An updated examination of the perception of barriers for pharmacogenomics implementation and the usefulness of drug/gene pairs in Latin America and the Caribbean.

Pharmacogenomics (PGx) is considered an emergent field in developing countries. Research on PGx in the Latin American and the Caribbean (LAC) region remains scarce, with limited information in some populations. Thus, extrapolations are complicated, especially in mixed populations. In this paper, we reviewed and analyzed pharmacogenomic knowledge among the LAC scientific and clinical community and examined barriers to clinical application. We performed a search for publications and clinical trials in the field worldwide and evaluated the contribution of LAC. Next, we conducted a regional structured survey that evaluated a list of 14 potential barriers to the clinical implementation of biomarkers based on their importance. In addition, a paired list of 54 genes/drugs was analyzed to determine an association between biomarkers and response to genomic medicine. This survey was compared to a previous survey performed in 2014 to assess progress in the region. The search results indicated that Latin American and Caribbean countries have contributed 3.44% of the total publications and 2.45% of the PGx-related clinical trials worldwide thus far. A total of 106 professionals from 17 countries answered the survey. Six major groups of barriers were identified. Despite the region's continuous efforts in the last decade, the primary barrier to PGx implementation in LAC remains the same, the "need for guidelines, processes, and protocols for the clinical application of pharmacogenetics/pharmacogenomics". Cost-effectiveness issues are considered critical factors in the region. Items related to the reluctance of clinicians are currently less relevant. Based on the survey results, the highest ranked (96%-99%) gene/drug pairs perceived as important were CYP2D6/tamoxifen, CYP3A5/tacrolimus, CYP2D6/opioids, DPYD/fluoropyrimidines, TMPT/thiopurines, CYP2D6/tricyclic antidepressants, CYP2C19/tricyclic antidepressants, NUDT15/thiopurines, CYP2B6/efavirenz, and CYP2C19/clopidogrel. In conclusion, although the global contribution of LAC countries remains low in the PGx field, a relevant improvement has been observed in the region. The perception of the usefulness of PGx tests in biomedical community has drastically changed, raising awareness among physicians, which suggests a promising future in the clinical applications of PGx in LAC.

Pharmacogenetics and ethnicity: relevance for clinical implementation, clinical trials, pharmacovigilance and drug regulation in Latin America.

Congress of Pharmacogenetics and Personalized Medicine. Ethnicity, clinical implementation and regulatory environment (MESTIFAR 2016 Quito) Quito, Ecuador, 19-21 May 2016. The Ibero-American Network of Pharmacogenetics and Pharmacogenomics (RIBEF) was created in 2006 with the main aim of promoting personalized medicine and collaborative pharmacogenetics research in Spanish- and Portuguese-speaking countries in America and the Iberian Peninsula. The final goal of this initiative was the inclusion of Latin American populations that may benefit from the implementation of personalized medicine in drug therapy. Several initiatives have been promoted including the MESTIFAR project, which aimed to analyze the ethnicity, genotype and/or metabolic phenotype in Ibero-American populations. To date, 6060 healthy volunteers have been analyzed; among them, 2571 were admixed, 1824 were Caucasians, 1395 were Native Americans, 174 were Jews and 96 were Afro-descendants. Due to the large genetic variability within Latin Americans, ethnicity may be a relevant factor for the clinical implementation of personalized medicine. Moreover, the present status of clinical implementation and the future perspectives of pharmacogenetics, pharmacovigilance and clinical trials for drug regulation in Latin America compared with the EMA-Pharmacogenomics Working Party and the US FDA initiatives were analyzed.

Interactions between herbal remedies and medicinal drugs--considerations about Cuba.

The use of herbal products to treat a wide range of conditions is rapidly leading to increased intake of phytochemicals. This is one of the main reasons for reinforcing the surveillance of the safety, efficacy and quality control of traditional and complementary medicines. Herbal preparations can interact with a drug at pharmacokinetic, pharmacodynamic and pharmacogenetic levels. In this article interactions between herbal products and conventional medicines are reviewed. Reports about side effects of traditional medicines and main interactions between herbal medicines and conventional drugs in Cuba are also included. Herbal products are currently not subject to the rigorous testing indispensable for conventional drugs. However, if potential drug interactions are to be predicted, it is essential that the ability of herbal products to interfere with drug-metabolizing enzyme systems is fully established.

Preventing hepatocyte oxidative stress cytotoxicity with Mangifera indica L. extract (Vimang).

Vimang is an aqueous extract of Mangifera indica used in Cuba to improve the quality of life in patients suffering from inflammatory diseases. In the present study we evaluated the effects of Vimang at preventing reactive oxygen species (ROS) formation and lipid peroxidation in intact isolated rat hepatocytes. Vimang at 20, 50 and 100 microg/ml inhibited hepatocyte ROS formation induced by glucose-glucose oxidase. Hepatocyte cytotoxicity and lipid peroxidation induced by cumene hydroperoxide was also inhibited by Vimang in a dose and time dependent manner at the same concentration. Vimang also inhibited superoxide radical formation by xanthine oxidase and hypoxanthine. The superoxide radical scavenging and antioxidant activity of the Vimang extract was likely related to its gallates, catechins and mangiferin content. To our knowledge, this is the first report of cytoprotective antioxidant effects of Vimang in cellular oxidative stress models.

Prophylactic use of epidermal growth factor reduces ischemia/reperfusion intestinal damage.

Ischemia/reperfusion of mesenteric vessels is a useful model for acute vascular insufficiency and the early stages of multiorgan failure, conditions associated with high morbidity and mortality. Epidermal growth factor (EGF) is a potent mitogen that shows potential for use in intestinal injury. We therefore examined its influence on this model. Male Sprague-Dawley rats received human recombinant EGF (2 mg/kg i.p., n = 14) or saline (n = 16); 25 minutes before arterial clamping of the superior mesenteric artery (ischemic period) for 60 minutes followed by a final 60-minute reperfusion period. Additional rats were not operated on (controls, n = 7) or had sham operation (laparotomy only, n = 10). Ischemia/reperfusion caused macroscopic damage affecting 56%, 51 to 67% (median, interquartile range), of small intestinal length and intraluminal bleeding. Malondialdehyde levels (free radical marker) increased eightfold compared to nonoperated animals (2400, 2200 to 2700 micro mol/mg protein versus 290, 250 to 350 micro mol/mg protein, P < 0.01) and myeloperoxidase levels (marker for inflammatory infiltrate) increased 15-fold (3150, 2670 to 4180 U/g tissue versus 240, 190 to 250 U/g tissue, P < 0.01). Pretreatment with EGF reduced macroscopic injury to 11%, 0 to 15%; prevented intraluminal bleeding; and reduced malondialdehyde and myeloperoxidase levels by approximately 60% and 90% (all P < 0.01 versus non-EGF-treated). Mesenteric ischemia/reperfusion also damaged the lungs and kidneys and increased serum tumor necrosis factor-alpha levels (circulating cytokine activity marker). EGF pretreatment also reduced these changes. These studies provide preliminary evidence that EGF is a novel therapy for the early treatment or prevention of intestinal damage and multiorgan failure resulting from mesenteric hypoperfusion.

Inhibitory effects of Spirulina in zymosan-induced arthritis in mice.

The anti-inflammatory effect of microalgae Spirulina was studied in zymosan-induced arthritis in mice. Four days after the intra-articular injection of zymosan (15 mg/ml), Spirulina (100 and 400 mg/kg perorally) was administered to animals for 8 days. The mice were than killed and beta-glucuronidase was measured in the synovial fluid. Each knee joint was totally removed for histopathological studies. Spirulina significantly reduced the levels of beta-glucuronidase that had been increased by zymosan. Histopathological and ultrastructural studies showed inhibition of the inflammatory reaction, whereas no destruction of cartilage, well-preserved chondrocytes, and normal rough endoplasmic reticulum and mitochondria were seen. The anti-arthritic effect exerted by Spirulina as shown in this model may be at least partly due to the previously reported antiinflammatory and antioxidative properties of its constituent, phycocyanin. To our knowledge, this is the first report on the anti-inflammatory effect of Spirulina in an experimental model of arthritis.

Actividad antioxidante de la ficocianina frente a radicales peroxílicos y la peroxidación lipídica microsomal / Antioxidant activity of phycocyaning againts peroxyl radicals and microsomal lipid peroxidation

La ficocianina es una biliproteína que se extrae de las algas verdeazules como la Spirulina (Arthospira) máxima. Esta proteína porta 3 grupos cromogénicos (tetrapirroles lineales) por unidad monométrica, que poseen una estructura muy similar a la de la bilirrubina, que es un reconocido antioxidante endógeno. Por otra parte se conoce que otros derivados de las porfirinas, como la clorofila alfa, presentan propiedades antioxidantes. Teniendo en cuenta estos antecedentes, en este trabajo el propósito fue evaluar si la ficocianina presentaba propiedades antioxidantes frente a radicales peroxílicos en diferentes condiciones experimentales como fueron: 1. disminución de la banda de absorción a 620 nm, asociada con la integridad del cromógeno, al reaccionar con radicales peroxílicos; 2. protección de hematíes humanos de la lisis inducida por radicales peroxílicos; 3. inhibición de la peroxidación lipídica microsomal inducida por Fe+2 -ascórbico. Los resultados indicaron que los grupos cromóforos de la ficocianina reaccionaban rápidamente con los radicales peroxílicos, mecanismo por el cual la biliproteína era capaz de proteger los hematíes de la lisis celular y de inhibir la peroxidación lipídica microsomal

Actividad antioxidante de la ficocianina frente a radicales peroxílicos y la peroxidación lipídica microsomal / Antioxidant activity of phycocyaning againts peroxyl radicals and microsomal lipid peroxidation

La ficocianina es una biliproteína que se extrae de las algas verdeazules como la Spirulina (Arthospira) máxima. Esta proteína porta 3 grupos cromogénicos (tetrapirroles lineales) por unidad monométrica, que poseen una estructura muy similar a la de la bilirrubina, que es un reconocido antioxidante endógeno. Por otra parte se conoce que otros derivados de las porfirinas, como la clorofila alfa, presentan propiedades antioxidantes. Teniendo en cuenta estos antecedentes, en este trabajo el propósito fue evaluar si la ficocianina presentaba propiedades antioxidantes frente a radicales peroxílicos en diferentes condiciones experimentales como fueron: 1. disminución de la banda de absorción a 620 nm, asociada con la integridad del cromógeno, al reaccionar con radicales peroxílicos; 2. protección de hematíes humanos de la lisis inducida por radicales peroxílicos; 3. inhibición de la peroxidación lipídica microsomal inducida por Fe+2 -ascórbico. Los resultados indicaron que los grupos cromóforos de la ficocianina reaccionaban rápidamente con los radicales peroxílicos, mecanismo por el cual la biliproteína era capaz de proteger los hematíes de la lisis celular y de inhibir la peroxidación lipídica microsomal(AU)