Structure-based drug design studies of the interactions ofent-kaurane diterpenes derived from Wedelia paludosa with the Plasmodium falciparumsarco/endoplasmic reticulum Ca2+-ATPase PfATP6

Malaria is responsible for more deaths around the world than any other parasitic disease. Due to the emergence of strains that are resistant to the current chemotherapeutic antimalarial arsenal, the search for new antimalarial drugs remains urgent though hampered by a lack of knowledge regarding the molecular mechanisms of artemisinin resistance. Semisynthetic compounds derived from diterpenes from the medicinal plant Wedelia paludosawere tested in silico against the Plasmodium falciparumCa2+-ATPase, PfATP6. This protein was constructed by comparative modelling using the three-dimensional structure of a homologous protein, 1IWO, as a scaffold. Compound 21 showed the best docking scores, indicating a better interaction with PfATP6 than that of thapsigargin, the natural inhibitor. Inhibition of PfATP6 by diterpene compounds could promote a change in calcium homeostasis, leading to parasite death. These data suggest PfATP6 as a potential target for the antimalarial ent-kaurane diterpenes.

Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors

Reverse transcriptase (RT) is a multifunctional enzyme in the human immunodeficiency virus (HIV)-1 life cycle and represents a primary target for drug discovery efforts against HIV-1 infection. Two classes of RT inhibitors, the nucleoside RT inhibitors (NRTIs) and the nonnucleoside transcriptase inhibitors are prominently used in the highly active antiretroviral therapy in combination with other anti-HIV drugs. However, the rapid emergence of drug-resistant viral strains has limited the successful rate of the anti-HIV agents. Computational methods are a significant part of the drug design process and indispensable to study drug resistance. In this review, recent advances in computer-aided drug design for the rational design of new compounds against HIV-1 RT using methods such as molecular docking, molecular dynamics, free energy calculations, quantitative structure-activity relationships, pharmacophore modelling and absorption, distribution, metabolism, excretion and toxicity prediction are discussed. Successful applications of these methodologies are also highlighted.

A molecular platform for the diagnosis of multidrug-resistant and pre-extensively drug-resistant tuberculosis based on single nucleotide polymorphism mutations present in Colombian isolates of Mycobacterium tuberculosis

Developing a fast, inexpensive, and specific test that reflects the mutations present in Mycobacterium tuberculosis isolates according to geographic region is the main challenge for drug-resistant tuberculosis (TB) control. The objective of this study was to develop a molecular platform to make a rapid diagnosis of multidrug-resistant (MDR) and extensively drug-resistant TB based on single nucleotide polymorphism (SNP) mutations present in therpoB, katG, inhA,ahpC, and gyrA genes from Colombian M. tuberculosis isolates. The amplification and sequencing of each target gene was performed. Capture oligonucleotides, which were tested before being used with isolates to assess the performance, were designed for wild type and mutated codons, and the platform was standardised based on the reverse hybridisation principle. This method was tested on DNA samples extracted from clinical isolates from 160 Colombian patients who were previously phenotypically and genotypically characterised as having susceptible or MDR M. tuberculosis. For our method, the kappa index of the sequencing results was 0,966, 0,825, 0,766, 0,740, and 0,625 forrpoB, katG, inhA,ahpC, and gyrA, respectively. Sensitivity and specificity were ranked between 90-100% compared with those of phenotypic drug susceptibility testing. Our assay helps to pave the way for implementation locally and for specifically adapted methods that can simultaneously detect drug resistance mutations to first and second-line drugs within a few hours.

Causes for the underreporting of adverse drug events by health professionals: a systematic review

Objective: Identifying the main causes for underreporting of Adverse Drug Reaction (ADR) by health professionals. Method: A systematic review carried out in the following databases: LILACS, PAHO, SciELO, EMBASE and PubMed in the period between 1992 and 2012. Descriptors were used in the search for articles, and the identified causes of underreporting were analyzed according to the classification of Inman. Results: In total, were identified 149 articles, among which 29 were selected. Most studies were carried out in hospitals (24/29) for physicians (22/29), and pharmacists (10/29). The main causes related to underreporting were ignorance (24/29), insecurity (24/29) and indifference (23/29). Conclusion: The data show the eighth sin in underreporting, which is the lack of training in pharmacovigilance. Therefore, continuing education can increase adherence of professionals to the service and improve knowledge and communication of risks due to drug use.


Cumulative Vulnerability: A Case Study on intrafamilial violence, Drug Addiction and Adolescent Pregnancy

A pregnant adolescent’s vulnerability increases when she is a victim of intrafamilial violence and drug addiction, which cause physical and biopsychosocial damage to the mother and her baby. Objective Present and analyze the case of an adolescent who is addicted to drugs, pregnant and the victim of lifelong intrafamilial violence. Method A case study based on a semi-structured interview conducted in the Obstetrics Emergency Unit at the Teaching Hospital of the University of São Paulo. The data were interpreted and analyzed using Content Analysis. Results intrafamilial violence experienced at the beginning of the adolescent’s early relationships seriously affected her emotional maturity, triggering the development of psychopathologies and leaving her more susceptible to the use and abuse of alcohol and other drugs. The adolescent is repeating her history with her daughter, reproducing the cycle of violence. Conclusion Adolescent pregnancy combined with intrafamilial violence and drug addiction and multiplies the adolescent’s psychosocial vulnerability increased the adolescent’s vulnerability.

An integrative review of drug utilization by the elderly in primary health care

ABSTRACT OBJECTIVE To identify knowledge produced about drug utilization by the elderly in the primary health care context from 2006 to 2014. METHOD An integrative review of the PubMed, LILACS, BDENF, and SCOPUS databases, including qualitative research papers in Portuguese, English, and Spanish. It excluded papers with insufficient information regarding the methodological description. RESULTS Search found 633 papers that, after being subjected to the inclusion and exclusion criteria, made up a corpusof 76 publications, mostly in English and produced in the United States, England, and Brazil. Results were pooled in eight thematic categories showing the current trend of drug use in the elderly, notably the use of psychotropics, polypharmacy, the prevention of adverse events, and adoption of technologies to facilitate drug management by the elderly. Studies point out the risks posed to the elderly as a consequence of changes in metabolism and simultaneous use of several drugs. CONCLUSION There is strong concern about improving communications between professionals and the elderly in order to promote an exchange of information about therapy, and in this way prevent major health complications in this population.

Origin of samples of Cannabis sativa through insect fragments associated with compacted hemp drug in South America

Origin of samples of Cannabis sativa through insect fragments associated with compacted hemp drug in South America. Insects associated with a seizure of Cannabis sativa L. may indicate the origin of the illicit drug. Nevertheless, no work regarding this subject has been previously published for South America. In the present investigation, seven kilograms of vegetal material (C. sativa) were inspected for insect fragments. Three species were identified and used to test the origin of the seizure of cannabis plant material: Euschistus heros (Fabricius, 1794), Thyanta perditor (Fabricius, 1794) (Heteroptera, Pentatomidae), and Cephalotes pusillus (Klug, 1824) (Hymenoptera, Formicidae). These insect species restricted the geographic origin of the drug to the Neotropical region, and their distribution patterns showed an overlap of the State of Mato Grosso (Brazil), Argentina, and Paraguay. Based on this information, two of the three major C. sativa growing areas in South America were excluded: (1) the Colombian territory and (2) northeastern Brazil.