Cathepsin S as a biomarker of low-grade inflammation, insulin resistance, and cardiometabolic disease risk

Cathepsin S is a protease important in major histocompatibility complex (MHC) class II antigen presentation and also in degrading the extracellular matrix. Studies, most of them experimental, have shown that cathepsin S is involved in different pathological conditions such as obesity, inflammation, atherosclerosis, diabetes, and cancer.    The overall hypothesis of this report is that high levels of circulating cathepsin S, is a biomarker that reflects pathology induced by inflammation and obesity. The overall aim of this report was to investigate possible associations between circulating cathepsin S, inflammation, glucometabolic disturbance, and its associated diseases in the community. As cathepsin S appears to be a novel risk marker for several pathological conditions, we also wanted to examine the effect of dietary intervention on circulating cathepsin S concentrations.    This thesis is based on data from three community-based cohorts, the Uppsala longitudinal study of adult men (ULSAM), the prospective investigation of the vasculature in Uppsala seniors (PIVUS), and a post-hoc study from the randomized controlled NORDIET trial.    In the first study, we identified a cross-sectional positive association between serum cathepsin S and two markers of cytokine-mediated inflammation, CRP and IL-6. These associations were similar in non-obese individuals. In longitudinal analyses, higher cathepsin S at baseline was associated with higher CRP and IL-6 levels after six years of follow-up. In the second study, we identified a cross-sectional association between increased serum levels of cathepsin S and reduced insulin sensitivity. These associations were similar in non-obese individuals. No significant association was observed between cathepsin S and insulin secretion. In longitudinal analysis, higher cathepsin S levels were associated with an increased risk of developing diabetes during the six-year follow-up. In the third study, we found that higher serum levels of cathepsin S were associated with increased mortality risk. Moreover, in the ULSAM cohort, serum cathepsin S was independently associated with cause-specific mortality from cardiovascular disease and cancer. In the fourth study, we identified that adherence to an ad libitum healthy Nordic diet for 6 weeks slightly decreased the levels of plasma cathepsin S in normal or marginally overweight individuals, relative to the control group. Changes in circulating cathepsin S concentrations were correlated with changes in body weight, LDL-C, and total cholesterol.    Conclusion: This thesis shows that circulating cathepsin S is a biomarker that independently reflects inflammation, insulin resistance, the risk of developing diabetes, and mortality risk. Furthermore, a Nordic diet moderately reduced cathepsin S levels in normal-weight and overweight men and women. This effect may be partially mediated by diet-induced weight loss and possibly by reduced LDL-C concentrations. 

Voltammetric determination of L-dopa using an electrode modified with trinuclear ruthenium ammine complex (Ru-red) supported on Y-type zeolite

The L-dopa is the immediate precursor of the neurotransmitter dopamine. Unlike dopamine, L-dopa easily enters the central nervous system and is used in the treatment of Parkinson's disease. A sensitive and selective method is presented for the voltammetric determination of L-dopa in pharmaceutical formulations using a carbon paste electrode modified with trinuclear ruthenium ammine complex [(NH3)(5)Ru-III-O-Ru-IV(NH3)(4)-O-Ru-III(NH3)(5)](6+) (Ru-red) incorporated in NaY zeolite. The parameters which influence on the electrode response (paste composition, potential scan rate, pH and interference) were also investigated. The optimum conditions were found to an electrode composition (m/m) of 25% zeolite containing 6.7% Ru, 50% graphite and 25% mineral oil in acetate buffer at pH 4.8. Voltammetric peak currents showed a linear response for L-dopa concentration in the range between 1.2 x 10(-4) and 1.0 x 10(-2) Mol l(-1) (r = 0.9988) with a detection limit of 8.5 x 10(-5) mol l(-1). The variation coefficient for a 1.0 x 10(-3) mol l(-1) L-dopa (n = 10) was 5.5%. The results obtained for L-dopa in pharmaceutical formulations (tablet) was in agreement with compared official method. In conclusion, this study has illustrated that the proposed electrode modified with Ru-red incorporated zeolite is suitable valuable for selective measurements of L-dopa. (C) 2004 Elsevier B.V. All rights reserved.

Cerebellar Cognitive Affective Syndrome in Machado Joseph Disease: Core Clinical Features

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Association of apolipoprotein E polymorphism in late-onset Alzheimer's disease and vascular dementia in Brazilians

The genetic basis for dementias is complex. A common polymorphism in the apolipoprotein E (APOE) gene is considered to be the major risk factor in families with sporadic and late-onset Alzheimer's disease as well as in the general population. The distribution of alleles and genotypes of the APOE gene in late-onset Alzheimer's disease (N = 68), other late-life dementias (N = 39), and in cognitively normal controls (N = 58) was determined, as also was the risk for Alzheimer's disease associated with the epsilon4 allele. Peripheral blood samples were obtained from a total of 165 individuals living in Brazil aged 65-82 years. Genomic DNA was amplified by the polymerase chain reaction and the products were digested with HhaI restriction enzyme. APOE epsilon2 frequency was considerably lower in the Alzheimer's disease group (1%), and the epsilon3 allele and epsilon3/epsilon3 genotype frequencies were higher in the controls (84 and 72%, respectively) as were the epsilon4 allele and epsilon3/epsilon4 genotype frequencies in Alzheimer's disease (25 and 41%, respectively). The higher frequency of the epsilon4 allele in Alzheimer's disease confirmed its role as a risk factor, while epsilon2 provided a weak protection against development of the disease. However, in view of the unexpectedly low frequency of the epsilon4 allele, additional analyses in a more varied Brazilian sample are needed to clarify the real contribution of apolipoprotein E to the development of Alzheimer's disease in this population.

Possible association between Carney complex and multiple endocrine neoplasia type 1 phenotypes

Complexo de Carney (CNC) e neoplasia endócrina múltipla tipo 1 (MEN1) são formas de neoplasias endócrinas múltiplas de herança autossômica dominante. O diagnóstico do CNC ocorre quando dois critérios maiores (lentiginose, doença nodular pigmentosa primária das adrenais, mixomas cardíacos e cutâneos, acromegalia, neoplasia testicular, carcinoma de tireóide) são observados e/ou um critério maior associado a um critério suplementar (familiar afetado, mutação do gene PRKAR1A) ocorre. Por outro lado, o diagnóstico de MEN1 dá-se pela detecção de dois ou mais tumores localizados na glândula hipofisária, paratireóide e/ou células pancreáticas. O presente caso descreve um homem de 55 anos, com diagnóstico de acromegalia, hiperparatireoidismo primário e carcinoma papilífero de tireóide, exibindo critérios diagnósticos para as duas condições descritas. Embora possa ter ocorrido apenas uma associação esporádica, ou a acromegalia per se tenha predisposto ao carcinoma papilífero, novos mecanismos moleculares podem estar envolvidos.

Hydroxymethylnitrofurazone:Dimethyl-beta-cyclodextrin Inclusion Complex: A Physical-Chemistry Characterization

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Analysis of the association of polymorphism in the osteoprotegerin gene with susceptibility to chronic kidney disease and periodontitis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Assessment of vitamin A status in chronic obstructive pulmonary disease patients and healthy smokers

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Feline cholangitis/ chonlangiohepatitis complex secondary to Platynosomum fastosum infection in a cat.

Platynosomiasis has been associated with cholangitis/cholangiohepatitis complex in domestic cats. Despite being typically asymptomatic, some individuals may develop severe disease resulting in hepatic cirrhosis. Definitive diagnosis by means of parasite eggs direct visualization is not always possible and complementary tests should be associated. This paper reports a case of a three-year-old female cat with anorexia and jaundice. Ultrasound and biochemistry laboratory findings as well as liver biopsy were not conclusive. Definitive diagnosis of intense Platynosomum fastosum infestation was only possible through direct examination of biliary fluid at necropsy, stressing the importance of including platynosomiasis, commonly an underdiagnosed disease, among differential diagnoses of feline liver diseases.

At least two indigenous species of the Bemisia tabaci complex are present in Brazil

Bemisia tabaci is one of the most important global agricultural insect pests, being a vector of emerging plant viruses such as begomoviruses and criniviruses that cause serious problems in many countries. Although knowledge of the genetic diversity of B. tabaci populations is important for controlling this pest and understanding viral epidemics, limited information is available on this pest in Brazil. A survey was conducted in different locations of São Paulo and Mato Grosso states, and the phylogenetic relationships of B. tabaci individuals from 43 populations sampled from different hosts were analysed based on partial mitochondrial cytochrome oxidase 1 gene (mtCOI) sequences. According to the recently proposed classification of the B. tabaci complex, which employs the 3.5% mtCOI sequence divergence threshold for species demarcation, most of the specimens collected were found to belong to the Middle East-Asia Minor 1 species, which includes the invasive populations of the commonly known B biotype, within the Africa/Middle East/Asia Minor high-level group. Three specimens collected from Solanun gilo and Ipomoea sp. were grouped together and could be classified in the New World species that includes the commonly known A biotype. However, six specimens collected from Euphorbia heterophylla, Xanthium cavanillesii and Glycine maxima could not be classified into any of the 28 previously proposed species, although according to the 11% mtCOI sequence divergence threshold, they belong to the New World high-level group. These specimens were classified into a new recently proposed species named New World 2 that includes populations from Argentina. Middle East-Asia Minor 1, New World and New World 2 were differentiated by RFLP analysis of the mtCOI gene using TaqI enzyme. Taq I analysis in silico also differentiates these from Mediterranean species, thus making this method a convenient tool to determine population dynamics, especially critical for monitoring the presence of this exotic pest in Brazil. © 2012 Blackwell Verlag, GmbH.

White matter abnormalities associated with Alzheimer's disease and mild cognitive impairment: A critical review of MRI studies

In this article, the authors aim to present a critical review of recent MRI studies addressing white matter (WM) abnormalities in Alzheimer's disease (AD) and mild cognitive impairment (MCI), by searching PubMed and reviewing MRI studies evaluating subjects with AD or MCI using WM volumetric methods, diffusion tensor imaging and assessment of WM hyperintensities. Studies have found that, compared with healthy controls, AD and MCI samples display WM volumetric reductions and diffusion tensor imaging findings suggestive of reduced WM integrity. These changes affect complex networks relevant to episodic memory and other cognitive processes, including fiber connections that directly link medial temporal structures and the corpus callosum. Abnormalities in cortico-cortical and cortico-subcortical WM interconnections are associated with an increased risk of progression from MCI to dementia. It can be concluded that WM abnormalities are detectable in early stages of AD and MCI. Degeneration of WM networks causes disconnection among neural cells and the degree of such changes is related to cognitive decline. © 2013 2013 Expert Reviews Ltd.

Cross-mating experiments detect reproductive compatibility between Triatoma sherlocki and other members of the Triatoma brasiliensis species complex

Phylogenetic approaches based on mitochondrial DNA variation (fragments of Cyt B and 16S ribosomal RNA) have revealed Triatoma sherlocki as the most recent species addition to the Triatoma brasiliensis species complex; a monophyletic group which includes T. brasiliensis, Triatoma melanica, and Triatoma juazeirensis. T. sherlocki is the most differentiated among all species of this complex: it is unable to fly, possesses longer legs than the other members, and has reddish tonality in some parts of its exochorion. We question whether these species are reproductively compatible because of this pronounced morphological differentiation, and therefore, we present a series of cross breeding experiments that test compatibility between T. sherlocki and other members of the T. brasiliensis complex. We extended our analyses to include crosses between T. sherlocki and Triatoma lenti, because the latter has been suggested as a possible member of this complex. T. sherlocki male. ×. T. lenti female pairs failed to produce hybrids. All other crosses of T. sherlocki and members of T. brasiliensis species complex, as well as backcrosses, produced viable offspring through the third generation. This study stresses the importance of searching for the features that may isolate members of the T. brasiliensis species complex. © 2013 Elsevier B.V.

Distributional potential of the Triatoma brasiliensis species complex at present and under scenarios of future climate conditions

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Metabolic profiling by ultra-performance liquid chromatography-mass spectrometry and parallel factor analysis for the determination of disease biomarkers in Eucalyptus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The effect of conventional mechanical periodontal treatment on red complex microorganisms and clinical parameters in Down syndrome periodontitis patients: a pilot study

Periodontal disease (PD) is induced by a complex microbiota, such as Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola (together called the red complex), which triggers intense inflammatory reaction. Down syndrome (DS) individuals demonstrate a high prevalence of PD compared with those who are otherwise chromosomally normal (euploids). This pilot study aimed to evaluate the effect of non-surgical periodontal treatment in DS chronic periodontitis patients on clinical and microbiological parameters. Patients with chronic periodontitis, 23 DS and 12 euploids (control group), were submitted to non-surgical mechanical periodontal treatment, followed by maintenance for 45 days. Clinical parameters after periodontal treatment were similar in diseased and healthy sites, independent of the genetic background. Diseased sites of DS and control patients harbored similar levels of P. gingivalis and T. forsythia at baseline, but significantly higher levels of T. denticola were found in DS patients. Increased levels of P. gingivalis at healthy sites were found in DS individuals. Non-surgical periodontal therapy decreased the levels of red complex microorganisms and improved the tested clinical parameters of diseased sites in both groups. However, the levels of red complex bacteria were higher in diseased sites of DS patients after the periodontal treatment. We conclude in this pilot study that, although the mechanical periodontal treatment seemed to be effective in DS subjects over a short-term period, the red complex bacteria levels did not decrease significantly in diseased sites, as occurred in controls. Therefore, for DS patients, it seems that the conventional non-surgical periodontal therapy should be improved by utilizing adjuvants to reduce the presence of periodontopathogens.