Physicochemical stability evaluation of liquid extemporaneous preparation based on tretinoin for administration via enteral tuve

Objective: The purpose of the study was to evaluate the content and physicochemical stability of a liquid oral formulation obtained from ATRA gelatin capsules in an oil/water vehicle, given the demand for this formulation for intubated patients undergoing treatment for acute promyelocytic leukemia. Methods: Analyzes were performed using High Performance Liquid Chromatography (HPLC) coupled to a UV detector, using a C-18 column. The run was performed with a mobile phase composed of ultrapure water with 0.5% glacial acetic acid (v/v) as solvent A and acetonitrile as solvent B, in an isocratic run (25:75) (A/B) with a flow of 1 mL/min, temperature at 30°C and detection at 355 nm. The sample injection was 10 μL and the run time was 12 min. The oral formulations were prepared from ATRA (Vesanoid, FQM) in mineral oil/ultrapure water (3:7) (v/v) by dissolution process and heating at 40°C, in oral dosers protected from light and kept under refrigeration (2 – 8°C). Analyzes were performed on days 1, 2, 3, 7, 9 and 14. Results: The extemporaneous preparation showed acceptable visual physical stability, with a change in appearance due to the hardening of aqueous phase, corrected by heating the formulation in water bath at 40°C. The ATRA content was considered adequate until D3 according to the Brazilian Pharmacopeia (FB) 6th edition, presenting 103.3%, 94.8% and 95.6%, on days 1, 2 and 3, respectively. The concentration of isotretinoin, a degradation product, varied from 0.16% to 1.44%, between days 1 and 14, respectively. Conclusion: The results suggested that the liquid oral preparation presented satisfactory content and physicochemical stability for up 48 hours after preparation, when stored protected from light and under refrigeration, as recommended by RDC 67/2007

Roles of Nitric Oxide and Prostaglandins in the Sustained Antihypertensive Effects of Acanthospermum hispidum

Although Acanthospermum hispidum is used in Brazilian folk medicine as an antihypertensive, no study evaluated its effects on a renovascular hypertension and ovariectomy model. So, this study investigated the mechanisms involved in the antihypertensive effects of an ethanol-soluble fraction obtained from A. hispidum (ESAH) using two-kidney-one-clip hypertension in ovariectomized rats (2K1C plus OVT). ESAH was orally administered at doses of 30, 100, and 300 mg/kg, daily, for 28 days, after 5 weeks of surgery. Enalapril (15 mg/kg) and hydrochlorothiazide (25 mg/kg) were used as standard drugs. Diuretic activity was evaluated on days 1, 7, 14, 21, and 28. Systolic, diastolic, and mean blood pressure and heart rate were recorded. Serum creatinine, urea, thiobarbituric acid reactive substances, nitrosamine, nitrite, aldosterone, vasopressin levels, and ACE activity were measured. The vascular reactivity and the role of nitric oxide (NO) and prostaglandins (PG) in the vasodilator response of ESAH on the mesenteric vascular bed (MVB) were also investigated. ESAH treatment induced an important saluretic and antihypertensive response, therefore recovering vascular reactivity in 2K1C plus OVT-rats. This effect was associated with a reduction of oxidative and nitrosative stress with a possible increase in the NO bioavailability. Additionally, a NO and PG-dependent vasodilator effect was observed on the MEV

Estudo das biomoléculas encontradas na cifomedusa Phyllorhiza punctata : isolamento e caracterização estrutural

Orientador : Guilherme L. SassakiDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Programa de Pós-Graduação em Bioquímica. Defesa: Curitiba, 2005Inclui bibliografiaResumo: A cifomedusa Phyllorhiza punctata é nativa da fauna marinha australiana, no litoral paranaense foram coletados exemplares os quais foram submetidos a analises para determinação de seus compostos, como lipídeos e carboidratos. Uma grande diversidade de ácidos graxos foi encontrada, constituindo-se de ácidos graxos saturados, monoinsaturados e poliinsaturados. O ácido graxo C22:6 3 considerado como biomarcador de micro-algas da divisão Dinophyta foi encontrado e atribuído à simbiose existente entre P. punctata e micro-algas desta divisão. Ácidos graxos poliinsaturados totalizaram 31,1% na medusa intacta, porém estavam ausentes nos braços orais e na umbrela estes ácidos graxos somaram 26,8%, considerando que as microalgas foram observadas na umbrela, elas poderiam ser as responsáveis pela síntese destes ácidos graxos. A composição de ácidos graxos e monossacarídeos apresentou diferenças em diferentes partes do corpo da medusa. Os ácidos graxos mais abundantes foram o ácido palmítico e o ácido esteárico e os monossacarídeos foram arabinose e glucose encontrados em todas as partes do corpo em concentrações diferentes. Extrações lipídicas foram realizadas utilizando misturas de solventes orgânicos e dois glicolipídeos foram encontrados, purificados por cromatografia em coluna e em camada delgada de sílica gel. Os glicolipídeos foram caracterizados estruturalmente por análises de cromatografia gasosa e espectrometria de massa (CG-EM e ESI-MS) e espectroscopia de ressonância magnética nuclear (RMN). Os experimentos RMN bidimensional (COSY, TOCSY e HMQC) forneceram importantes informações sobre a estrutura dos glicolipídeos que foram identificados como monogalactosildiacilglicerídeo (MGD) e sulfoquinovosildiacilglicerídeo (SQDG). Extrações, aquosa e alcalina, forneceram frações contendo carboidratos e proteínas. No extrato alcalino foi encontrado um polissacarídeo, purificado e, então caracterizado por RMN de 13C e análise de seus derivados metilados por CG-EM. O polissacarídeo consistia de uma -glucana ramificada, que foi identificada como glicogênio de acordo com o número e a posição das ramificações, no entanto como amido pela coloração e perfil de absorbância quando complexado com lugol

Effects of o,p’-DDE, a Mitotane Metabolite, in an Adrenocortical Carcinoma Cell Line

In South Brazil, the incidence of pediatric adrenocortical carcinoma (ACC) is higher than in other regions and countries worldwide. The ACC treatment includes therapy with mitotane, the only adrenolytic drug approved by the FDA. The mitotane metabolism occurs via two main reactions: the β-hydroxylation, which yields the final product o,p’-DDA, and the α-hydroxylation, which will give the final product o,p’-DDE. It is speculated that o,p’-DDE may be an active metabolite since it has a cytotoxic effect on adrenocortical carcinoma cells (H295R). No further studies have been conducted to confirm this hypothesis; however, it was found that mitotane and its metabolites are present at significantly different concentrations in the plasma of the patients. Our study aimed to assess the in vitro effects of o,p’-DDE and o,p’-DDD in cell death pathways, oxidative parameters, and interaction with adrenal CYP’s involved in the steroidogenic process in the H295R cell line. It was found that o,p’-DDE had a different effect than the o,p’-DDD on apoptosis, inhibiting this cell death pathway, but it promotes cell necrosis at higher concentrations. In contrast to o,p’-DDD, the o,p’-DDE did not have effects on the different oxidative parameters evaluated, but exhibited stimulatory interactions with steroidogenic CYP’s, at intermediate concentrations. Therefore, we demonstrated important cell effects of o,p’-DDE; its plasma levels during mitotane therapy should be monitored as an important therapeutic parameter

Phytochemical profile of morphologically selected yerba-mate progenies

ABSTRACT Yerba-mate (Ilex paraguariensis St. Hil) is a native South American species. Plant progenies are populations that differ in terms of their productivity, morphology and phytochemical profile. This study aimed to determine the concentration of primary and secondary metabolites, such as antioxidants, in leaves, of yerba-mate progenies selected based on morphological characteristics. We evaluated the centesimal composition of secondary metabolites in the leaves of five yerba-mate plants. Methylxanthines and phenolic compounds were determined by UPLC-PDA, and antioxidant activity by measuring DPPH scavenging. Significant differences were found in centesimal composition and the contents of caffeine, theobromine, rutin and chlorogenic acid, as well as antioxidant activities, in selected progenies. The IC50 values were correlated with the chlorogenic acid levels (r2 = 0.5242) and soluble content (r2 = 0.7686). The morphological characteristics observed in yerba-mate leaves can be used as a tool for plant selection, to obtain matrices with different phytochemical profiles as a genetic material source