A relaxometric method for the assessment of intestinal permeability based on the oral administration of gadolinium‐based MRI contrast agents

Herein, a new relaxometric method for the assessment of intestinal permeability based on the oral administration of clinically approved gadolinium (Gd)‐based MRI contrast agents (CAs) is proposed. The fast, easily performed and cheap measurement of the longitudinal water proton relaxation rate (R₁) in urine reports the amount of paramagnetic probe that has escaped the gastrointestinal tract. The proposed method appears to be a compelling alternative to the available methods for the assessment of intestinal permeability. The method was tested on the murine model of dextran sulfate sodium (DSS)‐induced colitis in comparison with healthy mice. Three CAs were tested, namely ProHance®, MultiHance® and Magnevist®. Urine was collected for 24 h after the oral ingestion of the Gd‐containing CA at day 3–4 (severe damage stage) and day 8–9 (recovery stage) after treatment with DSS. The Gd content in urine measured by ¹H relaxometry was confirmed by inductively coupled plasma‐mass spectrometry (ICP‐MS). The extent of urinary excretion was given as a percentage of excreted Gd over the total ingested dose. The method was validated by comparing the results obtained with the established methodology based on the lactulose/mannitol and sucralose tests. For ProHance and Magnevist, the excreted amounts in the severe stage of damage were 2.5–3 times higher than in control mice. At the recovery stage, no significant differences were observed with respect to healthy mice. Overall, a very good correlation with the lactulose/mannitol and sucralose results was obtained. In the case of MultiHance, the percentage of excreted Gd complex was not significantly different from that of control mice in either the severe or recovery stages. The difference from ProHance and Magnevist was explained on the basis of the (known) partial biliary excretion of MultiHance in mice. Copyright © 2016 John Wiley & Sons, Ltd.     

The impact of bilateral cerebellar damage on theory of mind,empathy and decision making

The extensive infarction affecting the posterior vermis and the medial and posterior regions of both cerebellar hemispheres, as well as the small central pontine lesion, seems to have disrupted multiple cerebral and brainstem cerebellar loops. These loops process information related to many cognitive domains, behavior and emotion, including decision making, empathy and theory of mind.     

Síndrome metabólica em trabalhadores de um hospital universitário

IntroductionMetabolic syndrome (MS) is a major health problem, and has economic effects on enterprises. The workplace is thus an important environment for primary prevention of risk factors for cardiovascular disease.ObjectiveTo determine the prevalence of MS and variables related to its development in hospital workers.MethodsWe performed a cross-sectional study of 740 workers in a large university hospital. Socioeconomic variables, anthropometric and blood pressure measurements, and laboratory exams were analyzed. MS was defined according to the criteria of the International Diabetes Federation.ResultsOf the 740 workers, 72.4% were female and mean age was 34.9±9.5 years; 27.8% worked the morning shift, 20.3% the afternoon shift, 34.1% office hours, and 17.8% the night shift. As to educational level, 86.6% had finished high school or college. Waist circumference was high in 55.4%. Overall MS prevalence was 12.8%, 16.2% in males and 11.6% in females. Logistic regression analysis showed an independent association between MS and the following variables: elementary education, period of employment >10 years, office hours shift, and age group.ConclusionA diagnosis of MS was affected by age, educational level, work shift, and prolonged period of employment. Hospital workers do not differ from other populations and also need stimuli to make preventive changes to their behavior to modify cardiovascular risk factors.     

Antitumoral Effects of D-Fraction from Grifola Frondosa (Maitake) Mushroom in Breast Cancer

D-Fraction is protein-bound β-1,6 and β-1,3 glucans (proteoglucan) extracted from the edible and medicinal mushroom Grifola frondosa (Maitake). The antitumoral effect of D-Fraction has long been exclusively attributed to their immunostimulatory capacity. However, in recent years increasing evidence showed that D-Fraction directly affects the viability of canine and human tumor cells, independent of the immune system. Previously, we have reported that D-Fraction modulates the expression of genes associated with cell proliferation, cell death, migration, invasion, and metastasis in MCF7 human breast cancer cells. Therefore, the purpose of the current study is to investigate if this modulation of gene expression by Maitake D-Fraction really modulates tumor progression. In the present work, we demonstrate for the first time that Maitake D-Fraction is able to act directly on mammary tumor cells, modulating different cellular processes involved in the development and progression of cancer. We demonstrate that D-Fraction decreases cell viability, increases cell adhesion, and reduces the migration and invasion of mammary tumor cells, generating a less aggressive cell behavior. In concordance with these results, we also demonstrate that D-Fraction decreases tumor burden and the number of lung metastases in a murine model of breast cancer.     

Nuclear DNA replication and repair in parasites of the genus Leishmania: Exploiting differences to develop innovative therapeutic approaches

Leishmaniasis is a common tropical disease that affects mainly poor people in underdeveloped and developing countries. This largely neglected infection is caused by Leishmania spp, a parasite from the Trypanosomatidae family. This parasitic disease has different clinical manifestations, ranging from localized cutaneous to more harmful visceral forms. The main limitations of the current treatments are their high cost, toxicity, lack of specificity, and long duration. Efforts to improve treatments are necessary to deal with this infectious disease. Many approved drugs to combat diseases as diverse as cancer, bacterial, or viral infections take advantage of specific features of the causing agent or of the disease. Recent evidence indicates that the specific characteristics of the Trypanosomatidae replication and repair machineries could be used as possible targets for the development of new treatments. Here, we review in detail the molecular mechanisms of DNA replication and repair regulation in trypanosomatids of the genus Leishmania and the drugs that could be useful against this disease.     

Variants in genes of innate immunity,appetite control and energy metabolism are associated with host cardiometabolic health and gut microbiota composition

ABSTRACT

Identifying the genetic and non-genetic determinants of obesity and related cardiometabolic dysfunctions is cornerstone for their prevention, treatment, and control. While genetic variants contribute to the cardiometabolic syndrome (CMS), non-genetic factors, such as the gut microbiota, also play key roles. Gut microbiota is intimately associated with CMS and its composition is heritable. However, associations between this microbial community and host genetics are understudied. We contribute filling this gap by genotyping 60 variants in 39 genes of three modules involved in CMS risk, measuring cardiometabolic risk factors, and characterizing gut microbiota in a cohort of 441 Colombians. We hypothesized that CMS risk variants were correlated with detrimental levels of clinical parameters and with the abundance of disease-associated microbes. We found several polymorphisms in genes of innate immunity, appetite control, and energy metabolism that were associated with metabolic dysregulation and microbiota composition; the associations between host genetics and cardiometabolic health were independent of the participants’ gut microbiota, and those between polymorphisms and gut microbes were independent of the CMS risk. Associations were also independent of the host genetic ancestry, diet and lifestyle. Most microbes explaining genetic-microbiota associations belonged to the families Lachnospiraceae and Ruminococcaceae. Multiple CMS risk alleles were correlated with increased abundance of beneficial microbiota, suggesting that the phenotypic outcome of the evaluated variants might depend upon the genetic background of the studied population and its environmental context. Our results provide additional evidence that the gut microbiota is under the host genetic control and present pathways of host–microbe interactions.     

Detection of Lymphatic Micrometastases in Patients With Stages I and II Colorectal Cancer: Impact on Five-Year Survival

PURPOSE: Despite having removed the whole macroscopic disease (curative intent surgery), one of five patients with Stages I and II colorectal cancer will develop recurrence. Lymphatic micrometastases detected by immunohistochemistry could be one of explanation for recurrence and cancer-related death in patients without lymph node involvement at light microscopy. However, the biologic importance of micrometastases remains unclear. This study was designed to determine the impact of micrometastases in five-year survival in patients with Stages I and II colorectal cancer.METHODS: This retrospective study included patients operated on between May 1989 and January 1999 for colorectal cancer without histopathologic lymph node involvement. Patients who received any adjuvant therapy were excluded. Immunohistochemical staining of the lymph nodes was performed with antipancytokeratin antibodies. Follow-up data were obtained from the clinical database and death certificates. Survival was estimated by the Kaplan-Meier method and compared by the log-rank test.RESULTS: Micrometastases were observed in 26 of 90 patients (28.9 percent). The mean follow-up time was 90.7 (range, 11–160) months. Seventeen cancer-related deaths occurred during follow-up (18.9 percent), 6 of them in patients with micrometastases (23.1 percent) and 11 in patients without micrometastases (17.2 percent; P = 0.559). Cancer-specific five-year survival was 87 percent in the whole group and 81 percent in patients positive for micrometastases vs. 90 percent in negative patients (P = 0.489).CONCLUSIONS: The presence of micrometastases in patients with Stages I and II colorectal cancer seems not to have any impact on cancer-specific survival.Supported by the Apertus Research Program (Andromaco Pharmaceutical Company) and by The National Public Grant (FONDECYT #1000556).     

An exploratory pilot study on the involvement of APOE,HFE, C9ORF72 variants and comorbidities in neurocognitive and physical performance in a group of HIV-infected people

Metabolic Brain Disease - Cognitive decline of aging is modulated by chronic inflammation and comorbidities. In people with HIV-infection (PWH) it may also be affected by HIV-induced inflammation,...     

Influence of the HLA-DQB1*0201 allele on the immune response in a Schistosoma mansoni infection

We previously reported the association of the major histocompatibility complex class II HLA-DQB1*0201 allele with hepatosplenic schistosomiasis. The aim of this study was to evaluate the cytokine responses of peripheral blood mononuclear cells (PBMCs) and the serum levels of immunoglobulin isotypes. The study population was selected from a schistosomiasis endemic area. No significant differences in cytokine profiles were detected in PBMCs stimulated with Schistosoma mansoni soluble egg antigen (SEA), regardless of the subjects DQB1*0201 genotype or infection status. However, previously infected DQB1*0201 positive individuals had significantly lower levels of IgG4 compared to DQB1*0201 negative individuals (P<0.05).