El nuevo rol de la vitamina D

A diferencia de otras vitaminas presentes en muchos alimentos, la principal fuente de la vitamina D es la síntesis que se realiza en la piel ante la exposición a la radiación solar ultravioleta, mientras que solo está presente en algunos peces de mar. El descubrimiento de que existen receptores para vitamina D en todo el cuerpo, y las enzimas necesarias para la síntesis de la hormona activa 1-25(OH2) VitD (o calcitriol), resultó un hito inesperado.Facultad de Ciencias Médica

Genetic polymorphism, medical therapy and sequential cardiac function in patients with heart failure

FUNDAMENTO: Variantes funcionais do gene da enzima conversora da angiotensina (ECA) podem estar associados com a resposta à terapia em portadores de insuficiência cardíaca (IC). OBJETIVO: Testar a hipótese de diferenças na avaliação ecocardiográfica seqüencial da fração de ejeção do ventrículo esquerdo de pacientes com IC em tratamento farmacológico, inclusive com inibidores da ECA, em relação ao polimorfismo de inserção (I) e deleção (D) do gene da ECA. MÉTODOS: Estudamos 168 pacientes (média de idade 43,3±10,1 anos), 128 (76,2%) dos quais homens, com IC e ecocardiogramas seqüenciais. O polimorfismo I/D foi determinado por reação em cadeia da polimerase. A fração de ejeção do ventrículo esquerdo (FEVE) foi analisada comparativamente aos genótipos. Mais de 90% dos pacientes estavam tomando inibidores da ECA. RESULTADOS: Houve um aumento significantemente maior na FEVE média em pacientes com o alelo D, em comparação com pacientes com genótipo II (p = 0,01) após um seguimento médio de 38,9 meses. O alelo D foi associado com aumento de 8,8% na FEVE média no mesmo período. Além disso, observou-se uma tendência para um efeito do "número de cópias" do alelo D sobre o aumento da FEVE média com o tempo: uma diferença de 3,5% na variação da FEVE entre os pacientes com genótipos II e ID (p = 0,03) e de 5% entre os pacientes com genótipos II e DD (p = 0,02). CONCLUSÃO: O polimorfismo de deleção do gene da ECA pode estar associado com a resposta ao tratamento farmacológico com inibidores da ECA em portadores de IC. Outros estudos controlados poderão contribuir para uma melhor compreensão das influências genéticas sobre a resposta à terapia.BACKGROUND: Functional variants of angiotensin-converting enzyme (ACE) gene may be associated with response to therapy in patients with heart failure (HF). OBJECTIVE: To test the hypothesis of differences in sequential echocardiographic evaluations of left ventricular ejection fraction in patients with HF on medical therapy, including ACE inhibitors in relation to insertion (I) / deletion (D) polymorphism of the ACE gene. METHODS: We studied 168 patients (mean age 43.3±10.1 years), 128 (76.2%) men, with HF and sequential echocardiograms. The I/D polymorphism was determined by polymerase chain reaction. Left ventricular ejection fraction (LVEF) was analyzed comparatively to genotypes. More than 90% of patients were on ACE inhibitors. RESULTS: There was a significantly greater increase in mean LVEF in patients with the D allele compared to patients with the II genotype (p=0.01) after a mean follow-up of 38.9 months. The D allele was associated with an increase of 8.8% in mean LVEF over the same period. Furthermore, there was a tendency toward a D allele "copy number" effect on the increase of mean LVEF over time: a 3.5% difference in LVEF variation between patients with the II and the ID genotypes (p = 0.03) and a 5% difference between patients with the II and DD genotypes (p=0.02). CONCLUSION: ACE gene deletion polymorphism may be operative in response to medical treatment that included ACE inhibitors in patients with HF. Further controlled studies may contribute to better understanding of genetic influences on response to therapy

Progressive dyspnea and a right atrial mass in an 80-year-old man

Hepatocellular carcinoma (HCC) is among the five most frequent causes of cancer death worldwide, according to the WHO. The disease is related to alcohol abuse, viral infections, and other causes of cirrhosis, and unfortunately, in some developed countries, the incidence shows an increasing trend. Although the diagnosis of the HCC often relies upon the context of a chronic hepatopathy, some cases may present a silent course, and the initial symptoms ensue when the disease is in an advanced stage with no chance for any therapeutic attempt. The clinical picture of the HCC is varied, and unexpected forms may surprise the clinician. One of the unusual presentations of the HCC is shock by the blockage of the venous return to the right atrium by the inferior vena cava infiltration. Herein we present a case of an old patient who sought medical care complaining of dyspnea. The clinical workup disclosed a right thorax pleural effusion and imaging exams depicted a mass in the right hepatic lobe, invasion of the inferior vena cava (IVC) and the right atrium (RA). During the attempts of clinical investigation, the patient passed away. The autopsy disclosed an HCC involving the right hepatic lobe, with the invasion of the IVC and the RA. The authors highlight the importance of recognizing the bizarre presentation of not so rare diseases

No evidence for an association between the -36A>C phospholamban gene polymorphism and a worse prognosis in heart failure

Background: In Brazil, heart failure leads to approximately 25,000 deaths per year. Abnormal calcium handling is a hallmark of heart failure and changes in genes encoding for proteins involved in the re-uptake of calcium might harbor mutations leading to inherited cardiomyopathies. Phospholamban (PLN) plays a prime role in cardiac contractility and relaxation and mutations in the gene encoding PLN have been associated with dilated cardiomyopathy. In this study, our objective was to determine the presence of the -36A>C alteration in PLN gene in a Brazilian population of individuals with HF and to test whether this alteration is associated with heart failure or with a worse prognosis of patients with HF. Methods: We genotyped a cohort of 881 patients with HF and 1259 individuals from a cohort of individuals from the general population for the alteration -36A>C in the PLN gene. Allele and genotype frequencies were compared between groups (patients and control). In addition, frequencies or mean values of different phenotypes associated with cardiovascular disease were compared between genotypic groups. Finally, patients were prospectively followed-up for death incidence and genotypes for the -36A>C were compared regarding mortality incidence in HF patients. Results: No significant association was found between the study polymorphism and HF in our population. In addition, no association between PLN -36A>C polymorphism and demographic, clinical and functional characteristics and mortality incidence in this sample of HF patients was observed. Conclusion: Our data do not support a role for the PLN -36A>C alteration in modulating the heart failure phenotype, including its clinical course, in humans

Beta-2 adrenergic receptor gene polymorphisms Gln27Glu, Arg16Gly in patients with heart failure

<p>Abstract</p> <p>Background -</p> <p>Beta-2 adrenergic receptor gene polymorphisms Gln27Glu, Arg16Gly and Thr164Ile were suggested to have an effect in heart failure. We evaluated these polymorphisms relative to clinical characteristics and prognosis of alarge cohort of patients with heart failure of different etiologies.</p> <p>Methods -</p> <p>We studied 501 patients with heart failure of different etiologies. Mean age was 58 years (standard deviation 14.4 years), 298 (60%) were men. Polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism.</p> <p>Results -</p> <p>During the mean follow-up of 12.6 months (standard deviation 10.3 months), 188 (38%) patients died. Distribution of genotypes of polymorphism Arg16Gly was different relative to body mass index (χ²= 9.797;p = 0.04). Overall the probability of survival was not significantly predicted by genotypes of Gln27Glu, Arg16Gly, or Thr164Ile. Allele and haplotype analysis also did not disclose any significant difference regarding mortality. Exploratory analysis through classification trees pointed towards a potential association between the Gln27Glu polymorphism and mortality in older individuals.</p> <p>Conclusion -</p> <p>In this study sample, we were not able to demonstrate an overall influence of polymorphisms Gln27Glu and Arg16Gly of beta-2 receptor gene on prognosis. Nevertheless, Gln27Glu polymorphism may have a potential predictive value in older individuals.</p