A nanochitosan-D-galactose formulation increases the accumulation of primaquine in the liver.

Primaquine is the mainstream antimalarial drug to prevent Plasmodium vivax relapses. However, this drug can induce hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency. Nanostructure formulations of primaquine loaded with D-galactose were used as a strategy to target the drug to the liver and decrease the hemolytic risks. Nanoemulsion (NE-Pq) and nanochitosan (NQ-Pq) formulations of primaquine diphosphate containing D-galactose were prepared and characterized by their physicochemistry properties. Pharmacokinetic and biodistribution studies were conducted using Swiss Webster mice. A single dose of 10 mg/kg of each nanoformulation or free primaquine solution was administered by gavage to the animals, which were killed at 0.5, 1, 2, 4, 8, and 24 hours. Blood samples and tissues were collected, processed, and analyzed by high-performance liquid chromatography. The nanoformulation showed sizes around 200 nm (NE-Pq) and 400 nm (NQ-Pq) and physicochemical stability for over 30 days. Free primaquine solution achieved higher primaquine Cmax in the liver than NE-Pq or NQ-Pq at 0.5 hours. However, the half-life and mean residence time (MRT) of primaquine in the liver were three times higher with the NQ-Pq formulation than with free primaquine, and the volume distribution was four times higher. Conversely, primaquine's half-life, MRT, and volume distribution in the plasma were lower for NQ-Pq than for free primaquine. NE-Pq, on the other hand, accumulated more in the lungs but not in the liver. Galactose-coated primaquine nanochitosan formulation showed increased drug targeting to the liver compared to free primaquine and may represent a promising strategy for a more efficient and safer radical cure for vivax malaria.

Protective actions of human tissue kallikrein gene in transgenic rat hearts.

In this study, we used an experimental model of cardiac hypertrophy to explore the role of the kallikrein-kinin system (KKS) in cardiac protection in transgenic rats harboring the human tissue kallikrein gene, TGR(hKLK1). Tissue kallikrein cleaves low-molecular-weight kininogen to produce kinin peptides, which bind to kinin receptors and trigger a wide spectrum of biological effects. The transgene, under the control of the zinc-inducible metallothionein promoter, was expressed in most tissues including the heart, kidney, lung and brain. These animals were subjected to treatment with thyroid hormone in order to promote cardiac hypertrophy. Induction of cardiac hypertrophy revealed a marked protective effect caused by the expression of the kallikrein transgene, evidenced by the significantly reduced cardiac weight gain and the lower enhancement in the cardiac expression of atrial natriuretic peptide and collagen III, markers for hypertrophy and fibrosis, respectively. In conclusion, our data show that expression of tissue kallikrein exerts antihypertrophic and antifibrotic actions in the heart.

Biochemical and hormonal parameters of goats kept in a controlled environment consuming water with different levels of salinity / [Parâmetros bioquímicos e hormonais de caprinos consumindo água com diferentes níveis de salinidade mantidos em ambiente controlado]

The objective of this work was to evaluate the biochemical and hormonal variables of Moxotó and Canindé goats submitted to two temperatures - 26.0±0.6 (thermoneutral) and 32.0±1.2°C (above thermal comfort zone) - and consuming water with three levels of salinity (1.0, 6.0 and 12.0 dSm-1). Thirty-six animals (18 of each breed) were used, with an average age of 5.0±0.6months and an average weight of 20.0±2.3kg, housed in metabolic cages inside a climate chamber. The animals were distributed in a completely randomized design with a 2 × 2 × 3 factorial scheme (2 breeds, 2 temperatures and 3 levels of salinity) and three replications. The glucose and urea had a significant effect (P>0.05) according to water salinity. Glucose, cholesterol, protein, albumin, globulin, aspartate aminotransferase and hormones (T4, T3 and cortisol) varied according to temperature (P<0.05). There was a significant effect of time on hormonal variables (P<0.05). Biochemical and hormonal variables changed according to temperature and day shift, so that metabolism was reduced in the animals under thermal stress and accelerated when animals were in the thermal comfort zone.(AU)

O objetivo do trabalho foi avaliar as variáveis bioquímicas e hormonais de caprinos das raças Moxotó e Canindé, submetidos a duas temperaturas (26,0±0,6ºC e 32,0±1,2ºC), termoneutra e acima da zona de conforto térmico, respectivamente), consumindo água com três níveis de salinidade (1,0, 6,0 e 12,0dSm-1), utilizando-se 36 animais (18 de cada raça), com idade média de 5,0±0,6 meses e peso médio de 20,0±2,3kg, alojados em gaiolas metabólicas no interior de uma câmara climática. Os animais foram distribuídos em um delineamento inteiramente ao acaso, com esquema fatorial de 2 x 2 x 3 (2 raças, 2 temperaturas e 3 níveis de salinidade) e três repetições. A glicose e a ureia apresentaram efeito significativo (P<0,05) em função da salinidade da água. Glicose, colesterol, proteína, albumina, globulina, AST e hormônios (T4, T3 e cortisol) variaram conforme as temperaturas (P<0,05). Observou-se efeito significativo do horário sobre as variáveis hormonais (P<0,05). As variáveis bioquímicas e hormonais sofrem alterações em função da temperatura e do turno do dia, de modo que o metabolismo é reduzido em animais sob estresse térmico e acelerado quando os animais encontram-se na zona de conforto térmico.(AU)

Systemic availability of prophylactic cefuroxime in patients submitted to coronary artery bypass grafting with cardiopulmonary bypass.

Cardiopulmonary bypass and hypothermia (HCPB) is a procedure commonly used during heart surgery, representing a risk factor for the patient by promoting extensive haemodilution and profound physiological changes. Cefuroxime is used for the prevention of infection following heart surgery, and several dose schemes have been suggested for prophylaxis with cefuroxime. The objective of the present study was to assess, in a comparative manner, the systemic availability of cefuroxime administered intravascularly as a bolus dose of 1.5 g to 17 patients having heart surgery with or without HCPB. Plasma cefuroxime concentrations were determined by high-pressure liquid chromatography-UV, and the following values, expressed as medians, were obtained for the study group compared with controls: 69.1 vs. 62.7 mg/L (1st h), 35.8 vs. 26.0mg/L (3rd h), 14.6 vs. 8.7 mg/L (6th h, P<0.05), 6.1 vs. 3.0mg/L (9th h, P<0.05) and 2.6 vs. 1.0mg/L (12th h, P<0.05). Despite the differences recorded during the study period as a consequence of HCPB, low antibiotic concentrations were found as early as 6h post dose for both groups investigated. Thus, the low systemic availability of cefuroxime after the administration of a 1.5-g dose may not protect against postoperative infections. The data obtained permit us to recommend a change in the dose scheme in order to maintain adequate plasma levels of cefuroxime.

Evaluation of the Anti-inflammatory Activity of Atorvastatin and its Effect on Alveolar Diameter in a Model of Elastase-induced Emphysema in Rats.

Statins are cholesterol-lowering agents and some of them, like simvastatin, have anti-inflammatory effects. In this study, we evaluated the effect of atorvastatin on nitric oxide (NO) release, leukocytes levels and alveolar diameter related to the inflammatory process associated with elastase-induced emphysema in rats. 32 rats were divided into 4 groups, n=8: control (C), atorvastatin (A), emphysema (E), and emphysema+atorvastatin (EA). On day 0 (zero), groups C and A received intratracheal instillation of saline (0.2 ml), and groups E and EA received elastase (0.2 ml). Groups A and EA received atorvastatin (20 mg/kg) and C and E received vehicle, by gavage, for 25 days. Animals were euthanized, slices of lung stained and the alveolar diameters measured. Data obtained show that the treatment with atorvastatin (EA group) did not reduce the alveolar diameter (35.3 vs. 32.3), NO (2.7 vs. 3.0 µM) or the leukocyte count (111 vs. 136) compared with the E group, indicating that different statins, like simvastatin or atorvastatin, have different behavior in inflammatory processes like in elastase-induced development of emphysema in rats.