Trissoralen um medicamento de baixa dosagem: estudos termoanalíticos da compatibilidade do fármaco-excipientes e determinação de parâmetros de qualidade para cápsulas magistrais

The trioxsalen (Tri) is a low-dose drug used in the treatment of psoriasis and other skin diseases. The aim of the study was applying the thermal analysis and complementary techniques for characterization, evaluation of the trioxsalen stability and components of manipulated pharmaceutical formulations. The thermal behavior of the Tri by TG/DTG-DTA in dynamic atmosphere of synthetic air and nitrogen showed the same profile with a melting peak followed by a volatilization-related event. From the curves TG / DTG is observed a single stage of mass loss. By heating the drug in the stove at temperatures of 80, 240 and 260 °C, it had no change in chemical structure through the techniques of XRD, HPLC, MIR, OM and SEM. From the non-isothermal and isothermal TG kinetic studies was possible to calculate the activation energy and reaction order for the Tri. The drug showed good thermal stability. Studies on drug-excipient compatibility showed interaction of trissoralen with sodium lauryl sulfate 1:1. There was no interaction with aerosol, pregelatinized starch, sodium starch glycolate, cellulose, croscarmellose sodium, magnesium stearate, lactose and mannitol.The characterization of three trioxsalen formulations at concentrations of 2.5, 5, 7.5, 10, 12.5 and 15 mg was performed by DSC, TG / DTG, XRD, NIR and MIR. The PCA classification method based on spectral data from the NIR and MIR of trissoralen formulations allows successful differentiation into three groups. The formulation 3 was the one that best showed analytical profile with the following composition of aerosil excipients, pre-gelatinized starch and cellulose. The activation energy of the volatilization process of the drug was determined in binary mixtures and formulation 3 through fitting and isoconversional methods. The binary mixture with sodium starch glycolate and lactose showed differences in kinetic parameters compared to the drug isolated. The thermoanalytical techniques (DSC and TG / DTG) were shown to be promising methodologies for quantifying trioxsalen obtained by the linearity, selectivity, no use solvents, without sample preparation, speed and practicality.

Lâminas de água salina e doses de adubação orgânica na produção de palma Miúda adensada no semiárido

Cactus pear is an important forage for livestock in semi-arid region of Brazil, due to its adaptation to climate conditions in this region, high productivity and nutritional value. The yield of this cactus has positively responded to techniques such as planting density, fertilization and cutting managements, however, in Rio Grande do Norte State, only certain areas have favorable climate conditions to the development of this crop. Drip irrigation, with a small amount of water, has proven to be an alternative to the viability of cactus pear cultivation in these areas. The research aimed to evaluate the effects of different levels of saline water and manure organic fertilization on the morphological characteristics and production of fresh and dry matter of the prickly-pear cactus cv. Miúda (Nopalea cochenillifera Salm Dick) in a dense planting system. The experiment was conducted at the Experimental Station of Terras Secas (EMPARN), Pedro Avelino, latitude 5°31'21" South and longitude 36°23'14" West. The soil was classified as Typical Cambisol Haplicum Carbonate and the water used in irrigation, C4S1T3 (5,25 dS.m-1), with planting spacing of 2.0 x 0.25 m (20,000 plants ha-1). A completely randomized design in a split plot was used, where water levels (0, 7.5, 15.0 and 30.0 mm month-1) with 10 days intervals, were the main plots and organic fertilization (0 , 25 and 50 Mg ha-1 yr-1) the subplots, with four replicates. The measured morphological characteristics were number of cladodes, height and volume of the plant; length, width, perimeter, thickness, area and cladodes area index, fresh and dry matter production, dry matter content, water use efficiency (WUE) and damage promoted by cochineal pest (Diaspis echinocacti) and soft rot (Erwinia carotovora). There was no influence (P>0.05) of organic fertilization on most variables, particularly in relation to the production of fresh and dry matter. The water levels had a significant influence (P<0.05) on most variables, promoting higher height and volume of the plants, larger and thicker cladodes, and increase on fresh and dry matter production (13.55 Mg DM ha-1 yr-1). The absence of irrigation caused a significant expansion in plant damage caused by the cochineal pest and when irrigated with different water levels there was an increase in damage and stand loss, caused by soft rot, been more intense at the higher water level.

Modulação pela progesterona da sensibilidade dolorosa a estímulos mecânicos e isquêmicos em mulheres saudáveis e jovens

BRUNO, S. S. ; SOUSA, M. B. C. . Modulação pela progesterona da sensibilidade dolorosa a estímulos mecânicos e isquêmicos em mulheres saudáveis e jovens. RBGO. Revista Brasileira de Ginecologia e Obstetrícia , v. 30, p. 306-311, 2008

Avaliação da fidedignidade dos ensaios de esteróides fecais realizados no Laboratório de Medidas Hormonais do Departamento de Fisiologia da UFRN

NASCIMENTO, H. G. ; FERNANDES, L. C. ; SOUSA, M. B. C. . Avaliação da fidedignidade dos ensaios de esteróides fecais realizados no Laboratório de Medidas Hormonais do Departamento de Fisiologia da UFRN. Publica , v. 2, p. 39-48, 2006.

Translocação bacteriana para o pulmão na icterícia obstrutiva experimental em ratos

RESUMO: Objetivo: Tem sido demonstrado que a icterícia obstrutiva provoca depressão do sistema imunológico, mudança no padrão de colonização bacteriana dos intestinos e passagem de bactérias da luz intestinal para a circulação porta e sistêmica. Estudo experimental em ratos procurou observar a possibilidade de translocação bacteriana para os pulmões após a ligadura do colédoco. Método: Foram utilizados 20 ratos Wistar pesando de 178 a 215g, separados aleatoriamente em dois grupos iguais. Nos ratos do grupo I foi feita a ligadura do colédoco e nos do grupo II apenas a manipulação do colédoco com pinça atraumática (sham operation). No sétimo dia de observação os animais foram mortos com superdose de anestésico, sangue foi colhido para dosagem de bilirrubinas e os pulmões ressecados sob condições assépticas. Metade de cada pulmão foi homogeneizada e semeada em meios de cultura ágar McConkey e ágar sangue. A outra metade serviu para exame histopatológico –coloração hematoxilina e eosina. Os dados foram analisados pelo teste t, com significância 0,05. Resultados: revelaram bilirrubina total em média 18,7±3,6 no grupo I e 0,7±0,2 no grupo II. No grupo I foram isoladas colônias de Klebsiela sp nos pulmões de 30% dos animais e E. coli em 20%, e os escores histopatológicos atingiram a média 6,2±2,08. No grupo II não foram detectadas bactérias nos pulmões e os escores do exame histopatológico atingiram 1,8±1,16. A diferença dos dados analisados mostrou-se significativa (p<0,05). Conclusões: Concluiu-se que a icterícia obstrutiva por ligadura do colédoco em ratos provocou translocação de germes Gram-negativos para os pulmões e resultou em alterações histopatológicas significativas.

Efeito da sinvastatina na sepse abdominal de ratos diabéticos

Analisar se o pré-tratamento com sinvastatina em modelo experimental de sepse abdominal é benéfico em ratos diabéticos. Métodos: Cinquenta e seis ratos Wistar foram aleatoriamente distribuídos em: grupo não diabético (n-28) e grupo diabetes induzido por estreptozotocina (n=28). Sepse abdominal por ligadura e punção do ceco foi induzida em 14 ratos diabéticos e em 14 não diabéticos. Os demais 28 animais foram alocados em grupo sham. Os grupos de ratos com sepse e os sham (cada com sete animais) foram tratados com microemulsão oral de simvastatina (20 mg kg-1 day-1) e solução salina 0,9%, respectivamente. Sangue periférico foi usado para dosagem de TNFa, IL-1b, IL-6, proteína C reativa, procalcitonina, contagem de leucócitos e neutrófilos em todos os animais. A análise estatística foi realizada pela ANOVA e teste de Tukey, com p<0,05. Resultados: A sinvastatina reduziu a mortalidade nos ratos diabéticos. Os valores séricos de TNF-a, IL-1b, IL-6, proteína C reativa, procalcitonina, leucócitos e neutrófilos mostraram-se mais baixos nos ratos diabéticos e não diabéticos com sepse, tratados com sinvastatina, do que nos tratados com solução salina. Conclusão: A sinvastatina teve efeito antiinflamatório, que pode ter resultado em proteção contra a sepse em ratos diabéticos

Efeitos da aplicação tópica do mel de melipona subnitida em feridas infectadas de ratos

Avaliar efeitos do uso tópico do mel da abelha silvestre Melipona subnitida na evolução de feridas infectadas de pele. Método: Ratos Wistar foram distribuídos aleatoriamente em grupos de 6, anestesiados com tiopental sódico 20mg/Kg IP e cetamina 30mg/Kg IM e submetidos a exérese de segmento de 1 cm2 de pele total do dorso. Os ratos do grupo C (não infectado) foram tratados com solução salina sobre a ferida diariamente e no grupo MEL (não infectado) as feridas foram tratadas com mel uma vez por dia. Nos grupos C/I e MEL/I as feridas foram inoculadas com solução polimicrobiana. Culturas foram feitas 24 horas após. Caracterizada a infecção, as feridas foram tratadas com solução salina e mel, respectivamente. No terceiro dia de tratamento foi feita nova cultura. Após epitelização foi contado o tempo de cicatrização e as feridas foram biopsiadas para histopatologia e dosagem de TNF-a, IL-1b e IL-6 no tecido. Resultados: O tempo médio de cicatrização do grupo MEL/I foi menor que nos demais grupos(P<0,05). Verificou-se que a densidade de colágeno, leucócitos, fibroblastos e dosagem de citocinas (especialmente TNF) foi maior no grupo infectado e tratado com mel que nos demais grupos. Houve significante redução de bactérias Gram-negativas e positivas nas feridas após o tratamento com mel. Conclusão: O uso tópico de mel de Melipona subnitida em feridas infectadas da pele de ratos estimulou a resposta imunológica, reduziu a infecção e o tempo de cicatrização

Effects of simvastatin in abdominal sepsis in rats

Statins are widely recognized as hypolipemic drugs, but some studies have observed anti-inflammatory and immunomodulatory effects, known as pleiotropic. The aims of this work was to study possible anti-inflammatory effects of simvastatin in abdominal sepsis. Serum pro-inflammatory cytokines and leukocytes count were determined in an experimental model of abdominal sepsis, using cecal ligation and puncture (CLP) in rats. Methods: Twenty eigth Wistar rats weighing 285±12g were randomly divided in: CLP/Sinvastatin rats (n=7), treated with 10 mg/Kg of oral simvastatin 18 and 2 hs berofe CLP; CLP/Saline group rats (n=7), treated with oral saline; group Sham/Simvastatin (n=7), treated with simvastatin, and group Sham/Saline (n=7), treated with saline. Serum TNF-α, IL-1β and IL-6 by ELISA and total leukocytes, neutrophils, lymphocytes, and eosinophils were determined 24 hs after CLP. ANOVA and Tukey test were used considering significant p<0.05. Results: It was demonstrated that serum TNF-α, IL-1β and IL-6 were respectively 364,8±42pg/mL; 46,3±18pg/mL and 28,4±13pg/mL in CLP/Sinvastatin rats, significantly lower (p<0.05) than in group CLP/Saline (778,5±86pg/ml; 176,9±46pg/ ml; 133,6±21 pg/ml, respectively). The same results were observed in total leukocytes and neutrophils counts. Conclusion: These results clearly demonstrate that simvastatin is an effective agent that reduces cytokines levels and leukocyte count in sepsis, independently of its well-known lipid-lowering effects. Thus, HMG-CoA reductase inhibitors like simvastatin have important anti-inflammatory effects in abdominal sepsis in rats

A nicotina atua como fator deletério na reparação da parede abdominal

Objetivo: Avaliar o efeito da nicotina na cicatrização da camada musculoaponeurótica da parede abdominal. Métodos: Estudo experimental em que foram usados 16 ratos da raça Wistar pesando em média 210±8g, separados aleatoriamente em 2 grupos de 8. Nos animais do grupo A foi implantado disco de nicotina (Nicotinel Ò) na dose de 5mg/Kg de peso/dia no subcutâneo da região dorsal, trocado a cada dois dias, a partir do 5º dia antes da operação em que foi feita laparotomia mediana de 5 cm, até o 10o dia de observação. No grupo B (controle) foram usados discos de celulose com o mesmo diâmetro. Tubo de silicone multiperfurado foi implantado no subcutâneo a 1cm da lesão da parede abdominal. A camada musculoaponeurótica e a pele foram suturadas com fio de nylon 5-0. No 10º dia pós-operatório foi colhido 1ml de líquido seroso do tubo de silicone por punção percutânea para dosagem de pO2 e os animais receberam dose letal de anestésico. Foi ressecado um segmento da camada musculoaponeurótica com 2cm de largura para tensiometria, em seguida processado e corado em HE e tricrômico de Masson para análise quantitativa dos dados histopatológicos em sistema digitalizado. A análise estatística foi feita pelo ANOVA e teste Newman-Keuls, com significância 0,05. Resultados: No grupo A a pO2 do líquido tecidual atingiu o valor 17,75±3,4 mmHg e no grupo B (controle) a pO2 = 40,75±6,4 mmHg (p<0,01). A resistência à tensão apresentou o valor de 728,5±161,75gf no grupo A e 1241,6±232gf no grupo de controle (p<0,01), coincidindo com os achados da pO2. A densidade média dos elementos histopatológicos estudados foi de 105±17,1 nos animais do grupo A e 146,2±8,8 no grupo B (p<0,01). Conclusão: após avaliação da pO2 tecidual, tensiometria e histopatologia, concluiu-se que a nicotina por via subcutânea exerce efeito deletério sobre a cicatrização de lesões da parede abdominal de ratos

Avaliação da concentração de retinol em fígados frescos e congelados de frangos das linhagens Cobb e Ross

The intake of adequate quantities of food, including those rich in vitamins, is necessary for a healthy life. The lack of vitamin A has been characterized as a public health problem in developing countries, however, a high intake of vitamin A can result in toxic and teratogenics effects. High concentrations of vitamin A have been observed in the livers of animals. The objective of this study was to assess the levels of retinol in chicken livers and verify the effect of frozen storage on these levels. 64 livers from two chicken strains, Cobb and Ross, were used, came from four different farms. We examined 32 livers from each strain, 8 samples from each farm. Liver sample were homogenized individually, then 4 aliquots were taken from each sample. One of aliquots was analyzed immediately after slaughter (T0), the others were analyzed after 30, 60 and 90 days of storage at -18oC (T30, T60 and T90, respectively). Retinol dosage in the liver was determined by High Performance Liquid Chromatography (HPLC). The levels of retinol varied significantly according to the strain. The mean retinol value in the fresh samples was 6678.0 ± 1337.7 and 8324.1 ± 1158.5 µg/100g in the Cobb and Ross strain, respectively. Values of 4258 ± 918.7 ± 1391.7 and 4650.5 ± 1391.7 μg/100g were found after 90 days of storage for Cobb and Ross strain, respectively. The liver freezing caused a significant reduction in their levels of retinol, causing a loss of up to 44% with respect to fresh livers. The reduction in retinol levels occurred from 30 days of storage. Even with the losses from the frozen, the ingestion of a typical portion of 100 g of liver, regardless the chicken strain analyzed, surpass all recommendations of consumption and the maximum tolerable intake of vitamin A (3000 μg/day) for adults

Estudo de ß-glucanas extraídas dos fungos Geastrum saccatum e Polyporos dermoporus: características químicas e atividades biológicas

Fungal polysaccharides have received a great deal of attention due to itsbecause of their potential use in a wide rangegreat variety fromof industries. Some studies have demonstrated that polysaccharides extracted offrom basidiomycetes they have presented significant properties as anti-inflammatory, antimicrobial, antioxidant and anti-tumoral properties. In spite of thisDespite these potential properties, these mushrooms have not been insufficiently investigated, and the great number of antibiotics number produced forby these organisms suggests that they canmay be a new source of bioactives composites source. In tThe present work, reports onlated the chemical composition, potential antioxidant, antiinflammatory and citotoxycity of extracted polymers extracted offrom the fruits bodies of the fungiius Geastrum saccatum and Polyporus dermoporus, native mushrooms of the Atlantic forest inof the state of the Rio Grande do Norte, Brazil. The Cchemical analyses had revealed ademonstrated text of total sugar rates of 65% and 49%, and proteins of 7.0% for in extracts of G. saccatum and P. dermoporus extracts, respectively. The analyses ofNMR spectroscopy of RMN had demonstrated that these extracts are composites forof a complex involving β- glucans and- proteins complex. The inhibition of the formation of superoxide radicals formation was of 88.4% in G. saccatum and 83.3% in P. dermoporus, and 75 and 100% for inhibition of hydroxyls radicals inhibition. TopicalThe topic application of extracts the 10, 30 and 50 mg/kg extract in BALBc mice with cutaneous inflammation induced byfor croton oil demonstrated to inhibitedion of ear edema of ear and cells polimorfonuclears cells atin the inflamed siteplace, being this reply more effective in lower concentrations being more effective. The evaluation of the glucans of G. saccatum and P. dermoporus glucans under induced pleurisy for carrageenan-induced pleurisya of showed the antiinflammatory action of these composites., being analyzed tThe frame number in the pleural exudates and thedosage of nitric oxide dosage was also analyzed. The cytotoxic action of these polymers was analyzed throughthrough the mitochondrial function (MTT). The incubation of the glucans with mononuclear cells of the peripheral blood demonstrated that the extracted glucans extracted fromof G. saccatum havepossess a moderate cytotoxic action. These results suggest that these mushrooms possess polymers formed byfor a complex glucana-protein complex, with antiinflammatory and antioxidant actions

Influência do tempo e dose de heparina em modelo de peritonite aguda

In the last years, heparin has become target of many studies related to inflammation due its ability of biding to proteins involved on immune response. Recently, it was demonstrated, at our laboratory, using a thIoglycollate-induced peritonitis model, heparin s capacity of reduce cellular influx into the peritoneal cavity, 3 hours after the inflammatory stimulus. Once neutrophilic infiltration is highest around 8 hours after the inflammatory stimulus, at the present work, using the same peritonitis model, it was assessed heparin s ability of keeping the interference on leukocyte infiltration, 8 hours after inflammation induction. Moreover, using cellular differential count, it was evaluated how the cellular populations involved in the inflammatory process would be affected by the treatment. Eight hours after the inflammatory stimulus, only heparin dosage of 1 μg/Kg was able to reduce the cellular influx to peritoneum, 62.8% of reduction when compared to positive control (p < 0.001). Furthermore, heparin dosage of 15 μg/Kg presented a pro-inflammatory effect in whole blood verified by the increase of 60.9% (p < 0.001) and 117.8% (p < 0.001) on neutrophils and monocytes proportion, respectively, when compared to positive control. In addition, this dosage also presented a neutrophilic proportion on peritoneal fluid 27.3% higher than positive control (p < 0.05). This duality between anti- and pro-inflammatory effects at different times corroborates studies that attribute a pleiotropic immunomodulator role to heparin.

Efeito sacietogênico de um novo inibidor de tripsina da paçoca do amendoim com aumento plasmático de colecistocinina (cck)

Obesity is increasing, reaching epidemic levels in many regions of the world. Studies have shown that consumption of peanuts influences on weight control and this influence may be due to the action of trypsin inhibitors sacietogênica that condition increased plasma colescistocinina (CCK). Moreover, the peanut has other health benefits, and these assignments are guaranteed to increase their production and consumption of several of its products, including the paçoca peanut. The aim of this study was to identify the presence of a trypsin inhibitor in paçoca peanut and evaluate its effect on food intake, weight gain and histomorphological changes in swiss mice (n = 8) and Wistar rats (n = 6). Experimental diets were prepared based on the AIN-93G and supplemented with tack or peanut trypsin inhibitor partially purified paçoca peanut (AHTI). After each treatment, the animals were anesthetized and euthanized, their bloods were collected by cardiac puncture for the determination of CCK and other biochemical parameters (glucose, triglycerides, total cholesterol, high density lipoprotein, low density lipoprotein, glutamic-pyruvic transaminase, glutamic oxaloacetic transaminase and albumin) and their pancreas removed for histologic and morphometric analysis. The supplementation with paçoca peanut and the AHTI showed a decrease of body weight gain and food intake in both mice and rats, due to the satiety, since the animals showed no evidence of impairment of nutritional status conditioned by consumption the AHTI. There were also observed biochemical or morphological important when compared with controls. However, AHTI led to increased secretion of CCK, a peptide sacietogênico. Thus, these results indicate that AHTI present in paçoca peanut, is able to enhance the secretion of plasma CCK and thereby reduce the weight gain associated with lower food intake of experimenta animals

Atividade antioxidante e antiproliferativa de extratos de folhas de Plukenetia volubilis L. (EUPHORBIACEAE)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Estudo da adição de argila expandida na formulação de concretos leves

Lightweight concrete has been the subject of several studies towards the development of new building materials. Emphasis has been given on the particle size effect and nature of aggregates used as raw materials. The present study includes an analysis of the materials that make this kind of concrete, analyzes of mechanical properties such as compressive and tensile strength, in addition to assessments of the interface concrete aggregate/matrix interface, porosity and absorption profile of chloride ions in lightweight concrete based on expanded clay. The experiments were carried out by molding cylindrical samples 100 mm in diameter and 200 mm in height. The dosage experiments were performed without additives or with the addition of minerals: (T1) 1: 2.01: 1.10: 0.78 (T2) 1: 2.00: 1.32 : 0.62 - (T3) 1 :1.93 :1.54: 0.47 (cement : sand : expanded clay 0500 : expanded clay 1506).The water to cement ratio was set to 0.43. Expanded clay minerals with different average particle sizes were used, i.e., 9.5 mm/0500 and 19 mm/1506. The larger aggregate was coated by a glassy layer, yielding lower water absorption characteristics to the concrete. The results showed that the use of light expanded clay aggregates is a technically interesting solution to the production of lightweight concrete for construction applications