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1.
Braz. j. biol ; 83: e247422, 2023. tab, graf
Artigo em Inglês | LILACS-Express | MEDLINE, LILACSEXPRESS | ID: biblio-1285631

RESUMO

Abstract Plasmodium falciparum resistance to Chloroquine (CQ) is a significant cause of mortality and morbidity worldwide. There is a paucity of documented data on the prevalence of CQ-resistant mutant haplotypes of Pfcrt and Pfmdr1 genes from malaria-endemic war effected Federally Administered Tribal Areas of Pakistan. The objective of this study was to investigate the prevalence of P. falciparum CQ-resistance in this area. Clinical isolates were collected between May 2017 and May 2018 from North Waziristan and South Waziristan agencies of Federally Administrated Trial Area. Subsequently, Giemsa-stained blood smears were examined to detect Plasmodium falciparum. Extraction of malarial DNA was done from microscopy positive P. falciparum samples, and P. falciparum infections were confirmed by nested PCR (targeting Plasmodium small subunit ribosomal ribonucleic acid (ssrRNA) genes). All PCR confirmed P. falciparum samples were sequenced by pyrosequencing to find out mutation in Pfcrt gene at codon K76T and in pfmdr1 at codons N86Y, Y184F, N1042D, and D1246Y. Out of 121 microscopies positive P. falciparum cases, 109 samples were positive for P. falciparum by nested PCR. Pfcrt K76T mutation was found in 96% of isolates, Pfmdr1 N86Y mutation was observed in 20%, and 11% harboured Y184F mutation. All samples were wild type for Pfmdr1 codon N1042D and D1246Y. In the FATA, Pakistan, the frequency of resistant allele 76T remained high despite the removal of CQ. However, current findings of the study suggest complete fixation of P. falciparum CQ-resistant genotype in the study area.


Resumo A resistência do Plasmodium falciparum à cloroquina (CQ) é uma causa significativa de mortalidade e morbidade em todo o mundo. Há uma escassez de dados documentados sobre a prevalência de haplótipos mutantes CQ-resistentes dos genes Pfcrt e Pfmdr1 da guerra endêmica da malária em áreas tribais administradas pelo governo federal do Paquistão. O objetivo deste estudo foi investigar a prevalência de resistência a CQ de P. falciparum nesta área. Isolados clínicos foram coletados entre maio de 2017 e maio de 2018 nas agências do Waziristão do Norte e do Waziristão do Sul da Área de Ensaio Administrada Federalmente. Posteriormente, esfregaços de sangue corados com Giemsa foram examinados para detectar Plasmodium falciparum. A extração do DNA da malária foi feita a partir de amostras de P. falciparum positivas para microscopia, e as infecções por P. falciparum foram confirmadas por nested PCR (visando genes de ácido ribonucleico ribossômico de subunidade pequena de Plasmodium (ssrRNA)). Todas as amostras de P. falciparum confirmadas por PCR foram sequenciadas por pirosequenciamento para descobrir a mutação no gene Pfcrt no códon K76T e em pfmdr1 nos códons N86Y, Y184F, N1042D e D1246Y. De 121 microscopias de casos positivos de P. falciparum, 109 amostras foram positivas para P. falciparum por nested PCR. A mutação Pfcrt K76T foi encontrada em 96% dos isolados, a mutação Pfmdr1 N86Y foi observada em 20% e 11% abrigou a mutação Y184F. Todas as amostras eram do tipo selvagem para o códon N1042D e D1246Y de Pfmdr1. No FATA, Paquistão, a frequência do alelo resistente 76T permaneceu alta apesar da remoção de CQ. No entanto, as descobertas atuais do estudo sugerem a fixação completa do genótipo resistente a CQ de P. falciparum na área de estudo.

2.
Braz J Biol ; 83: e247219, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34468526

RESUMO

Military conflicts have been significant obstacles in detecting and treating infectious disease diseases due to the diminished public health infrastructure, resulting in malaria endemicity. A variety of violent and destructive incidents were experienced by FATA (Federally Administered Tribal Areas). It was a struggle to pursue an epidemiological analysis due to continuing conflict and Talibanization. Clinical isolates were collected from Bajaur, Mohmand, Khyber, Orakzai agencies from May 2017 to May 2018. For Giemsa staining, full blood EDTA blood samples have been collected from symptomatic participants. Malaria-positive microscopy isolates were spotted on filter papers for future Plasmodial molecular detection by nested polymerase chain reaction (nPCR) of small subunit ribosomal ribonucleic acid (ssrRNA) genes specific primers. Since reconfirming the nPCR, a malariometric study of 762 patients found 679 positive malaria cases. Plasmodium vivax was 523 (77%), Plasmodium falciparum 121 (18%), 35 (5%) were with mixed-species infection (P. vivax plus P. falciparum), and 83 were declared negative by PCR. Among the five agencies of FATA, Khyber agency has the highest malaria incidence (19%) with followed by P. vivax (19%) and P. falciparum (4.1%). In contrast, Kurram has about (14%), including (10.8%) P. vivax and (2.7%) P. falciparum cases, the lowest malaria epidemiology. Surprisingly, no significant differences in the distribution of mixed-species infection among all five agencies. P. falciparum and P. vivax were two prevalent FATA malaria species in Pakistan's war-torn area. To overcome this rising incidence of malaria, this study recommends that initiating malaria awareness campaigns in school should be supported by public health agencies and malaria-related education locally, targeting children and parents alike.


Assuntos
Plasmodium , Criança , Humanos , Epidemiologia Molecular , Paquistão/epidemiologia , Plasmodium/genética , Plasmodium falciparum/genética , Plasmodium vivax/genética
3.
Braz J Biol ; 83: e247422, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34431917

RESUMO

Plasmodium falciparum resistance to Chloroquine (CQ) is a significant cause of mortality and morbidity worldwide. There is a paucity of documented data on the prevalence of CQ-resistant mutant haplotypes of Pfcrt and Pfmdr1 genes from malaria-endemic war effected Federally Administered Tribal Areas of Pakistan. The objective of this study was to investigate the prevalence of P. falciparum CQ-resistance in this area. Clinical isolates were collected between May 2017 and May 2018 from North Waziristan and South Waziristan agencies of Federally Administrated Trial Area. Subsequently, Giemsa-stained blood smears were examined to detect Plasmodium falciparum. Extraction of malarial DNA was done from microscopy positive P. falciparum samples, and P. falciparum infections were confirmed by nested PCR (targeting Plasmodium small subunit ribosomal ribonucleic acid (ssrRNA) genes). All PCR confirmed P. falciparum samples were sequenced by pyrosequencing to find out mutation in Pfcrt gene at codon K76T and in pfmdr1 at codons N86Y, Y184F, N1042D, and D1246Y. Out of 121 microscopies positive P. falciparum cases, 109 samples were positive for P. falciparum by nested PCR. Pfcrt K76T mutation was found in 96% of isolates, Pfmdr1 N86Y mutation was observed in 20%, and 11% harboured Y184F mutation. All samples were wild type for Pfmdr1 codon N1042D and D1246Y. In the FATA, Pakistan, the frequency of resistant allele 76T remained high despite the removal of CQ. However, current findings of the study suggest complete fixation of P. falciparum CQ-resistant genotype in the study area.


Assuntos
Antimaláricos , Plasmodium falciparum , Alelos , Antimaláricos/farmacologia , Cloroquina/farmacologia , Resistência a Medicamentos/genética , Proteínas de Membrana Transportadoras/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Paquistão , Plasmodium falciparum/genética , Proteínas de Protozoários/genética
4.
Mol Biol (Mosk) ; 53(4): 674-684, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31397441

RESUMO

Acriflavine resistance protein B (AcrB) serves as prototype for multidrug resistance (MDR) efflux transporters of resistance nodulation division (RND) superfamily. AcrB has been proven as potential drug target with many synthetic and natural inhibitors have been identified such as those belonging to pyranopyridine, naphthamide and pimozide classes. The plant derived alkaloid inhibitors represented by reserpine has been found to inhibit both ATP binding cassette and major facilitator efflux transporters. In this study we report the reserpine induced inhibition of RND transporter AcrB. The preliminary docking analysis hints that reserpine shares its binding site with ciprofloxacin, a known substrate of AcrB and could possibly act as competitive inhibitor. For in vitro validation, AcrB from Salmonella typhi was cloned under the control of tac promoter and resulting vector was introduced into E. coli C41(DE3). Under autoinduced conditions, cells overexpressing AcrB transporter were subjected to combined dose of ciprofloxacin and reserpine. The combined exposure resulted in enhanced ciprofloxacin-induced growth inhibition of cells expressing AcrB transporter as compared to control cells transformed with vector of backbone sequence. Time kill analysis further confirmed these findings. To the best of our knowledge, this is first study to show that exposure to reserpine induces inhibition of AcrB. The assay developed in this study allows simple and reproducible detection of substrate/inhibitor effects upon AcrB and related efflux transporters.


Assuntos
Proteínas de Escherichia coli/antagonistas & inibidores , Proteínas Associadas à Resistência a Múltiplos Medicamentos/antagonistas & inibidores , Reserpina/farmacologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Testes de Sensibilidade Microbiana , Reprodutibilidade dos Testes
5.
J Am Med Dir Assoc ; 20(10): 1340-1343.e2, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31201101

RESUMO

Patients with obstructive sleep apnea (OSA) have increased postoperative complications that are important for patient safety and healthcare utilization. Questionnaires help identify patients at risk for OSA; however, among older adults who preoperatively self-administered OSA questionnaires, the frequency of postoperative Medical Emergency Team Activation (META), rapid response, code blue, code stroke, is unknown. OBJECTIVES: Identify whether having OSA questionnaires completed by patients is feasible in the preoperative clinic. Determine the frequency of META among older patients at risk for OSA. DESIGN AND INTERVENTION: Cohort of prospective patients independently completed 2 OSA questionnaires in a preoperative clinic, STOP-Bang (SB) and ISNORED (IS). Observers blinded to questionnaire responses recorded incidence of META. SETTING AND PARTICIPANTS: Of the 898 consecutive patients approached in the preoperative assessment clinic and surgical navigation center, 575 (64%) consented and completed the questionnaires in <5 minutes and were included in the analysis. MEASURES: Sleep questionnaire responses and frequency of inpatient postoperative META. RESULTS: With an affirmative response to ≥3 questions on either questionnaire, 65% of patients enrolled were at risk for OSA. Of these, 3.1% sustained an META. In patients at risk for OSA, META occurred in 7.6% (SB+) and 7.2% (IS+) vs 2.5% (SB+) and 1.7% (IS+) for low risk. METAs were disproportionately higher among patients aged ≥65 years (6.3% vs 1.7%; P < .018), American Society of Anesthesiologists (ASA) physical status class ≥3, and IS+. All patients with META positively answered ≥3 of 15 components of the 2 questionnaires. CONCLUSIONS/IMPLICATIONS: Preoperative, self-administration of SB and IS questionnaires is feasible. Overall, 65% of those with affirmative responses to ≥3 questions were at risk for OSA and associated with a disproportionate number of postoperative META in older patients. Additionally, risk of OSA identified by preoperative sleep questionnaires was associated with postoperative META among older adults. Use of clinical tools and OSA questionnaires may improve preoperative identification of META in this population.


Assuntos
Serviço Hospitalar de Emergência , Equipe de Assistência ao Paciente , Cuidados Pré-Operatórios , Sono , Inquéritos e Questionários , Estudos de Viabilidade , Feminino , Humanos , Masculino , Estudos Prospectivos , Apneia Obstrutiva do Sono
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