Acute and subchronic effects of petroleum on the freshwater fish Hoplias aff. malabaricus

Abstract Petroleum water soluble fraction (WSF) impairs organisms, but damages may vary among cell and tissue levels. The aim of the present study was to evaluate the acute (24 h, 48 h, 72 h) and subchronic effects (36 days) of WSF (0%, 25% and 100%) in juveniles of the Neotropical top predator fish Hoplias aff. malabaricus. The effects of WSF were evaluated at a molecular level using the comet assay and micronucleus test for genome damage; and at a morphological level through histological identification of liver pathologic lesions. In both acute and subchronic exposure we found low levels of DNA damage ( 10% of comet tail) and non-significant frequency of micronucleus in WSF exposed fish. The most significant liver lesions in WSF exposed fish were fatty vacuolization, hypertrophy and focal necrosis. Since these tissue injuries were progressive and persistent, their irreversibility may negatively affect fish recruitment, even in a such resistant top predator.

Resumo A fração solúvel de petróleo (WSF) prejudica os organismos, porém os danos podem variar entre os níveis celular e tecidual. O objetivo do presente estudo foi avaliar o efeito agudo (24 h, 48 h e 72 h) e subcrônico (36 dias) da WSF (0%, 25% e 100%) em juvenis do peixe neotropical predador topo Hoplias aff. malabaricus. Os efeitos da WSF foram avaliados no nível molecular utilizando o ensaio do cometa e o teste do micronúcleo para o dano genômico e no nível morfológico através da identificação histológica de lesões patológicas no fígado. Em ambas exposições (aguda e subcrônica) encontramos baixos níveis de dano no DNA ( 10% de DNA na cauda do cometa) e frequência de micronúcleos não significativa em peixes expostos a WSF. As lesões mais significativas no fígado dos peixes expostos a WSF foram a vacuolização lipídica, hipertrofia e focos de necroses. Como estas lesões foram progressivas e persistentes, sua irreversibilidade pode afetar negativamente o recrutamento dos peixes, mesmo sendo um predador topo resistente.

Exogenous application of salicylic acid induces salinity tolerance in eggplant seedlings

Abstract Under salt stress conditions, plant growth is reduced due to osmotic, nutritional and oxidative imbalance. However, salicylic acid acts in the mitigation of this abiotic stress by promoting an increase in growth, photosynthesis, nitrogen metabolism, synthesis of osmoregulators and antioxidant enzymes. In this context, the objective was to evaluate the effect of salicylic acid doses on the growth and physiological changes of eggplant seedlings under salt stress. The experiment was conducted in a greenhouse, where the treatments were distributed in randomized blocks using a central composite matrix Box with five levels of electrical conductivity of irrigation water (CEw) (0.50; 1.08; 2.50; 3.92 and 4.50 dS m-1), associated with five doses of salicylic acid (SA) (0.00; 0.22; 0.75; 1.28 and 1.50 mM), with four repetitions and each plot composed of three plants. At 40 days after sowing, plant height, stem diameter, number of leaves, leaf area, electrolyte leakage, relative water content, and total dry mass were determined. ECw and SA application influenced the growth and physiological changes of eggplant seedlings. Increasing the ECw reduced growth in the absence of SA. Membrane damage with the use of SA remained stable up to 3.9 dS m-1 of ECw. The relative water content independent of the CEw increased with 1.0 mM of SA. The use of SA at the concentration of 1.0 mM mitigated the deleterious effect of salinity on seedling growth up to 2.50 dS m-1 of ECw.

Resumo Em condições de estresse salino, o crescimento das plantas é reduzido, em virtude, do desequilíbrio osmótico, nutricional e oxidativo. Contudo, o ácido salicílico atua na mitigação desse estresse abiótico por promover incremento no crescimento, fotossíntese, metabolismo do nitrogênio, síntese de osmorreguladores e enzimas antioxidantes. Nesse contexto, objetivou-se avaliar o efeito de doses de ácido salicílico sobre o crescimento e alterações fisiológicas de mudas de berinjela sob estresse salino. O experimento foi conduzido em casa de vegetação, onde os tratamentos foram distribuídos em blocos ao acaso utilizando uma matriz composta central Box com cinco níveis de condutividade elétrica da água de irrigação (CEa) (0,50; 1,08; 2,50; 3,92 e 4,50 dS m-1), associada a cinco doses de ácido salicílico (AS) (0,00; 0,22; 0,75; 1,28 e 1,50 mM), com quatro repetições e cada parcela composta por três plantas. Aos 40 dias após a semeadura, foram determinados a altura da planta, diâmetro do caule, número de folhas, área foliar, vazamento de eletrólito, teor relativo de água e massa seca total. A CEa e a aplicação de AS influenciaram no crescimento e nas alterações fisiológicas das mudas de berinjela. O aumento da CEa reduziu o crescimento na ausência de AS. O dano de membrana com o uso de AS manteve-se estável até 3,9 dS m-1 de CEa. O conteúdo relativo de água independentemente da CEa aumentou com 1 mM de SA. O uso de AS na concentração de 1 mM mitigou o efeito deletério da salinidade no crescimento das mudas até 2,50 dS m-1 de CEa.

Acute and subchronic effects of petroleum on the freshwater fish Hoplias aff. malabaricus / Efeitos agudo e subcrônico do petróleo no peixe de água doce Hoplias aff. malabaricus

Abstract Petroleum water soluble fraction (WSF) impairs organisms, but damages may vary among cell and tissue levels. The aim of the present study was to evaluate the acute (24 h, 48 h, 72 h) and subchronic effects (36 days) of WSF (0%, 25% and 100%) in juveniles of the Neotropical top predator fish Hoplias aff. malabaricus. The effects of WSF were evaluated at a molecular level using the comet assay and micronucleus test for genome damage; and at a morphological level through histological identification of liver pathologic lesions. In both acute and subchronic exposure we found low levels of DNA damage (< 10% of comet tail) and non-significant frequency of micronucleus in WSF exposed fish. The most significant liver lesions in WSF exposed fish were fatty vacuolization, hypertrophy and focal necrosis. Since these tissue injuries were progressive and persistent, their irreversibility may negatively affect fish recruitment, even in a such resistant top predator.

Resumo A fração solúvel de petróleo (WSF) prejudica os organismos, porém os danos podem variar entre os níveis celular e tecidual. O objetivo do presente estudo foi avaliar o efeito agudo (24 h, 48 h e 72 h) e subcrônico (36 dias) da WSF (0%, 25% e 100%) em juvenis do peixe neotropical predador topo Hoplias aff. malabaricus. Os efeitos da WSF foram avaliados no nível molecular utilizando o ensaio do cometa e o teste do micronúcleo para o dano genômico e no nível morfológico através da identificação histológica de lesões patológicas no fígado. Em ambas exposições (aguda e subcrônica) encontramos baixos níveis de dano no DNA (< 10% de DNA na cauda do cometa) e frequência de micronúcleos não significativa em peixes expostos a WSF. As lesões mais significativas no fígado dos peixes expostos a WSF foram a vacuolização lipídica, hipertrofia e focos de necroses. Como estas lesões foram progressivas e persistentes, sua irreversibilidade pode afetar negativamente o recrutamento dos peixes, mesmo sendo um predador topo resistente.

Exogenous application of salicylic acid induces salinity tolerance in eggplant seedlings / Aplicação exógena de ácido salicílico induz tolerância à salinidade em mudas de berinjela

Abstract Under salt stress conditions, plant growth is reduced due to osmotic, nutritional and oxidative imbalance. However, salicylic acid acts in the mitigation of this abiotic stress by promoting an increase in growth, photosynthesis, nitrogen metabolism, synthesis of osmoregulators and antioxidant enzymes. In this context, the objective was to evaluate the effect of salicylic acid doses on the growth and physiological changes of eggplant seedlings under salt stress. The experiment was conducted in a greenhouse, where the treatments were distributed in randomized blocks using a central composite matrix Box with five levels of electrical conductivity of irrigation water (CEw) (0.50; 1.08; 2.50; 3.92 and 4.50 dS m-1), associated with five doses of salicylic acid (SA) (0.00; 0.22; 0.75; 1.28 and 1.50 mM), with four repetitions and each plot composed of three plants. At 40 days after sowing, plant height, stem diameter, number of leaves, leaf area, electrolyte leakage, relative water content, and total dry mass were determined. ECw and SA application influenced the growth and physiological changes of eggplant seedlings. Increasing the ECw reduced growth in the absence of SA. Membrane damage with the use of SA remained stable up to 3.9 dS m-1 of ECw. The relative water content independent of the CEw increased with 1.0 mM of SA. The use of SA at the concentration of 1.0 mM mitigated the deleterious effect of salinity on seedling growth up to 2.50 dS m-1 of ECw.

Resumo Em condições de estresse salino, o crescimento das plantas é reduzido, em virtude, do desequilíbrio osmótico, nutricional e oxidativo. Contudo, o ácido salicílico atua na mitigação desse estresse abiótico por promover incremento no crescimento, fotossíntese, metabolismo do nitrogênio, síntese de osmorreguladores e enzimas antioxidantes. Nesse contexto, objetivou-se avaliar o efeito de doses de ácido salicílico sobre o crescimento e alterações fisiológicas de mudas de berinjela sob estresse salino. O experimento foi conduzido em casa de vegetação, onde os tratamentos foram distribuídos em blocos ao acaso utilizando uma matriz composta central Box com cinco níveis de condutividade elétrica da água de irrigação (CEa) (0,50; 1,08; 2,50; 3,92 e 4,50 dS m-1), associada a cinco doses de ácido salicílico (AS) (0,00; 0,22; 0,75; 1,28 e 1,50 mM), com quatro repetições e cada parcela composta por três plantas. Aos 40 dias após a semeadura, foram determinados a altura da planta, diâmetro do caule, número de folhas, área foliar, vazamento de eletrólito, teor relativo de água e massa seca total. A CEa e a aplicação de AS influenciaram no crescimento e nas alterações fisiológicas das mudas de berinjela. O aumento da CEa reduziu o crescimento na ausência de AS. O dano de membrana com o uso de AS manteve-se estável até 3,9 dS m-1 de CEa. O conteúdo relativo de água independentemente da CEa aumentou com 1 mM de SA. O uso de AS na concentração de 1 mM mitigou o efeito deletério da salinidade no crescimento das mudas até 2,50 dS m-1 de CEa.

Autotransfusão imediata em cão - relato de caso / Instant autotransfusion in dog - case report

As hemorragias podem levar à morte, em caso de não interrupção e recuperação da volemia. A substituição do sangue pode ser realizada por transfusão homóloga ou autóloga. Na transfusão homóloga, o sangue é obtido de um doador, na autotransfusão ou transfusão autóloga, o sangue é coletado do próprio paciente. Objetivou-se relatar a autotransfusão em um cão como um método simples, rápido e barato, e discutir esse procedimento como uma alternativa emergencial para clínicas e hospitais que não possuem bancos de sangue ou animais doadores. Foi atendido um cão Rottweiler fêmea, 42,8kg, 10 anos de idade, com queixa principal de tumor mamário e para realização de castração. Após o procedimento, a paciente apresentou hemoperitônio, sendo encaminhada para novo procedimento cirúrgico, durante o qual se observou grande quantidade de sangue livre na cavidade abdominal. Foi realizada a autotransfusão de emergência, pela técnica das duas seringas, devido à indi1111sponibilidade de sangue ou animal doador no momento do procedimento cirúrgico emergencial, demonstrando ser uma opção eficiente, econômica, de fácil acesso e segura, por ser uma transfusão normotérmica, apresentar diminuição do risco de sobrecarga circulatória e por ser o sangue compatível, devendo ser mais explorada, pois existem poucos dados descritos na literatura.(AU)

Hemorrhages can lead to death in case of non-interruption and recovery of blood volume. Blood replacement may be performed by homologous or autologous transfusion. In homologous transfusion, blood is obtained from a donor, in autotransfusion or autologous transfusion, blood is collected from the patient himself. We aimed to report autotransfusion in a dog as a simple, quick, and inexpensive method, and discuss it as an emergency alternative for clinics and hospitals that do not have blood banks or animal donors. A female Rottweiler dog, 42.8kg, 10 years of age, was treated with a primary complaint of mammary tumor and for castration. After the procedure the patient presented hemoperitoneum, being referred to a new surgical procedure, where a large amount of free blood was observed in the abdominal cavity. The emergency autotransfusion was performed by the two syringes technique, due to the unavailability of blood or donor animal at the time of the emergency surgical procedure, proving to be an efficient, economical, easily accessible and safe option because it is a normothermic transfusion, risk of circulatory overload and blood is compatible. It should be more exploited because there are few data described in the literature.(AU)

Cytological and molecular detection of Leishmania spp. in different biological tissues of dogs in areas endemic for visceral leishmaniasis / Detecção citológica e molecular de Leishmania spp. em diferentes amostras biológicas de cães em áreas endêmicas para leishmaniose visceral

Devido à ampla distribuição da leishmaniose visceral (LV) no Brasil e à importância dos cães no ciclo de transmissão dessa zoonose, o presente estudo teve como objetivo avaliar a ocorrência de Leishmania spp. e caracterizar a espécie circulante em diferentes tecidos biológicos de cães da Baixada Cuiabana, Mato Grosso, Brasil. Amostras de sangue, linfonodo e medula óssea foram coletadas de 205 cães para realização de análise parasitológica por citologia e análise molecular por meio da nested PCR (nPCR) e do sequenciamento . Dos 205 cães estudados, 34 (16,58%) animais foram positivos pela nPCR, dos quais 12 possuíam formas amastigotas de Leishmania spp. na citologia. Amostras positivas na nPCR foram sequenciadas e caracterizadas como Leishmania (Leishmania) infantum. A sensibilidade da nPCR nas amostras de medula óssea, linfonodo e sangue foi de 94,87%, 91,8% e 98%, respectivamente, enquanto a especificidade foi de 100% para todas as amostras. O presente estudo relata a ocorrência de LV canina em 16,58% dos cães analisados, caracterizando a L. infantum como agente causador. Entre as amostras avaliadas, a medula óssea foi a única a apresentar concordância substancial entre as técnicas de nPCR e citologia (k = 0,643), sendo considerada a amostra mais adequada para o diagnóstico da doença. Os resultados ampliam o conhecimento de espécies de Leishmania infectando cães no Brasil, destacando a importância da identificação etiológica em áreas com escassos dados moleculares.(AU)

Peritonite piogranulomatosa por Nocardia concava em cão - relato de caso / Piogranulomatous peritonitis by Nocardia concava in dog - Case Report

Nocardiose é causada por bactérias do gênero Nocardia do subgrupo Actinomycetos, que são Gram-positivas aeróbicas, filamentosas e podem apresentar ramificações. O diagnóstico baseia-se na presença de lesão inflamatória, com o microrganismo morfologicamente compatível, associada ao isolamento e à identificação microbiológica e molecular. Este trabalho tem por objetivo relatar um caso de nocardiose em canino, que desenvolveu inflamação piogranulomatosa peritoneal seis meses após ovariossalpingo-histerectomia. O animal apresentava hipertermia, distensão abdominal, taquipneia, polidipsia, hiporexia, mucosas hipocoradas e fezes pastosas. Os achados laboratoriais evidenciaram anemia leve e leucocitose por neutrofilia com desvio à esquerda e hipoalbuminemia. Uma massa na região mesogástrica e efusão peritoneal foram evidenciadas por meio da ultrassonografia abdominal. O líquido foi classificado como exsudato piogranulomatoso, e o animal submetido à laparotomia exploratória para lavagem abdominal e remoção da massa. Após procedimentos terapêuticos, ocorreu piora clínica e óbito. Peritonite piogranulomatosa foi a principal alteração anatomopatológica a qual foi associada à Nocardia spp. Molecularmente, a espécie isolada se aproxima da N. concava, por meio da análise filogenética. Essa espécie já foi descrita como causa de infecção em humanos na Ásia, no entanto não há registros na literatura na espécie canina, sendo este o primeiro relato.(AU)

Nocardiosis is caused by an aerobic, gram-positive, ramificated and filamentous bacteria of the Nocardia genus, subgroup Actinomycetos. The diagnosis is based on the presence of the inflammatory lesions with the morphologically compatible microorganism associated with microbiological and molecular isolation and identification. The objective of this work is to report a case of nocardiosis in a canine that developed peritoneal pyogranulomatous inflammation six months after ovariosalpingohisterectomy. The animal had hyperthermia, abdominal distention, tachypnea, polydipsia, hyporexia, hypocorous mucosae and pasty feces. The laboratory findings revealed mild anemia and leukocytosis due to neutrophilia with left deviation and hypoalbuminemia. A mass in the mesogastric region and peritoneal effusion were evidenced by abdominal ultrasonography. The fluid was classified as pyogranulomatous exudate and the animal underwent exploratory laparotomy for abdominal lavage and mass removal. Despite the therapeutic procedures and clinical alterations the dog died. Piogranulomatous peritonitis was the main anatomopathological alteration which was associated with Nocardia spp. Molecularly, the isolated species approaches the N. concava species through phylogenetic analysis. This specie was described as a cause of infection in humans in Asia; however, there are no records in literature on the canine species, being this the first report.(AU)

Development and validation of a quantification method for α-humulene and trans-caryophyllene in Cordia verbenacea by high performance liquid chromatography

ABSTRACT Acheflan® herbal medicine is the first medicine developed and produced in Brazil using Cordia verbenacea DC., Boraginaceae, essential oil as a constituent. C. verbenacea has anti-inflammatory properties, which have been directly related to α-humulene and trans-caryophyllene. Currently, the quantification of α-humulene and trans-caryophyllene in C. verbenacea has only been described by GC-MS. Although this technique is widely used it cannot be directly applied to finished medicinal products since they contain aqueous constituents. In this context, the objective of this work was to develop a methodology for quantifying C. verbenacea in raw materials and in pharmaceutical formulations using liquid chromatography. The Box-Behnken experimental design was used successfully to optimize the analytical method. The method developed in this study was validated and proven to be effective in the proper separation of α-humulene and trans-caryophyllene. In addition, the developed method was applied to commercial formulations (cream and aerosol) containing C. verbenacea essential oil, which resulted in very satisfactory separation without interference from excipients. C. verbenacea oil contains four times higher concentrations of trans-caryophyllene than α-humulene. Therefore, we propose that trans-caryophyllene can be used as a marker of C. verbenacea essential oil. Evaluation of trans-caryophyllene content would be especially valuable for applications where the concentrations are very low such as in permeation and release studies of dermatological formulations.

Dermatite fúngica associada à Rhodotorula glutinis em cão - Canis familiaris ): relato de caso / Fungal dermatitis associated to Rhodotorula glutinis in dog (Canis familiaris): case report

O fungo Rhodotorula sp. era considerado como não patogênico, mas, com o aumento de casos de humanos imunossuprimidos nas últimas duas décadas, as espécies R. mucilaginosa, R. glutinis e R. minuta se tornaram agentes potencialmente patogênicos. Poucos relatos clínicos veterinários associados à Rhodotorula spp. foram descritos, e o objetivo deste trabalho foi descrever um caso de dermatite fúngica causada por R. glutinis em cão imunossuprimido devido à leishmaniose visceral e osteossarcoma, na cidade de Cuiabá-Mato Grosso. Um cão, macho, 11 anos, sem raça definida, foi trazido ao Hospital Veterinário apresentando lesões de pele com diagnóstico de dermatofitose e foi prescrito tratamento tópico à base de óleo de melaleuca, sem melhora após um mês de tratamento. O animal retornou ao Hospital Veterinário com hemorragia na região lesionada da cauda, e foi realizada biópsia para exames microbiológico e histopatológico. Nas análises microbiológica e histopatológica, foi isolada uma levedura e detectada a presença de estrutura semelhante a leveduras na coloração de prata, respectivamente. A levedura isolada foi identificada como R. glutinis por meio do sequenciamento do DNA. Um novo tratamento foi instituído, sem melhora do quadro clínico. O animal foi diagnosticado também com leishmaniose e osteossarcoma, provavelmente ocasionando a immunossupressão, e seu quadro evoluiu a óbito.(AU)

The fungi Rhodotorula sp was considered nonpathogenic, but with the increase of immunosuppressed humans in the last two decades, the species R. mucilaginosa, R. glutinis and R. minuta became potentially pathogenic agents. There have been few veterinary clinical reports associated with Rhodotorula spp. and this work aims to describe the first case of fungal dermatitis caused by R. glutinis in immunosuppressed dog due to visceral leishmaniasis and osteosarcoma in the city of Cuiabá-Mato Grosso. An 11-year-old male mongrel dog was examined to the Veterinary Hospital with skin lesions and the diagnosis was dermatophytosis and the treatment was implemented with topical tea tree oil for one month, but the treatment failed. The animal returned to the Veterinary Hospital with bleeding in the injured area of the tail and biopsy was performed for microbiological and histopathology evaluation. In the microbiological and histopathological analysis, yeast was isolated and yeast-like structures in silver staining were observed, respectively. The isolated yeast was identified as R. glutinis by DNA sequencing. A new treatment was implemented without clinical improvement. The animal was diagnosed with leishmaniasis and osteosarcoma, which probably caused immunosuppression, and its clinical conditions evolved to death.(AU)

Ocular manifestations of leishmaniasis in a cat: first case report from Brazil / Manifestações oculares da leishmaniose em um gato: primeiro relato de caso do Brasil

An 8-year-old domestic short hair female cat initially presented with bilateral uveitis with pseudotumoral appearance. The patient tested negative for feline immunodeficiency virus (FIV), feline leukemia virus (FeLV) and Toxoplasma gondii. Histopathology of a granulomatous lesion on the upper left conjunctiva revealed amastigotes compatible with Leishmania spp. Aqueous humor was aspired and the diagnosis was confirmed after isolation of promastigotes cultivated in biphasic NNN medium and by positive polymerase chain reaction (PCR) for Leishmania infantum. Treatment with allopurinol (10mg/kg/ BID/PO) was commenced and a natural insect repellent was prescribed. Six months of treatment with allopurinol associated with the initial topical medications helped to improve ocular signs. Leishmaniasis should be considered as a differential diagnosis in cats presenting uveitis with pseudotumoral appearance. To our knowledge, this is the first report of feline leishmaniasis with ocular manifestation in Brazil, in which diagnosis was confirmed by aqueous humor analysis.(AU)

Uma gata, sem raça definida, de oito anos de idade, foi atendida inicialmente com uveíte bilateral, com aparência pseudotumoral em íris. Foi realizado teste para o vírus da imunodeficiência felina (FIV), da leucemia felina (FeLV) e de Toxoplasma gondii, obtendo-se resultados negativos. O exame histopatológico da conjuntiva superior do olho esquerdo revelou amastigotas compatíveis com Leishmania spp. Foi realizada paracentese, e promastigotas foram isoladas no humor aquoso, cultivadas em meio NNN bifásica. Reação em cadeia da polimerase (PCR) confirmou diagnóstico positivo para Leishmania infantum. Tratamento com alopurinol (10mg/kg/BID/PO) foi iniciado, e um repelente natural de insetos foi prescrito. Seis meses de tratamento com alopurinol associado aos medicamentos tópicos iniciais ajudaram a melhorar os sinais oculares. Leishmaniose deve ser considerada como um diagnóstico diferencial nos gatos que apresentam uveíte com aparência pseudotumoral de íris. Até o presente momento, este é o primeiro relato de leishmaniose felina com manifestação exclusivamente ocular da doença no Brasil cujo diagnóstico foi confirmado por meio de análise de humor aquoso.(AU)

Feasibility Study of Water Saving Measures in Higher Education Buildings: A Case Study of the University of Aveiro.

Aims: Evaluate the water savings potential and financial viability of water saving measures in in higher education buildings Study Design: The study follows an observational approach to characterize the current performance of existing buildings in terms of water consumption and evaluate the potential for increasing water efficiency. Place and Duration of Study: Buildings of the Chemistry, Civil Engineering, Communication and Arts, Environment and Planning, and Mathematics Departments and the Pedagogic Complex of the University of Aveiro, Portugal, between May 2013 and July 2014. Methodology: Water efficiency audits complemented with limited monitoring and simulation of investment scenarios. Results: The payback period of the investment required to implement the measures was found to be less than 7 months in all the cases, with average water savings potential of 28% and ranging from 9% up to 37%. Conclusion: Water savings measures are attractive solutions for university buildings in Portugal, particularly the older ones, because of their environmental and financial performance and the low investment required.

Segregated Delivery of Rifampicin and Isoniazid from Fixed Dose Combination Bilayer Tablets for the Treatment of Tuberculosis.

Aims: Develop an anti-tuberculosis (TB) Fixed Dose Combination (FDC) tablet containing an immediate release layer (IRL) composed of both rifampicin (RIF) and pyrazinamide (PYR) and a retarded release layer (RRL) comprised of isoniazid (INH) which would allow segregated delivery of RIF and INH. Study Design: Trials were conducted on the pre-formulations and formulations to assess the compatibility of excipients and obtain a modified release profile, for an IRL consisting of both RIF and PYR and a RRL containing INH. Place and Duration of Study: This study was performed at the Laboratory of Pharmaceutical Industrial Technology, Drug and Pharmaceutical Department, Faculty of Pharmacy, between March 2008 and April 2010. Methodology: Preformulation studies were performed on RIF and PYR, alone and in combination with excipients. The pharmacopeic attributes of the distinct layers and the FDC tablets were evaluated for hardness, friability and disintegration time. The FDC bilayer tablets were analyzed for their drug content and cumulative dissolution of the drug. Results: Fourier transform infrared, x-ray diffraction and differential scanning calorimetry results revealed the presence of amorphous and crystalline RIF forms and no potentially relevant incompatibilities were identified in the kneaded system containing RIF, PYR and excipients. In vitro drug release from the FDC tablets revealed that the intragranular addition of croscarmellose sodium into the IRL rendered a cumulative dissolution of RIF and PYR within the limits of simulated gastric fluid. And, for RRL, the most effective retardant matrix excipient was found to be hydroxypropyl methylcellulose. Conclusion: Segregated delivery of RIF and INH from bilayer tablets is an option for the development of immediate release FDC tablets and the retarded release of INH, this strategy proved suitable for preventing contact of these two drugs under acidic conditions. This finding suggested that RIF had a high in vivo bioavailability which qualifies this FDC for future bioavailability studies.

Role of the extracellular matrix in variations of invasive pathways in lung cancers

Among the most common features of highly invasive tumors, such as lung adenocarcinomas (AD) and squamous cell carcinomas (SqCC), is the massive degradation of the extracellular matrix. The remarkable qualitative and quantitative modifications of hyaluronidases (HAases), hyaluronan synthases (HAS), E-cadherin adhesion molecules, and the transforming growth factor β (TGF-β) may favor invasion, cellular motility, and proliferation. We examined HAase proteins (Hyal), HAS, E-cadherin, and TGF-β profiles in lung AD subtypes and SqCC obtained from smokers and non-smokers. Fifty-six patients, median age 64 years, who underwent lobectomy for AD (N = 31) and SqCC (N = 25) were included in the study. HAS-1, -2 and -3, and Hyal-1 and -3 were significantly more expressed by tumor cells than normal and stroma cells (P < 0.01). When stratified according to histologic types, HAS-3 and Hyal-1 immunoreactivity was significantly increased in tumor cells of AD (P = 0.01) and stroma of SqCC (P = 0.002), respectively. Tobacco history in patients with AD was significantly associated with increased HAS-3 immunoreactivity in tumor cells (P < 0.01). Stroma cells of SqCC from non-smokers presented a significant association with HAS-3 (P < 0.01). Hyal, HAS, E-cadherin, and TGF-β modulate a different tumor-induced invasive pathway in lung AD subgroups and SqCC. HAases in resected AD and SqCC were strongly related to the prognosis. Therefore, our findings suggest that strategies aimed at preventing high HAS-3 and Hyal-1 synthesis, or local responses to low TGF-β and E-cadherin, may have a greater impact in lung cancer prognosis.

Development and validation of HPLC and UV spectrophotometric methods for the determination of lumiracoxib in tablets

In this study, two methods, based on high-performance liquid chromatography (HPLC) and UV spectrophotometry, were developed and validated for the quantitative determination of lumiracoxib in tablets. The HPLC was carried out on a column of propylsulfonic acid bonded to silica gel (250 x 4.6 mm; 5 mium), with a mobile phase of phosphate buffer (pH 7.4; 10 mM)-water-acetonitrile (10:40:50, v/v/v) fl owing at 1.0 mL/min and detection of the drug at 278 nm. The UV method was based on absorbance at 275 nm, with ethanol as solvent. Both assays were linear over the concentration range of 2–30 miug/mL (R approximate 0.999), as wellas accurate and precise, with recoveries between 98 and 100% and relative standard deviation (%RSD) smaller that 2.0%. The proposed methods are highly sensitive, precise and accurate and were successfully applied to the quantitation of lumiracoxib in the commercial formulation. The spectrophotometric method is a simple, cheap and less time-consuming method. However, the chromatographic method is selective for the determination of the degradation products of lumiracoxib.

Distúrbio cognitivo transitório associado a atividade epileptiforme generalizada ou difusa durante o eletrencefalograma / Transient cognitive impairment during generalized or diffuse epileptiform EEG discharges

Epileptiform EEG discharges (EED) are a frequent finding in people with epilepsy, and may occur in other clinical conditions. Formal testing during EEG recording may demonstrate transitory cognitive impairment (TCI). Thirty patients (27 with epilepsy) with generalized or diffuse EED on a previous examination were studied. The interaction between EED and cognitive tasks was evaluated on subsequent EEG. The numbers of correct or incorrect answers were compared with the occurrence or absence of EED. Results were analyzed by non parametric tests. TCI was characterized in 43.3% of the patients. In 23.3% the EED were rare and it was not possible to evaluate the occurrence of TCI. The findings confirm that otherwise subclinical EED may be accompanied by TCI. There is a need of research to evaluate the relevance of TCI and to determine when EED should be treated.

Atividade epileptiforme (AE) no eletrencefalograma (EEG) é achado comum entre as crises epilépticas e, menos freqüentemente, em outras condições clínicas. AE "subclínica" pode estar acompanhada de distúrbio cognitivo transitório (DCT). Foram estudados 30 pacientes (27 com epilepsia) com AE generalizada ou difusa, freqüente, em EEG inicial. Em EEG subseqüente, foi avaliado o desempenho em testes de classificação visual de animais e objetos, discriminação de cores, memória verbal e auditiva, reconhecimento de padrões e estimação de tempo. Foi comparado, estatisticamente, o número de respostas corretas ou incorretas durante a AE e fora dela. DCT foi caracterizado em 43,3% dos casos. Em 23,3% a AE foi rara, não permitindo avaliação de DCT. Assim, pôde ser caracterizado comprometimento transitório de atividades cognitivas durante AE até então considerada "subclínica". Há necessidade de pesquisar a importância desse fator em pacientes com comprometimento cognitivo e de caracterizar as situações de eventuais benefícios na medicação dirigida à AE.

Influence of acute renal failure on the mononuclear phagocytic system

Several studies show the ability of macrophages to remove particles injected into the bloodstream. This function seems to be increased in the presence of acute renal failure. The objective of the present study was to assess the phagocytic function of the main organs (spleen, liver and lung) of the mononuclear phagocytic system in renal and postrenal failures. Fifteen rats (250-350 g) were divided into three groups (N = 5): group I - control; group II - ligature of both ureters, and group III - bilateral nephrectomy. On the third postoperative day, all animals received an iv injection of 1 ml/kg 99mTc sulfur colloid. Blood samples were collected for the assessment of plasma urea, creatinine, sodium, and potassium concentrations and arterial gasometry. Samples of liver, spleen, lung and blood clots were obtained and radioactivity was measured. Samples of liver, spleen, lung and kidney were prepared for routine histopathological analysis. Plasma urea, creatinine and potassium concentrations in groups II and III were higher than in group I (P<0.05). Plasma sodium concentrations in groups II and III were lower than in group I (P<0.05). Compensated metabolic acidosis was observed in the presence of postrenal failure. Group II animals showed a lower level of radioactivity in the spleen (0.98) and lung (2.63), and a higher level in the liver (105.51) than control. Group III animals showed a lower level of radioactivity in the spleen (11.94) and a higher level in the liver (61.80), lung (11.30) and blood clot (5.13) than control. In groups II and III liver steatosis and bronchopneumonia were observed. Renal and postrenal failures seem to interfere with blood clearance by the mononuclear phagocytic system