RÉSUMÉ
Chemotherapeutic drugs and radiotherapy are fundamental treatments to combat cancer, but, often, the doses in these treatments are restricted by their non-selective toxicities, which affect healthy tissues surrounding tumors. On the other hand, drug resistance is recognized as the main cause of chemotherapeutic treatment failure. Rosmarinic acid (RA) is a polyphenol of the phenylpropanoid family that is widely distributed in plants and vegetables, including medicinal aromatic herbs, consumption of which has demonstrated beneficial activities as antioxidants and anti-inflammatories and reduced the risks of cancers. Recently, several studies have shown that RA is able to reverse cancer resistance to first-line chemotherapeutics, as well as play a protective role against toxicity induced by chemotherapy and radiotherapy, mainly due to its scavenger capacity. This review compiles information from 56 articles from Google Scholar, PubMed, and ClinicalTrials.gov aimed at addressing the role of RA as a complementary therapy in cancer treatment.
Sujet(s)
Cinnamates , Depsides , Résistance aux médicaments antinéoplasiques , Tumeurs , , Depsides/pharmacologie , Depsides/composition chimique , Depsides/usage thérapeutique , Cinnamates/pharmacologie , Cinnamates/usage thérapeutique , Cinnamates/composition chimique , Humains , Tumeurs/traitement médicamenteux , Résistance aux médicaments antinéoplasiques/effets des médicaments et des substances chimiques , Antinéoplasiques/pharmacologie , Antinéoplasiques/usage thérapeutique , Animaux , Antioxydants/pharmacologie , Antioxydants/usage thérapeutiqueRÉSUMÉ
Caffeic acid (CA) is a polyphenol belonging to the phenylpropanoid family, commonly found in plants and vegetables. It was first identified by Hlasiwetz in 1867 as a breakdown product of caffetannic acid. CA is biosynthesized from the amino acids tyrosine or phenylalanine through specific enzyme-catalyzed reactions. Extensive research since its discovery has revealed various health benefits associated with CA, including its antioxidant, anti-inflammatory, and anticancer properties. These effects are attributed to its ability to modulate several pathways, such as inhibiting NFkB, STAT3, and ERK1/2, thereby reducing inflammatory responses, and activating the Nrf2/ARE pathway to enhance antioxidant cell defenses. The consumption of CA has been linked to a reduced risk of certain cancers, mitigation of chemotherapy and radiotherapy-induced toxicity, and reversal of resistance to first-line chemotherapeutic agents. This suggests that CA could serve as a useful adjunct in cancer treatment. Studies have shown CA to be generally safe, with few adverse effects (such as back pain and headaches) reported. This review collates the latest information from Google Scholar, PubMed, the Phenol-Explorer database, and ClinicalTrials.gov, incorporating a total of 154 articles, to underscore the potential of CA in cancer prevention and overcoming chemoresistance.
Sujet(s)
Acides caféiques , Tumeurs , Humains , Acides caféiques/usage thérapeutique , Acides caféiques/pharmacologie , Tumeurs/traitement médicamenteux , Tumeurs/métabolisme , Animaux , Antioxydants/usage thérapeutique , Antioxydants/pharmacologie , Antinéoplasiques/usage thérapeutiqueRÉSUMÉ
Chemotherapeutic drugs are indispensable in cancer treatment, but their effectiveness is often lessened because of non-selective toxicity to healthy tissues, which triggers inflammatory pathways that are harmful to vital organs. In addition, tumors' resistance to drugs causes failures in treatment. Chlorogenic acid (5-caffeoylquinic acid, CGA), found in plants and vegetables, is promising in anticancer mechanisms. In vitro and animal studies have indicated that CGA can overcome resistance to conventional chemotherapeutics and alleviate chemotherapy-induced toxicity by scavenging free radicals effectively. This review is a summary of current information about CGA, including its natural sources, biosynthesis, metabolism, toxicology, role in combatting chemoresistance, and protective effects against chemotherapy-induced toxicity. It also emphasizes the potential of CGA as a pharmacological adjuvant in cancer treatment with drugs such as 5-fluorouracil, cisplatin, oxaliplatin, doxorubicin, regorafenib, and radiotherapy. By analyzing more than 140 papers from PubMed, Google Scholar, and SciFinder, we hope to find the therapeutic potential of CGA in improving cancer therapy.
Sujet(s)
Acide chlorogénique , Résistance aux médicaments antinéoplasiques , Tumeurs , Humains , Acide chlorogénique/pharmacologie , Acide chlorogénique/usage thérapeutique , Tumeurs/traitement médicamenteux , Tumeurs/métabolisme , Résistance aux médicaments antinéoplasiques/effets des médicaments et des substances chimiques , Animaux , Antinéoplasiques/usage thérapeutique , Antinéoplasiques/pharmacologieRÉSUMÉ
During the summer of 2022, a cluster of Madagascar periwinkle plants with white and mauve flowers were observed with foliar mild yellow mosaic symptoms on a private property in Harlingen, Cameron County, Texas. The symptoms were reproduced on mechanically inoculated periwinkle and Nicotiana benthamiana plants. Virions of 776 to 849 nm in length and 11.7 to 14.8 nm in width were observed in transmission electron microscopy of leaf dip preparations made from symptomatic periwinkle leaves. High-throughput sequencing (HTS) analysis of total RNA extracts from symptomatic leaves revealed the occurrence of two highly divergent variants of a novel Potyvirus species as the only virus-like sequences present in the sample. The complete genomes of both variants were independently amplified via reverse transcriptase PCR, cloned, and Sanger sequenced. The 5' and 3' of the genomes were acquired using random amplification of cDNA ends methodology. The assembled virus genomes were 9,936 and 9,944 nucleotides (nt) long, and they shared 99.9 to 100% identities with the respective HTS-derived genomes. Each genome encoded hypothetical polyprotein of 3,171 amino acids (aa) (362.6 kilodaltons [kDa]) and 3,173 aa (362.7 kDa), respectively, and they shared 77.3/84.4% nt/aa polyprotein identities, indicating that they represent highly divergent variants of the same Potyvirus species. Both genomes also shared below-species-threshold polyprotein identity levels with the most closely phylogenetically related known potyviruses, thus indicating that they belong to a novel species. The name periwinkle mild yellow mosaic virus (PwMYMV) is given to the potyvirus with complete genomes of 9,936 nt for variant 1 (PwMYMV-1) and 9,944 nt for variant 2 (PwMYMV-2). We propose that PwMYMV be assigned into the genus Potyvirus (family Potyviridae).
RÉSUMÉ
Investigations conducted during the spring 2020 season to diagnose the associated viral agent of a severe mosaic disease of wheat in a Texas Panhandle field revealed the presence of wheat Eqlid mosaic virus (WEqMV; genus Tritimovirus, family Potyviridae) in the analyzed samples. The complete genome sequences of two WEqMV isolates were determined, and each was found to be 9,634 nucleotides (nt) in length (excluding the polyA tail) and to contain 5' and 3' untranslated regions of 135 nt and 169 nt, respectively, based on rapid amplification of cDNA ends (RACE) assays. Both sequences contained an open reading frame (ORF) of 9,330 nt encoding a polyprotein of 3,109 amino acids (aa). The ORF sequences of the two isolates were 100% identical to each other, but only 74.7% identical to that of the exemplar WEqMV-Iran isolate, with 85.7% aa sequence identity in the encoded polyprotein. The Texas WEqMV isolates also diverged significantly from WEqMV-Iran in the individual proteins at the nt and aa levels. This is the first report of WEqMV in the United States and the first report of this virus outside of Iran, indicating an expansion of its geographical range.
Sujet(s)
Virus des mosaïques , Potyviridae , Texas , Triticum , Potyviridae/génétique , Régions 3' non traduites/génétique , Acides aminés , Nucléotides , PolyprotéinesRÉSUMÉ
Crinum sp. (family Amaryllidaceae) is an ornamental flower bulb that is commonly called crinum lily, cape lily, cemetery plant, spider lily, and swamp lily. In April 2023, two plants of Crinum sp. var. Maiden's Blush with yellow stripe symptoms (Fig. S1) were submitted to the Texas Plant Virus Diagnostic Laboratory, Weslaco, TX for virus diagnosis. Due to the resemblance of the observed symptoms to those described for potyviruses infecting ornamental flower bulbs (Pearson et al. 2009), total RNA extracts were made from each sample using the SpectrumTM Plant Total RNA Kit (Sigma-Aldrich, USA), according to the manufacturer's protocol. Complementary DNA (cDNA) was synthesized from 2 µg total RNA per sample with Oligo(dT) primers using the PrimeScript™ 1st strand cDNA Synthesis Kit (Takara Bio, USA) as recommended by the manufacturer. A 2µL aliquot of each cDNA template was initially subjected to PCR using the generic primer pair CIFor/CIRev (Ha et al., 2008) that targets a fragment of the cylindrical inclusion (CI) body of potyviruses. The expected ~700 bp DNA band was amplified from both samples using the Taq DNA polymerase, dNTPack kit (Sigma-Aldrich). The amplicons were cloned and sequenced (three recombinant clones per sample) as described by Hernandez et al. (2021) and the BLASTX analyses of the consensus sequence (GenBank acc. no. OR137018) returned significant hits only to nerine yellow stripe virus (NeYSV; Potyvirus, Potyviridae) at 100% query coverage. To further confirm the results, another pair of universal primers (Jordan et al. 2011) was used to amplify the expected â¼1,600 bp product specific to the partial nuclear inclusion body (NIb), coat protein (CP) cistron, and 3' untranslated region of potyviruses from the same samples. The amplicons were similarly cloned, and a consensus sequence obtained (OR137019). In pairwise comparisons, the partial CI sequence of NeYSV from Texas (NeYSV-TX; OR137018) shared 83% nucleotide (nt)/93% amino acids (aa) identities with the corresponding sequences of NeYSV isolate 63 (MT396083) from the United Kingdom. The partial (649 nt) NIb sequences of NeYSV-TX (OR137019) and the complete CP (OR137019) of NeYSV-TX shared 77-94%/88-94% and 83-99%/89-98% nt/aa identities with the corresponding sequences of global NeYSV isolates that were retrieved from GenBank. Phylogenetic analysis revealed a closer relationship between NeYSV-TX and the isolates Stenomesson (EU042758) and DC (MG012805) from the Netherlands and USA, respectively based on the partial NIb and CP cistrons (Fig. S2), suggesting that NeYSV-TX may have been introduced from foreign and/or domestic sources. NeYSV has been documented previously from the United Kingdom, the Netherlands, Australia, New Zealand, and India; its first report from the United States was a decade ago from Amaryllis belladonna in California (Guaragna et al. 2013). To the best of our knowledge, this is the first report of NeYSV in Texas, thus expanding the geographical range of the virus in the USA. Anecdotal information from the sample submitter implicated infected crinum lily bulbs as the likely source of NeYSV introduction into the property, with subsequent vegetative propagation of plants resulting in 100% incidence of symptomatic lilies (n>100) over time. Thus, the results underscore the importance of ensuring that only virus-free vegetative plant materials are distributed and propagated by florists to curtail virus spread.
RÉSUMÉ
Epothilone is a natural 16-membered macrolide cytotoxic compound produced by the metabolism of the cellulose-degrading myxobacterium Sorangium cellulosum. This review summarizes results in the study of epothilones against cancer with preclinical results and clinical studies from 2010-2022. Epothilone have mechanisms of action similar to paclitaxel by inducing tubulin polymerization and apoptosis with low susceptibility to tumor resistance mechanisms. It is active against refractory tumors, being superior to paclitaxel in many respects. Since the discovery of epothilones, several derivatives have been synthesized, and most of them have failed in Phases II and III in clinical trials; however, ixabepilone and utidelone are currently used in clinical practice. There is robust evidence that triple-negative breast cancer (TNBC) treatment improves using ixabepilone plus capecitabine or utidelone in combination with capecitabine. In recent years innovative synthetic strategies resulted in the synthesis of new epothilone derivatives with improved activity against refractory tumors with better activities when compared to ixabepilone or taxol. These compounds together with specific delivery mechanisms could be developed in anti-cancer drugs.
Sujet(s)
Antinéoplasiques , Épothilones , Tumeurs , Humains , Épothilones/pharmacologie , Épothilones/usage thérapeutique , Capécitabine/usage thérapeutique , Antinéoplasiques/pharmacologie , Antinéoplasiques/usage thérapeutique , Modulateurs de la polymérisation de la tubuline/pharmacologie , Modulateurs de la polymérisation de la tubuline/usage thérapeutique , Paclitaxel/pharmacologie , Paclitaxel/usage thérapeutique , Tumeurs/traitement médicamenteuxRÉSUMÉ
Background: The presence of polymorphisms in the TPMT gene is associated with adverse effects in patients treated with standard doses of thiopurine drugs. Scientific evidence recognizes significant ethnic differences in their frequencies and how their early identification can prevent clinical complications. Methods: 150 healthy residents of Aragua, Venezuela were enrolled. The SNPs c.460G>A and c.719A>G were detected by PCR-restriction fragment length polymorphism assay and c.238G>C by allele-specific PCR. Results: All genotype polymorphisms were heterozygous. TPMT*1/*3A, TPMT*1/*3C and TPMT*1/*2 genotypes were found in 4.0, 2.0 and 0.7%, respectively. Conclusion: 6.7% of individuals have an intermediate TPMT activity. These findings support the importance of prior genotyping of TPMT in Venezuelan patients who require thiopurine drug therapy.
Sujet(s)
Methyltransferases , Polymorphisme de nucléotide simple , Humains , Allèles , Fréquence d'allèle/génétique , Génotype , Hétérozygote , Methyltransferases/génétique , Polymorphisme de nucléotide simple/génétique , VenezuelaRÉSUMÉ
Cannabis sativa is one of the first medicinal plants used by humans. Its medical use remains controversial because it is a psychotropic drug whose use has been banned. Recently, however, some countries have approved its use, including for recreational and medical purposes, and have allowed the scientific study of its compounds. Cannabis is characterized by the production of special types of natural products called phytocannabinoids that are synthesized exclusively by this genus. Phytocannabinoids and endocannabinoids are chemically different, but both pharmacologically modulate CB1, CB2, GRP55, GRP119 and TRPV1 receptor activities, involving activities such as memory, sleep, mood, appetite and motor regulation, pain sensation, neuroinflammation, neurogenesis and apoptosis. Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are phytocannabinoids with greater pharmacological potential, including anti-inflammatory, neuroprotective and anticonvulsant activities. Cannabidiol is showing promising results for the treatment of COVID-19, due to its capability of acting on the unleashed cytokine storm, on the proteins necessary for both virus entry and replication and on the neurological consequences of patients who have been infected by the virus. Here, we summarize the latest knowledge regarding the advantages of using cannabinoids in the treatment of COVID-19.
RÉSUMÉ
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by gradual deterioration of cognitive function, memory, and inability to perform daily, social, or occupational activities. Its etiology is associated with the accumulation of ß-amyloid peptides, phosphorylated tau protein, and neuroinflammatory and oxidative processes in the brain. Currently, there is no successful pharmacological treatment for AD. The few approved drugs are mainly aimed at treating the symptoms; however, due to the increasing discovery of etiopathological factors, there are great efforts to find new multifunctional molecules to slow down the course of this neurodegenerative disease. The commercial Ginkgo biloba formulation EGb 761® and Huperzine A, an alkaloid present in the plant Huperzia serrata, have shown in clinical trials to possess cholinergic and neuroprotective activities, including improvement in cognition, activities of daily living, and neuropsychiatric symptoms in AD patients. The purpose of this review is to expose the positive results of intervention with EGb 761® and Huperzine in patients with mild to moderate AD in the last 10 years, highlighting the pharmacological functions that justify their use in AD therapy.
Sujet(s)
Maladie d'Alzheimer , Ginkgolides/usage thérapeutique , Activités de la vie quotidienne , Alcaloïdes/pharmacologie , Alcaloïdes/usage thérapeutique , Maladie d'Alzheimer/traitement médicamenteux , Ginkgolides/pharmacologie , Humains , Maladies neurodégénératives/traitement médicamenteux , Extraits de plantes/pharmacologie , Extraits de plantes/usage thérapeutique , Sesquiterpènes/pharmacologie , Sesquiterpènes/usage thérapeutiqueRÉSUMÉ
Colorectal cancer (CRC) is the second leading cause of cancer death worldwide and mostly affects men. Around 20% of its incidence is by familiar disposition due to hereditary syndromes. The CRC treatment involves surgery and chemotherapy; however, the side effects of treatments and the fast emergence of drug resistance evidence the necessity to find more effective drugs. Curcumin is the main polyphenol pigment present in Curcuma longa, a plant widely used as healthy food with antioxidant properties. Curcumin has synergistic effects with antineoplastics such as 5-fluorouracil and oxaliplatin, as well anti-inflammatory drugs by inhibiting cyclooxygenase-2 and the Nuclear factor kappa B. Furthermore, curcumin shows anticancer properties by inhibition of the Wnt/ß-catenin, Hedgehog, Notch, and the phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) signaling pathways implicated in the progression of CRC. However, the consumption of pure curcumin is less suitable, as the absorption is poor, and the metabolism and excretion are high. Pharmacological formulations and essential oils of the plant improve the curcumin absorption, resulting in therapeutical dosages. Despite the evidence obtained in vitro and in vivo, clinical studies have not yet confirmed the therapeutic potential of curcumin against CRC. Here we reviewed the last scientific information that supports the consumption of curcumin as an adjuvant for CRC therapy.
Sujet(s)
Tumeurs colorectales/traitement médicamenteux , Curcumine/pharmacologie , Adjuvants pharmaceutiques , Anti-inflammatoires non stéroïdiens/pharmacologie , Antinéoplasiques/pharmacologie , Antioxydants/pharmacologie , Lignée cellulaire tumorale , Traitement médicamenteux adjuvant/méthodes , Tumeurs colorectales/thérapie , Curcuma/métabolisme , Curcumine/métabolisme , Humains , Facteur de transcription NF-kappa B/métabolisme , Phosphatidylinositol 3-kinase/métabolisme , Extraits de plantes , Récepteurs Notch/métabolisme , Transduction du signal/effets des médicaments et des substances chimiques , Sérine-thréonine kinases TOR/métabolisme , bêta-Caténine/métabolismeRÉSUMÉ
Watermelon (Citrullus lanatus) and other cucurbits are cultivated globally, and Texas ranks among its top 5 producers in the U.S. In July 2020, plants with virus-like disease symptoms consisting of mild leaf crinkling and yellow mosaic patterns were observed in a 174-ha watermelon field in Burleson Co., TX; disease incidence was visually estimated at 5%. Total nucleic acids were extracted from leaf tissues of 5 randomly sampled plants (Dellaporta 1983) and their equimolar amounts were made into a composite sample that was used for cDNA library construction with TruSeq Stranded Total RNA with Ribo-Zero Plant Kit (Illumina). The cDNA library was sequenced on the Illumina NextSeq 500 platform, generating ~37M single-end reads (each 75 nt), which were analyzed as per Al Rwahnih et al. (2018). Of these, 58,200 and 27,500 reads mapped to the genomes of watermelon crinkle leaf-associated virus 1 (WCLaV-1) and WCLaV-2 (Xin et al. 2017), respectively, along with 4 other virus-specific reads (data not shown). The near complete RNA1-RNA3 segments of WCLaV-1 (354-652X) and WCLaV-2 (144-258X) were generated from the mapped reads and they shared ≥96% nt identities with published RNA segments of both viruses. The results were verified by RT-PCR using newly designed primers WCLaV-1vRP: 5'-GGTGAGTTAGTGTGTCTGAAGG/WCLaV-1cRP: 5'-GAGGTTGCCTGAGGTGATAAG to target 881 bp of the RNA1-encoded RNA-dependent RNA polymerase (RdRP), WCLaV-1vMP: 5'-GAAGGTTTGCTCCCTTGAAATG/WCLaV-1cMP: 5'-GACTGTGGCTGAAGAGTCTATG target 538 bp of the RNA2-encoded movement protein (MP), and WCLaV-1vNP: 5'-CGAATAGACTCTGGAGGGTAGA/WCLaV-1cMP: 5'-GAAAGCAAGAAAGCTGGCTAAA target 786 bp of the RNA3-encoded nucleoprotein (NP). Similarly, the WWCLaV-2-specific primers WCLaV-2vRP: 5'-GTCTCACATTCCTGCACTAACT/WCLaV-2cRP: 5'-ATCGGTCCTGGGTTATTTGTATC target 968 bp of the RdRP, WCLaV-2vMP: 5'-GACTTCAGAACCTCAACATCCA/WCLaV-2cMP: 5'-CAAGGGAGAGTGCTGACAAA target 562 bp of the MP, and WCLaV-2vNP: 5'-ATTCCCAGTGAGAGCAACAA/WCLaV-2cMP: 5'-GAGGTGGAGGTAGGAAAGAAAG target 449 bp of the NP. Fresh cDNA synthesized from the 5 samples with PrimeScript First Strand cDNA synthesis kit (Takara Bio) were tested by PCR with all 6 primer pairs using the PrimeSTAR GXL DNA Polymerase kit (Takara Bio). Three of the 5 samples were positive for both viruses and one sample was positive for each virus. The obtained products from 4 samples were cloned individually into pJET1.2/Blunt vector (Thermo Scientific, USA), followed by bidirectional Sanger-sequencing of the plasmids with the GenElute Five-Minute Plasmid Miniprep kit (Sigma-Aldrich). In pairwise comparisons, the partial RNA1-RNA3 sequences of WCLaV-1 (GenBank accession nos. MW559074-82) shared 100% nt/aa identities with each other and with corresponding sequences of WCLaV-1 isolate KF-1 from China (KY781184-86). The partial RNA1-RNA3 sequences of WCLaV-2 (MW559083-91) shared 97-100% nt/96-100% aa identities with each other and with corresponding sequences of WCLaV-2 isolate KF-15 from China (KY781187-89). This is the first report of WCLaV-1 and WCLaV-2 in Texas and the first record of both viruses in the U.S. and elsewhere outside of China. Both negative-sense, single-stranded RNA viruses represent a novel taxon in the family Phenuiviridae (order Bunyavirales) (Xin et al. 2017). While aspects of the biology of both viruses are yet to be elucidated, our results expand their geographical range. The detection primers developed here will be useful for screening cucurbits germplasm to avert their spread.
RÉSUMÉ
A virus-like disease characterized by foliar yellow blotch symptoms and resembling those described for cilantro yellow blotch disease in California was observed in a 4.05-ha cilantro (Coriandrum sativum) cv. Santo field in Hidalgo County, Texas during spring 2019. Disease incidence at harvest was estimated at â¼20%, and the affected plants were rendered unmarketable. Foliar systemic chlorosis symptoms were observed on sap-inoculated Nicotiana occidentalis plants (n = 3) using inocula from symptomatic cilantro. Total RNA aliquots from 11 randomly collected leaf tissue samples (symptomatic = 7, asymptomatic = 4) were pooled into a composite cilantro RNA sample which was analyzed by high throughput sequencing (HTS). Analyses of the obtained 15.7 million raw reads (76 nt each) yielded virus-specific contigs that mapped to the genomes of alfalfa mosaic virus (AMV), beet pseudoyellows virus (BPYV), and lettuce chlorosis virus (LCV). Virus-specific primers designed from the HTS-derived sequences were used to screen the samples in two-step RT-PCR assays, resulting in the detection of AMV+BPYV in 3 of 7 symptomatic cilantro samples, AMV+LCV in 4 of 7 symptomatic cilantro samples, and AMV alone in the 4 asymptomatic cilantro and sap-inoculated N. occidentalis samples. The results represent the first reports of the natural infection of cilantro by BPYV and LCV and implicate the mixed infection of a Crinivirus and AMV in cilantro yellow blotch disease.
Sujet(s)
Virus de la mosaïque de la luzerne , Coriandrum , Californie , Maladies des plantes , TexasRÉSUMÉ
CYP2D6 is an important cytochrome P450 enzyme that plays an important role in the metabolism of about 25% of currently prescribed drugs. The presence of polymorphisms in the CYP2D6 gene may modulate enzyme level and activity, thereby affecting individual responses to pharmacological treatments. The most prevalent diseases in the admixed population from Venezuela are cardiovascular and cancer, whereas viral, bacterial and parasitic diseases, particularly malaria, are prevalent in Amerindian populations; in the treatment of these diseases, several drugs that are metabolized by CYP2D6 are used. In this work, we reviewed the data on CYP2D6 variability and predicted metabolizer phenotypes, in healthy volunteers of two admixed and five Amerindian populations from Venezuela. The Venezuelan population is very heterogeneous as a result of the genetic admixture of three major ethnical components: Europeans, Africans and Amerindians. There are noticeable inter-regional and inter-population differences in the process of mixing of this population. Hitherto, there are few published studies in Venezuela on CYP2D6; therefore, it is necessary to increase research in this regard, in particular to develop studies with a larger sample size. There is a considerable amount of work remaining before CYP2D6 is integrated into clinical practice in Venezuela.
Sujet(s)
Cytochrome P-450 CYP2D6/génétique , Variation génétique/génétique , Cytochrome P-450 CYP2D6/métabolisme , Volontaires sains , Humains , Phénotype , VenezuelaRÉSUMÉ
Two isolates of a novel bipartite begomovirus, tentatively named malvastrum bright yellow mosaic virus (MaBYMV), were molecularly characterized from naturally infected plants of the genus Malvastrum showing bright yellow mosaic disease symptoms in South Texas. Six complete DNA-A and five DNA-B genome sequences of MaBYMV obtained from the isolates ranged in length from 2,608 to 2,609 nucleotides (nt) and 2,578 to 2,605 nt, respectively. Both genome segments shared a 178- to 180-nt common region. In pairwise comparisons, the complete DNA-A and DNA-B sequences of MaBYMV were most similar (87-88 % and 79-81 % identity, respectively) and phylogenetically related to the corresponding sequences of sida mosaic Sinaloa virus-[MX-Gua-06]. Further analysis revealed that MaBYMV is a putative recombinant virus, thus supporting the notion that malvaceous hosts may be influencing the evolution of several begomoviruses. The design of new diagnostic primers enabled the detection of MaBYMV in cohorts of Bemisia tabaci collected from symptomatic Malvastrum sp. plants, thus implicating whiteflies as potential vectors of the virus.
Sujet(s)
Begomovirus/génétique , Animaux , Begomovirus/classification , Begomovirus/isolement et purification , ADN viral/génétique , Génome viral , Hemiptera/virologie , Vecteurs insectes/virologie , Malvaceae/virologie , Phylogenèse , Maladies des plantes/virologie , Recombinaison génétique , TexasRÉSUMÉ
Las alteraciones de la diferenciación sexual (ADS) son patologías originadas por trastornos en una de las tres etapas sucesivas de dicha diferenciación: cromosómica (XX, XY), gonadal (testículo, ovario) o fenotípica. El objetivo del trabajo fue dar a conocer la forma de presentación de las ADS en pacientes provenientes de las regiones Capital y Centro Occidental de Venezuela. Se incluyeron diecisiete pacientes y se elaboraron los árboles genealógicos, se realizó evaluación clínica, estudios hormonales, citogenéticos, imagenología y determinación de marcadores del gen SRY y microsatélites del cromosoma Y. En función de la evaluación clínica y los datos obtenidos de los exámenes practicados, se efectuaron los diagnósticos siguientes: a) Doce corresponden a ADS 46,XX , de los cuales siete pacientes tienen ADS por exceso de andrógenos, un caso con reversión sexual, un ADS ovotesticular, un caso con síndrome malformativo, uno con disgenesia gonadal y uno con hipogonadismo, b) Cuatro presentan ADS 46,XY (un paciente con síndrome de Smith-Lemli-Opitz II, uno con síndrome malformativo y dos casos con hipogonadísmo), c) Un caso de ADS por alteración cromosómica 46,XXY (síndrome de Klinefelter). En relación a la edad de la primera consulta, la mayor parte (47,1%) se realizó en menores de 5 años, referidos por ambigüedad sexual con necesidad de resolver la identificación del sexo; en la pubertad los pacientes consultan por alteraciones en los caracteres sexuales secundarios y amenorrea (adolescentes); en la adultez por infertilidad. Los resultados permitieron realizar un mejor asesoramiento genético y contribuir a mejorar la calidad de vida de los pacientes y sus grupos familiares.
Disorders of sexual differentiation (DSD) are pathologies characterized by an atypical development of chromosomal (XX, XY) gonadal (testis, ovary) or phenotypical sex. The objective of this work was to inform the presentation forms of SDS in patients from the Capital and West Center regions of Venezuela. Seventeen patients were included and the pedigrees, clinical evaluation, hormonal studies, cytogenetic, imaging and identification of SRY gene markers and Y chromosome microsatellites were made. Depending on the clinical evaluation and data from examinations carried out, the following diagnoses were made: a)Twelve patients correspond to DSD 46, XX, of which seven patients have DSD by androgen excess, a case with sex reversal a ovotesticular DSD, a case with malformation syndrome, one with gonadal dysgenesis and one hypogonadism; b) Four patients presented DSD 46, XY (a patient with Smith-Lemli-Opitz syndrome II, one malformation syndrome and two cases with hypogonadism) c) A case of ADSs by chromosomal abnormality 46,XXY (Klinefelter syndrome). In relation to age of first consultation, the majority (47.1%) was performed in children under 5 years, referred by sexual ambiguity with need to address sex identification. In puberty, the patients consult due to alterations in secondary sexual characteristics and amenorrhea in teenagers, in adulthood due to infertility. The results helped to make a better genetic counseling and to improve the quality of life of patients and their families.
RÉSUMÉ
El objetivo del estudio fue determinar la frecuencia de las variantes del gen CYP2D6: *4, *6 y *10 y predecir el fenotipo metabolizador en una muestra de 145 individuos no consanguíneos, aparentemente sanos, residentes del estado Aragua, Venezuela. Los genotipos fueron determinados mediante ensayos de reacción en cadena de la polimerasa seguidos de digestión con endonucleasas de restricción. La predicción del fenotipo metabolizador se realizó con base al sistema Activity score. Las frecuencias de CYP2D6 *4, *6 y *10 fueron de 14,5%, 0,3% y 1%, respectivamente; un porcentaje significativo de individuos fueron categorizados como metabolizador rápido heterocigoto/metabolizador intermedio (23,5%) y metabolizador lento (4,1%). Esta información tiene impacto clínico potencial, porque CYP2D6 interviene en el metabolismo de fármacos de prescripción frecuente como: carvedilol, captopril, cloroquina, codeína, fluoxetina, fluvastatina, haloperidol, idarrubicina, indinavir, imatinib, loperamida, nifedipina, ondansetrón y tamoxifeno...
The aim of this study was to determine the CYP2D6: * 4, * 6 and * 10 gene variants frequency and to predict the metabolizer phenotype in a sample of 145 unrelated apparently healthy individuals residing in the state of Aragua, Venezuela. Genotypes were determined by Polymerase chain reaction assays followed by restriction endonucleases digestion. The metabolizer phenotype prediction was made based on the activity score system. The frequencies of CYP2D6 * 4, * 6 and * 10 allelic variants were 14.5%, 0.3% and 1%. A significant percentage of individuals were categorized as heterozygote-extensive/intermediate (23.5%) and poor metabolizers (4.1%), this information has potential clinical impact, because the CYP2D6 protein is involved in the metabolism of drugs frequently prescribed as: carvedilol, captopril, chloroquine, codeine, fluoxetine, fluvastatin, haloperidol, idarubicin, indinavir, imatinib, loperamide, nifedipine, ondansetron and tamoxifen...
Sujet(s)
Humains , Mâle , Adulte , Femelle , Adulte d'âge moyen , Pharmacogénétique , Phénotype , Génotype , VenezuelaRÉSUMÉ
The aim of this study was to determine the CYP2D6: * 4, * 6 and * 10 gene variants frequency and to predict the metabolizer phenotype in a sample of 145 unrelated apparently healthy individuals residing in the state of Aragua, Venezuela. Genotypes were determined by Polymerase chain reaction assays followed by restriction endonucleases digestion. The metabolizer phenotype prediction was made based on the activity score system. The frequencies of CYP2D6 * 4, * 6 and * 10 allelic variants were 14.5%, 0.3% and 1%. A significant percentage of individuals were categorized as heterozygote-extensive/intermediate (23.5%) and poor metabolizers (4.1%), this information has potential clinical impact, because the CYP2D6 protein is involved in the metabolism of drugs frequently prescribed as: carvedilol, captopril, chloroquine, codeine, fluoxetine, fluvastatin, haloperidol, idarubicin, indinavir, imatinib, loperamide, nifedipine, ondansetron and tamoxifen.
Sujet(s)
Cytochrome P-450 CYP2D6/génétique , Fréquence d'allèle , Préparations pharmaceutiques/métabolisme , Allèles , Génotype , Humains , Phénotype , VenezuelaRÉSUMÉ
Repeated exposure to human immunodeficiency virus (HIV) does not always result in seroconversion. Modifications in coreceptors for HIV entrance to target cells are one of the factors that block the infection. We studied the frequency of Delta-32 mutation in ccr5 gene in Medellin, Colombia. Two hundred and eighteen individuals distributed in three different groups were analyzed for Delta-32 mutation in ccr5 gene by polymerase chain reaction (PCR): 29 HIV seropositive (SP), 39 exposed seronegative (ESN) and 150 individuals as a general population sample (GPS). The frequency of the Delta-32 mutant allele was 3.8 for ESN, 2.7 for GPS and 1.7 for SP. Only one homozygous mutant genotype (Delta-32/Delta-32) was found among the ESN (2.6). The heterozygous genotype (ccr5/Delta-32) was found in eight GPS (5.3), in one SP (3.4) and in one ESN (2.6). The differences in the allelic and genotypic frequencies among the three groups were not statistically significant. A comparison between the expected and the observed genotypic frequencies showed that these frequencies were significantly different for the ESN group, which indirectly suggests a protective effect of the mutant genotype (Delta-32/Delta-32). Since this mutant genotype explained the resistance of infection in only one of our ESN persons, different mechanisms of protection must be playing a more important role in this population.