(-)-tarchonanthuslactone Exerts A Blood Glucose-increasing Effect In Experimental Type 2 Diabetes Mellitus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)A number of studies have proposed an anti-diabetic effect for tarchonanthuslactone based on its structural similarity with caffeic acid, a compound known for its blood glucose-reducing properties. However, the actual effect of tarchonanthuslactone on blood glucose level has never been tested. Here, we report that, in opposition to the common sense, tarchonanthuslactone has a glucose-increasing effect in a mouse model of obesity and type 2 diabetes mellitus. The effect is acute and non-cumulative and is present only in diabetic mice. In lean, glucose-tolerant mice, despite a slight increase in blood glucose levels, the effect was not significant.20350385049Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Institute of Chemistry/UNICAMPFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [proc. 13/07607-8]FAPESP [11/50514-5, 12/09254-2, 10/08673-6, 2009/53606-8

Skin picking treatment with the Rothbaum cognitive behavioral therapy protocol : a randomized clinical trial

Introduction: Although behavioral therapies can effectively treat skin picking disorder (SPD), there is no standardized treatment for improving SPD and its comorbidities and there is no group intervention option. This trial aimed to adapt the Rothbaum trichotillomania protocol to SPD (Study 1) and test its efficacy for treating SPD and comorbidities in individual and group formats (Study 2). Methods: The adapted protocol was applied to 16 SPD patients, who were allocated to group or individual treatment (Study 1). Afterwards, 54 patients were randomly allocated to treatment in an individual (n=27) or group format (n=27) (Study 2). In both studies, assessments of SPD severity, anxiety, depression, clinical status and skin lesion severity were performed at baseline and the endpoint. Results: The adapted protocol was feasible in both treatment modalities (Study 1) and led to high SPD remission rates (individual 63%; group 52%), with no significant difference between intervention types (p = 0.4) (Study 2). SPD, anxiety, and depression symptoms and objective patient lesion measures improved after treatment. There was large effect size for SPD symptom improvement in both treatment types (Cohen’s d: group = 0.88; individual = 1.15) (Study 2). Conclusion: The adapted Rothbaum protocol was effective for SPD remission, comorbidities, and skin lesions, both in individual and group formats

Biotinidase deficiency: Genotype-biochemical phenotype association in Brazilian patients

[EN] The association between the BTD genotype and biochemical phenotype [profound biotinidase deficiency (BD), partial BD or heterozygous activity] is not always consistent. This study aimed to investigate the genotype-biochemical phenotype association in patients with low biotinidase activity. Methods All exons, the 5'UTR and the promoter of the BTD gene were sequenced in 72 Brazilian individuals who exhibited low biotinidase activity. For each patient, the expected biochemical phenotype based on the known genotype was compared with the observed biochemical phenotype. Additional non-genetic factors that could affect the biotinidase activity were also analysed. Most individuals were identified by neonatal screening (n = 66/72). When consecutive results for the same patient were compared, age, prematurity and neonatal jaundice appeared to affect the level of biotinidase activity. The biochemical phenotype at the time of the second blood collection changed in 11/22 patients compared to results from the first sample. Three novel variants were found: c.1337T>C (p.L446P), c.1466A>G (p.N489S) and c.962G>A (p.W321*). Some patients with the same genotype presented different biochemical phenotypes. The expected and observed biochemical phenotypes agreed in 68.5% of cases (concordant patients). The non-coding variants c.-183G>A, c.-315A>G and c.-514C>T were present in heterozygosis in 5/17 discordant patients. In addition, c.- 183G>A and c.-514C>T were also present in 10/37 concordant patients. The variants found in the promoter region do not appear to have a strong impact on biotinidase activity. Since there is a disparity between the BTD genotype and biochemical phenotype, and biotinidase activity may be affected by both genetic and non-genetic factors, we suggest that the diagnosis of BD should be based on more than one measurement of plasma biotinidase activity. DNA analysis can be of additional relevance to differentiate between partial BD and heterozygosity.SIThis study received financial support from Fundo de Incentivo à Pesquisa e Eventos/Hospital de Clínicas de Porto Alegre (FIPE-HCPA) for research materials and publication fee. Post Graduate Program in Genetics and Molecular Biology (Universidade Federal do Rio Grande do Sul) funded the translation. ECN has a commercial affiliation (CTN Diagnósticos) which did not have any role or financial contribution to this research. TB have fellowship from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Capes). FS had fellowship from the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS). IVDS, MRSC and PASF have fellowships from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). HB receives a research grant of Orphan Europe. The funders did no provide support in the form of salaries for any author, and did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section

A triple-blinded crossover study to evaluate the short-term safety of sweet manioc starch for the treatment of glycogen storage disease type Ia

BACKGROUND: Glycogen storage disease type 1a (GSD Ia) is characterized by severe fasting hypoglycemia. The clinical management includes the administration of uncooked cornstarch (UCCS). Although such a diet approach is effective in achieving euglycemia, its impact on the quality of life of patients should be considered. In vitro analyses suggest a longer release of glucose when using sweet manioc starch (SMS). METHODS: We compared the efficacy and safety of the administration of SMS and UCCS during a short-fasting challenge in patients with GSD Ia in a randomized, triple-blind, phase I/II, cross-over study. GSD Ia patients aged ≥ 16 years and treated with UCCS were enrolled. Participants were hospitalized for two consecutive nights, receiving UCCS or SMS in each night. After the administration of the starches, glucose, lactate and insulin levels were measured in 1-h interval throughout the hospitalization period. The procedures were interrupted after 10 h of fasting or in a hypoglycemic episode ( 25 kg/m(2)) participated in the study. The average fasting period was 8.2 ± 2.0 h for SMS and 7.7 ± 2.3 h for UCCS (p = 0.04). SMS maintained euglycemia for a greater period over UCCS. Increased lactate concentrations were detected even in absence of hypoglycemia, not being influenced by the different starches investigated (p = 0.17). No significant difference was found in total cholesterol, HDL, triglycerides and uric acid levels in both arms. None of the patients showed severe adverse events. CONCLUSIONS: SMS appears to be non-inferior to UCCS in the maintenance of euglycemia, thus emerging as a promising alternative to the treatment of GSD Ia

Three-Dimensional and Biomimetic Technology in Cardiac Injury After Myocardial Infarction: Effect of Acellular Devices on Ventricular Function and Cardiac Remodelling

Dilated cardiomyopathy (DMC) of ischemic or non-ischemic aetiology remains a lethal condition nowadays. Despite early percutaneous or medical revascularization after an acute myocardial infarct (AMI), many patients still develop DMC and severe heart failure due to cardiac remodelling. Possibility of regenerating myocardium already damaged or at least inducing a more positive cardiac remodelling with use of biodegradable scaffolds has been attempted in many experimental studies, which can be cellular or acellular. In the cellular scaffolds, the cells are incorporated in the structure prior to implantation of the same into the injured tissue. Acellular scaffolds, in turn, are composites that use one or more biomaterials present in the extracellular matrix (ECM), such as proteoglycans non-proteoglycan polysaccharide, proteins and glycoproteins to stimulate the chemotaxis of cellular/molecular complexes as growth factors to initiate specific regeneration. For the development of scaffold, the choice of biomaterials to be used must meet specific biological, chemical and architectural requirements like ECM of the tissue of interest. In acute myocardial infarction, treating the root of the problem by repairing injured tissue is more beneficial to the patient. Inducing more constructive forms of endogenous repair. Thus, patches of acellular scaffolds capable of mimicking the epicardium and ECM should be able to attenuate both cardiac remodelling and adverse cardiac dysfunction

Morphology, morphometry and ultrastructure of the Amazonian manatee (Sirenia: Trichechidae) spermatozoa

This study describes the morphological, morphometric and ultrastructural characteristics of the Amazonian manatee Trichechus inunguis (Natterer, 1883) spermatozoon. The spermatozoa were obtained from a urine sample of an adult T. inunguis kept in captivity. The spermatozoa were analyzed by light and transmission electron microscopy. The head of Amazonian manatee spermatozoa had a flat oval shape and a well distinguishable midpiece. The mean dimensions of the spermatozoa were: head length, 7.49 ± 0.24 µm; head width, 3.53 ± 0.19 µm; head thickness, 1.61 ± 0.13 µm; midpiece length, 11.36 ± 0.34 µm; flagellum length, 40.91 ± 1.94 µm; total tail length, 52.16 ± 1.06 µm; total spermatozoon length, 60.08 ± 1.40 µm. The Amazonian manatee spermatozoa were similar in shape to other sirenian spermatozoa; however, presenting a different size. This study describes, for the first time, the morphometric and ultrastructural characteristics of the Amazonian manatee spermatozoa, and also demonstrates the possible use of spermatozoa retrieved from urine samples for biological studies

Handling Time and Bite Mass Mechanisms in Large Herbivores: Contrasts between Sward Structure and Grazing Methods

Grazing is a time-dependent process where jaw movements of prehension, handling and chewing compete with them (Laca et al. 1994; Ungar et al. 2006). The grazing efficiency is dependent of bite mass and time per bite. Bite mass has been related to sward structure by forage height, structural components (Cangiano et al. 2002). In rotational stocking this effect becomes more pronounced, especially under high grazing down levels. Consequently, there is a progressive reduction in short-term intake rate (Fonseca et al. in press). New management targets should be proposed based on the predominant influence of sward structure in short-term intake rate by grazing animals (Carvalho et al. 2007). We hypothesise that intake potential of animals grazing tropical pastures will be reduced due to higher constraints in bite formation when compared to temperate pastures. This study aimed to investigate the intake process of heifers under the influence of different sward heights and grazing down levels in two contrasting - tropical and temperate - forage species

A Model of DENV-3 Infection That Recapitulates Severe Disease and Highlights the Importance of IFN-γ in Host Resistance to Infection

There are few animal models of dengue infection, especially in immunocompetent mice. Here, we describe alterations found in adult immunocompetent mice inoculated with an adapted Dengue virus (DENV-3) strain. Infection of mice with the adapted DENV-3 caused inoculum-dependent lethality that was preceded by several hematological and biochemical changes and increased virus dissemination, features consistent with severe disease manifestation in humans. IFN-γ expression increased after DENV-3 infection of WT mice and this was preceded by increase in expression of IL-12 and IL-18. In DENV-3-inoculated IFN-γ−/− mice, there was enhanced lethality, which was preceded by severe disease manifestation and virus replication. Lack of IFN-γ production was associated with diminished NO-synthase 2 (NOS2) expression and higher susceptibility of NOS2−/− mice to DENV-3 infection. Therefore, mechanisms of protection to DENV-3 infection rely on IFN-γ-NOS2-NO-dependent control of viral replication and of disease severity, a pathway showed to be relevant for resistance to DENV infection in other experimental and clinical settings. Thus, the model of DENV-3 infection in immunocompetent mice described here represents a significant advance in animal models of severe dengue disease and may provide an important tool to the elucidation of immunopathogenesis of disease and of protective mechanisms associated with infection

Rarity of monodominance in hyperdiverse Amazonian forests.

Tropical forests are known for their high diversity. Yet, forest patches do occur in the tropics where a single tree species is dominant. Such "monodominant" forests are known from all of the main tropical regions. For Amazonia, we sampled the occurrence of monodominance in a massive, basin-wide database of forest-inventory plots from the Amazon Tree Diversity Network (ATDN). Utilizing a simple defining metric of at least half of the trees ≥ 10 cm diameter belonging to one species, we found only a few occurrences of monodominance in Amazonia, and the phenomenon was not significantly linked to previously hypothesized life history traits such wood density, seed mass, ectomycorrhizal associations, or Rhizobium nodulation. In our analysis, coppicing (the formation of sprouts at the base of the tree or on roots) was the only trait significantly linked to monodominance. While at specific locales coppicing or ectomycorrhizal associations may confer a considerable advantage to a tree species and lead to its monodominance, very few species have these traits. Mining of the ATDN dataset suggests that monodominance is quite rare in Amazonia, and may be linked primarily to edaphic factors