Captopril oral solution for pediatric use: formulation, stability study and palatability assessment in vivo

Abstract he aim of this work was to develop an oral solution of captopril at 5 mg/mL preservative-free. Two formulations were prepared, one containing sweetener (formulation 1) and the other without this excipient (formulation 2). The results found of validation parameters from analytical method performed by HPLC for captopril were, linearity 0.9998, the limit of detection 15.71 µg/mL, the limit of quantification 47.60 µg/mL, repeatability 1.05%, intermediate precision 2.42%, accuracy intraday 101,53%, accuracy inter-day 99.85%. Moreover, the results found for captopril disulfide were, linearity 0.9999, limit of detection 0.65 µg/mL, limit of quantification 1.96 µg/mL, repeatability 2.28%, intermediate precision 1.51%, accuracy intraday 101.36%, accuracy inter-day 100.29%. The appearance of formulations was clear and colorless, pH measures were 3.12 and 3.04, dosage of captopril and captopril disulfide were 99.45% and 99.82%, 0.24% and 0.12% for formulation 1 and formulation 2, respectively. The stability study demonstrated that the concentration of captopril and captopril disulfide in the formulations was > 90% and below 3%, respectively. The in vivo palatability study in animals and humans showed that Formulation 1 containing the sweetener had better acceptance. Thus, the sweetener was able to improve the unpleasant taste of the formulation

Effects of copaiba oil on dermonecrosis induced by Loxosceles intermedia venom.

BACKGROUND: Accidents caused by spiders of the genus Loxosceles constitute an important public health problem in Brazil. The venom of Loxosceles sp induces dermonecrosis at the bite site and systemic disease in severe cases. Traditional medicine based on plant-derived products has been proven to reduce the local effects of envenomation. The present study verified the healing effects of copaiba oil on lesions induced by the venom of L. intermedia. METHODS: Cutaneous lesions were induced on the backs of rabbits by intradermal injection of L. intermedia venom. Copaiba oil was applied topically 6 hours after injection; the treatment was repeated for 30 days, after which animal skins were removed and processed for histopathological analysis. Blood samples were also collected before and 24 hours after venom inoculation to measure the hematological parameters. RESULTS: Compared to the control group, the platelet count was reduced significantly in all groups inoculated with venom, accompanied by a decreased number of heterophils in the blood. The minimum necrotic dose (MND) was defined as 2.4 µg/kg. Topical treatment with copaiba oil demonstrated a differentiated healing profile: large skin lesions were observed 10 days after venom inoculation, whereas formation of a thick crust, without scarring was observed 30 days after venom inoculation. Histopathological analysis showed no significant difference after treatment. Nevertheless, the copaiba oil treatment induced a collagen distribution similar to control skin, in marked contrast to the group that received only the spider venom injection. CONCLUSIONS: We conclude that copaiba oil may interfere in the healing process and thus propose it as a possible topical treatment for cutaneous lesions induced by L. intermedia venom.

Effects of copaiba oil on dermonecrosis induced by Loxosceles intermedia venom

Accidents caused by spiders of the genus Loxosceles constitute an important public health problem in Brazil. The venom of Loxosceles sp induces dermonecrosis at the bite site and systemic disease in severe cases. Traditional medicine based on plant-derived products has been proven to reduce the local effects of envenomation. The present study verified the healing effects of copaiba oil on lesions induced by the venom of L. intermedia. Methods: Cutaneous lesions were induced on the backs of rabbits by intradermal injection of L. intermedia venom. Copaiba oil was applied topically 6 hours after injection; the treatment was repeated for 30 days, after which animal skins were removed and processed for histopathological analysis. Blood samples were also collected before and 24 hours after venom inoculation to measure the hematological parameters. Results: Compared to the control group, the platelet count was reduced significantly in all groups inoculated with venom, accompanied by a decreased number of heterophils in the blood. The minimum necrotic dose (MND) was defined as 2.4 μg/kg. Topical treatment with copaiba oil demonstrated a differentiated healing profile: large skin lesions were observed 10 days after venom inoculation, whereas formation of a thick crust, without scarring was observed 30 days after venom inoculation. Histopathological analysis showed no significant difference after treatment. Nevertheless, the copaiba oil treatment induced a collagen distribution similar to control skin, in marked contrast to the group that received only the spider venom injection. Conclusions: We conclude that copaiba oil may interfere in the healing process and thus propose it as a possible topical treatment for cutaneous lesions induced by L. intermedia venom.(AU)

Malnutrition alters the cardiovascular responses induced by central injection of tityustoxin in Fischer rats.

Scorpion envenoming and malnutrition are considered two important public health problems in Brazil, involving mainly children. Both these conditions are more common among the economically stratified lower income portion of the population, thus suggesting that these factors should be analyzed concomitantly. It is known that cardiorespiratory manifestations, as cardiac arrhythmias, arterial hypertension and hypotension, pulmonary edema and circulatory failure are the main "causa mortis" of scorpion envenomation. Additionally, there are evidences in the literature that deficiencies in dietary intake endanger the CNS and modify the cardiovascular homeostasis. Then, the objective of this work is to evaluate the protein malnourished effect on cardiovascular responses induced by tityustoxin (TsTX, an α-type toxin extracted from the Tityus serrulatus scorpion venom). Fischer rats (n = 20) were injected i.c.v. with TsTX and divided in control and malnorished groups, which were, respectively, submitted to a control and a low-protein diet. Arterial pressure recordings were done until death of the animals. Although both groups presented an increased mean arterial pressure after TsTX injection, this increase was smaller and delayed in malnourished rats, when compared to control rats. In addition, heart rate increased only in rats from the control group. Finally, malnourished rats had an increase in survival time (9:9/13.5 vs. 15.5:10.5/18 min; p = 0.0009). In summary, our results suggest that the protein restriction attenuates the cardiovascular manifestations resulting from TsTX action on CNS.

Exosomes Function in Pro- and Anti-Angiogenesis.

Exosomes, a group of small vesicles (30-100 nm), originate when the inward budding of the endosomal membrane forms multivesicular bodies (MVBs). Exosomes are released into the extracellular space when the MVBs fuse with the plasma membrane. Numerous studies have indicated that exosomes play critical roles in mediating cell-to-cell communication. Also, exosomes are believed to possess a powerful capacity in regulating cell survival/death, inflammation and tumor metastasis, depending on the particular array of molecules contained within a particular population of exosomes. This mini-review will summarize dual roles of exosomes derived from different types of cells (i.e. endothelial cells, tumor cells, platelets, bone-marrow stem cells, cardiomyocytes, myocardial progenitor cells and among others) in endothelial cell proliferation, migration and tube-like formation. In particular, this review will focus on the therapeutic potential of exosomes as a natural nano-particle for delivering pro-/anti-angiogenic factors (proteins, mRNAs and microRNAs) into endothelial cells.