Special care in dental curriculum: A transversal axis for integrating oral health with systemic health.

AIMS: Distance between dentistry and medicine is a traditional and historical obstacle that affects multiple levels of the health system, especially the health policies to improve health service quality. Changes in dental education, especially involving the adoption of integrative health models in professional development, are considered essential for reducing this gap. We aimed to show a dental curriculum focused on special care as a tool for medicine-dentistry integration. METHODS: In this study, we present a new proposal for an undergraduate dental curriculum in which topics related to special care are addressed transversally and are the core for interdisciplinary integration of oral health with systemic health. We also describe how themes related to dental home care and hospital dentistry were included in this course as basic professional competencies. RESULTS AND CONCLUSION: This initiative is aligned with the global trend to adopt educational systems that contribute to the reduction of health care inequalities and improve health service quality.

Gremlin-1 potentiates the dedifferentiation of VSMC in early stages of atherosclerosis.

Vascular smooth muscle cells (VSMC) are highly specialized, and exhibit a contractile phenotype when mature and fully differentiated, being responsible for vessel homeostasis and blood pressure control. In response to pro-atherogenic stimuli VSMC alter their state of differentiation, increase proliferation and migration, resulting in SMC phenotypes ranging from contractile to synthetic. This variability is observed in cell morphology and expression level of marker genes for differentiation status. There is growing evidence that bone morphogenetic protein (BMP) signaling is involved in vascular diseases, including atherosclerosis. Here, we evaluated in vitro the role of specific agonists/antagonists belonging to the BMP pathway on dedifferentiation of VSMC harvested during early stages of atherosclerosis. RESULTS: Comparing primary VSMC isolated from aortas of susceptible ApoE-/- animals fed 8 weeks of western diet with their littermate controls fed usual diet, we observed that recombinant BMP4 was able to reduce SM22-alpha and alpha actin gene expression indicating dedifferentiation was under way. Unexpectedly, treatment with recombinant Gremlin-1, a known BMP antagonist, also reduced 4-6.5 folds gene expression of SM22-alpha, alpha-actin and, calponin, exclusively in VSMC from ApoE-/- animals, independently on the diet consumed. CONCLUSION: Our data show that BMP4 is capable of modulating of SM22-alpha and alpha actin gene expression, indicative of cell dedifferentiation in VSMC. Additionally, we report for first time that Gremlin-1 acts independently of the BMP pathway and selectively on VSMC from susceptible animals, reducing the expression of all genes evaluated.

Effects of clomiphene citrate on male obesity-associated hypogonadism: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Obesity causes secondary hypogonadism (HG) in men. Standard testosterone (T) replacement therapy improves metabolic parameters but leads to infertility. OBJECTIVE: To evaluate clomiphene citrate (CC) treatment of adult men with male obesity-associated secondary hypogonadism (MOSH). DESIGN: Single-center, randomized, double-blind, placebo-controlled trial. PARTICIPANTS: Seventy-eight men aged 36.5 ± 7.8 years with a body mass index (BMI) > 30 kg/m2, total testosterone (TT) ≤ 300 ng/dL, and symptoms in the ADAM questionnaire. INTERVENTION: Random allocation to receive 50 mg CC or placebo (PLB) for 12 weeks. OUTCOMES: (1) Clinical features: ADAM and sexual behavior questionnaires; (2) hormonal profile: serum TT, free T, estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex hormone-binding globulin (SHBG); (3) body composition: BMI, waist circumference, and bioelectric impedance analysis; (4) metabolic profile: blood pressure, fasting blood glucose, HbA1c, insulin, HOMA-IR, and lipid profile; (5) endothelial function: flow-mediated dilation of the brachial artery, quantitative assessment of endothelial progenitor cells and serum sICAM-1, sVCAM-1, and selectin-sE levels; (6) safety aspects: hematocrit, serum prostate-specific antigen, International Prostate Symptom Score, and self-reported adverse effects. RESULTS: There was an improvement in one sexual complaint (weaker erections; P < 0.001); increases (P < 0.001) in TT, free T, E2, LH, FSH, and SHBG; and improvements in lean mass (P < 0.001), fat-free mass (P = 0.004), and muscle mass (P < 0.001) in the CC group. CC reduced HDL (P < 0.001). No statistically significant differences were seen in endothelial function. CONCLUSIONS: CC appeared to effectively improve the hormonal profile and body composition. CC may be an alternative treatment for MOSH in adult men.

Toxicological profile of IQG-607 after single and repeated oral administration in minipigs: An essential step towards phase I clinical trial.

IQG-607 is an anti-tuberculosis drug candidate, with a promising safety and efficacy profile in models of tuberculosis infection both in vitro and in vivo. Here, we evaluated the safety and the possible toxic effects of IQG-607 after acute and 90-day repeated administrations in minipigs. Single oral administration of IQG-607 (220 mg/kg) to female and male minipigs did not result in any morbidity or mortality. No gross lesions were observed in the minipigs at necropsy. Repeated administration of IQG 607 (65, 30, or 15 mg/kg), given orally, for 90 days, in both male and female animals did not cause any mortality and no significant body mass alteration. Diarrhea and alopecia were the clinical signs observed in animals dosed with IQG-607 for 90 days. Long-term treatment with IQG-607 did not induce evident alterations of blood cell counts or any hematological parameters. Importantly, the repeated schedule of administration of IQG-607 resulted in increased cholesterol levels, increased glucose levels, decrease in the globulin levels, and increased creatinine levels over the time. Most necropsy and histopathological alterations of the organs from IQG-607-treated groups were also observed for the untreated group. In addition, pharmacokinetic parameters were evaluated. IQG-607 represents a potential candidate molecule for anti-tuberculosis drug development programs. Its promising in vivo activity and mild to moderate toxic events detected in this study suggest that IQG-607 represents a candidate for clinical development.

First experience with multiple mini interview for medical school admission in Brazil: Does it work in a different cultural scenario?

PURPOSE: Evaluation of non-cognitive skills never has been used in Brazil. This study aims to evaluate Multiple Mini Interviews (MMI) in the admission process of a School of Medicine in São Paulo, Brazil. METHODS: The population of the study comprised 240 applicants summoned for the interviews, and 96 raters. MMI contributed to 25% of the applicants' final grade. Eight scenarios were created with the aim of evaluating different non-cognitive skills, each one had two raters. At the end of the interviews, the applicants and raters described their impressions about MMI. The reliability of the MMI was analyzed using the Theory of Generalization and Many-Facet Rasch Model (MFRM). RESULTS: The G-study showed that the general reliability of the process was satisfactory (coefficient G = 0.743). The MMI grades were not affected by the raters' profile, time of interview (p = 0.715), and randomization group (p = 0.353). The Rasch analysis showed that there was no misfitting effects or inconsistent stations or raters. A significant majority of the applicants (98%) and all the raters believed MMIs were important in selecting students with a more adequate profile to study medicine. CONCLUSIONS: The general reliability of the selection process was excellent, and it was fully accepted by the applicants and raters.

Dact1, a Wnt-Pathway Inhibitor, Mediates Human Mesangial Cell TGF-ß1-Induced Apoptosis.

Chronic kidney disease (CKD) is a worldwide public health problem that affects millions of men and women of all ages and racial groups. Loss of mesangial cells (MC) represents an early common feature in the pathogenesis of CKD. Transforming growth factor-ß1 (TGF-ß1) is a key inducer of kidney damage and triggers several pathological changes in renal cells, notably MC apoptosis. However, the mechanism of MC apoptosis induced by TGF-ß1 remains elusive. Here, we demonstrate for the first time a novel regulatory pathway in which the disheveled-binding antagonist of ß-catenin 1 (Dact1) gene is upregulated by TGF-ß1, inducing MC apoptosis. We also show that the inhibitory effect of Dact1 and TGF-ß1 on the transcriptional activation of the pro-survival Wnt pathway is the mechanism of death induction. In addition, Dact1 mRNA/protein levels are increased in kidney remnants from 5/6 nephrectomized rats and strongly correlate with TGF-ß1 expression. Together, our results point to Dact1 as a novel element controlling MC survival that is causally related to CKD progression. J. Cell. Physiol. 232: 2104-2111, 2017. © 2016 Wiley Periodicals, Inc.

Preclinical molecular imaging: development of instrumentation for translational research with small laboratory animals.

OBJECTIVE:: To present the result of upgrading a clinical gamma-camera to be used to obtain in vivo tomographic images of small animal organs, and its application to register cardiac, renal and neurological images. METHODS:: An updated version of the miniSPECT upgrading device was built, which is composed of mechanical, electronic and software subsystems. The device was attached to a Discovery VH (General Electric Healthcare) gamma-camera, which was retired from the clinical service and installed at the Centro de Imagem Pré-Clínica of the Hospital Israelita Albert Einstein. The combined system was characterized, determining operational parameters, such as spatial resolution, magnification, maximum acceptable target size, number of projections, and acquisition and reconstruction times. RESULTS:: Images were obtained with 0.5mm spatial resolution, with acquisition and reconstruction times between 30 and 45 minutes, using iterative reconstruction with 10 to 20 iterations and 4 projection subsets. The system was validated acquiring in vivo tomographic images of the heart, kidneys and brain of normal animals (mice and adult rats), using the radiopharmaceuticals technetium-labeled hexakis-2-methoxy-isobutyl isonitrile (99mTc-Sestamibi), technetium-labeled dimercaptosuccinic acid (99mTc-DMSA) and technetium-labeled hexamethyl propyleneamine oxime (99mTc-HMPAO). CONCLUSION:: This kind of application, which consists in the adaptation for an alternative objective of already existing instrumentation, resulted in a low-cost infrastructure option, allowing to carry out large scale in vivo studies with enhanced quality in several areas, such as neurology, nephrology, cardiology, among others. OBJETIVO:: Apresentar o resultado da adaptação de uma gama câmara clínica para uso dedicado na obtenção de imagens tomográficas in vivo de órgãos de pequenos animais de experimentação, e de sua aplicação na obtenção de imagens cardíacas, renais e neurológicas. MÉTODOS:: Foi construída uma versão atualizada do dispositivo de adaptação miniSPECT, composto por três subsistemas: mecânico, eletrônico e de software. O dispositivo foi montado em uma câmara Discovery VH da General Electric Healthcare, retirada do serviço clínico e instalada no Centro de Imagem Pré-Clínica do Hospital Israelita Albert Einstein. O sistema combinado foi caracterizado, determinando parâmetros de funcionamento como resolução espacial, magnificação, limites de tamanho dos alvos de estudo, número de projeções, tempo de registro e tempo de reconstrução das imagens tomográficas. RESULTADOS:: Foram obtidas imagens com resolução espacial de até 0,5mm, com tempos de registro e reconstrução de 30 a 45 minutos, utilizando reconstrução iterativa com 10 a 20 iterações e 4 subconjuntos de projeções. O sistema foi validado obtendo imagens tomográficas in vivo do coração, dos rins e do cérebro de animais normais (camundongos e ratos adultos), utilizando os radiofármacos hexaquis-2-metoxi-isobutil-isonitrila marcado com 99mTc (Sestamibi-99mTc), ácido dimercaptosuccínico marcado com 99mTc (DMSA-99mTc) e hexametil-propileno-amina-oxima marcada com 99mTc (HMPAO-99mTc). CONCLUSÃO:: Este tipo de aplicação, que consiste na adaptação para um objetivo alternativo de instrumentação já existente, constituiu-se em uma opção de infraestrutura de baixo custo, que permite realizar estudos in vivo em larga escala, com qualidade aprimorada, em áreas diversas, como neurologia, nefrologia, cardiologia, entre outras.

Preclinical molecular imaging: development of instrumentation for translational research with small laboratory animals / Imagem molecular pré-clínica: desenvolvimento de instrumentação para pesquisa translacional com pequenos animais

ABSTRACT Objective: To present the result of upgrading a clinical gamma-camera to be used to obtain in vivo tomographic images of small animal organs, and its application to register cardiac, renal and neurological images. Methods: An updated version of the miniSPECT upgrading device was built, which is composed of mechanical, electronic and software subsystems. The device was attached to a Discovery VH (General Electric Healthcare) gamma-camera, which was retired from the clinical service and installed at the Centro de Imagem Pré-Clínica of the Hospital Israelita Albert Einstein. The combined system was characterized, determining operational parameters, such as spatial resolution, magnification, maximum acceptable target size, number of projections, and acquisition and reconstruction times. Results: Images were obtained with 0.5mm spatial resolution, with acquisition and reconstruction times between 30 and 45 minutes, using iterative reconstruction with 10 to 20 iterations and 4 projection subsets. The system was validated acquiring in vivo tomographic images of the heart, kidneys and brain of normal animals (mice and adult rats), using the radiopharmaceuticals technetium-labeled hexakis-2-methoxy-isobutyl isonitrile (99mTc-Sestamibi), technetium-labeled dimercaptosuccinic acid (99mTc-DMSA) and technetium-labeled hexamethyl propyleneamine oxime (99mTc-HMPAO). Conclusion: This kind of application, which consists in the adaptation for an alternative objective of already existing instrumentation, resulted in a low-cost infrastructure option, allowing to carry out large scale in vivo studies with enhanced quality in several areas, such as neurology, nephrology, cardiology, among others.

RESUMO Objetivo: Apresentar o resultado da adaptação de uma gama câmara clínica para uso dedicado na obtenção de imagens tomográficas in vivo de órgãos de pequenos animais de experimentação, e de sua aplicação na obtenção de imagens cardíacas, renais e neurológicas. Métodos: Foi construída uma versão atualizada do dispositivo de adaptação miniSPECT, composto por três subsistemas: mecânico, eletrônico e de software. O dispositivo foi montado em uma câmara Discovery VH da General Electric Healthcare, retirada do serviço clínico e instalada no Centro de Imagem Pré-Clínica do Hospital Israelita Albert Einstein. O sistema combinado foi caracterizado, determinando parâmetros de funcionamento como resolução espacial, magnificação, limites de tamanho dos alvos de estudo, número de projeções, tempo de registro e tempo de reconstrução das imagens tomográficas. Resultados: Foram obtidas imagens com resolução espacial de até 0,5mm, com tempos de registro e reconstrução de 30 a 45 minutos, utilizando reconstrução iterativa com 10 a 20 iterações e 4 subconjuntos de projeções. O sistema foi validado obtendo imagens tomográficas in vivo do coração, dos rins e do cérebro de animais normais (camundongos e ratos adultos), utilizando os radiofármacos hexaquis-2-metoxi-isobutil-isonitrila marcado com 99mTc (Sestamibi-99mTc), ácido dimercaptosuccínico marcado com 99mTc (DMSA-99mTc) e hexametil-propileno-amina-oxima marcada com 99mTc (HMPAO-99mTc). Conclusão: Este tipo de aplicação, que consiste na adaptação para um objetivo alternativo de instrumentação já existente, constituiu-se em uma opção de infraestrutura de baixo custo, que permite realizar estudos in vivo em larga escala, com qualidade aprimorada, em áreas diversas, como neurologia, nefrologia, cardiologia, entre outras.

Agreement on the prescription of antimicrobial drugs.

BACKGROUND: There is universal awareness of the difficulties faced by doctors when prescribing antimicrobials. METHODS: Over a six-month period patients hospitalized in the ICU and under treatment with antibiotics and/or antifungals were eligible to participate in the study. The data were assessed by two infectious diseases specialists. Once completed, all case forms were sent independently to both evaluators (TZSC and ARM) by e-mail. Based on the data received, the evaluator completed a form automatically generated on the e-mail and returned it to the original mailbox for further analysis. We assessed the level of agreement between infectious disease specialists and the physicians directly responsible for the decision to begin antimicrobial therapy, as well as to assess the appropriateness of the regimen prescribed. RESULTS: Among the antimicrobial regimens prescribed to the 177 patients, 36% were considered inappropriate by specialist #1 and 38% were considered inappropriate by specialist #2. We found 78% agreement by at least one of the infectious disease specialists with the prescribed antimicrobial regimen, and in 49% of cases both specialists agreed with the prescribed regimen. Both disagreed with the prescribed regimen in 22% of the cases and they disagreed between themselves in 29% of the cases. CONCLUSION: This study highlights the difficulties in prescribing effective empirical antimicrobial therapy--they are of such magnitude that even two specialists in infectious diseases, well acquainted with our hospital's resistance patterns and our patients' profiles have considerable disagreement.

BMP-2 and -4 produced by vascular smooth muscle cells from atherosclerotic lesions induce monocyte chemotaxis through direct BMPRII activation.

OBJECTIVE: Monocytes and macrophages, together with vascular smooth muscle cells (VSMCs), play key roles at all stages of atherogenesis. There is also growing evidence that BMP signaling is involved in vascular diseases, including atherosclerosis. Here we evaluate the role played by the BMP agonist/antagonist axis in monocyte recruitment during atherogenesis. METHODS AND RESULTS: Using ApoE-/- mice and BMPs, Gremlin and BMPRII siRNAs we show that BMPs (2 and 4) and their antagonist Gremlin are co-expressed in murine and human atherosclerotic vessels. Additionally, those genes are co-expressed and upregulated in cultured vascular smooth muscle cells early in atherosclerosis formation in ApoE-/- mice. Furthermore, we demonstrate that BMP-2 and -4 produced in atherosclerotic VSMCs promote, whereas Gremlin inhibits, monocyte chemoattraction. Finally, we demonstrate that chemotaxis induction occurs through direct BMP receptor II (BMPRII) activation. CONCLUSION: These findings suggest that the balance between BMPs (2 and 4) and Gremlin levels modulate crosstalk processes between vascular and immune cells and ultimately the homeostasis in normal vasculature. They also indicate that under pro-atherogenic conditions, BMP signaling prevails, favoring monocyte recruitment and inflammation. Manipulation of BMP signaling may enable the identification of novel molecular approaches for preventing, stabilizing, and reverting atherosclerosis.

ID1 inhibits USF2 and blocks TGF-ß-induced apoptosis in mesangial cells.

Mesangial cells (MC) play an essential role in normal function of the glomerulus. Phenotypic changes in MC lead to the development of glomerular diseases such as diabetic nephropathy and glomerulosclerosis. The late phase of diabetic glomerulopathy is characterized by MC death and fibrosis. Current data highlight the transforming growth factor (TGF)-ß as a trigger of the pathological changes observed in MC, including death by apoptosis. However, the mechanisms and mediators involved in this process are still poorly understood. Identification of novel elements involved in MC death may provide a better understanding of the pathophysiology of glomerular diseases. Here, we show that bone morphogenetic proteins (BMPs; known antagonists of the profibrotic effects of TGF-ß in the kidney) strongly induce inhibitor of DNA binding (ID1) mRNA transcription and protein expression in human MC. ID genes have been implicated in cell survival control and are constitutively expressed in MC. We show that BMPs and ID1 exert an anti-apoptotic effect in MC by inhibition of USF2 transcriptional activity. On the other hand, TGF-ß upregulates USF2, increasing BAX (proapoptotic gene) levels and apoptosis rates. Taken together, our results point to a novel molecular pathway that modulates MC apoptosis, which is potentially involved in the pathogenesis of glomerular diseases.

Prevenção de eventos tromboembólicos em portadores de fibrilação atrial - novos anticoagulantes / Prevention of thromboembolic events in patients with atrial fibrillation – new anticoagulants

The authors present alternatives for the treatment of cardiac arrhythmias. Its detection is based on the use of different methods that record the cardiac electrical activity. The treatment involves intervening in the underlying disorder, antiarrhythmic drugs, stimulation and cardiac defibrillation devices, and, less often, surgery. The technological advances in the last two decades have provided greater efficiency in diagnoses and therapy. Atrial fibrilation patients will benefit from a new set of anticoagulant drugs tested in the past three years. The potential advantages include greater safety and efficacy, as well as convenience for not requiring frequent laboratory controls.

Os autores apresentam as alternativas terapêuticas para o tratamento das arritmias cardíacas. Sua detecção baseia-se no uso de diferentes métodos de registro da atividade elétrica cardíaca. O tratamento envolve intervenção sobre o distúrbio de base, drogas antiarrítmicas, dispositivos de estimulação e desfibrilação cardíaca e, em casos infrequentes, cirurgia. Avanços tecnológicos nas últimas duas décadas têm propiciado maior eficiência diagnóstica e terapêutica nesse campo. Pacientes portadores de fibrilação atrial vão se beneficiar de um novo conjunto de drogas anticoagulantes testadas nos últimos 3 anos. As vantagens potenciais incluem maior segurança e eficácia, assim como comodidade por dispensarem controles laboratoriais frequentes.

Prevention of thromboembolic events in patients with atrial fibrillation - new anticoagulants.

The authors present alternatives for the treatment of cardiac arrhythmias. Its detection is based on the use of different methods that record the cardiac electrical activity. The treatment involves intervening in the underlying disorder, antiarrhythmic drugs, stimulation and cardiac defibrillation devices, and, less often, surgery. The technological advances in the last two decades have provided greater efficiency in diagnoses and therapy. Atrial fibrilation patients will benefit from a new set of anticoagulant drugs tested in the past three years. The potential advantages include greater safety and efficacy, as well as convenience for not requiring frequent laboratory controls.

Glucose-insulin infusion reduces kidney injury in an experimental model of ischemic nephropathy.

BACKGROUND/AIMS: intensive insulin therapy may reduce renal dysfunction during severe illness in adult patients. We evaluated the effects of insulin-glucose (IG) in normoglycemic rats subjected to ischemia-reperfusion (I/R)-induced acute kidney injury. METHODS: animals received intravenous infusions of 5% glucose [control (C)] or IG for 96 h. I/R was induced by means of bilateral renal artery clamping for 45 min. Serum creatinine (sCr) and urea (sUr) levels were evaluated before and up to 72 h after injury. Tissue samples were evaluated 72 h after I/R on a scale of 0 (normal) to 4 (above 75%) in relation to the extent of kidney injury. RESULTS: after 48 h of I/R, sCr and sUr were increased 2- to 4-fold in C as compared to sham-operated controls (p < 0.05). IG produced significant improvements in renal function (p < 0.05). Upon histopathological analysis, the IG group presented less tubular damage in comparison to the C group: level 1, 60 versus 20%; level 2, 20 versus 30%; level 3, 20 versus 30%, and level 4, 0 versus 20%, respectively (n = 10; p = 0.057). CONCLUSION: our results suggest that IG infusion attenuates the renal damage induced by severe I/R independently of blood glucose control. This strategy may constitute a therapeutic option for the prevention and treatment of ischemic renal injury.

Uma estratégia para redução de risco cardiovascular em pacientes transplantados renais / A strategy to improve the cardiovascular risk factor profile in renal transplant patients

FUNDAMENTO: A doença cardiovascular representa a principal causa de morbidade, mortalidade e perda de função do enxerto em receptores de transplante renal (RTR). O tratamento agressivo dos fatores de risco é fortemente recomendado. Entretanto, há um gap entre a terapia baseada em evidência recomendada e o manejo cardiovascular eficaz nesta população. OBJETIVO: Estabelecer uma estratégia de controle de fatores de risco cardiovascular para RTR. MÉTODOS: O risco cardiovascular de 300 RTR de uma Unidade de Transplante Renal foi avaliado através dos critérios de Framingham. Intervenções nos fatores de risco modificáveis foram sugeridas aos médicos assistentes através de cartas anexadas aos prontuários dos pacientes, incluindo modificações no estilo de vida, controle de pressão arterial e uso de tratamento anti-plaquetário e hipolipemiante. Os perfis dos fatores de risco foram re-avaliados depois de 6 e 12 meses. RESULTADOS: A maioria dos pacientes apresentava alto risco cardiovascular (58 por cento). Após 12 meses, a proporção de pacientes recebendo tratamento anti-plaquetário, anti-hipertensivo ou hipolipemiante tinha aumentado de forma significante (29 para 51 por cento, 83 para 92 por cento e 3 para 46 por cento, p < 0,001, respectivamente). Os níveis de colesterol total e triglicérides diminuíram (de 237 para 215 mg/dl, p = 0,001 e 244 para 221 mg/dl, p = 0,03). Embora uma redução não-significante nos níveis de LDL-colesterol tenha sido observada (136 para 116 mg/dl, p = 0,12), os pacientes que iniciaram terapia com estatinas nos primeiros 6 meses do estudo apresentaram uma redução significante de 25 por cento no LDL-colesterol (159 para 119 mg/dl, p < 0,001). A proporção de pacientes com avaliação completa de lipídios no plasma também aumentou (27 por cento para 49 por cento, p < 0,001). CONCLUSÃO: Nossos resultados sugerem que uma estratégia simples e de baixo custo melhora de forma significante o perfil de risco cardiovascular de RTR, ...

BACKGROUND: Cardiovascular disease represents the leading cause of morbidity, mortality and graft function loss in renal transplant recipients (RTR). Aggressive treatment of risk factors is strongly advocated. However, there is a gap between recommended evidence-based therapy and effective cardiovascular management in that population. OBJECTIVE: To establish a cardiovascular risk factor control strategy for RTR. METHODS: The cardiovascular risk of 300 RTR of a renal transplant unit was assessed using the Framingham criteria. Interventions on modifiable risk factors were suggested to attending physicians by letters attached to patients' charts, including lifestyle modifications, blood pressure control and use of antiplatelet and lipid-lowering therapy. Risk factor profiles were re-evaluated after 6 and 12 months. RESULTS: Most patients were at high cardiovascular risk (58 percent). After 12 months, the proportion of patients on antiplatelet, antihypertensive and lipid-lowering therapy was significantly increased (29 to 51 percent, 83 to 92 percent and 3 to 46 percent, p < 0.001, respectively). Total cholesterol and triglyceride levels decreased (237 to 215 mg/dl, p = 0.001 and 244 to 221 mg/dl, p = 0.03). Although a non-significant reduction in LDL levels was observed (136 to 116 mg/dl, p = 0.12), patients starting statins within the first 6 months of the study presented a significant 25 percent reduction in LDL (159 to 119 mg/dl, p < 0.001). The proportion of patients with complete plasma lipid evaluation was also increased (27 percent to 49 percent, p < 0.001). CONCLUSION: Our results suggest that a simple, inexpensive strategy significantly improves the cardiovascular risk profile of RTR, potentially translating into marked benefits for long-term graft function and life expectancy.

[A strategy to improve the cardiovascular risk factor profile in renal transplant patients].

BACKGROUND: Cardiovascular disease represents the leading cause of morbidity, mortality and graft function loss in renal transplant recipients (RTR). Aggressive treatment of risk factors is strongly advocated. However, there is a gap between recommended evidence-based therapy and effective cardiovascular management in that population. OBJECTIVE: To establish a cardiovascular risk factor control strategy for RTR. METHODS: The cardiovascular risk of 300 RTR of a renal transplant unit was assessed using the Framingham criteria. Interventions on modifiable risk factors were suggested to attending physicians by letters attached to patients' charts, including lifestyle modifications, blood pressure control and use of antiplatelet and lipid-lowering therapy. Risk factor profiles were re-evaluated after 6 and 12 months. RESULTS: Most patients were at high cardiovascular risk (58%). After 12 months, the proportion of patients on antiplatelet, antihypertensive and lipid-lowering therapy was significantly increased (29 to 51%, 83 to 92% and 3 to 46%, p < 0.001, respectively). Total cholesterol and triglyceride levels decreased (237 to 215 mg/dl, p = 0.001 and 244 to 221 mg/dl, p = 0.03). Although a non-significant reduction in LDL levels was observed (136 to 116 mg/dl, p = 0.12), patients starting statins within the first 6 months of the study presented a significant 25% reduction in LDL (159 to 119 mg/dl, p < 0.001). The proportion of patients with complete plasma lipid evaluation was also increased (27% to 49%, p < 0.001). CONCLUSION: Our results suggest that a simple, inexpensive strategy significantly improves the cardiovascular risk profile of RTR, potentially translating into marked benefits for long-term graft function and life expectancy.

Labeling of human mesenchymal stem cells with quantum dots allows tracking of transplanted cells engrafted in infarcted pig hearts / A marcação de células-tronco mesenquimais humanas com quantum dots possibilita a identificação de células transplantadas enxertadas em corações de porcos após o infarto do miocárdio

Objective: The purpose of this paper was to validate fluorescent quantum dots QD as a cell marker for tracking human mesenchymal stem cells in vivo, using a pre-clinical model of acute myocardium infarction. Methods: Human umbilical cord mesenchymal stem cells were isolated and expanded in vitro. Mesenchymal stem cells were labeled with QD 655. Myocardium infarction induction in pigs was performed by occluding the left descending coronary artery for 60 minutes, with a balloon catheter. One day after the myocardium infarction, intracoronary injection of mesenchymal stem cells was performed. One week after cell transplantation, the animals were killed; their hearts were removed and underwent histological examination Results: All the mesenchymal stem cells were labeled with QD 655. The labeling process did not affect viability, proliferation, and osteogenic and adipogenic differentiation potential of the cells. Labeled mesenchymal stem cells were easily tracked in the histological sections of the infarcted area. Cells were observed with a frequency of two per section, while no cells were observed in the remote myocardium. Conclusion: These results indicate that QD 655 labeling is an efficient tool for tracking mesenchymal stem cells in vivo

Objetivo: Avaliar uma nova modalidade de marcação celular com quantum dots QD fluorescentes em células-tronco mesenquimais humanas (CTM), transplantadas em um modelo pré-clínico de infarto agudo do miocárdio. Métodos: CTM de cordão umbilical humano foram isoladas e expandidas in vitro. CTM foram marcadas passivamente com o nanocristal QD 655. A indução do infarto foi realizada pela cateterização e oclusão por 60 minutos da artéria coronária descendente anterior esquerda sob fluoroscopia. Um dia após o infarto, CTM foram transplantadas por via intracoronária. Uma semana após o transplante de CTM, os animais foram sacrificados e os corações removidos e analisados histologicamente. Resultados: Todas as CTM foram efetivamente marcadas com QD 655. A marcação não afetou a viabilidade, a taxa de proliferação e a capacidade de diferenciação em osteoblastos e adipócitos das células. CTM marcadas foram facilmente identificadas em cortes histológicos das áreas de infarto/borda de infarto com frequência média de duas células por corte histológico, enquanto que na região remota não foi detectada qualquer marcação. Conclusão: Os resultados indicam que a marcação de CTM com QD 655 é eficiente para rastreamento de células mesenquimais in vivo

The bone morphogenetic protein antagonist gremlin promotes vascular smooth muscle cell apoptosis.

BACKGROUND: Previous studies from our laboratory demonstrated that gremlin significantly increases vascular smooth muscle cell (VSMC) proliferation and migration. The present study investigates gremlin expression in the initial stages of rat carotid balloon injury and its effects on VSMC apoptosis. METHODS: Gremlin mRNA expression was evaluated in rat carotids and cultured VSMCs by quantitative PCR. Apoptosis was analyzed in A7r5 cells and rabbit primary VSMCs following gremlin gene overexpression or silencing by chromatin morphology and caspase-3 activity. RESULTS: Vascular injury promoted a significant decrease in gremlin mRNA levels. In addition, platelet-derived growth factor, angiotensin II and transforming growth factor (TGF)-beta1 promoted coordinated regulation of gremlin and bone morphogenetic protein (BMP)-4 expression in opposite directions according to the confluence status of VSMC culture. In A7r5 cells, gremlin overexpression was able to increase apoptosis, as demonstrated by chromatin morphology and caspase-3 activity, while BMP administration promoted opposite effects. Finally, in agreement with our results, gremlin gene silencing effectively suppressed apoptosis in A7r5 cells and rabbit VSMCs. CONCLUSION: Gremlin is regulated by growth factors and vascular injury and is involved in modulation of VSMC apoptosis. Modifications of gremlin expression during vascular injury may contribute to the apoptosis resistance of VSMCs.

Adult stem cells therapy for the heart: [review] / Uso terapêutico de células-tronco em Cardiologia: [revisão]

Acute myocardial infarction causes irreversible loss of cardiomyocytes and endothelial cells compromising the cardiac function of patients. For some patients, current therapeutic approaches are not sufficient to prevent myocardial remodeling, which aggravates the disease. The potential of many types of adult bone marrow-derived progenitor cells in replacing damaged myocardium with functional cells has been investigated in several clinical and experimental studies. It has been demonstrated that these cells have an overall beneficial effect on heart function although the mechanism or multiple mechanisms involved have not been elucidated yet. Here, it will be reviewed some aspects of this fast-growing and controversial of adult autologous progenitor/stem cells for cardiac repair.

O infarto agudo do miocárdio causa perda irreversível de cardiomiócitos e células endoteliais, que compromete a função cardíaca dos pacientes. Para alguns indivíduos, as abordagens terapêuticas atuais não são suficientes para evitar um remodelamento miocárdico, o que agrava a doença. O potencial de vários tipos de células progenitoras adultas derivadas da medula óssea para substituir o miocárdio lesado com células funcionais, tem sido investigado em vários estudos clínicos e experimentais. Já se demonstrou que tais células têm um efeito benéfico geral na função cardíaca, mas o mecanismo ou os diversos mecanismos envolvidos não foram ainda elucidados. Neste artigo revisamos alguns aspectos deste campo controverso e de rápida evolução – uso de células progenitoras/tronco autólogas de adultos para reparo cardíaco.