ADAM10: Biomarker of mild cognitive impairment but not of cognitive frailty.

Mild cognitive impairment (MCI) associated with physical frailty gave rise to the new concept of cognitive frailty. Previous studies have suggested that MCI may represent a condition that precedes Alzheimer's disease (AD), in view of its higher conversion rate to dementia, when compared with the conversion rate of cognitively healthy older adults. Therefore, and considering that MCI represents a reversible condition, the identification of biomarkers for this condition is imperative to early diagnosis. Accordingly, this study aimed to assess whether the platelet and plasma levels of ADAM10 could be related with the concomitant conditions of MCI and physical frailty, in order to support a new blood-based biomarker for the construct of cognitive frailty. Sixty-one adults aged 60 years or older participated in this study. The results showed that ADAM10 levels are reduced in platelets (p < 0.05) and increased in plasma (p < 0.05) of older adults with MCI compared to healthy controls, regardless of the physical frailty condition. The analysis of the ROC curve of ADAM10 in platelets showed sensitivity and specificity of 72.7 and 73.9%, respectively, to correct differentiate between participants with preserved cognition from those with MCI. For plasma samples, ADAM10 presented 62.5 and 90.0%, sensitivity and specificity respectively, to differentiate the aforementioned conditions. Together with other clinical criteria blood ADAM10 could be a relevant, low-invasive, low-cost and fast processing biomarker tool to help in the early and accurate diagnosis of MCI, however this marker was not able to identify cognitive frailty.

Previous hepatitis E virus infection, cirrhosis and insulin resistance in patients with chronic hepatitis C.

BACKGROUND: Hepatitis E virus (HEV) infection in patients with pre-existing liver disease has shown high morbidity and lethality. The consequences of HEV superinfection in patients with chronic hepatitis C virus (HCV) infection are not fully understood. This study aimed to evaluate the association between the presence of anti-HEV antibodies, liver cirrhosis, and insulin resistance. METHODS: A total of 618 patients chronically infected with HCV were included from three reference centers for viral hepatitis in São Paulo, Brazil. Presence of anti-HEV IgG was assessed by enzyme-linked immunosorbent assay (WANTAI HEV-IgG ELISA). RESULTS: The seroprevalence of anti-HEV in patients with cirrhosis was significantly higher than in patients without cirrhosis (13.2% vs 8%, OR=1.74, p=0.04). Seropositivity for anti-HEV, adjusted for sex, age, and HCV genotype showed an association trend with hepatic cirrhosis (aOR=1.75, p=0.059). Presence of HEV antibodies, adjusted for age, body mass index and cirrhosis, was shown to be independently associated with insulin resistance (aOR: 4.39; p=0.045). CONCLUSION: Patients with chronic hepatitis C are under risk of hepatitis E virus superinfection in Brazil. The trend toward association between cirrhosis and previous HEV infection suggests that it may accelerate liver fibrosis in patients with chronic hepatitis C. In addition, previous infection by HEV is independently associated with insulin resistance in the studied population, which may be an extra-hepatic manifestation of hepatitis E that persists after resolution of the active infection, and may contribute to fibrosis progression.

Previous hepatitis E virus infection, cirrhosis and insulin resistance in patients with chronic hepatitis C

ABSTRACT Background: Hepatitis E virus (HEV) infection in patients with pre-existing liver disease has shown high morbidity and lethality. The consequences of HEV superinfection in patients with chronic hepatitis C virus (HCV) infection are not fully understood. This study aimed to evaluate the association between the presence of anti-HEV antibodies, liver cirrhosis, and insulin resistance. Methods: A total of 618 patients chronically infected with HCV were included from three reference centers for viral hepatitis in São Paulo, Brazil. Presence of anti-HEV IgG was assessed by enzyme-linked immunosorbent assay (WANTAI HEV-IgG ELISA). Results: The seroprevalence of anti-HEV in patients with cirrhosis was significantly higher than in patients without cirrhosis (13.2% vs 8%, OR = 1.74, p = 0.04). Seropositivity for anti-HEV, adjusted for sex, age, and HCV genotype showed an association trend with hepatic cirrhosis (aOR = 1.75, p = 0.059). Presence of HEV antibodies, adjusted for age, body mass index and cirrhosis, was shown to be independently associated with insulin resistance (aOR: 4.39; p = 0.045). Conclusion: Patients with chronic hepatitis C are under risk of hepatitis E virus superinfection in Brazil. The trend toward association between cirrhosis and previous HEV infection suggests that it may accelerate liver fibrosis in patients with chronic hepatitis C. In addition, previous infection by HEV is independently associated with insulin resistance in the studied population, which may be an extra-hepatic manifestation of hepatitis E that persists after resolution of the active infection, and may contribute to fibrosis progression.

Estatinas: uma revisão sobre aspectos vasculares / Statins: a review about vascular aspects

As estatinas tornaram-se os fármacos redutores de lipídios mais amplamente prescritos na maioria dos países. Os efeitos que não dependem dessa redução são chamados de pleiotrópicos, entre os quais pode-se citar: melhora na função endotelial, recrutamento de novas células precursoras endoteliais, efeitos antioxidantes e efeitos antiinflamatórios. Em uma revisão sistemática da literatura nacional e internacional pelo indexador Medline/PubMed, utilizando os unitermos: estatinas, disfunção endotelial, óxido nítrico, endotelina, neovascularização e antiinflamatório, observouse que nos últimos anos foram atribuídas outras propriedades às estatinas. As estatinas atuam sobre as células do endotélio vascular interferindo na biodisponibilidade de óxido nítrico e endotelina-1 e recrutamento de novas células precursoras endoteliais; possui ainda efeitos antioxidante e antiinflamatório. Tais efeitos são mediados pela redução dos níveis dos intermediários da via do ácido mevalônico, os chamados isoprenóides, responsáveis por uma série de vias de sinalização intracelular. Esses conhecimentos podem fornecer benefícios adicionais sob a forma de redução de risco, representando novas perspectivas de tratamento, auxiliando no entendimento dos benefícios encontrados e ajudando a prevenir riscos com o uso prolongado destes fármacos, o que pode causar um impacto positivo na redução dos altos índices de morbimortalidade em pacientes portadores de doenças cardiovasculares. Assim, apesar das limitações relacionadas a ações multifatoriais, novos estudos considerando esses efeitos e uma maior compreensão dos mecanismos lipídicos e pleiotrópicos das estatinas podem mudar alguns paradigmas referentes ao desenvolvimento de novas terapias cardiovascula

In most countries, statins have become the most commonly prescribed lipid-lowering drugs. Effects that do not depend on this reduction are called pleiotropic effects and some of them are: improved endothelial function, recruitment of new endothelial precursor cells and antioxidant and anti-inflammatory effects. In a systematic review of national and international literature using the Medline/Pubmed database and using the keywords statins, endothelial dysfunction, nitric oxide, endothelin, revascularization and anti-inflammatory, we found that new statin properties were discovered in the last years. Statins act on vascular endothelium cells by interfering in the availability of nitric oxide and endothelin-1 and by recruiting new endothelial precursor cells. It also has antioxidant and anti-inflammatory effects. Such effects are brought about by reducing the levels of isoprenoids, intermediates of the mevalonic acid pathway, which are responsible for a number of intracellular signal pathways. This knowledge can provide additional benefits such as risk reduction and new treatment perspectives, aiding in understanding the benefits and preventing the risks associated with rolonged use of these drugs, which, in its turn, may reduce the morbidity and mortality rates of individuals with cardiovascular diseases. Thus, despite the limitations associated with multifactorial actions, new studies considering these effects and a better understanding of lipid and pleiotropic statin mechanisms may change some paradigms associated with the development of new cardiovascular therapies