Efeito anti-inflamatório do heparinóide isolado do camarão Litopenaeus vannamei sobre a peritonite aguda

In recent years the heparin has been the subject of several studies that aim to expand its use as a therapeutic agent, due to its ability to modulate the activity of various proteins that play important roles in the regulation of pathophysiological processes. In several experiments and preclinical trials, heparin has demonstrated an anti-inflammatory role. However, its clinical use is limited, due to its strong anticoagulant activity and hemorrhagic complications. For this reason, considerable efforts have been employed in discovery of heparin analogous (heparinoid) with reduced side effects, that retain the anti-inflammatory properties of heparin. In this context, a heparinoid obtained from the head of Litopenaeus vannamei shrimp, which presents a structural similarity to heparin, showed, in previous studies, anti-inflammatory activity in a model of acute peritonitis with reduced anticoagulant effect in vitro and low hemorrhagic activity. Thus, the present work had as objective to evaluate the effect the heparinoid of the cephalothorax of gray shrimp on the acute inflammatory response in different times (3 or 6 hours after the induction of inflammatory stimulus), using the model of acute peritonitis induced in mice. It was also analyzed the HL effect over the activity of elastase, an enzyme involved in leukocyte recruitment. Furthermore to check if the different doses of heparin and heparinoid change the hemostatic balance in vivo, was assessed the effect of these compounds on the plasma clotting time in animals submitted to inflammation. The results show that in 3 hours, all doses of heparinoid were able to prevent efficiently in the acute inflammatory process without any anticoagulant effects, unlike the extrapolation dose of heparin, which has induced a large hemorrhage due its high anticoagulant activity. However, 6 hours after induction of inflammation, only the dosages of 0.1 and 1.0 μg/Kg of heparin and 1.0 μg/Kg of heparinoid kept anti-migratory effect, without changing of the hemostatic balance. These results indicate that the anti-migratory effect of theses compounds depends on the dosage and time of inflammatory stimulus. The HL and heparin were also able to inhibit the activity of the enzyme elastase. The discovery of this bioactive compound in the cephalothorax of shrimps can arouse great interest in biotechnology, since this compound could be useful as a structural model interesting for the development of new therapeutic agents for peritonitis

Ensaio clínico duplo-cego controlado e randômico, comparando a eficácia da Clofazimina com a Cloroquina, no tratamento das lesões cutâneas do Lúpus Eritematoso Sistêmico

PURPOSE: To evaluate the capacity of clofazimine (CFZ) to control cutaneous activity of systemic lupus erythematosus (SLE), compared with chloroquine diphosphate (CDP). METHODS: A prospective, randomized, controlled, double blind clinical trial was carried out in thirty-three patients with SLE and cutaneous lesions (malar rash and/or discoid lupus and/or subacute cutaneous lupus), after approval by the respective Ethics Committee. Sixteen patients received clofazimine - 100mg/day (CFZ group) and 17 received chloroquine diphosphate - 250mg/day (CDP group), during six months. Both groups applied broad-spectrum sunscreens twice a day. The dose of prednisone was kept stable during the study. Cutaneous lesions were evaluated by 2 blinded observers and photographed at baseline and at months 1, 2, 4 and 6. RESULTS: Thirty-three patients began and 27 completed the 6 months of treatment. The groups were homogeneous and comparable in terms of demographic and clinical characteristics. Five CFZ-patients and one CDP-patients dropped out due to severe flare of disease requiring other treatment. At the end of the study, 12 CFZ-patients (75%) and 14 CDP-patients (82,4%) presented complete or near-complete remission of skin lesions; intention-to-treat analysis showed no significant difference in the response rates between groups. Side effects in both groups were frequent, but patients didn t have to discontinue the drugs. CONCLUSIONS: Clofazimine and chloroquine were effective in controlling cutaneous lesions in SLE patients

Micropartículas de poli (ácido lático-co-ácido glicólico) obtidas por spray drying para a liberação prolongada de metotrexato

Methotrexate (MTX) is a drug used in the chemotherapy of some kind of cancers, autoimmune diseases and non inflammatory resistant to corticosteroids uveits. However, the rapid plasmatic elimination limits its therapeutic success, which leads to administration of high doses to maintain the therapeutic levels in the target tissues, occurring potential side effects. The aim of this study was to obtain spray dried biodegradable poly-lactic acid co-glycolic acid (PLGA) microparticles containing MTX. Thus, suitable amounts of MTX and PLGA were dissolved in appropriate solvent system to obtain solutions at different ratios drug/polymer (10, 20, 30 and 50% m/m). The physicochemical characterizing included the quantitative analysis of the drug using a validate UV-VIS spectrophotometry method, scanning electron microscopy (SEM), infrared spectrophotometry (IR), thermal analyses and X-ray diffraction analysis. The in vitro release studies were carried out in a thermostatized phosphate buffer pH 7.4 (0.05 M KH2PO4) medium at 37°C ± 0.2 °C. The in vitro release date was subjected to different kinetics release models. The MTX-loaded PLGA microparticles showed a spherical shape with smooth surface and high level of entrapped drug. The encapsulation efficiency was greater then 80%. IR spectroscopy showed that there was no chemical bond between the compounds, suggesting just the possible occurrence of hydrogen bound interactions. The thermal analyses and X-ray diffraction analysis shown that MTX is homogeneously dispersed inside polymeric matrix, with a prevalent amorphous state or in a stable molecular dispersion. The in vitro release studies confirmed the sustained release for distinct MTX-loaded PLGA microparticles. The involved drug release mechanism was non Fickian diffusion, which was confirmed by Kornmeyer-Peppas kinetic model. The experimental results demonstrated that the MTX-loaded PLGA microparticles were successfully obtained by spray drying and its potential as prolonged drug release system.

Nanopartíulas de magnetita com oxacilina obtida por moagem de alta energia para aplicações biomédicas

The drug targeting has been the subject of extensive studies in order to develop site-specific treatments that minimize side effects and become more effective anticancer therapy. Despite considerable interest in this class, drugs like antibiotics also have limitations, and have been neglected. Using new pharmaceutical technologies, the use of magnetic vectors appear as promising candidate for drug delivery systems in several studies. Small magnetic particles bound to the drug of interest can be modulated according to the orientation of a magnet outside the body, locating and holding in a specific site. In this work, we propose the use of High Energy Milling (HEM) for synthesis of a magnetic vector with characteristics suitable for biomedical applications by intravenous administration, and for the formation of an oxacillin-carrier complex to obtain a system for treating infections caused by Staphylococcus aureus. The results of the variation of milling time showed that the size and structural properties of the formed material change with increasing milling time, and in 60 hours we found the sample closest to the ideal conditions of the material. The vector-drug system was studied in terms of structural stability and antimicrobial activity after the milling process, which revealed the integrity of the oxacillin molecule and its bactericidal action on cultures of Staphylococcus aureus ATCC

Parâmetros eletrocardiográficos e valores séricos e urinários de sódio e potássio em cães tratados com furosemida

The serum and urine Na+ and K+ levels and their relationship with electrocardiography characteristics,were studied in 15 male adult mongrel dogs, treated twice-a-day,with 2, 4, 8mg/kg of live weight doses of furosemide and furosemide associated with KCl during 35 days. Urine samples were analyzed weekly in order to determine the Na+ and K+ concentrations and to evaluate the urinary excretion of both cations. Electrocardiography was performed simultaneously, using limb derivations, speed 50mm/sec and calibration of 1 cm corresponding to 1mV. Data showed decreased seric concentrations of Na+ and Ki, increase in Na+ fractional excretion between days 7 and 21 of the treatment, slower heart rate and longer PR, QRS and QT intervals in the ECG. Briefly 2mg/kg furosemide associated with KCl was the most suitable treatment since it induced lesser side effects.

Intraoperative topical administration of mitomycin C, in different concentrations, on the cicatrization of mioplasties of the dorsal rectus of rabbits

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Uso de morfina, xilazina e meloxicam para o controle da dor pós-operatória em cadelas submetidas à ovariossalpingo-histerectomia

Foram realizados estudos empregando-se analgésicos por via epidural e subcutânea em cadelas de diferentes raças e idades, submetidas à castração mediante celiotomia. Vinte animais foram tranquilizados e anestesiados com tiletamina-zolazepam, e aleatoriamente distribuídos em quatro grupos (n=5), de acordo com o fármaco e a via de administração. Os do grupo morfina (GM) foram submetidos à anestesia epidural no espaço lombossacro, com morfina (0,1mg/kg) associada ao cloreto de sódio a 0,9%. Aos do grupo xilazina (GX), foram administrados xilazina (0,2mg/kg) e cloreto de sódio a 0,9%. Os do grupo meloxicam (GME) receberam 0,2mg/kg do anti-inflamatório meloxicam associado ao cloreto de sódio a 0,9%, injetado pela via subcutânea. Os do grupo-controle (CG) receberam apenas cloreto de sódio a 0,9%. O volume final para as injeções epidurais foi padronizado para 0,3mL/kg. A mensuração inicial da concentração de cortisol plasmático, do ritmo cardíaco, da frequência respiratória e os parâmetros comportamentais foram registrados imediatamente antes do procedimento cirúrgico (M1). Registros adicionais foram apresentados às 2, 6, 12 e 24 horas após o procedimento cirúrgico (M2, M3, M4 e M5, respectivamente). As variáveis comportamentais foram avaliadas por meio de sinais clínicos e seus respectivos escores. em GX foram observadas depressão respiratória, bradicardia e concentração de cortisol mais alta do que o registrado no GM. A analgesia obtida pelo meloxicam foi considerada ineficiente. É possível concluir que a morfina, via epidural, promoveu menor incidência de efeitos colaterais e melhor analgesia e bem-estar animal.

Expression of matrix metalloproteinases, type IV collagen, and interleukin-10 in rabbits treated with morphine after lamellar keratectomy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Comparison of analgesia provided by lidocaine, lidocaine-morphine or lidocaine-tramadol delivered epidurally in dogs following orchiectomy

ObjectiveTo evaluate and compare the postoperative analgesia provided by epidural lidocaine, lidocaine/morphine or lidocaine/tramadol in dogs following elective orchiectomy.Study designProspective experimental trial.AnimalsThirty-six mongrel dogs aged 2-8 years old, weighing 6.6-22 kg.MethodsThe dogs received 6.0 mg kg-1 of lidocaine combined with 1.0 mg kg-1 of tramadol, 0.1 mg kg-1 of morphine or 0.01 mL kg-1 of 0.9% NaCl epidurally. Analgesia was assessed at 4, 8, 12, 18 and 24 hours (T4, T8, T12 and T24) after the offset of lidocaine using a scale composed of physiologic and behavioral parameters. Rescue analgesia with morphine (0.2 mg kg-1, IM) was performed if the evaluation score exceeded 10 during the postoperative period. The scores over time were analyzed using the Friedman's two-way analysis of variance and the comparison between groups was made by the Kruskal-Wallis test with statistical significances accepted if p < 0.05.ResultsThere were no differences in the pain scores between the morphine and tramadol groups over time and no rescue analgesia was administered. In the NaCl group, rescue analgesia was needed at T4, T8 and T12. Within this group, the final evaluation times (T18 and T24) had lower pain scores than at T4, T8 and T12.Conclusions and clinical relevanceEpidural lidocaine/tramadol provided an analgesic effect comparable to that of epidural lidocaine/morphine during the first 12 hours after surgical castration without substantial side effects, suggesting that tramadol may be an effective postoperative analgesic in dogs submitted to this surgical procedure.

Direito fundamental à saúde: parâmetros e alternativas para sua concretização no Brasil

If, on one hand, only with the 1988 Federal Constitution the right to health began to receive the treatment of authentic fundamental social right; on the other, it is certain since then, the level of concretization reached as to such right depicts a mismatch between the constitutional will and the will of the rulers. That is because, despite the inherent gradualness of the process of concretization of the fundamental social rights, the Brazilian reality, marked by a picture of true chaos on public health routinely reported on the evening news, denatures the priority status constitutionally drew for the right to health, demonstrating, thus, that there is a clear deficit in this process, which must be corrected. This concern regarding the problem of the concretization of the social rights, in turn, is underlined when one speaks of the right to health, since such right, due to its intimate connection with the right to life and human dignity, ends up assuming a position of primacy among the social rights, presenting itself as an imperative right, since its perfect fruition becomes an essential condition for the potential enjoyment of the remaining social rights. From such premises, this paper aims to provide a proposal for the correction of this problem based upon the defense of an active role of the Judiciary in the concretization of the right to health as long as grounded to objective and solid parameters that come to correct, with legal certainty, the named deficit and to avoid the side effects and distortions that are currently beheld when the Judiciary intends to intervene in the matter. For that effect, emerges as flagship of this measure a proposition of an existential minimum specific to the right to health that, taking into account both the constitutionally priority points relating to this relevant right, as well as the very logic of the structuring of the Sistema Único de Saúde - SUS inserted within the core of the public health policies developed in the country, comes to contribute to a judicialization of the subject more in alignment with the ideals outlined in the 1988 Constitution. Furthermore, in the same intent to seek a concretization of the right to health in harmony with the constitutional priority inherent to this material right, the research alerts to the need to undertake a restructuring in the form of organization of the Boards of Health in order to enforce the constitutional guideline of SUS community participation, as well as the importance of establishing a new culture budget in the country, with the Constitution as a compass, pass accurately portray a special prioritization directed constitutional social rights, especially the right to health

Eficácia da imunoterapia no tratamento de pitiose facial em equino

Background: Pythiosis in horses is a proliferative and ulcerative disease that primarily affects the skin and subcutaneous tissue of limbs, thoracic-abdominal region and head. This disease sometimes can also affect limb bones or cause tumoral masses in abdomen. Usually, the cutaneous cases are confused with habronemiasis. The disease is more common in marshy areas, places with formation of slow drainage ponds and aquatic vegetation under high temperatures. The aim of this study was to describe the development of facial lesions in a horse caused by pythiosis in Cuiaba, Mato Grosso, and, additionally to discuss relevant issues regarding the diagnosis, clinical course and response to immunotherapy treatment.Case: One five years old mare of unknown breed, created in property located in the Cerrado region, had a wound on its face difficult to be healed and non-responsive to several treatments based on ivermectin and organophosphate administrated by either topical or systemic via. The animal was assisted on the farm of origin by the veterinary team of the Clinical Medicine sector, of the Veterinary Hospital, Universidade Federal de Mato Grosso (HOVET-UFMT). on the occasion of the visit, which occurred 60 days after onset of signs, the animal showed a circular single large lesion, ulcerative with serous discharge on the right part of its face, between the eyes and nostrils. There were some necrotic foci with sinus, from which kunkers were extracted; a condition compatible with pythiosis. The diagnosis was confirmed by histology, ELISA and PCR.Discussion: Assuming pythiosis from data obtained from the survey and profile of the lesion (secretory aspect, emaciation and presence of sinus and kunkers), immunotherapy treatment was immediately applied. The advanced clinical aspects and the fact that early diagnosis and treatment are essentials to satisfactory therapeutic response were also taken into consideration for starting the treatment. The remission of signs was achieved after five subcutaneous applications with 14 days between each application. From the second application, it was observed clinical improvement and after 60 days of treatment there was almost complete remission of signs. The signs for a satisfactory response in the injury site followed the order of decreasing secretory aspect, decreasing borders, decrease the itching and bringing the edges together with the formation of a thin layer of crust on the surface. Pythiosis cases with lesions on the face and lower abdomen are commonly confused with habronemiasis by macroscopic and widespread similarity between technicians and attendants, and essential support to the diagnosis through laboratory tests, which in turn are still underutilized. In this case, the authors demonstrated the therapeutic efficacy of immunotherapy as an advantage, considering the possibility of applying it in cases of lesions in areas of difficult surgical access, treatment conditions in the field, with low cost and ease of application. Further studies approaching this alternative therapy are necessary, since side effects have been observed in some cases.

Effect of the insecticides abamectin and lufenuron on eggs and larvae of Chrysoperla externa under laboratory conditions

The side effects of two insecticides/acaricides, abamectin and lufenuron, on the eggs and larvae of Chrysoperla externa (Hagen) were studied in the laboratory (25 +/- 2degreesC, 62 +/- 10% RH and 12-h photophase). The analytical methods used were those proposed by the International Organization for Biological Control (IOBC)-Working Group for 'Pesticides and Beneficial Organisms'. Chrysoperla externa egg viability was not affected by abamectin. Neonate larvae from abamectin sprayed eggs as well as first, second and third instar larvae that were directly treated, developed normally and yielded normal adults. Lufenuron presented no adverse effects on egg survival. However, lufenuron induced high mortality in neonate larvae from treated eggs. These neonates, as well as lufenuron treated first and second instar larvae could not molt. In the third instar, high pupal mortality occurred. The results showed that abamectin is innocuous and that lufenurom is toxic to Chrysoperla externa eggs and larvae.

Seletividade Fisiológica de Endossulfam e Deltametrina às Operárias de A. chartifex spiriti For. (Hymenoptera: Formicidae) em Agroecossistema Cacaueiro do Sudeste da Bahia

Avaliou-se o efeito dos inseticidas endossulfam e deltametrina sobre a formiga predadora Azteca chartifex spiriti For., em cultivo do cacaueiro no Sudeste da Bahia, conforme padronização da International Organization for Biological and Integrated Control (IOBC), West Palaearctic Regional Section (WPRS), com algumas modificações. Os testes foram: a) contato; b) pulverização direta; c) persistência. Nos testes de contato, operárias foram expostas a um filme fresco e seco dos inseticidas, aplicado sobre cristalizadores. Nos testes de aspersão, as formigas foram diretamente pulverizadas com os agroquímicos às concentrações recomendadas para o controle de tripes e percevejos. Os insetos foram mantidos a 25±2°C, 65±10% UR e fotofase de 12h. A sobrevivência foi avaliada após 24h e a intervalos variáveis de tempo. Nos testes de persistência, as operárias foram confinadas em cristalizadores e expostas ao contato com folhas de cacaueiro tratadas previamente no campo, sob as mesmas condições controladas. Desenvolveram-se experimentos a um, três, seis, 10, 18 e 32 dias após a aplicação (DAA). Deltametrina foi considerado seletivo nos testes de contato e pulverização direta, não sendo necessária a condução dos testes de persistência em folhas para este inseticida. Endossulfam foi altamente tóxico nos testes de contato e pulverização direta, entretanto, apresentou-se levemente persistente no terceiro teste. A análise conjunta dos três tipos de testes sugere que ambos os inseticidas são seletivos para a espécie benéfica, podendo ser recomendadosem Programas de MIP em agroecossistema cacaueiro. A metodologia proposta pela IOBC/WPRS possibilita estabilidade dos resultados, permitindo sua adaptação e utilização para o fim proposto.

Environmental Fate of Neonicotinoids and Classification of Their Potential Risks to Hypogean, Epygean, and Surface Water Ecosystems in Brazil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Efeito do exercício físico e estatinas na função muscular em animais com dislipidemia

As estatinas são utilizadas no tratamento das dislipidemias, com grande tolerância; no entanto, vários efeitos colaterais podem surgir, destacando-se miopatia. A prática regular do exercício físico (EF) produz modificações favoráveis no perfil lipídico; entretanto, pode gerar lesões musculares. OBJETIVO: Avaliar o efeito da associação entre exercício físico e estatinas na função muscular, pela análise histológica, em modelo experimental animal com dislipidemia. MÉTODOS: Foram utilizados 80 ratos machos Wistar, distribuídos em oito grupos, incluindo animais submetidos à dieta hipercolesterolêmica (DH), sinvastatina com (G1) e sem (G2) EF; DH e fluvastatina, com (G3) e sem EF (G4); alimentados com ração comercial (RC) na presença (G5) e ausência de (G6) EF; DH submetidos (G7) ou não (G8) a EF. A DH foi administrada por 90 dias, as estatinas e prática de EF em esteira rolante por oito semanas. Os animais foram sacrificados, e o músculo sóleo retirado para análise histológica. Aplicaram-se os testes t de Student pareado e análise multivariada, com nível significante para p < 0,05. RESULTADOS: As principais alterações histológicas encontradas foram fibras de diferentes diâmetros, atróficas, em degeneração, splitting, edema, infiltrado inflamatório. Essas alterações foram observadas em 90% dos animais do grupo G1, 80% do G2, 70% do G3, 30% do G4, 40% do G5 e 30% do G7. Nos grupos G6 e G8 identificaram-se fibras musculares com morfologia preservada. CONCLUSÕES: Na avaliação histológica muscular, a associação entre fluvastatina, sinvastatina e exercício físico acarreta alterações morfológicas com predomínio no uso da sinvastatina, variando de grau leve a grave, no músculo sóleo de ratos, induzidos pelos inibidores da HMG-CoA redutase.