This study suggests that a pharmaceutical care program may provide important contributions to reduce haemoglobin A1C in type 2 diabetes patients. Moreover, the promotion of the rational use of drugs may be better achieved in a context of pharmaceutical care programs in Brazil.
Purpose:To evaluate and characterize the wound healing process profile induced by allantoin incorporated in soft lotion oil/water emulsion using the planimetric and histological methods. Methods: Female Wistar rats (n=60) were randomly assigned to 3 experimental groups: (C) control group-without treatment; (E) group treated with soft lotion O/W emulsion excipients; (EA) group treated with soft lotion O/W emulsion containing allantoin 5%. The emulsions either containing or not allantoin were topically administered for 14 days and the wound area was evaluated by planimetry and by qualitative and quantitative histological analysis of open wound model. Results:The data which were obtained and analyzed innovate by demonstrating, qualitatively and quantitatively, by histological analysis, the profile of healing process induced by allantoin. The results suggest that the wound healing mechanism induced by allantoin occurs via the regulation of inflammatory response and stimulus to fibroblastic proliferation and extracellular matrix synthesis. Conclusion: This work show, for the first time, the histological wound healing profile induced by allantoin in rats and demonstrated that it is able to ameliorate and fasten the reestablishment of the normal skin. Key words: Wound Healing. Allantoin. Histology. Animal Experimentation. Rats. RESUMOObjetivo: Avaliar e caracterizar o perfil cicatricial induzido pela alantoína incorporada em uma emulsão óleo/água, sob os aspectos planimétrico e histológico. Métodos: Ratos Wistar fêmeas (n=60) foram agrupados aleatoriamente em três grupos experimentais grupo controle -sem tratamento (C); grupo tratado com emulsão pura (E); grupo tratado com emulsão contendo 5% de alantoína (EA). As emulsões contendo ou não alantoína foram administradas topicamente durante 14 dias e a área da ferida foi avaliada por planimetria e por análise histológica qualitativa e quantitativa em modelo de ferida aberta. Resultados: Na análise planimétrica não foi observado diferenças significativas entre os grupos experimentais. Os resultados da análise histológica sugerem que o mecanismo de cicatrização induzido pela alantoína ocorre via controle da resposta inflamatória e estímulos à proliferação fibroblástica e síntese de matrix extracelular de maneira mais intensa e rapidamente em relação aos grupos controles. Conclusão: Este trabalho mostra pela primeira vez o perfil histológico de cicatrização induzido pela alantoína em ratos, demonstrando ser capaz de melhorar e acelerar o processo de reconstituição da pele. Descritores: Cicatrização de Feridas. Alantoína. Histologia. Experimentação Animal. Ratos.
Ethanolic extract of Lychnophora trichocarpha and some of its bioactive compounds may be promising agents for the treatment of gouty arthritis since they possesses both anti-hiperuricemic and anti-inflammatory properties.
The ethyl acetate and aqueous extracts from Campomanesia adamantium showed antinociceptive and anti-inflammatory effects supporting the use of the plant in folk medicine. The results suggest that anti-oedematogenic effect promoted by aqueous extract involves several anti-inflammatory mechanisms of action. The antinociceptive effect shown by aqueous extract can be due to the modulation of release of inflammatory mediators involved in nociception. The anti-inflammatory effects of AE and of its isolated flavonols may be attributed to inhibition of pro-inflammatory cytokines production, TNF-α and NO and to the increased of IL-10 production.
Chagas disease is a neglected parasitic disease caused by the protozoan Trypanosoma cruzi. New antitrypanosomal options are desirable to prevent complications, including a high rate of cardiomyopathy. Recently, a natural substance, lychnopholide, has shown therapeutic potential, especially when encapsulated in biodegradable polymeric nanocapsules. However, little is known regarding possible adverse effects of lychnopholide. Here we show that repeated-dose intravenous administration of free lychnopholide (2.0 mg/kg/day) for 20 days caused cardiopathy and mortality in healthy C57BL/6 mice. Echocardiography revealed concentric left ventricular hypertrophy with preserved ejection fraction, diastolic dysfunction and chamber dilatation at end-stage. Single cardiomyocytes presented altered contractility and Ca2+ handling, with spontaneous Ca2+ waves in diastole. Acute in vitro lychnopholide application on cardiomyocytes from healthy mice also induced Ca2+ handling alterations with abnormal RyR2-mediated diastolic Ca2+ release. Strikingly, the encapsulation of lychnopholide prevented the cardiac alterations induced in vivo by the free form repeated doses. Nanocapsules alone had no adverse cardiac effects. Altogether, our data establish lychnopholide presented in nanocapsule form more firmly as a promising new drug candidate to cure Chagas disease with minimal cardiotoxicity. Our study also highlights the potential of nanotechnology not only to improve the efficacy of a drug but also to protect against its adverse effects.
The main objective of the present study was to evaluate the reduction in halofantrine (Hf) toxicity, an antimalarial drug frequently associated with QT interval prolongation in electrocardiogram, by its entrapment in poly-epsilon-caprolactone nanocapsules (NC). The acute lethal dose (LD(100)) of Hf.HCl experimentally observed was 200 mg/kg whereas the calculated LD(50) was 154 mg/kg. In contrast, the LD(100) for Hf-NC was 300 mg/kg with a longer mean time to death than Hf.HCl. The calculated LD(50) was 249 mg/kg for Hf-NC. The Hf entrapped in PCL NC presented a greater efficacy than PLA-PEG NC and than Hf solution in P. berghei-infected mice at 1 mg/kg. The cardiovascular parameters, ECG and arterial blood pressure, were evaluated in anaesthetized Wistar rats after the IV administration of a single, especially high dose (100 and 150 mg/kg) of halofantrine base loaded-nanocapsules (Hf-NC) or halofantrine chlorhydrate (Hf.HCl) solution. It was observed that Hf solution caused prolongation of the QT and PR intervals of the ECG; however, this effect was significantly (P<0.001) reduced when Hf was administered entrapped in nanocapsules. The treatment with Hf.HCl induced a pronounced bradycardia and severe hypotension leading to death. The effect of Hf-NC upon heart rate was reduced from 58 to 75% for 100 and 150 mg/kg, respectively, when compared with Hf.HCl solution. These findings show that the encapsulation of halofantrine reduces the QT interval prolongation of ECG in rats and suggest that a modification of drug distribution was possible by using nanocapsules. Hf encapsulation was the main factor responsible for the significant reduction in cardiac toxicity observed.
Artemether (ATM) cardiotoxicity, its short half-life and low oral bioavailability are the major limiting factors for its use to treat malaria. The purposes of this work were to study free-ATM and ATM-loaded poly-ε-caprolactone nanocapules (ATM-NC) cardiotoxicity and oral efficacy on Plasmodium berghei-infected mice. ATM-NC was obtained by interfacial polymer deposition and ATM was associated with polymeric NC oily core. For cardiotoxicity evaluation, male black C57BL6 uninfected or P. berghei-infected mice received, by oral route twice daily/4 days, vehicle (sorbitol/carboxymethylcellulose), blank-NC, free-ATM or ATM-NC at doses 40, 80 or 120 mg kg-1. Electrocardiogram (ECG) lead II signal was obtained before and after treatment. For ATM efficacy evaluation, female P. berghei-infected mice were treated the same way. ATM-NC improved antimalarial in vivo efficacy and reduced mice mortality. Free-ATM induced significantly QT and QTc intervals prolongation. ATM-NC (120 mg kg-1) given to uninfected mice reduced QT and QTc intervals prolongation 34 and 30%, respectively, compared with free-ATM. ATM-NC given to infected mice also reduced QT and QTc intervals prolongation, 28 and 27%, respectively. For the first time, the study showed a nanocarrier reducing cardiotoxicity of ATM given by oral route and it was more effective against P. berghei than free-ATM as monotherapy.
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