Leaf extracts of Campomanesia xanthocarpa positively regulates atherosclerotic-related protein expression.

Atherosclerosis is caused by a monocyte-mediated inflammatory process that, in turn, is stimulated by cytokines and adhesion molecules. Monocytes are then differentiated into macrophages, leading to the formation of arterial atherosclerotic plaques. Recently, guavirova leaf extracts from Campomanesia xanthocarpa (EG) have shown potential effects on the treatment of plaque formation by reducing cholesterol, LDL levels and serum oxidative stress. We evaluated the effect of EG on the viability of human monocytic and endothelial cell lines at three time points (24, 48 and 72 hours) and whether it can modulate the migration and in vitro expression of CD14, PECAM-1, ICAM-1, HLA-DR and CD105. Cell viability was affected only at higher concentrations and times. We observed decreased ICAM-1 expression in cells treated with 50 µg/ml EG and CD14 expression with IFN-γ and without IFN-γ. CD14 also decreased endothelial cell expression in the presence of IFN-γ and GE. We also found decreased expression of PECAM-1 when treated with EG and IFN-γ. In addition, EG-treated endothelial cells showed higher migration than the control group. Reduced expression of these markers and increased migration may lead to decreased cytokines, which may be contributing to decreased chronic inflammatory response during atherosclerosis and protecting endothelial integrity.

Complement-fixing donor-specific anti-HLA antibodies and kidney allograft failure.

Detection of donor-specific antibodies (DSA) has improved the risk classification and post-transplant evaluation of kidney recipients. Moreover, assessment of DSA C1q-binding ability has been shown to improve the individual risk classification of transplant patients for allograft loss, especially when detected after transplantation. The aim of this study was to evaluate the additional clinical impact of C1q-binding DSA detection in a population that was extensively monitored for DSA and MFI alterations. Forty-two kidney allograft recipients were followed-up at multiple time points for up to 5 years after transplantation for the presence of anti-HLA DSA-IgG total. The samples that were positive for these antibodies were retrospectively tested for the presence of complement-binding antibodies. Overall, 24 patients presented DSA, 29% (7) of which also produced complement-binding DSA. Compared to patients with non-C1q-binding DSA and non-sensitized patients, patients with C1q-binding DSA after transplantation had the lowest allograft survival rate at 5 years (p = 0.042) and showed a lower estimated glomerular filtration rate (based on the Modification of Diet in Renal Disease formula) during the post-transplant follow-up period (p = 0.01). Thus, post-transplant monitoring for complement-binding DSA is a useful tool for predicting individuals most at risk for allograft failure, and might also be beneficial for evaluation of immunosuppression regimens.

Evaluation of oxidative stress and brain-derived neurotrophic factor levels related to crack-use detoxification.

Crack is a central nervous system stimulant extracted from the Erythroxylum coca plant. It is considered the most potent and addictive form of cocaine, and its euphoric effects are attained within a few seconds after consumption. Alteration of biological markers of oxidative stress and brain-derived neurotrophic factor (BDNF) could be related to the severity of crack withdrawal symptoms in patients undergoing rehabilitation. Thus, the objective of this study was to evaluate if the crack consumption and the drug detoxification process during 14 days in hospitalization regime was able to modify the oxidative status and BDNF levels, in male crack-abstinent patients. The crack detoxification process increased the glutathione (GSH), total thiol content (GST), nitric oxide (NO), and superoxide dismutase (SOD) levels, and reduced the mean BDNF levels. Moreover, a positive correlation was found between the number of hospital admission days and SOD values and between the GST levels and crack-use time after 14 days of detoxification. Furthermore, a negative correlation between the frequency of crack use and NO levels on the first day of hospitalization was also found. In conclusion, the results of this study indicated that crack consumption causes increased oxidative stress in drug users and that the detoxification process during 14 days was sufficient to improve oxidative parameters and antioxidant defenses of the patients, which could positively contribute to rehabilitation process. In addition, we also observed a great variability in the BDNF levels of the patients during the detoxification process, resulting in a reduction in the mean values of this neurotrophin.

Inhibitory effect of Campomanesia xanthocarpa in platelet aggregation: Comparison and synergism with acetylsalicylic acid.

BACKGROUND AND AIMS: Cardiovascular diseases of thrombotic origin are related to high mortality and standard therapeutic agent used in this case is acetylsalicylic acid (ASA), but serious adverse events may occur. However, recent data has suggested the plant Campomanesia xanthocarpa has antiplatelet activity and could be a viable alternative. In this study we investigated the effects of the encapsulated powder of this plant in human platelet aggregation. METHODS: 23 healthy subjects were randomly divided into three groups: (1) ASA (100mg), (2) C. xanthocarpa (1000mg) or (3) synergism (500mg of C. xanthocarpa plush 50mg of ASA); daily for five days. Antiplatelet activity was determined by turbidimetric method using ADP or arachidonic acid (AA) agonists before, 5 and 8days after treatments. RESULTS: Treatment with C. xanthocarpa and synergism caused a reduction of 8±13.5% and 12.5±5% in platelet aggregation induced by ADP after 5days of treatment, respectively, returning to basal levels after 8days. For AA agonist, 5days of treatment with C. xanthocarpa, ASA or synergism caused a reduction of 46±15%, 36±12% and 69.3±6% in platelet aggregation, respectively, and first two groups returned to baseline values 8days after treatment ended. Synergism group prolonged antiplatelet effect maintaining aggregation reduction after 8days the end of treatment. CONCLUSION: C. xanthocarpa showed antiplatelet action when stimulated by agonist AA, and contributed to the antiplatelet effect when associated with ASA for both agonists, allowing dose reduction to 50mg.

Evaluation of Salt Intake, Urinary Sodium Excretion and Their Relationship to Overhydration in Chronic Kidney Disease Patients.

The purpose of this study was to estimate sodium intake in a group of patients with chronic kidney disease (CKD) and to correlate the results with the urinary excretion values of sodium and signs of fluid overload. We included patients with CKD in different stages. Urinary sodium was measured in 24 h urine samples. Body composition monitor (BCM) was used to estimate the hydration status. Sixty patients (38 ± 15 ml/min of GFR) presented 4.14 ± 1.71 g/24 h of urinary sodium excretion. Overhydration was detected in 50% of the patients by the BCM. There was a positive correlation between the measured sodium excretion values and BCM, ICW, ECW and TBW. In conclusion, markers of overhydration evaluated by BCM were positively correlated with urinary sodium excretion.

Efeitos da cirurgia metabólica no portador de diabetes mellitus tipo 2 / Effects of metabolic surgery in diabetes mellitus type 2 patients

JUSTIFICATIVA E OBJETIVOS: O diabetes mellitus tipo 2) é a principal causa de doença renal terminal. O tratamento inicial da progressão da nefropatia diabética engloba o controle estrito da hiperglicemia, hiperfiltração e hipertensão. Algumas cirurgias envolvendo derivações intestinais melhoram a homeostase da glicose.Os objetivos deste estudo são avaliar os efeitos da cirurgia metabólica em pacientes com diabetes mellitus tipo 2. MÉTODOS:Estudo retrospectivo. Foram revisados prontuários de 17 pacientes diabéticos que foram submetidos à cirurgia de derivação do intestino proximal. Para comparar as variáveis foram utilizados os testes t de Student e Wilcoxon. Um valor de p<0,05 foi considerado estatisticamente significativo. RESULTADOS:A média da idade dos pacientes foi de 52,1 ± 3,5 anos e houve predomínio do sexo masculino (59%). Ocorreu redução estatisticamente significativa no peso, índice de massa corpórea, colesterol total, glicemia de jejum e hemoglobina glicada (p<0,05). Entretanto, não houve diferença estatisticamente significativa nos níveis de colesterol-HDL, colesterol-LDL, triglicerídeos, creatinina,depuração de creatinina, microalbuminúria e proteinúria de 24h (p>0,05). CONCLUSÃO: Os presentes dados sugerem que a cirurgia de derivação do intestino proximal, além da perda de peso, favorece o controle do diabetes mellitus tipo 2. Estudos com maior seguimento e número de pacientes são necessários para melhor definição do papel da cirurgia metabólica no tratamento do diabetes.

BACKGROUND AND OBJECTIVES: Type 2 diabetes mellitus is the leading cause of end-stage renal disease worldwide. Initial treatment in the progression of diabetic nephropathy includes strict control of hyperglycemia, hyperfiltration and arterial hypertension. Certain operations involving intestinal diversions improve glucose homeostasis. The objective of this study is to evaluate the effects of metabolic surgery in diabetes mellitus type 2 patients. METHODS: This is a retrospective study. We reviewed medical records of 17 diabetic patients who had undergone laparoscopic duodenal-jejunal exclusion. To compare the variables Student t and Wilcoxon tests were used. A p value < 0.05 was considered statistically significant. RESULTS: Patients mean age was 52.1 ± 3.5 years and 59% of them were male. There was a statistical significant decrease in weight, body mass index, total cholesterol, fasting glucose and glycosylated hemoglobin (p< 0.05). However, there was no statistical significant difference in levels of HDL-cholesterol, LDL-cholesterol, triglycerides, creatinine, creatinine clearance, microalbuminuria and proteinuria (p > 0.05). CONCLUSION: Our data suggest that laparoscopic duodenal-jejunal exclusion, in addition to weight loss, favors glycemic control in type 2 diabetes. Studies with longer follow-up and a larger number of patients are necessary to better define the role of metabolic surgery in the treatment of diabetes.

Marcadores clínicos e bioquímicos de gravidade do diabetes mellitus gestacional / Clinical and biochemical markers of gravity of gestational diabetes mellitus

O diabetes mellitus gestacional (DMG) é uma patologia da segunda metade da gestação caracterizada por uma insulinorresistência que está intimamente relacionada ao resultado perinatal adverso e se não diagnosticada e tratada pode trazer sérios problemas tanto para a mãe quanto para o feto. O objetivo deste trabalho foi realizar uma revisão da literatura sobre marcadores clínicos e bioquímicos de gravidade do DMG. Trata-se de uma revisão de literatura nas bases de dados PubMed, SciELO e Cochrane. Foram selecionados 50 artigos, mas apenas 25 tiveram relevância para serem discutidos nesta revisão. Após análise pôde-se concluir que com os novos critérios-diagnósticos e um aumento na incidência dessa patologia é de grande valia identificar marcadores clínicos e bioquímicos que estão relacionados aos resultados perinatais adversos e à necessidade de tratamento complementar à dieta

The gestational diabetes mellitus (GDM) is a second half of pregnancy disease characterized by insulin resistance that is closely related to perinatal outcome and if undiagnosed and untreated can cause serious problems for both mother and fetus. The objective of this study was to review the literature on clinical and biochemical markers of GDM severity. This is a literature review in PubMed, SciELO and Cochrane. Fifty articles were selected, but only 25 were relevant to be discussed in this review. After their analysis it was concluded that with the new diagnostic criteria and an increased incidence of this pathology is of great value to identify clinical and laboratory markers that are related to adverse perinatal outcomes and the need to supplement the diet treatment

Immune regulatory properties of multipotent mesenchymal stromal cells: Where do we stand?

Multipotent mesenchymal stromal cells (MSC) can be isolated and efficiently expanded from almost every single body tissue and have the ability of self-renewal and differentiation into various mesodermal cell lineages. Moreover, these cells are considered immunologically privileged, related to a lack of surface expression of costimulatory molecules required for complete T cell activation. Recently, it has been observed that MSC are capable of suppressing the immune response by inhibiting the maturation of dendritic cells and suppressing the function of T lymphocytes, B lymphocytes and natural killer cells in autoimmune and inflammatory diseases as a new strategy for immunosuppression. The understanding of immune regulation mechanisms by MSC is necessary for their use as immunotherapy in clinical applications for several diseases.

Uncovering the vasorelaxant effect induced by Vale do São Francisco red wine: a role for nitric oxide.

The aim of this study was to investigate the mechanisms underlying the vasorelaxant effect induced by the polyphenolic compounds found in red wine from Vale do São Francisco. In phenylephrine (10 µM) precontracted mesenteric artery rings, the red wine caused a concentration-dependent relaxation (maximum response to phenylephrine 10 µM = 87.5% ± 6.5%, n = 10). After endothelium removal, the vasorelaxant effect elicited by red wine was attenuated (28.4% ± 4.9%, n = 10). In addition, the vasorelaxant effect induced by red wine in rings pretreated with 100 µM of N(w)-nitro-l-arginine methyl ester and 10 µM of 1H-[1,2,4] oxadiazolo-[4,3-a]-quinoxalin-1-one was attenuated (23.4% ± 5.1%, n = 7 and 11.8% ± 2.7%, n = 6, respectively). Pretreatment with atropine did not affect the vasorelaxant effect induced by red wine (81% ± 3.9%, n = 6). Furthermore, in rabbit aortic endothelial cell line, red wine 100 and 300 µg/mL caused concentration-dependent increases in nitric oxide levels (58 ± 1; 82 ± 7.9; Δ% of fluorescence, n = 5, respectively). In conclusion, we suggest that the alcohol free-lyophilized red wine induces an endothelium-dependent vasorelaxant effect due, at least in part, to a secondary increase in the concentration of nitric oxide and that this effect might be associated with phenolic compounds found in the red wine.

Glycemic and lipidic profile in diabetic patients undergoing dialysis / Controle glicêmico e lipídico no paciente diabético em diálise

OBJECTIVE: The aim of this study is to assess the clinical care pattern and to compare the lipid and glycemic profile in a group of diabetic patients undergoing both hemodialysis (HD) and peritoneal dialysis (PD) and to correlate these data using biomarkers of cardiovascular risk. SUBJECTS AND METHODS: The first phase consisted in performing a survey on demographic data, questions about the medical team and glycemic control. In the second phase, patients were assessed through laboratorial data on their glycemic and lipid profile at a single center for HD and PD. RESULTS: 91 patients was the total population; 70 patients (77 percent) answered the survey; 66 patients (94 percent) considered the nephrologist the physician responsible for caring for their glycemic control. Second phase: 59 patients were assessed, 29 undergoing HD and 30 undergoing PD. Fifty-seven percent of the patients had HbA1c above 7 percent; the level of glycemic markers in patients undergoing peritoneal dialysis was significantly higher than in patients undergoing hemodialysis: HbA1c (9.37 ± 0.5) vs. (7.37 ± 0.49) p < 0.01; fasting glycemia (170 ± 15) vs. (126 ± 15) mg/dL p < 0.05. We found a positive correlation between HbA1c and hyperfibrinogenemia (r = 0.4437, p < 0.0005). CONCLUSIONS: The data reveal that glycemic control in diabetic patients undergoing renal replacement therapy (RRT) is neglected. Peritoneal dialysis is related to the worst level of glycemic markers, possibly due to the glucose content in the dialysis solution, and higher levels from HbA1c have a positive correlation with hyperfibrinogenesis in this population.

OBJETIVO: Avaliar as características dos cuidados clínicos dos pacientes em diálise, comparar o controle glicêmico e lipídico entre os pacientes diabéticos em hemodiálise (HD) e em diálise peritoneal (DP) e correlacionar os dados laboratoriais com biomarcadores de risco cardiovascular. SUJEITOS E MÉTODOS: A primeira etapa consistiu de um questionário abordando variáveis demográficas, questões sobre a equipe multidisciplinar, incluindo a equipe médica e sobre o controle glicêmico. Na segunda, os pacientes foram avaliados com exames laboratoriais para controle glicêmico e perfil lipídico numa unidade de HD e DP. RESULTADOS: Dos 91 pacientes avaliados, setenta (77 por cento) responderam ao questionário. Destes, 66 (94 por cento) consideraram o nefrologista o médico responsável pelo cuidado do seu controle glicêmico. Na segunda etapa, foram avaliados 59 pacientes: 29 em HD e 30 em DP. Cinquenta e sete por cento dos pacientes diabéticos em diálise apresentaram HbA1c acima de 7 por cento, sendo que aqueles em diálise peritoneal apresentam níveis de marcadores glicêmicos significativamente piores do que os pacientes diabéticos em HD, HbA1c: (9,37 ± 0,5) vs. (7,37 ± 0,49) p < 0.01; glicemia de jejum: (170 ± 15) vs. (126 ± 15) mg/dL, p < 0.05. Encontramos uma correlação positiva entre HbA1c e hiperfibrinogenemia (r = 0.4437, p < 0.0005). CONCLUSÕES: Nossos dados permitem inferir que o controle glicêmico da população diabética em terapia renal de substituição (TRS) é negligenciado. A diálise peritoneal está relacionada com piora nos níveis de marcadores glicêmicos, possivelmente em decorrência do conteúdo de glicose das soluções de diálise, e os níveis elevados de HbA1c estão associados com hiperfibrinogenemia nesta população.

Sevelamer carbonate reduces inflammation and endotoxemia in an animal model of uremia.

BACKGROUND: Renal failure is associated with activation of inflammatory response, but the mechanisms behind this observation and potential anti-inflammatory strategies are yet to be defined. Endotoxin (ET) translocation from the intestinal lumen can potentially trigger systemic inflammatory response, and ET binding represents a potential anti-inflammatory strategy in renal failure. The aim of this study was to evaluate the ET-binding capacity of sevelamer carbonate in an animal model of renal failure. MATERIAL AND METHODS: Rats were 5/6 nephrectomized to induce uremia (U) and sham-operated rats were allocated to receive normal chow (controls) or a diet with 3% sevelamer carbonate added (+SC) for 60 days. Tumor necrosis factor-α (TNF-α) and ET were measured in plasma on days 7, 30 and 60 in all animals. RESULTS: Renal failure induced an inflammatory response, since TNF-α levels were undetectable in all control animals in contrast to the uremic group (3.18 ± 0.62, 2.58 ± 0.54 and 1.86 ± 0.47 pg/ml, respectively, on days 7, 30 and 60; p < 0.05 at all time points). Similarly, uremic rats presented an increase in ET levels (0.038 ± 0.007 EU/ml) when compared to sham-operated animals (0.008 ± 0.006 EU/ml; p < 0.05). During the study, TNF-α levels in U + SC rats were significantly lower compared with U-control animals (p < 0.05). Similarly, ET levels in U + SC rats were lower when compared with U-control rats (p < 0.005). CONCLUSION: In conclusion, induction of renal failure triggered inflammation and induced endotoxemia in this experimental model of chronic kidney disease, which were reduced by sevelamer treatment. This data suggests that sevelamer carbonate induces an anti-inflammatory effect in parallel to a reduction in ET.

Are purified or expanded cord blood-derived CD133+ cells better at improving cardiac function?

Endothelial progenitor cells (EPCs), which express the CD133 marker, can differentiate into mature endothelial cells (ECs) and create new blood vessels. Normal angiogenesis is unable to repair the injured tissues that result from myocardial infarction (MI). Patients who have high cardiovascular risks have fewer EPCs and their EPCs exhibit greater in vitro senescence. Human umbilical cord blood (HUCB)-derived EPCs could be an alternative to rescue impaired stem cell function in the sick and elderly. The aim of this study was to purify HUCB-derived CD133(+) cells, expand them in vitro and evaluate the efficacy of the purified and expanded cells in treating MI in rats. CD133(+) cells were selected for using CD133-coupled magnetic microbeads. Purified cells stained positive for EPC markers. The cells were expanded and differentiated in media supplemented with fetal calf serum and basic fibroblast growth factor, insulin-like growth factor-I and vascular endothelial growth factor (VEGF). Differentiation was confirmed by lack of staining for EPC markers. These expanded cells exhibited increased expression of mature EC markers and formed tubule-like structures in vitro. Only the expanded cells expressed VEGF mRNA. Cells were expanded up to 70-fold during 60 days of culture, and they retained their functional activity. Finally, we evaluated the therapeutic potential of purified and expanded CD133(+) cells in treating MI by intramyocardially injecting them into a rat model of MI. Rats were divided into three groups: A (purified CD133(+) cells-injected); B (expanded CD133(+) cells-injected) and C (saline buffer-injected). We observed a significant improvement in left ventricular ejection fraction for groups A and B. In summary, CD133(+) cells can be purified from HUCB, expanded in vitro without loosing their biological activity, and both purified and expanded cells show promising results for use in cellular cardiomyoplasty. However, further pre-clinical testing should be performed to determine whether expanded CD133(+) cells have any clinical advantages over purified CD133(+) cells.

Glycemic and lipidic profile in diabetic patients undergoing dialysis.

OBJECTIVE: The aim of this study is to assess the clinical care pattern and to compare the lipid and glycemic profile in a group of diabetic patients undergoing both hemodialysis (HD) and peritoneal dialysis (PD) and to correlate these data using biomarkers of cardiovascular risk. SUBJECTS AND METHODS: The first phase consisted in performing a survey on demographic data, questions about the medical team and glycemic control. In the second phase, patients were assessed through laboratorial data on their glycemic and lipid profile at a single center for HD and PD. RESULTS: 91 patients was the total population; 70 patients (77%) answered the survey; 66 patients (94%) considered the nephrologist the physician responsible for caring for their glycemic control. Second phase: 59 patients were assessed, 29 undergoing HD and 30 undergoing PD. Fifty-seven percent of the patients had HbA1c above 7%; the level of glycemic markers in patients undergoing peritoneal dialysis was significantly higher than in patients undergoing hemodialysis: HbA1c (9.37 ± 0.5) vs. (7.37 ± 0.49) p < 0.01; fasting glycemia (170 ± 15) vs. (126 ± 15) mg/dL p < 0.05. We found a positive correlation between HbA1c and hyperfibrinogenemia (r = 0.4437, p < 0.0005). CONCLUSIONS: The data reveal that glycemic control in diabetic patients undergoing renal replacement therapy (RRT) is neglected. Peritoneal dialysis is related to the worst level of glycemic markers, possibly due to the glucose content in the dialysis solution, and higher levels from HbA1c have a positive correlation with hyperfibrinogenesis in this population.

Expression of cardiac function genes in adult stem cells is increased by treatment with nitric oxide agents.

Mesenchymal stem cells (MSCs) have received special attention for cardiomyoplasty because several studies have shown that they differentiate into cardiomyocytes both in vitro and in vivo. Nitric oxide (NO) is a free radical signaling molecule that regulates several differentiation processes including cardiomyogenesis. Here, we report an investigation of the effects of two NO agents (SNAP and DEA/NO), able to activate both cGMP-dependent and -independent pathways, on the cardiomyogenic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) and adipose tissue-derived stem cells (ADSCs). The cells were isolated, cultured and treated with NO agents. Cardiac- and muscle-specific gene expression was analyzed by indirect immunofluorescence, flow cytometry, RT-PCR and real-time PCR. We found that untreated (control) ADSCs and BM-MSCs expressed some muscle markers and NO-derived intermediates induce an increased expression of some cardiac function genes in BM-MSCs and ADSCs. Moreover, NO agents considerably increased the pro-angiogenic potential mostly of BM-MSCs as determined by VEGF mRNA levels.

Formação in vitro de túbulos capilares a partir de células de sangue de cordão umbilical humano com perspectivas para aplicação terapêutica / In vitro formation of capillary tubules from human umbilical cord blood cells with perspectives for therapeutic application

OBJETIVO: As células progenitoras endoteliais (CPE), caracterizadas pelo marcador CD133+, contribuem para a neovascularização, e o aumento no número dessas células pode ser uma ferramenta terapêutica promissora. O sangue de cordão umbilical humano contém um número significante de CPE, sugerindo a possibilidade do uso destas células para a revascularização de tecidos isquêmicos. O objetivo desse trabalho foi analisar a funcionalidade das células CD133+ diferenciadas in vitro. MÉTODOS: As células diferenciadas foram caracterizadas por citometria de fluxo; a expressão do mRNA de VEGF foi avaliada por RT-PCR e a funcionalidade, por meio de ensaios de formação de túbulos capilares. RESULTADOS: As células diferenciadas perderam os marcadores de CPE, mantiveram em níveis baixos os marcadores das linhagens hematopoética e monocíticas e aumentaram a expressão dos marcadores de células endoteliais adultas. As células diferenciadas apresentaram transcritos no mRNA de VEGF e mostraram-se capazes de formar túbulos capilares in vitro. CONCLUSÃO: As células CD133+ diferenciadas in vitro em células endoteliais demonstraram serem funcionalmente ativas, abrindo perspectiva para seu uso futuro em aplicações terapêuticas.

OBJECTIVE: Endothelial progenitor cells (EPC) caracterized by the CD133+ marker, contribute to the neovascularization. Increasing EPC number in vitro could be a promising therapeutic tool. Human umbilical cord blood maintains a significant number of EPC, suggesting the possibility to use these cells to induce the revascularization of ischemic tissues. The aim of this study was to analize the in vitro function of differentiated CD133+ cells. METHODS: Cells were characterized by flow cytometry, VEGF mRNA expression was evaluated by the RT-PCR analysis and the functionally by essays of capillary tubes formation. RESULTS: Differentiated cells lost EPC markers, maintained low levels of markers for hematopoietic and monocytic cell lines and increased the expression of adult endothelial cell markers. Differentiated cells expressed VEGF mRNA and were capable to induce in vitro capillary tubules formation. CONCLUSION: CD133+ cells differentiated into endothelial cells in vitro are functionally active initiating the possibility of their use in future therapeutic applications.

Characteristics and causes of immune dysfunction related to uremia and dialysis.

From the immunologic viewpoint, chronic kidney disease (CKD) is characterized by disorders of both the innate and adaptive systems, generating a complex and still not fully understood immune dysfunction. Markers of a chronically activated immune system are closely linked to several complications of CKD and represent powerful predictors for mortality in the CKD population. On the other hand, CKD patients respond poorly to vaccination and to challenges such as bacterial infection. Interestingly, the main causes of death in patients with CKD are cardiovascular and infectious diseases, both being pathologic processes closely linked to immune function. Therefore, accelerated tissue degeneration (as a consequence of chronic inflammation) and increased rate of sepsis (because of a poorly orchestrated immune response) represent the most important targets for interventions aiming to reduce mortality in CKD patients. Understanding the mechanisms behind the immune dysfunction that is peculiar to CKD generates a perspective to improve outcomes in this group of patients.

[Clinical protocol for selection of the candidates for islet transplantation]. / Protocolo clínico para seleção de candidatos ao transplante de ilhotas.

BACKGROUND: Our intention is to describe the clinical profile of the candidates for islet transplantation in Curitiba, Brazil. METHODS: The clinical evaluation was organized in stages: Screening, Initial Evaluation, Evaluation and Waiting List. Candidates' inclusion criteria were hypoglycemia unawareness, glycemic imbalance, chronic progressive diabetic complications, 18-65 years of age and at least 5 years of type 1 diabetes evolution. RESULTS: From September 2003 through September 2006, 92 candidates were clinically evaluated, and 25 fulfilled the Screening criteria, being selected at this stage. The main reason for exclusion was insulin requirement of more than 0.7 IU/kg/day. At the Initial Evaluation, seven of the 25 patients were excluded as have not agreed to sign the informed consent. Until now, 4 candidates completed the Evaluation stage and two of them are currently enlisted. CONCLUSIONS: Candidates for islet transplantation must be rigorously evaluated. Two patients fulfilled all the selection criteria and are currently enlisted.

Protocolo clínico para seleção de candidatos ao transplante de ilhotas / Clinical protocol for selection of the candidates for islet transplantation

OBJETIVO: Descrever o perfil clínico dos candidatos ao programa de transplante de ilhotas da Pontifícia Universidade Católica do Paraná (PUC-PR), em Curitiba. MÉTODOS: O processo de avaliação clínica foi estruturado em etapas: triagem, pré-avaliação, avaliação e lista de espera. Os critérios de inclusão utilizados foram: ocorrência de hipoglicemia assintomática, complicações crônicas progressivas da doença, idade entre 18 e 65 anos e pelo menos cinco anos de doença. RESULTADOS: De setembro de 2003 a setembro de 2006 foram avaliados 92 candidatos, dos quais 25 preencheram os critérios de triagem, sendo selecionados para pré-avaliação. O principal motivo de não qualificação foi o uso de insulina em dose > 0,7 UI/kg/d. Dos 25 candidatos incluídos na pré-avaliação, sete não concordaram em assinar o termo de consentimento. Quatro candidatos completaram todas as etapas de seleção, porém apenas dois permanecem em lista de espera. CONCLUSÕES: Os candidatos ao transplante de ilhotas devem ser rigorosamente selecionados. Dois pacientes preencheram todos os critérios e encontram-se em lista de espera.

BACKGROUND: Our intention is to describe the clinical profile of the candidates for islet transplantation in Curitiba, Brazil. METHODS: The clinical evaluation was organized in stages: Screening, Initial Evaluation, Evaluation and Waiting List. Candidates’ inclusion criteria were hypoglycemia unawareness, glycemic imbalance, chronic progressive diabetic complications, 18-65 years of age and at least 5 years of type 1 diabetes evolution. RESULTS: From September 2003 through September 2006, 92 candidates were clinically evaluated, and 25 fulfilled the Screening criteria, being selected at this stage. The main reason for exclusion was insulin requirement of more than 0.7 IU/kg/day. At the Initial Evaluation, seven of the 25 patients were excluded as have not agreed to sign the informed consent. Until now, 4 candidates completed the Evaluation stage and two of them are currently enlisted. CONCLUSIONS: Candidates for islet transplantation must be rigorously evaluated. Two patients fulfilled all the selection criteria and are currently enlisted.

In vitro formation of capillary tubules from human umbilical cord blood cells with perspectives for therapeutic application.

OBJECTIVE: Endothelial progenitor cells (EPC) characterized by the CD133+ marker, contribute to the neovascularization. Increasing EPC number in vitro could be a promising therapeutic tool. Human umbilical cord blood maintains a significant number of EPC, suggesting the possibility to use these cells to induce the revascularization of ischemic tissues. The aim of this study was to analyze the in vitro function of differentiated CD133+ cells. METHODS: Cells were characterized by flow cytometry, VEGF mRNA expression was evaluated by the RT-PCR analysis and the functionally by essays of capillary tubes formation. RESULTS: Differentiated cells lost EPC markers, maintained low levels of markers for hematopoietic and monocytic cell lines and increased the expression of adult endothelial cell markers. Differentiated cells expressed VEGF mRNA and were capable to induce in vitro capillary tubules formation. CONCLUSION: CD133+ cells differentiated into endothelial cells in vitro are functionally active initiating the possibility of their use in future therapeutic applications.

Aspectos psicológicos de pacientes diabéticos candidatos ao transplante de ilhotas pancreáticas / Psychological aspects of diabetic patients candidates to the pancreatic islet transplantation

Pacientes candidatos ao Transplante de Ilhotas (TI) vêem o TI como uma forma idealizada de cura do Diabetes, colocando todas suas expectativas neste tratamento. É importante avaliar nestes pacientes aspectos psicológicos que possam interferir, tanto na compreensão do procedimento ser um estudo clínico, com resultados ainda incertos, quanto na necessidade de adesão durante as diversas fases do projeto. Entre março/2004 a março/2005 foram avaliados 13 candidatos ao TI, além de 2 reavaliações. Como instrumento interventivo foram aplicados entrevista psicodiagnóstica e teste projetivo HTP de Buck. Dez pacientes foram qualificados por apresentarem as seguintes características: estabilidade de humor, apoio familiar, julgamento adequado quanto à realidade do tratamento, comportamento de adesão e presença de estratégias de enfrentamento. Três pacientes foram contra-indicados por apresentarem indicadores de transtorno de humor, baixo repertório de enfrentamento, baixa tolerância à frustração e dificuldades de adesão. Nos 2 pacientes reavaliados, detectou-se indicadores de transtornos psiquiátricos, sendo encaminhados a serviço especializado(AU)

Diabetic patients see the pancreatic islet transplantation (IT) as an idealized form of cure of the disease, and put great expectations in this treatment. Then, it is important to evaluate psychological aspects that could interfere with the comprehension of the procedure being a clinical study with uncertain results, and with patient adherence at all stages of the project. From March/2004 to March/2005, thirteen IT candidates were evaluated and two of them were reevaluated after six months. Psycodiagnostic interview and HTP projective test of Buck were applied as intervention tools. Ten patients that presented the following characteristics were qualified: mood stability, family support, realistic judgment of the possible results of the treatment, adherence behavior and presence of coping strategies. IT were contraindicated for three patients presenting signs of mood disturbance, small repertoire of coping strategies, low tolerance to frustration and adherence difficulties. Those two patients reevaluated after six months showed signs of psychiatric alterations and were directed to a specialist(AU)