidos da proteína presente no abomaso e nas fezes foram influenciadas pela fonte protéica da dieta. As fontes nitrogenadas não afetaram significativamente a digestão de aminoácidos no intestino. A disponibilidade de aminoácidos no abomaso e a absorção no intestino apresentaram valores inferiores aos descritos na literatura, provavelmente porque, neste trabalho, os animais foram submetidos à restrição de ingestão. As fontes nitrogenadas testadas influenciaram a composição e a disponibilidade de aminoácidos em bovinos.

Improvement of antischistosomal activity of praziquantel by incorporation into phosphatidylcholine-containing liposomes

Praziquantel (PZQ) is effective against all known species of Schistosomes that infect humans. The failure of mass treatment of schistosomiasis has been attributed to the fact that therapy is not sufficiently long-lasting. This effect may be due to the low bioavailability of PZQ that has a low hydrosolubility and fast metabolism. Liposomes have been used to prolong drug levels. reduce the side effects, direct drugs to specific sites and increase bioavailability after administration. The aim of this work was to study the effect of phosphatidylcholine (PC)-containing liposomes to vehiculate PZQ to improve the treatment of schistosomiasis. The in vitro Study was carried out using Schistosoma mansoni parasites recovered by perfusion from the hepatic portal system of infected mice. Suspensions of liposomes with PZQ and free PZQ were administered p.o. in mice after 14 days of infection. The effect of both preparations in vitro on S. mansoni culture was similar. In the in vivo test, PZQ-liposomes caused a decrease in amounts of eggs and parasites. Liposomes improve the antischistosomal activity of praziquantel. This can be used as a starting point to investigate alternative administration routes or dosage forms and to examine the mechanism of intestinal absorption of PRZ © 2005 Elsevier B.V. All rights reserved.

Food-dependent, exercise-induced gastrointestinal distress

Among athletes strenuous exercise, dehydration and gastric emptying (GE) delay are the main causes of gastrointestinal (GI) complaints, whereas gut ischemia is the main cause of their nausea, vomiting, abdominal pain and (blood) diarrhea. Additionally any factor that limits sweat evaporation, such as a hot and humid environment and/or body dehydration, has profound effects on muscle glycogen depletion and risk for heat illness. A serious underperfusion of the gut often leads to mucosal damage and enhanced permeability so as to hide blood loss, microbiota invasion (or endotoxemia) and food-born allergen absorption (with anaphylaxis). The goal of exercise rehydration is to intake more fluid orally than what is being lost in sweat. Sports drinks provide the addition of sodium and carbohydrates to assist with intestinal absorption of water and muscle-glycogen replenishment, respectively. However GE is proportionally slowed by carbohydrate-rich (hyperosmolar) solutions. on the other hand, in order to prevent hyponatremia, avoiding overhydration is recommended. Caregiver's responsibility would be to inform athletes about potential dangers of drinking too much water and also advise them to refrain from using hypertonic fluid replacements.

Cloning, sequencing and expression analysis of the equine hepcidin gene by real-time PCR

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

THE ASSESSMENT OF ZINC STATUS BY THE ZINC TOLERANCE-TEST IN THYROID-DISEASE

Zinc status was evaluated in 12 hyperthyroid and in 7 hypothyroid patients in comparison with 8 euthyroid individuals by the oral zinc tolerance test and by the determination of urinary zinc excretion. Hyperthyroid patients presented a basal serum concentration similar to that of euthyroid individuals but greater urinary zinc excretion, indicating the occurrence of zinc depletion from tissues to the blood stream caused by the catabolism inherent in the hyperthyroid state. Hyperthyroidism also caused lower zinc assimilation by tissues after zinc ingestion. Hypothyroid individuals present lower basal zinc levels in serum than euthyroid and hyperthyroid individuals and urinary zinc excretion similar to that of euthyroid individuals. No changes in the parameters measured were observed after zinc load, suggesting reduced or delayed intestinal absorption and zinc assimilation by tissues. The present data are indicative of zinc deficiency, the lower intestinal zinc absorption probably being one of the contributing factors.

Effects of a leucine-rich diet on body composition during nutritional recovery in rats

OBJECTIVE: Protein malnutrition is characterized by a number of morphologic and physiologic alterations, including intestinal mucosal atrophy and impaired nutrient absorption. Impaired absorption accentuates nutritional deficiency and accelerates body weight loss and changes in body chemistry. Because leucine is a ketogenic and oxidative amino acid and stimulates the protein synthesis, we examined the ability of young rats to recover from protein malnutrition by feeding them a control balanced or a leucine-rich diet for 60 d.METHODS: At the end of the 60-d period, body, liver, and muscle weights; glucose, methionine, and leucine intestinal absorption; and carcass chemical composition were evaluated.RESULTS: Body weight gain was higher in the control balanced and leucine-rich groups than in control rats, indicating that adequate refeeding allows body weight to recover in these groups. Methionine and glucose absorptions were impaired in malnourished rats but were restored after nutritional recovery. The leucine-rich diet resulted in an increase in carcass collagen nitrogen but maintained the carcass structural nitrogen.CONCLUSIONS: These results indicated that leucine supplementation during nutritional recovery from protein malnutrition improves protein carcass restoration. However, the precise mechanism of the leucine effects involved in this response remains to be elucidated.

Prova de absorção de gordura em crianças.

To overcome the difficulties observed with fecal fat estimations, we studied fat absorption in 4 m to 12 years old children, assessing increments of serum triglycerides after administration of corn oil. Eighteen well-nourished children without gastrointestinal symptoms or parasites, 31 children with protein-calorie malnutrition (PCM), with or without protracted diarrhea and/or intestinal parasites and nine children with specific malabsorptive entities were studied. Serum triglycerides (TG) were measured before, 2 and 4 hours after the administration of 2 g/kg of corn oil per os. For control infants below 2 years no significant differences between the fasting level and those after 2 and 4 hours were observed. For children above this age significant absorption occurred by 2 hours but more intensively after 4 hours, an increment of TG above 35 mg% being considered normal. A good discrimination between TG increments of controls and malabsorptive children over 2 years was observed. In conclusion, the oral fat loading test, is applicable for children over 2 year of age. For infants below this age other schedules should be tested.

Cinética do transporte jejunal de glicose em ratos com deficiência de niacina.

The kinetic of jejunal glucose transport was studied using perfused rat jejunum in vivo. Ninety rats were fed a diet deficient in niacin and 90 a control diet. The jejunal loops of 7 groups of animal were infused each group with one of following solutions of glucose: 5, 10, 20, 40, 80, 160 and 300 mM/l. The Vmax and Km values were determined. The results showed that the vitamin-deficient rats absorbed less glucose independently of the amount infused and these animals had lower Vmax (133.7 microM/15 min/15 cm) and Km (192.1 mM/l) than control groups (294.1 microM/15 min/15 cm and 171.8 mM/l, respectively). In conclusion one can assume that niacin deficiency leads to a decreased glucose absorption in the jejunal loops, when tested as in our experimental model.

Transporte jejunal eletrogênico da glicose em ratos com deficiência de niacina.

The active electrogenic absorption of glucose was studied in 12 niacin deficient rats using a method for measuring changes in transmural potential difference across jejunal mucosa. The glucose was infused in 6 different concentrations (2.5; 5.0; 10.0; 20.0; 50.0 and 100.0 mM/L) at a constant rate of 1.7 ml per minute. The apparent kinetic parameters (Km and Pdmax) of active electrogenic transport were obtained graphically from curves of glucose transfer potentials. The results were compared with that obtained in a control group. The curve of glucose transfer potential in niacin deficient group was significantly lower than that of the control group. The apparent Km of niacin deficient group was greater than in the control group (16.1 x 12.7 mM/L). Furthermore, the Pdmax of the deficient group was lower than that of the control group (12.5 x 19.4 mV). The results showed that in niacin deficiency occurs a decreasing of the active electrogenic glucose absorption. One of the possible interpretation of the differences in the kinetic characteristics of electrogenic glucose transport would be a depleted energy supplement for the active transport in the enterocyte of the niacin deficient rats.