Launching a CDMO in Brazil aiming to develop biopharmaceuticals for clinical trials

The innovation timeline is expensive, risky, competitive, time-consuming, and labor-intensive. In order to overcome such challenges and optimize financial resources, pharmaceutical companies nowadays hire contract development and manufacturing organizations (CDMO) to help them. Based on the experience acquired first from the development of two biopharmaceuticals, the Heterologous Fibrin Sealant and the Apilic Antivenom, and more recently, during their respective clinical trials; the Center for the Study of Venoms and Venomous Animals (CEVAP) proposed to the Ministry of Health the creation of the first Brazilian CDMO. This groundbreaking venture will assist in converting a candidate molecule - from its discovery, proof of concept, product development, up to pilot batch production - into a product. The CDMO impact and legacy will be immense, offering service provision to the public and private sector by producing validated samples for clinical trials and academic training on translational research for those seeking a position in pharmaceutical industries and manufacturing platforms.(AU)

Comportamiento de los tumores de glándulas salivales en el Hospital Docente Vladimir Ilich Lenin / Salivary Gland Tumors Prevalence at Vladimir Ilich Lenin Teaching Hospital

Introducción: las neoplasias malignas de glándulas salivales constituyen del 3% al 5% de todos los cánceres de cabeza y cuello. La incidencia de los benignos ocurre entre la cuarta y sexta década de vida. La citología por aspiración con aguja fina es una técnica confiable, sensible, mínimamente invasiva y costo-efectiva en el diagnóstico de estas lesiones. Objetivo: describir el comportamiento de tumores de glándulas salivales. Método: se realizó un estudio de serie de casos. Se estudiaron 34 pacientes con resultados de biopsia con aspiración con aguja fina y biopsia quirúrgica que acudieron a Consulta de Cirugía Maxilofacial del Hospital Provincial Vladimir Ilich Lenin de Holguín de enero de 2014 a junio de 2016. Se utilizó el interrogatorio, el examen físico y se registró en una planilla, donde se recogieron las variables. Resultados: el adenoma pleomorfo se encontró en el 58,82% de los pacientes y la glándula parótida ocupó el 85,29%. El sexo masculino representó el 61,76%. El grupo de edades de 46 a 60 años representó el 44,11%. Se encontró una sensibilidad de 83,33%, especificidad del 89,28%, valor predictivo positivo de 62,5%, valor predictivo negativo de 96,15% y eficacia del 88,23%. Conclusiones: el adenoma pleomorfo fue el tumor más frecuente. Los tumores predominaron en el sexo masculino, en la edad entre 46 a 60 años y en glándula parótida. Se encontró una buena sensibilidad, moderada especificidad, buena eficacia, bajo valor predictivo positivo, alto valor predictivo negativo.

Introduction: malignant neoplasms of salivary glands make up 3% to 5% of all head and neck cancers. The incidence of the benign occurs between the fourth and sixth decade of life. Fine needle aspiration cytology is a reliable, sensitive, minimally invasive, and cost-effective technique in the diagnosis of these lesions. Objective: to describe the behavior of salivary gland tumors. Method: a descriptive, observational study was carried out on a series of cases. Thirty-four patients with biopsy results with fine needle aspiration and surgical biopsy were studied at the Maxillofacial Surgery Consultation of Vladimir Ilich Lenin Provincial Hospital in Holguin from January 2014 to June 2016. The interview and physical examination were used and were recorded on a spreadsheet, where the variables were collected. Results: the pleomorphic adenoma was found in 58.82% of the cases and the parotid gland was 85.29%. The male sex represented 61.76%. The age group of 46-60 years accounted for 44.11%. We found a sensitivity of 83.33%, specificity of 89.28%, positive predictive value 62.5%, negative predictive value 96.15% and efficacy of 88.23%. Conclusions: pleomorphic adenoma was the most frequent tumor. Tumors predominated in males, between 46 and 60 years of age and in the parotid gland. Good sensitivity, moderate specificity, good efficacy, low positive predictive value and high negative predictive value were found.

Trombolisis intravenosa en accidente cerebro vascular isquémico agudo en un hospital público de Chile: análisis prospectivo de 54 casos / Intravenous thrombolysis for ischemic stroke: experience in 54 patients

Background: Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) reduces disability in patients with ischemic stroke. However, its implementation in Chilean public general hospitals has been slow and faces some difficulties. Aim: To analyze the results of an intravenous thrombolysis protocol implementation in a public general hospital. Material and Methods: During a lapse of 28 months a standardized protocol for intravenous thrombolysis implemented in the emergency room of a public hospital, was prospectively evaluated. Fifty four patients with ischemic stroke were treated and assessed three months later as outpatients. Results: At three months of follow-up, 66.4% of patients subjected to thrombolysis had a favorable evolution, defined as having 0 to 1 points in the modified Rankin scale. Intracerebral hemorrhage rate was 11.1%, including 5.5% of symptomatic intracerebral hemorrhage. Four percent of patients had systemic bleeding complications after thrombolysis. The mortality rate was 14.8%. Conclusions: The success rates, mortality, and complications rate were comparable to the results obtained in international studies, despite of the absence of a stroke unit to manage stroke and its complications.

Accidente cerebrovascular isquémico en pacientes con trombo intracavitario: Experiencia con tratamientos distintos en fase aguda / Management of ischemic strokes derived from intraventricular thrombi: Report of two cases

The origin of 20% of ischemic strokes is a left ventricular thrombus. We report two patients with strokes originating from cardiac thrombi, treated in two different ways. A 42-year-old diabetic man admitted with a left parietal and occipital stroke. An echocardiogram showed a left ventricular thrombus. The patient was subjected to a surgical cardiac revascularization procedure and left ventricular thrombectomy. The postoperative evolution was uneventful and the patient was discharged on oral anticoagulation. On ambulatory follow up, no neurological deterioration was evidenced. A 38-year-old male admitted with an acute ischemic stroke, was subjected to thrombolysis with human plasminogen activator. An echocardiogram showed a left ventricular thrombus, considered the cause of the stroke. The patient was anticoagulated with heparin and discharged ten days after admission with oral anticoagulation. A new echocardiogram performed one month later, did not show the left ventricular thrombus.

Trombocitopenia severa como manifestación de un tumor testicular de células germinales con metástasis cardíaca intracavitaria / Testicular tumor with intracardiac metastasis presenting as severe thrombocytopenia

Se describe el caso de un hombre de 24 años que se presenta con Púrpura trombocitopénico, cuyo estudio ecocardiográfico y tomografía computada demostró masa tumoral ocupando las cavidades derechas. Se evidenció posteriormente un tumor testicular izquierdo con componentes de seminoma y teratoma. Se resecó el tumor testicular y posteriormente el tumor intracardíaco, con normalización del recuento plaquetario.

A 24 year old man presented with severe thrombocytopenia. An intracardiac mass was shown to be a metastasis from a malignant testicular tumor. Resection of the primary tumor and the intracardiac metastasis led to full recovery of thrombocytopenia.

Endocarditis infecciosa: características clínicas, complicaciones y mortalidad en 506 pacientes y factores pronósticos de sobrevida a 10 años (1998-2008). Estudio cooperativo nacional en endocarditis infecciosa en Chile (ECNEI-2) / Clinical characteristics, complications and mortality in 506 patients with infective endocarditis and determinants of survival rate at 10 years

Background: Rates ofmorbidity and mortality in Infective Endocarditis (IE) remain high and prognosis in this disease is still difficult and uncertain. Aim: To study IE in Chile in its active phase during inpatient hospital stay and long term survival rates. Material and Methods: Observational prospective national cohort study of 506 consecutive patients included between June 1,1998 and July 31, 2008, from 37 Chilean hospitals (secondary and tertiary centers) nationwide. Results: The main findings were the presence of Rheumatic valve disease in 22.1 % of patients, a history of intravenous drug abuse (IVDA) only in 0.7%, the presence of Staphylo-coccus aureus in 29.2% of blood cultures, negative blood cultures in 33.2%, heart failure in 51.7% and native valve involvement in 86% ofpatients. Echocardiographic diagnosis was achieved in 94% of patients. Hospital mortality was 26.1% and its prognostics factors were persisting infection (Odds ratio (OR) 6.43, Confidence Interval (CI) 1.45-28.33%), failure of medical treatment and no surgical intervention (OR 48.8; CI 6.67-349.9). Five and 10 years survival rates were 75.6 and 48.6%, respectively. The significant prognostic factors for long term mortality, determined by multivariate analysis were the presence of diabetes, Staphylococcus aureus infection, sepsis, heart failure, renal failure and lack of surgical treatment during the IE episode. Conclusions: The microbiologic diagnosis of IE must be urgently improved in Chile. Mortality rates are still high (26.1%) partly because of a high incidence of negative blood cultures and the need for more surgical valve interventions during in-hospital period. Long term prognostic factors for mortality should be identified early to improve outcome.

Mortalidad a 30 días y factores de riesgo preoperatorios en la cirugía de reemplazo valvular aórtico en Uruguay / Mortality to 30 days and risk factors in preoperative replacement surgery valvular aortic in Uruguay

El Fondo Nacional de Recursos (FNR) es un sistema nacional de financiación de medicina altamente especializada; financia 380 reemplazos valvulares aórticos (RVA) anualmente. Objetivo: evaluar la mortalidad a los 30 días de la cirugía y los factores de riesgo preoperatorios en los RVA realizados en Uruguay entre el 1 de enero de 2003 y el 31 de diciembre de 2007. Métodos: se incluyeron todos los pacientes operados de RVA aislado y combinado (RVAC) con by pass coronario. La base de datos del FNR registra todas las cirugías cardíacas realizadas en Uruguay. Realizamos un análisis de regresión logística binaria para desarrollar un modelo de riesgo.Resultados: incluimos 1.930 pacientes (edad promedio 68,4 años, masculino 60,2%); mortalidad a 30 días 6,6% (127), RVA aislado 5,6% (59/1061) y RVAC 7,8% (68/869). Las variables retenidas en el modelo fueron género femenino y edad entre 60-69 años (OR 4,96; IC95% 1,33-18,55), femenino entre 70-79 años (OR 3.6; IC95% 0,99-13,13) femenino y ³ 80 años (OR 4,86; IC95% 1,09-21,72), masculino y ³ 80 años (OR 6,97; IC95% 1,60-30,37), endocarditis infecciosa activa (OR 4,1; IC95% 1,28-13,11), fracción de eyección del ventrículo izquierdo (FEVI) disminuida: fracci{on de eyección (FE) 30%-50% (OR 1,84; IC95% 1,20-2,81) y FEVI < 30%, (OR 2,23; IC95% 1,32-3,78), cirugía cardíaca previa (OR 3,79; IC95% 2,25-6,36), situación crítica pre-operatoria (OR 6,18; IC95% 2,34-16,32) e insuficiencia cardíaca clase IV (OR 2,13; IC95% 0,97-4,66). La discriminación y la calibración interna del modelo fueron buenas (índice-C= 0,72 y p=0,928 en la prueba de Hosmer-Lemeshow, respectivamente). Conclusiones: la mortalidad a 30 días en el RVA fue 6,6% y estuvo asociada a factores propios del paciente ...

FNR is a national system to grant financing for highly specialized medical services; finances 380 aortic valve replacements (AVR) annually. Objective: to evaluate 30-day mortality and preoperative risk factors in AVR made in Uruguay between 1st January 2003 and 31st December 2007. Methods: all consecutive isolated AVR and combined with coronary bypass (AVRC) were included. Register of FNR database included data about all cardiac surgeries in the country. Multivariable logistic regression analysis was used for develop a risk model. Results: 1.930 patients (age 68,4 years, male 60,2%) were included. 30-day mortality was 6,6% (127), isolate AVR 5,6% (59/1.061) and AVRC 7,8% (68/869). Variables in the model were female and age between 60-69 years (OR 4,96; IC95% 1,33-18,55), female and age between 70-79 years (OR 3,6; IC95% 0,99-13,13), female and age 80 years (OR 4,86; IC95% 1,09-21,72), male and age 80 years (OR 6,97; IC95% 1,60-30,37), active endocarditis (OR 4,1; IC95% 1,28-13,11), diminished ejection fraction (EF): EF 30 to 50% (OR 1,84; IC95% 1,20-2,81) and EF <30% (OR 2,23; IC95% 1,32-3,78), previous cardiac surgery (OR 3,79; IC95% 2,25-6,36), preoperative critical state (OR 6.18; IC95% 2.34-16.32) and class IV cardiac failure of NYHA (OR 2.13; IC95% 0,97-4,66). The discrimination of logistic risk model was good (c-index: 0,72) and the internal calibration also (Hosmer-Lemeshow test, p=0,928).Conclusions: 30-day mortality in AVR was 6,6% and was associated to patient factors (age, sex), cardiovascular disease factors (active endocarditis, previous cardíac surgery, class IV of cardíac failure, EF) and to preoperative clinical state. The risk model could be useful for clinical decisions and patient information.

Terapia com células-tronco na síndrome do desconforto respiratório agudo / Stem cell therapy in acute respiratory distress syndrome

A síndrome do desconforto respiratório agudo é caracterizada por uma reação inflamatória difusa do parênquima pulmonar, podendo ser induzida por um insulto direto ao epitélio alveolar (síndrome do desconforto respiratório agudo pulmonar) ou indireto através do endotélio vascular (síndrome do desconforto respiratório agudo extrapulmonar). Acredita-se que uma terapia eficaz para o tratamento da síndrome do desconforto respiratório agudo deva atenuar a resposta inflamatória e promover adequado reparo da lesão pulmonar. O presente artigo apresenta uma breve revisão acerca do potencial terapêutico das células-tronco na síndrome do desconforto respiratório agudo. Essa revisão bibliográfica baseou-se em uma pesquisa sistemática de artigos experimentais e clínicos sobre terapia celular na síndrome do desconforto respiratório agudo incluídos nas bases de dados MedLine e SciELO nos últimos 10 anos. O transplante de células-tronco promove melhora da lesão inflamatória pulmonar e do conseqüente processo fibrótico, induzindo adequado reparo tecidual. Dentre os mecanismos envolvidos, podemos citar: diferenciação em células do epitélio alveolar e redução na liberação de mediadores inflamatórios e sistêmicos e fatores de crescimento. A terapia com células-tronco derivadas da medula óssea pode vir a ser uma opção eficaz e segura no tratamento da síndrome do desconforto respiratório agudo por acelerar o processo de reparo e atenuar a resposta inflamatória. Entretanto, os mecanismos relacionados à atividade antiinflamatória e antifibrogênica de tais células necessitam ser mais bem elucidados, limitando, assim, o seu uso clínico imediato.

Acute respiratory distress syndrome is characterized by an acute pulmonary inflammatory process induced by the presence of a direct (pulmonary) insult that affects lung parenchyma, or an indirect (extrapulmonary) insult that results from an acute systemic inflammatory response. It is believed that an efficient therapy for the acute respiratory distress syndrome should attenuate inflammatory response and promote adequate repair of the lung injury. This article presents a brief review on the use of stem cells and their potential therapeutic effect on the acute respiratory distress syndrome. This systematic review was based upon clinical and experimental acute respiratory distress syndrome studies included in the MedLine and SciElO database during the last 10 years. Stem cell transplant lead to an improvement in lung injury and fibrotic process by inducing adequate tissue repair. This includes alveolar epithelial cell differentiation,and also reduces pulmonary and systemic inflammatory mediators and secretion of growth factors. Stem cells could be a potential therapy for acute respiratory distress syndrome promoting lung repair and attenuating the inflammatory response. However, mechanisms involving their anti-inflammatory and antifibrinogenic effects require better elucidation, limiting their immediate clinical use in acute respiratory distress syndrome.

Brazilian law for scientific use of animals / Lei brasileira para o uso científico de animais

The Brazilian scientific community claimed for a definitive systematization and for comprehensive and realistic national rules, to provide guidance and regulation, instead of sanctions, so that the question of scientific research involving animals could be better contemplated. This is beginning to occur now with Law n.º 11.794, sanctioned by the President of the Republic on November 8, 2008. PURPOSE: To describe the evolution of Brazilian regimentation for scientific use of animals and to analyze Law n.º 11.794. METHODS: The legislation about the use of animals in teaching and in scientific research in Brazil and in Rio de Janeiro State was identified and discussed. RESULTS: Until now, there was no updated general and systematizing rule regarding animal vivisection and experimentation for didactic or scientific purposes. The only specific law dates back to1979 and was not regimented. More recent laws equated the practice of scientific experiments to acts of abuse and mistreatment of animals, when alternative technology was available. Municipal laws that restricted the scientific practice of vivisection and experimentation with animals were created in the cities of Rio de Janeiro and Florianopolis. CONCLUSION: With the claim and collaboration of the scientific community, the sanction of Law n.º 11.794 regarding to the scientific use of animals represented an invaluable advance in spite of the presence of some points that eventually may require another type of treatment. The new Law states that it will be regimented within 180 (one-hundred-and-eighty) days, when some of these points could be better elucidated.

A comunidade científica brasileira clamava por uma norma federal abrangente e realista, mais orientadora e reguladora, e menos sancionadora, na qual a questão do uso científico dos animais pudesse ser mais bem contemplada. Isto agora começa a se materializar, com a Lei n.º 11.794, sancionada pelo Presidente da República no dia 8 de novembro de 2008. OBJETIVO: Relatar a evolução na regulamentação brasileira sobre o uso científico de animais e analisar a Lei n.º 11.794. MÉTODOS: Foi identificada e discutida a evolução na legislação existente no Brasil e em alguns municípios brasileiros acerca da utilização de animais no treinamento e na pesquisa científica, até a sanção da nova Lei. RESULTADOS: Até agora, não existia norma geral sistematizadora atualizada referente à vivissecção e experimentação com animais, nem para fins didáticos, nem científicos. A única lei referente a esse tópico datava de 1979 e não chegou a ser regulamentada. Leis mais recentes equiparavam a prática de experimentos científicos aos atos de abuso e maus tratos de animais, na presença de tecnologia alternativa. Nos municípios do Rio de Janeiro e de Florianópolis foram criadas Leis Municipais que cerceavam a prática científica da vivissecção e da experimentação com animais. CONCLUSÃO: A partir do clamor e da colaboração da comunidade científica nacional, a sanção da Lei n.º 11.794, que trata do uso científico dos animais, representou um avanço inestimável, a despeito da presença de alguns pontos que, eventualmente, merecessem outro tipo de tratamento. A nova Lei menciona que ela deverá ser regulamentada em até 180 (cento e oitenta) dias, quando alguns desses pontos poderão ser mais bem esclarecidos.

Revisión a partir de un caso clínico: flegmasia cerulea dolens / Flegmasia cerulea dolens: clinical case and literature review

La Flegmasia Cerulea Dolens (FCD) es una complicación poco frecuente de la trombosis venosa profunda extensa. Caracterizada por edema masivo, dolor intenso y cianosis. En la trombosis y oclusión aguda de los troncos venosos proximales (ilíacas, vena cava inferior), la congestión puede alcanzar gran severidad, con atrapamiento masivo de líquido intersticial, lo que puede llevar a oliguria y al shock. La extremidad adquiere un aspecto céreo (flegmasia cerulea dolens) por compromiso del drenaje venoso de la extremidad. El aumento de presión intersticial puede llegar a interferir con la perfusión arterial, dando un color pálido (flegmasia alba dolens) e incluso producir isquemia distal en el pie (gangrena venosa), con una alta mortalidad asociada. Hasta el momento, no existe consenso en su tratamiento, la anticoagulación con heparina, trombectomía quirúrgica, terapia trombolítica, fasciotomía y la amputación han sido algunos de los tratamientos propuestos. Presentamos una revisión de flegmasia cerulea dolens en relación a un caso clínico.

The Phlegmasia caerulea dolens (PCD) is an uncommon, severe form of deep venous thrombosis. Characterized by massive edema, severe pain and cyanosis. In the acute thrombosis and occlusion of major venosus channels (iliac and cava inferior) the congestion can reach a massive intersticial fluid secuestration, that can lead to a oliguria and to a shock. The leg acquires a cereo aspect (phlegmasia caerulea dolens) by significantly compromised venous outflow. The increase of the interstitial pressure can interfere with the arterial perfusion, giving a pale color (phlegmasia alba dolens) and can even produce distal ischemia on the foot (venous gangrene), that is a cause of high mortality. Until now, there are no consensus about its treatment. Anticoagulation with heparin, surgical thrombectomy, trombolysis therapy, fasciotomy and amputation had been some of the purposed treatments. We present a review, related to a clinical case, of the Phlegmasia caerulea dolens.

Stem cells and respiratory diseases

Stem cells have a multitude of clinical implications in the lung. This article is a critical review that includes clinical and experimental studies of MedLine and SciElo database in the last 10 years, where we highlight the effects of stem cell therapy in acute respiratory distress syndrome or more chronic disorders such as lung fibrosis and emphysema. Although, many studies have shown the beneficial effects of stem cells in lung development, repair and remodeling; some important questions need to be answered to better understand the mechanisms that control cell division and differentiation, therefore enabling the use of cell therapy in human respiratory diseases.

As células-tronco têm uma infinidade de implicações clínicas no pulmão. Este artigo é uma revisão crítica que inclui estudos clínicos e experimentais advindos do banco de dados do MEDLINE e SciElo nos últimos 10 anos, onde foram destacados os efeitos da terapia celular na síndrome do desconforto respiratório agudo ou doenças mais crônicas, como fibrose pulmonar e enfisema. Apesar de muitos estudos demonstrarem os efeitos benéficos das células-tronco no desenvolvimento, reparo e remodelamento pulmonar; algumas questões ainda precisam ser respondidas para um melhor entendimento dos mecanismos que controlam a divisão celular e diferenciação, permitindo o uso da terapia celular nas doenças respiratórias.

Terapia celular nas doenças respiratórias / Cell therapy for respiratory diseases

As células-tronco são definidas como células indiferenciadas, com capacidade de se dividir por período indefinido, em cultura, e se diferenciar em diversos tipos celulares especializados, dependendo do estímulo ao qual são submetidas. Nesse artigo, será realizada uma revisão crítica dos efeitos da terapia com células-tronco em algumas doenças respiratórias tais como: síndrome do desconforto respiratório agudo, fibrose pulmonar, asma e enfisema. Estudos recentes têm mostrado os efeitos benéficos da administração de células-tronco endógenas e exógenas no desenvolvimento, reparo e remodelamento do pulmão em diversas doenças respiratórias. Entretanto, a biologia das células-tronco ainda é pouco entendida devido às limitações técnicas atuais, estando diversas questões ainda sem respostas. Portanto, mais estudos são necessários para ummelhor entendimento dos mecanismos que controlam a divisão e diferenciação dessas células, para que, assim, a terapia celular possa ser utilizada de maneira segura e eficaz em humanos.

Stem cells are defined as undifferentiated progenitors that can self-renew ad infinitum and differentiate into various specialized cell types depending on the stimulus to which they are submitted. In this article, we will perform a critical review of the effects of cell therapy in respiratory diseases such as: acute respiratory distress syndrome, pulmonary fibrosis, asthma,and emphysema. Recent studies have shown the beneficial effects of endogenous and exogenous stem cells in lung development, repair and remodeling in re spiratory diseases. However, the biology of stem cells remains poorly understood due to technical limitations, and some important questions need to be answered. More studies should be performed to better understand the mechanisms that control cell division and differentiation, therefore enabling the use of cell therapy in humanrespiratory diseases.

Rhodnius prolixus Malpighian tubules and control of diuresis by neurohormones

Rhodnius prolixus Malpighian tubules (MTs) are a good model for fluid and ion secretion studies in view of the dramatic postprandial diuresis, which follows its massive blood meals. Ingestion of a blood meal equals to 10-12 times their initial body mass, leads to rapid activation of high output by excretory system, which eliminates 40-50 percent of the fluid mass. Secretion of ions and water is stimulated 1000-fold by serotonin and diuretic hormone. These hormones cooperate synergistically to activate adenylate cyclase activity from MTs cells, which increase the level of intracellular cAMP. The anti-diuretic hormones have also an important role in the fluid maintenance of Rhodnius prolixus. Several hours after insect feeding occurs a reduction in urine flow, that has been thought to result from a decreased diuretic hormone release or from a novel mechanism of anti-diuresis involving insect cardioacceleratory peptide 2b (CAP2b) and cyclic GMP. In this article it is discussed how the hormone regulation of fluid transport is done in Rhodnius prolixus MTs.

Os túbulos de Malpighi (TMs) de Rhodnius prolixus são reconhecidos por serem excelentes modelos para o estudo da secreção de fluidos e íons devido a grande diurese que ocorre quando esses animais se alimentam de sangue. O inseto, após alimentação, pode aumentar seu peso corporal inicial em até 10-12 vezes, o que leva a rápida ativação do sistema excretor, que elimina 40-50 por cento do fluido corporal. A secreção de íons e água é estimulada 1000 vezes pela serotonina e pelos hormônios diuréticos. Esses hormônios agem sinergicamente ativando a adenil ciclase das células dos TMs, aumentando os níveis intracelulares de AMPc. Os hormônios anti-diuréticos também têm um importante papel na manutenção dos fluídos corporais do Rhodnius prolixus. Várias horas após a alimentação do inseto ocorre uma redução do fluxo urinário, o que foi sugerido ser decorrente da diminuição da liberação dos hormônios diuréticos ou da anti-diurese envolvendo o peptídeo cardioaceleratório 2b (CAP2b) e o GMPc. Neste artigo é discutida a regulação hormonal do transporte de fluido nos MTs de Rhodnius prolixus.

Screening for CLCN5 mutation in renal calcium stone formers patients

Trinta e cinco pacientes (23 homens e 12 mulheres) com idade de 35 ±13 anos apresentando nefrolitíase idiopática cálcica, nefrocalcinose ou insuficiência renal leve com nefrolitíase idiopática cálcica foram selecionados para análise de proteinúria de baixo peso molecular e a ocorrência de possíveis mutações no gene CLCN5. A razão entre a b2-microglobulina urinária e a creatinina urinária (b2M/Cr) foi muito elevada em uma mulher transplantada com nefrocalcinose ( > 3.23 mg/mmol) e levemente elevada em cinco pacientes ( > 0.052 ou < 1.0 mg/mmol) com manipulação urológica múltipla. Outros pacientes estudados mostraram uma razão b2M/Cr nos limites normais (0.003-0.052 mg/mmol) sem diferença entre os sexos (p > 0.05). A análise da mutação do gene do gene CLCN5 foi realizada em 26 pacientes dos 35 selecionados (11 com hipercalciúria idiopática; 6 homens com calciúria normal; 3 com leve insuficiência renal e 6 com nefrocalcinose) e não apresentou alteração em nenhum dos casos, mesmo naqueles com proteinúria de baixo peso molecular anormal. Conclusão: A mutação do gene do CLCN5 não é uma causa comum de calculose renal ou nefrocalcinose no grupo de pacientes brasileiros estudados.

The cystic fibrosis transmembrane regulator (CFTR) in the kidney

The cystic fibrosis transmembrane regulator (CFTR) is a Cl- channel. Mutations of this transporter lead to a defect of chloride secretion by epithelial cells causing the Cystic Fibrosis disease (CF). In spite of the high expression of CFTR in the kidney, patients with CF do not show major renal dysfunction, but it is known that both the urinary excretion of drugs and the renal capacity to concentrate and dilute urine is deficient. CFTR mRNA is expressed in all nephron segments and its protein is involved with chloride secretion in the distal tubule, and the principal cells of the cortical (CCD) and medullary (IMCD) collecting ducts. Several studies have demonstrated that CFTR does not only transport Cl- but also secretes ATP and, thus, controls other conductances such as Na+ (ENaC) and K+ (ROMK2) channels, especially in CCD. In the polycystic kidney the secretion of chloride through CFTR contributes to the cyst enlargement. This review is focused on the role of CFTR in the kidney and the implications of extracellular volume regulators, such as hormones, on its function and expression.

Movimentos sociais, democracia e intervenção sociológica / Social movement, democracy and sociologic intervention

Discute os movimentos sociais na sociedade pós-industrial utilizando o método de intervenção sociológica, que tem por objeto a natureza da ação coletiva, a partir do conceito de movimento social. Prossegue com as aplicações do método da intervenção sociológica no estudo das lutas sociais, na natureza da ação das relações sociais e no estudo dos atores sociais