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Paternal programming of breast cancer risk in daughters in a rat model: opposing effects of animal- and plant-based high-fat diets
No full textAbstract
Background
Although males contribute half of the embryo’s genome, only recently has interest begun to be directed toward the potential impact of paternal experiences on the health of offspring. While there is evidence that paternal malnutrition may increase offspring susceptibility to metabolic diseases, the influence of paternal factors on a daughter’s breast cancer risk has been examined in few studies.
Methods
Male Sprague-Dawley rats were fed, before and during puberty, either a lard-based (high in saturated fats) or a corn oil-based (high in n-6 polyunsaturated fats) high-fat diet (60 % of fat-derived energy). Control animals were fed an AIN-93G control diet (16 % of fat-derived energy). Their 50-day-old female offspring fed only a commercial diet were subjected to the classical model of mammary carcinogenesis based on 7,12-dimethylbenz[a]anthracene initiation, and mammary tumor development was evaluated. Sperm cells and mammary gland tissue were subjected to cellular and molecular analysis.
Results
Compared with female offspring of control diet-fed male rats, offspring of lard-fed male rats did not differ in tumor latency, growth, or multiplicity. However, female offspring of lard-fed male rats had increased elongation of the mammary epithelial tree, number of terminal end buds, and tumor incidence compared with both female offspring of control diet-fed and corn oil-fed male rats. Compared with female offspring of control diet-fed male rats, female offspring of corn oil-fed male rats showed decreased tumor growth but no difference regarding tumor incidence, latency, or multiplicity. Additionally, female offspring of corn oil-fed male rats had longer tumor latency as well as decreased tumor growth and multiplicity compared with female offspring of lard-fed male rats. Paternal consumption of animal- or plant-based high-fat diets elicited opposing effects, with lard rich in saturated fatty acids increasing breast cancer risk in offspring and corn oil rich in n-6 polyunsaturated fatty acids decreasing it. These effects could be linked to alterations in microRNA expression in fathers’ sperm and their daughters’ mammary glands, and to modifications in breast cancer-related protein expression in this tissue.
Conclusions
Our findings highlight the importance of paternal nutrition in affecting future generations’ risk of developing breast cancer
A clinical score to predict mortality in septic acute kidney injury patients requiring continuous renal replacement therapy: the HELENICC score
No full textAbstract
Background
This study aimed to identify predictors of early (7-day) mortality in patients with septic acute kidney injury (AKI) who required continuous renal replacement therapy (CRRT).
Methods
Prospective cohort of 186 septic AKI patients undergoing CRRT at a tertiary hospital, from October 2005 to November 2010.
Results
After multivariate adjustment, five variables were associated to early mortality: norepinephrine utilization, liver failure, medical condition, lactate level, and pre-dialysis creatinine level. These variables were combined in a score, which demonstrated good discrimination, with a C-statistic of 0.82 (95% CI = 0.76–0.88), and good calibration (χ
2 = 4.3; p = 0.83). SAPS 3, APACHE II and SOFA scores demonstrated poor performance in this population.
Conclusions
The HEpatic failure, LactatE, NorepInephrine, medical Condition, and Creatinine (HELENICC) score outperformed tested generic models. Future studies should further validate this score in different cohorts
Comparative genomics reveals high biological diversity and specific adaptations in the industrially and medically important fungal genus Aspergillus
No full textAbstract
Background
The fungal genus Aspergillus is of critical importance to humankind. Species include those with industrial applications, important pathogens of humans, animals and crops, a source of potent carcinogenic contaminants of food, and an important genetic model. The genome sequences of eight aspergilli have already been explored to investigate aspects of fungal biology, raising questions about evolution and specialization within this genus.
Results
We have generated genome sequences for ten novel, highly diverse Aspergillus species and compared these in detail to sister and more distant genera. Comparative studies of key aspects of fungal biology, including primary and secondary metabolism, stress response, biomass degradation, and signal transduction, revealed both conservation and diversity among the species. Observed genomic differences were validated with experimental studies. This revealed several highlights, such as the potential for sex in asexual species, organic acid production genes being a key feature of black aspergilli, alternative approaches for degrading plant biomass, and indications for the genetic basis of stress response. A genome-wide phylogenetic analysis demonstrated in detail the relationship of the newly genome sequenced species with other aspergilli.
Conclusions
Many aspects of biological differences between fungal species cannot be explained by current knowledge obtained from genome sequences. The comparative genomics and experimental study, presented here, allows for the first time a genus-wide view of the biological diversity of the aspergilli and in many, but not all, cases linked genome differences to phenotype. Insights gained could be exploited for biotechnological and medical applications of fungi
Pre-travel malaria chemoprophylaxis counselling in a public travel medicine clinic in São Paulo, Brazil
No full textAbstract
Background
Malaria is one of the most prevalent parasitic diseases in the world and represents a threat to travellers visiting endemic areas. Chemoprophylaxis is the prevention measure used in travel medicine, avoiding clinical manifestations and protecting against the development of severe disease and death.
Methods
Retrospective and descriptive analysis of malaria prevention data in travellers was recorded from a travel medicine clinic in São Paulo, Brazil, between January 2006 and December 2010. All the medical records of travellers, who had travelled to areas with risk of disease transmission, including Brazil, were analysed. Demographic characteristics of travellers, travel details and recommendations for preventing malaria were also seen.
Results
During the study period, 2836 pre-travel consultations were carried out on 2744 individuals (92 were consulted twice). The most common reasons for travelling were tourism and work. The most common destinations were Africa (24.5%), Europe (21.2%), Asia (16.6%) and locations within Brazil (14.9%). In general prophylaxis against malaria was recommended in 10.3% of all the consultations. African destinations vs Asian, Brazilian and other destinations and length of stay ≤30 days were independently associated with the higher odds of chemoprophylaxis recommendation after the logistic regression.
Conclusion
The prophylaxis against malaria was recommended in 10.3% of the consultations. The authors believe that a coherent measure of malaria prevention in Brazil and for international travellers would be to recommend for all parts of the North Brazil, avoidance of mosquito bites and immediate consultation of a physician in case of fever during or after the journey is recommended
Expenditures of medicine use in hypertensive/diabetic elderly and physical activity and engagement in walking: cross secctional analysis of SABE Survey
No full textAbstract\ud
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Background\ud
The literature shows the inverse association between physical activity level (PAL) and chronic diseases that have a significant burden over health care costs. However, in upper-middle income countries and in elderly population this information are scarce.\ud
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Objective\ud
To describe the annual drug expenditures for the hypertensive and diabetic elderly population in Brazil and to analyze the association with PAL and engagement in walking.\ud
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Methods\ud
This cross sectional study is part of SABE Survey and comprised 806 hypertensive and/or diabetic elderly (≥60 years old). The annual expenditures of medicine use was estimated for all medications for hypertension and/or diabetes they were taking. The PAL was considered insufficient when moderate physical activity was <150 min/week or vigorous physical activity was < 75 min/week. Engagement in walking was considered by at least 1 day a week. All expenditures were presented through the descriptive values (in American Dollars US) according PAL and engagement in walking. The association analysis between annual expenditures, PAL and engagement in walking were performed by multiple logistic regression models adjusted for gender, age and body mass index.\ud
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Results\ud
The average annual cost was higher in diabetic and insufficient physically activity elderly. The 1-year estimated.cost was US 73386,09 and 295% higher in insufficiently physically active. Older people who reported not walking had a higher risk to higher annual expenditures of medicine use (OR = 1.57, 95% CI 1.03–2.40).\ud
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Conclusions\ud
The annual expenditures of medicine use for controlling hypertension and diabetes of Brazilian elderly were higher and inversely associated with physical activity level and engagement in walking.The research was made possible by generous funding from the Brazilian\ud
funders FAPESP (Fundação de Amparo à Pesquisa do estado de São Paulo)\ud
and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior)
Genetic variation in the microsomal triglyceride transfer protein (−493G/T) is associated with hepatic steatosis in patients infected with hepatitis C virus
No full textAbstract\ud
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Background\ud
In chronic hepatitis C, the fibrosis progression rates are extremely variable and can be influenced by factors associated with the host, virus and environment. Among the associated metabolic factors, hepatic steatosis is characterized by an accumulation of triglycerides in hepatocytes. In the host, genetic determinants of hepatic steatosis are observed, such as single-nucleotide polymorphisms (SNPs) in the microsomal triglyceride transfer protein (MTTP) gene. The MTTP -493G/T SNP appears to play an important role in the regulation of gene expression and influences the plasma concentration of circulating low-density lipoprotein (LDL). The present study investigated the influence of this SNP in the development of hepatic steatosis in patients with chronic hepatitis C and evaluated the association of hepatic steatosis with certain characteristics of these patients and the hepatitis C virus (HCV).\ud
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Methods\ud
Two hundred thirty-nine patients with chronic hepatitis C were genotyped for the MTTP -493G⁄T SNP by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The association between hepatic steatosis and selected characteristics of the patient and virus was evaluated using bivariate and multivariate analyses.\ud
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Results\ud
The most prevalent MTTP -493G/T genotype was GG (46%) followed by GT (43.5%) and TT (10.5%). Multivariate analysis of the total cohort revealed associations between the presence of hepatic steatosis and inflammatory activity of moderate to high intensity (P < 0.001), advanced age (P = 0.010), elevated gamma glutamyl transpeptidase (GGT) levels (P = 0.010) and low LDL levels (P = 0.022). Hepatic steatosis was also associated with the TT/GT genotype of the MTTP -493G⁄T SNP in patients infected with HCV genotype 3 (P < 0.001).\ud
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Conclusions\ud
In chronic hepatitis C patients infected with HCV genotype 3 and with the TT/GT genotype of the MTTP -493G/T SNP, a significant increase in hepatic steatosis was observed, which may indicate that this SNP has a significant influence on the accumulation of triglycerides in hepatocytes. Furthermore, associations were observed between hepatic steatosis and inflammatory activity of moderate to high intensity, advanced age, elevated GGT and low LDL levels
The involvement of mast cells in the irinotecan-induced enteric neurons loss and reactive gliosis
No full textAbstract\ud
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Background\ud
The irinotecan (CPT-11) causes intestinal mucositis and diarrhea that may be related to changes in the enteric nervous system (ENS). In inflammatory condition, mast cells release a variety of pro-inflammatory mediators that can interact with the ENS cells. It has not been explored whether CPT-11 is able to alter the enteric glial and neuronal cell, and the role of mast cells in this effect. Therefore, this study was conducted to investigate the effect of CPT-11 on the enteric glial and neuronal cells, as well as to study the role of mast cells in the CPT-11-induced intestinal mucositis.\ud
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Methods\ud
Intestinal mucositis was induced in Swiss mice by the injection of CPT-11 (60 mg/kg, i.p.) once a day for 4 days following by euthanasia on the fifth day. To investigate the role of mast cells, the mice were pretreated with compound 48/80 for 4 days (first day, 0.6 mg/kg; second day, 1.0 mg/kg; third day, 1.2 mg/kg; fourth day, 2.4 mg/kg) to induce mast cell degranulation before the CPT-11 treatment.\ud
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Results\ud
Here, we show that CPT-11 increased glial fibrillary acidic protein (GFAP) and S100β gene and S100β protein expressions and decreased HuC/D protein expression in the small intestine segments. Concomitantly, CPT-11 enhanced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels and inducible nitric oxide synthase (iNOS) gene expression, associated with an increase in the total number macrophages (positive cells for ionized calcium-binding adapter molecule, Iba-1) and degranulated mast cells in the small intestine segments and caused significant weight loss. The pretreatment with compound 48/80, an inductor of mast cells degranulation, significantly prevented these CPT-11-induced effects.\ud
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Conclusions\ud
Our data suggests the participation of mast cells on the CPT-11-induced intestinal mucositis, macrophages activation, enteric reactive gliosis, and neuron loss.Funding for this study was provided by CAPES/DINTER grant number\ud
23038044935/2009-12 CAPES/Procad Grant number 23038.014449/2016-07
Impact of menopause and diabetes on atherogenic lipid profile: is it worth to analyse lipoprotein subfractions to assess cardiovascular risk in women?
No full textAbstract
Cardiovascular disease is the leading cause of death in women at advanced age, who are affected a decade later compared to men. Cardiovascular risk factors in women are not properly investigated nor treated and events are frequently lethal. Both menopause and type 2 diabetes substantially increase cardiovascular risk in the female sex, promoting modifications on lipid metabolism and circulating lipoproteins. Lipoprotein subfractions suffer a shift after menopause towards a more atherogenic lipid profile, consisted of hypertriglyceridemia, lower levels of both total high density lipoprotein (HDL) and its subfraction HDL2, but also higher levels of HDL3 and small low-density lipoprotein particles. This review discusses the impact of diabetes and menopause to the lipid profile, challenges in lipoprotein subfractions determination and their potential contribution to the cardiovascular risk assessment in women. It is still unclear whether lipoprotein subfraction changes are a major driver of cardiometabolic risk and which modifications are predominant. Prospective trials with larger samples, methodological standardizations and pharmacological approaches are needed to clarify the role of lipoprotein subfractions determination on cardiovascular risk prediction and intervention planning in postmenopausal women, with or without DM
Preconception allergen sensitization can induce B10 cells in offspring: a potential main role for maternal IgG
No full textAbstract\ud
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Background\ud
The mechanisms through which allergies can be inhibited after preconception immunization with allergens are not fully understood. We aimed to evaluate whether maternal immunization can induce a regulatory B (B10) cell population in offspring in concert with allergy inhibition.\ud
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Methods\ud
C57BL/6 females were or were not immunized with OVA and were mated with normal WT males. Their offspring were evaluated at 3 days of age or 20 days after neonatal immunization. Human peripheral B cells from atopic and non-atopic individuals were also evaluated.\ud
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Results\ud
Preconception OVA immunization induced B10 cells in offspring, and IL-10 production appeared to be critical for FcγRIIB upregulation in offspring B cells. Murine and human IL-10-producing B cells responded in vitro to IgG according to the atopic repertoire of the cells.\ud
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Conclusions\ud
Our results reveal that maternal immunization induces allergen-specific B10 cells in offspring and a pivotal role for the IgG repertoire in IL-10 production by murine and human B cells.This study was funded through a grant from the Laboratory of Medical Investigation-56,\ud
Medical School, University of Sao Paulo, Sao Paulo, Brazil (LIM-56\ud
HC-FMUSP), Grants #2015/17256-3, #2013/22820-0 and #2010/09004-0 from\ud
the São Paulo Research Foundation (FAPESP), and Grant #115603/2015-8 from\ud
The National Council for Scientifc and Technological Development (CNPq)