Use of Drugs that Act on the Cytochrome P450 System in the Elderly

OBJECTIVES: The objective of this study was to analyze medications that act on the cytochrome P450 (CYP450) enzymatic system and are used daily by non-institutionalized elderly individuals. METHODS: A cross-sectional population-based study of elderly individuals (> 60 years old) was conducted. All continuously used medications with hepatic metabolism via CYP450 that are classified as substrates, inducers or inhibitors were considered. For the analysis, elderly individuals were stratified according to age groups, and hepatic metabolism activity due to daily alcohol consumption and smoking were considered. RESULTS: Elderly individuals (396 in total: 222 women and 174 men) between 60 and 95 years of age (mean: 72.1) were assessed. Use of drugs that act on CYP450 was identified in 61.6% of the subjects. Drug use was observed among 16.2% of the subjects: three drugs among 9.8% and four or more among 6.3% of the subjects. The metabolic activities of the drugs used were classified as substrates (58.8%), inhibitors (14.9%), and inducers (4.3%). The main drugs used were beta-blockers and statins (as substrates), proton pump inhibitors and fluoxetine (as inhibitors), and prednisone and carbamazepine (as inducers). CONCLUSIONS: The results demonstrate that the elderly use high levels of medications that act on CYP450, thereby increasing the risk of drug interactions in a group that is already vulnerable to adverse drug effects

Habitable Zones in the Universe

Habitability varies dramatically with location and time in the universe. This was recognized centuries ago, but it was only in the last few decades that astronomers began to systematize the study of habitability. The introduction of the concept of the habitable zone was key to progress in this area. The habitable zone concept was first applied to the space around a star, now called the Circumstellar Habitable Zone. Recently, other, vastly broader, habitable zones have been proposed. We review the historical development of the concept of habitable zones and the present state of the research. We also suggest ways to make progress on each of the habitable zones and to unify them into a single concept encompassing the entire universe.Comment: 71 pages, 3 figures, 1 table; to be published in Origins of Life and Evolution of Biospheres; table slightly revise

Retrospective analysis of risk factors and gaps in prevention strategies for mother-to-child HIV transmission in Rio de Janeiro, Brazil

Background Despite great progress made in methods to prevent mother-to-child transmission of HIV (MTCT), delivery and uptake of these measures remains a challenge in many countries. Although the Brazilian Ministry of Health aimed to eliminate MTCT by 2015, infection still occured in 15–24% of infants born to HIV-infected mothers. We sought to identify remaining factors that constrain MTCT elimination. Methods We conducted a retrospective, matched case-control study by reviewing hospital charts of infants born to HIV-infected mothers between 1997 and 2014 at three MTCT reference hospitals in the Rio de Janeiro metropolitan area. Cases were defined as HIV-exposed children with two positive HIV tests before 18 months of age; controls were defined as HIV-exposed children with two negative HIV tests before 18 months of age. We performed bivariate and MTCT cascade analyses to identify risk factors for MTCT and gaps in prevention services. Results We included 435 infants and their mothers (145 cases, 290 controls). Bivariate analyses of MTCT preventative care (PMTCT) indicated that cases were less likely to complete all individual measures in the antenatal, delivery, and postnatal period (p < 0.05). Assessing completion of the PMTCT cascade, the sequential steps of PMTCT interventions, we found inadequate retention in care among both cases and controls, and cases were significantly less likely than controls to continue receiving care throughout the cascade (p < 0.05). Motives for incompletion of PMTCT measures included infrastructural issues, such as HIV test results not being returned, but were most often due to lack of care-seeking. Over the course of the study period, PMTCT completion improved, although it remained below the 95% target for antenatal care, HIV testing, and antenatal ART set by the WHO. Adding concern, evaluation of co-infections indicated that case infants were also more likely to have congenital syphilis (OR: 4.29; 95% CI: 1.66 to 11.11). Conclusions While PMTCT coverage has improved over the years, completion of services remains insufficient. Along with interventions to promote care-seeking behaviour, increased infrastructural support for PMTCT services is needed to meet the HIV MTCT elimination goal in Brazil as well as address rising national rates of congenital syphilis

Polymer Composites Containing Gated Mesoporous Materials for On-Command Controlled Release

Polyamidic nanofibrous membranes containing gated silica mesoporous particles, acting as carriers, are described as novel hybrid composite materials for encapsulation and on-command delivery of garlic extracts. The carrier system consists of MCM-41 solids functionalized in the outer surface, with linear polyamines (solid P1) and with hydrolyzed starch (solid P2), both acting as molecular gates. Those particles were adsorbed on electospun nylon-6 nanofibrous membranes yielding to composite materials M1 and M2. FE-SEM analysis confirmed the presence of particles incorporated on the nylon nanofibers. The release of the entrapped molecules (garlic extract) from the P1, P2, M1, and M2 materials was evaluated using cyclic voltammetry measurements. Electrochemical studies showed that at acidic pH P1 and M1 were unable to release their entrapped cargo (closed gate), whereas at neutral pH both materials release their loading (open gate). Dealing with P2 and M2 materials, in the absence of pancreatin a negligible release is observed (closed gate), whereas in the presence of enzyme the load is freely to diffuse to the solution. These newly developed composite nanomaterials, provide a homogeneous easy-to-handle system with controlled delivery and bioactive-protective features, having potential applications on pharmacology, medical and engineering fields.The authors wish to express their gratitude to the Generalitat Valenciana (Grisolia scholarship 2011/012, project PROM-ETEO/2009/016), Spanish Government (MINECO Projects AGL2012-39597-C02-01, AGL2012-39597-C02-02 and MAT2012-38429-C04-01) and the CIBER-BBN for their support. IILA thanks DISTAM and Universita degli di Milano for a specialization scholarship. We would also like to thank the Institut de Ciencia dels Materials (ICMUV) and to the Microscopy Service of the Universitat Politecnica de Valencia for technical support. We thank Roquette for the Glucidex samples.Acosta Romero, C.; Pérez Esteve, E.; Fuenmayor, CA.; Benedetti, S.; Cosio, MS.; Soto Camino, J.; Sancenón Galarza, F.... (2014). Polymer Composites Containing Gated Mesoporous Materials for On-Command Controlled Release. ACS Applied Materials and Interfaces. 6(9):6453-6460. https://doi.org/10.1021/am405939y645364606

Worldwide trends in the burden of asthma symptoms in school-aged children: Global Asthma Network Phase I cross-sectional study

Background: Asthma is the most common chronic disease in children globally. The Global Asthma Network (GAN) Phase I study aimed to determine if the worldwide burden of asthma symptoms is changing. Methods: This updated cross-sectional study used the same methods as the International study of Asthma and Allergies in Childhood (ISAAC) Phase III. Asthma symptoms were assessed from centres that completed GAN Phase I and ISAAC Phase I (1993–95), ISAAC Phase III (2001–03), or both. We included individuals from two age groups (children aged 6–7 years and adolescents aged 13–14 years) who self-completed written questionnaires at school. We estimated the 10-year rate of change in prevalence of current wheeze, severe asthma symptoms, ever having asthma, exercise wheeze, and night cough (defined by core questions in the questionnaire) for each centre, and we estimated trends across world regions and income levels using mixed-effects linear regression models with region and country income level as confounders. Findings: Overall, 119 795 participants from 27 centres in 14 countries were included: 74 361 adolescents (response rate 90%) and 45 434 children (response rate 79%). About one in ten individuals of both age groups had wheeze in the preceding year, of whom almost half had severe symptoms. Most centres showed a change in prevalence of 2 SE or more between ISAAC Phase III to GAN Phase I. Over the 27-year period (1993–2020), adolescents showed a significant decrease in percentage point prevalence per decade in severe asthma symptoms (–0·37, 95% CI –0·69 to –0·04) and an increase in ever having asthma (1·25, 0·67 to 1·83) and night cough (4·25, 3·06 to 5·44), which was also found in children (3·21, 1·80 to 4·62). The prevalence of current wheeze decreased in low-income countries (–1·37, –2·47 to –0·27], in children and –1·67, –2·70 to –0·64, in adolescents) and increased in lower-middle-income countries (1·99, 0·33 to 3·66, in children and 1·69, 0·13 to 3·25, in adolescents), but it was stable in upper-middle-income and high-income countries. Interpretation: Trends in prevalence and severity of asthma symptoms over the past three decades varied by age group, country income, region, and centre. The high worldwide burden of severe asthma symptoms would be mitigated by enabling access to effective therapies for asthma. Funding: International Union Against Tuberculosis and Lung Disease, Boehringer Ingelheim New Zealand, AstraZeneca Educational Grant, National Institute for Health Research, UK Medical Research Council, European Research Council, and Instituto de Salud Carlos III

Adaptive Immunity against Leishmania Nucleoside Hydrolase Maps Its C-Terminal Domain as the Target of the CD4+ T Cell–Driven Protective Response

Nucleoside hydrolases (NHs) show homology among parasite protozoa, fungi and bacteria. They are vital protagonists in the establishment of early infection and, therefore, are excellent candidates for the pathogen recognition by adaptive immune responses. Immune protection against NHs would prevent disease at the early infection of several pathogens. We have identified the domain of the NH of L. donovani (NH36) responsible for its immunogenicity and protective efficacy against murine visceral leishmaniasis (VL). Using recombinant generated peptides covering the whole NH36 sequence and saponin we demonstrate that protection against L. chagasi is related to its C-terminal domain (amino-acids 199–314) and is mediated mainly by a CD4+ T cell driven response with a lower contribution of CD8+ T cells. Immunization with this peptide exceeds in 36.73±12.33% the protective response induced by the cognate NH36 protein. Increases in IgM, IgG2a, IgG1 and IgG2b antibodies, CD4+ T cell proportions, IFN-γ secretion, ratios of IFN-γ/IL-10 producing CD4+ and CD8+ T cells and percents of antibody binding inhibition by synthetic predicted epitopes were detected in F3 vaccinated mice. The increases in DTH and in ratios of TNFα/IL-10 CD4+ producing cells were however the strong correlates of protection which was confirmed by in vivo depletion with monoclonal antibodies, algorithm predicted CD4 and CD8 epitopes and a pronounced decrease in parasite load (90.5–88.23%; p = 0.011) that was long-lasting. No decrease in parasite load was detected after vaccination with the N-domain of NH36, in spite of the induction of IFN-γ/IL-10 expression by CD4+ T cells after challenge. Both peptides reduced the size of footpad lesions, but only the C-domain reduced the parasite load of mice challenged with L. amazonensis. The identification of the target of the immune response to NH36 represents a basis for the rationale development of a bivalent vaccine against leishmaniasis and for multivalent vaccines against NHs-dependent pathogens

EDUCORE project: a clinical trial, randomised by clusters, to assess the effect of a visual learning method on blood pressure control in the primary healthcare setting

<p>Abstract</p> <p>Background</p> <p>High blood pressure (HBP) is a major risk factor for cardiovascular disease (CVD). European hypertension and cardiology societies as well as expert committees on CVD prevention recommend stratifying cardiovascular risk using the SCORE method, the modification of lifestyles to prevent CVD, and achieving good control over risk factors. The EDUCORE (Education and Coronary Risk Evaluation) project aims to determine whether the use of a cardiovascular risk visual learning method - the EDUCORE method - is more effective than normal clinical practice in improving the control of blood pressure within one year in patients with poorly controlled hypertension but no background of CVD;</p> <p>Methods/Design</p> <p>This work describes a protocol for a clinical trial, randomised by clusters and involving 22 primary healthcare clinics, to test the effectiveness of the EDUCORE method. The number of patients required was 736, all between 40 and 65 years of age (n = 368 in the EDUCORE and control groups), all of whom had been diagnosed with HBP at least one year ago, and all of whom had poorly controlled hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic ≥ 90 mmHg). All personnel taking part were explained the trial and trained in its methodology. The EDUCORE method contemplates the visualisation of low risk SCORE scores using images embodying different stages of a high risk action, plus the receipt of a pamphlet explaining how to better maintain cardiac health. The main outcome variable was the control of blood pressure; secondary outcome variables included the SCORE score, therapeutic compliance, quality of life, and total cholesterol level. All outcome variables were measured at the beginning of the experimental period and again at 6 and 12 months. Information on sex, age, educational level, physical activity, body mass index, consumption of medications, change of treatment and blood analysis results was also recorded;</p> <p>Discussion</p> <p>The EDUCORE method could provide a simple, inexpensive means of improving blood pressure control, and perhaps other health problems, in the primary healthcare setting;</p> <p>Trial registration</p> <p>The trial was registered with ClinicalTrials.gov, number NCT01155973 [<url>http://ClinicalTrials.gov</url>].</p