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1.
Bull Soc Pathol Exot ; 107(3): 151-8, 2014 Aug.
Artigo em Francês | MEDLINE | ID: mdl-24953144

RESUMO

Highly active antiretroviral therapy (HAART) has reduced morbidity and mortality of HIV but has led to an increasing metabolic cardiovascular risk. A cross-sectional study was conducted from May to September 2011 in Day Care Hospital for HIV-Patients of Bobo-Dioulasso. We included in this study 400 patients infected by HIVon antiretroviral therapy ≥ 6 months selected by a random draw. Metabolic syndrome was assessed according to the definitions of the IDF and ATP-III. The high risk of cardiovascular disease in 10 years was defined by a Framingham score ≥ 20%. The average age of our patients was 41.4 years [20-76]. 17% received an IP. The average duration of PI exposure was 35.5 months and 50.1 months for NNRTI. The prevalence of diabetes was 1.3% (95% CI: 0.5-3) and that of hypertension of 12.0 % (95% CI: 9.3-16). The prevalence of metabolic syndrome according to IDF was 10% (95% CI: 7.3-13.5) and the metabolic syndrome according to ATP-III 12.3% (95% CI: 9.3-16). The body mass index was higher (BMI 25.2 vs. 22.5 kg/m(2), p <10(-3) with ATPIII and BMI 26.6 vs. 22.4 kg/m(2), p <10(-3) with IDF), and duration exposure to ARVs longer in patients with metabolic syndrome regardless of the definition used (58.6 months vs 27.9 months). High cardiovascular risk was present in 1.8% (95% CI: 0.8 to 3.7) of our patients, all male more than half (n=4/7) of them were smoking. The choice of antiretroviral therapy must take into account its potential long-term toxicity. It should also strengthen supervision.


Assuntos
Terapia Antirretroviral de Alta Atividade , Doenças Cardiovasculares/etiologia , Infecções por HIV/tratamento farmacológico , Síndrome Metabólica/etiologia , Adulto , Idoso , Instituições de Assistência Ambulatorial , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Burkina Faso/epidemiologia , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , HIV-1 , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
2.
Rev Sci Tech ; 33(3): 893-901, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25812213

RESUMO

The seroprevalence of Rift Valley fever was determined in cattle, sheep and goats in selected areas of northern and central Burkina Faso. A total of 520 serum samples were screened for anti-Rift Valley fever virus immunoglobulin G (IgG) antibodies using an inhibition enzyme-linked immunosorbent assay (ELISA). An average seroprevalence of 7.67% (range 5% to 20%) was found in ruminants in Seno and Soum provinces, and prevalences of 20% and 22.5% in cattle in Yatenga and Oubritenga provinces, respectively. The location, species and age of the animals were found to influence the seroprevalence. All the ELISA IgG-positive samples were tested for IgM in a competitive ELISA and were found negative, thus ruling out recent infections. The IgG-positive samples, including weak positives, were further tested in a serum neutralisation test for neutralising antibodies and 54.5% of these samples tested positive. The results show that the virus is in circulation in central and northern regions of Burkina Faso, suggesting the need for improved surveillance and control systems to prevent future outbreaks and the consequent economic impact of the disease in Burkina Faso livestock.


Assuntos
Doenças dos Bovinos/epidemiologia , Doenças das Cabras/epidemiologia , Febre do Vale de Rift/epidemiologia , Doenças dos Ovinos/epidemiologia , Envelhecimento , Animais , Anticorpos Antivirais/sangue , Burkina Faso/epidemiologia , Bovinos , Ensaio de Imunoadsorção Enzimática/veterinária , Cabras , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Testes Sorológicos , Ovinos
3.
Bull Soc Pathol Exot ; 106(4): 239-43, 2013 Oct.
Artigo em Francês | MEDLINE | ID: mdl-24136661

RESUMO

The objective of this study was to evaluate the effectiveness and the clinical tolerance of a combination containing TDF/FTC/EFV in the treatment of HIV infection. This was a retrospective and descriptive study which included 196 adults infected by HIV-1 and treated by a combination containing TDF/FTC/EFV during 29 months in the daily hospital of Bobo Dioulasso. The median duration of follow-up was 7 months IQR [5-14 month]. The median age was 37 years IQR [31-45].With the initiation of treatment ARV, the median of the index of body mass was of 19 IQR [17-22]. The median of the lymphocytes TCD4 was 201/µl IQR [74-298/µl]. During the follow-up, we reported 25 deaths (12.8%). HIV-1 RNA plasma viral load was undetectable in 91.9% of the patients (124/135) at six months of treatment. The majority of the adverse effects of the treatment were of a neurosensory nature (40.5%). The TDF/FTC/EFV combination showed a good effectiveness in the treatment of the infection with HIV-1 in the first intention just as a good clinical tolerance.


Assuntos
Adenina/análogos & derivados , Antirretrovirais/uso terapêutico , Desoxicitidina/análogos & derivados , Infecções por HIV/tratamento farmacológico , Organofosfonatos/uso terapêutico , Oxazinas/uso terapêutico , Adenina/uso terapêutico , Adulto , Burkina Faso , Desoxicitidina/uso terapêutico , Combinação de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Combinação Efavirenz, Emtricitabina, Fumarato de Tenofovir Desoproxila , Feminino , Infecções por HIV/epidemiologia , HIV-1 , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
4.
Med Sante Trop ; 22(1): 107-9, 2012.
Artigo em Francês | MEDLINE | ID: mdl-22871792

RESUMO

The aim of our study was to investigate the prevalence of CMV antibodies among blood donors at a regional blood transfusion center in Ouagadougou. Blood collected from 115 donors was tested for specific anti-CMV antibodies as well as routine markers. The donors ranged in age from 18 to 53 years (mean: 28.78 ± 8.9 years), and 72.2% were men. In all, 4.3% were positive for HIV, 12.2% for HBs Ag, 2.6% for HCV, and 1.7% for syphilis. Nearly all donors (n=106, 92.2%) had CMV IgG antibodies, but only 12.2% (n=14) IgM antibodies, and all of the latter were also positive for IgG. CMV infection was not related to the donors' HIV status (p=0.66). The seroprevalence of CMV infection was not statistically related to gender, age or occupational status. There was no significant difference in the prevalence of any routine markers between donors positive and negative for CMV. The high rate of CMV antibodies indicates that CMV infection is widespread in Burkina Faso. Although it is thus unnecessary to test blood donors routinely for CMV, immunodepressed and other risk subjects should receive CMV-negative or leukocyte-depleted blood.


Assuntos
Anticorpos Antivirais/sangue , Doadores de Sangue , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/epidemiologia , Citomegalovirus/imunologia , Adolescente , Adulto , Burkina Faso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Adulto Jovem
5.
Med Sante Trop ; 22(4): 425-9, 2012.
Artigo em Francês | MEDLINE | ID: mdl-23360620

RESUMO

OBJECTIVE: Vaccination against Haemophilus influenzae type b was introduced in Burkina Faso on 1st January 2006. This study thus sought to determine the impact of the first 30 months of vaccination on admissions for Hib meningitis in the department of pediatrics at the Sourô-Sanou University Hospital in Bobo Dioulasso. METHODS AND PATIENTS: Retrospective study of children aged zero to 14 years hospitalized from 1st January 2004 to 30th June 2008 for acute bacterial meningitis (laboratory-confirmed). RESULTS: During the study period, 416 children were admitted for acute bacterial meningitis. The bacterium isolated was identified in 386 cases and unidentified in 30 cases. Hib meningitis accounted for 42.3 % of the cases of identified bacterial meningitis before the introduction of the vaccine (2004 to 2005). This rate declined to 11.8 % for the first 30 months of vaccination (p < 0.001). No cases of Hib meningitis have been reported in the first half of 2008. CONCLUSION: Admissions for Hib meningitis in the Department of Pediatrics have practically disappeared two years after the introduction of the Hib vaccine into Burkina Faso's expanded program on immunization.


Assuntos
Vacinas Anti-Haemophilus/uso terapêutico , Haemophilus influenzae tipo b , Meningite por Haemophilus/epidemiologia , Meningite por Haemophilus/prevenção & controle , Admissão do Paciente/estatística & dados numéricos , Adolescente , Cápsulas Bacterianas , Burkina Faso/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Fatores de Tempo
6.
Med Sante Trop ; 22(4): 412-6, 2012.
Artigo em Francês | MEDLINE | ID: mdl-23396480

RESUMO

INTRODUCTION: Acute bacterial meningitis constitutes a major public health problem in Burkina Faso, in part because of its high lethality rate, estimated in 2004 at 17.5%. Failure to confirm suspected cases of meningitis results in overestimating reported cases and incorrectly treating false positives. The latex particle agglutination test is a diagnostic alternative that overcomes these limitations. OBJECTIVE: Determine the bacteriological and therapeutic profile as well as the course of cases of acute meningitis confirmed by the latex agglutination test at Sourô-Sanou University Hospital. METHODS: This prospective longitudinal study took place over a one-year period (2008 to 2009). Data were collected from clinical and laboratory records. The diagnosis of meningitis was confirmed by testing for specific soluble antigens in the spinal fluid. We used the Pastorex(™) Meningitis Kit for that purpose. The threshold of significance selected for our study was 0.05. RESULTS: In all, 457 samples of spinal fluid from patients with suspected acute bacterial meningitis were analyzed and the latex test was performed in 438 of these samples: 154 (35.2%) were positive. The average age of our cases confirmed by the latex test was 13.2 ± 4.2 years old. This test confirmed more cases than any other method of identification. The therapeutic strategy used from one to four treatment agents. Streptococcus pneumoniae was the most virulent and the most lethal pathogen, with a 64.7% lethality rate. CONCLUSION: The earliness of the consultation and the treatment of the bacterial meningitis seem to have a positive effect on the course of disease.


Assuntos
Meningites Bacterianas/diagnóstico , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Bactérias/líquido cefalorraquidiano , Burkina Faso , Criança , Pré-Escolar , Feminino , Hospitais Universitários , Humanos , Lactente , Testes de Fixação do Látex , Estudos Longitudinais , Masculino , Meningites Bacterianas/líquido cefalorraquidiano , Microesferas , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
7.
Ann. afr. méd. (En ligne) ; 5(3): 1094-1105, 2012.
Artigo em Francês | AIM (África) | ID: biblio-1259170

RESUMO

La meningite bacterienne aigue (MBA) est une urgence medicale par ses complications potentielles; elle justifie un diagnostic et traitement precoces. La strategie nationale au Burkina Faso recommande une reference de tous les cas suspects au Centre Hospitalier Universitaire Souro Sanou; habilete a confirmer le diagnostic par analyse du liquide cephalo-rachidien. Methodes. Les auteurs; a travers une etude transversale et analytique; ont recherche les donnees epidemiocliniques des cas suspects referes; en vue de valider l'approche syndromique; dans l'orientation dudiagnostic de la meningite. La specificite; la sensibilite; et la valeur predictive positive des donnees cliniques ont ete determinees; par rapport a la confirmation apportee par la culture du LCR; selon les recommandations de STARD et de l'OMS. Resultats. Au total; 377 patients ont ete enregistres; soit un taux de 2;4; par rapport a l'ensemble des malades admis pendant la periode d'etude. La fievre (81;6) et la raideur de nuque (72;9) ont ete les observations cliniques les plus frequentes ; le bombement de la fontanelle (31;6) et les convulsions ( 23;1); etant l'apanage des patients pediatriques. La culture du liquide cephalorachidien (LCR) a ete positive chez 207 sujets (54;9) avec tableau clinique suggestif; et chez 97 patients sans triade symptomatique classique; meme si la fievre etait presente dans tous les cas (T. 38C). La specificite et la valeur predictive positive du tableau clinique etaient de 100dans la confirmation du diagnostic par la culture. Conclusion. Cette enquete montre la pertinence de l'examen clinique dans l'approche diagnostique de la MBA au niveau des centres de sante; tout en relevant le role determinant de la culture du LCR dans la confirmation de la pathologie


Assuntos
Líquido Cefalorraquidiano , Meningites Bacterianas/diagnóstico
9.
Artigo em Inglês | LILACS, VETINDEX | ID: lil-658998

RESUMO

We report herein the case of 19-year-old female farmer who suffered a double snakebite on the right foot. After an unsuccessful traditional treatment, she consulted a health center, 48 hours after the bite. Upon arrival at the hospital, she showed signs of severe damage, including hemorrhagic syndrome, extensive gangrene of the bitten limb and severe acute renal failure. Due to financial constraints, neither antivenom nor the scheduled amputation was performed. After 35 days of hospitalization, she returned home, against the advice of medical personnel. Our case summarizes the daily challenges of patients and practitioners that suffer snakebite envenomation in Bobo-Dioulasso, western Burkina Faso.(AU)


Assuntos
Humanos , Pacientes , Mordeduras de Serpentes , Mordeduras e Picadas , Antivenenos , Técnicas de Laboratório Clínico , Relatório de Pesquisa
10.
Med Trop (Mars) ; 71(1): 49-52, 2011 Feb.
Artigo em Francês | MEDLINE | ID: mdl-21585091

RESUMO

OBJECTIVE: The purpose of this study was to evaluate the bacterial profile and antimicrobial susceptibility of surgical site infection (SSI) as a basis for optimizing probabilistic antibiotherapy. MATERIALS AND METHODS: A 6-month transversal retrospective study was carried out at the Souro Sano Hospital Laboratory from November 1st, 2006 to April 30th, 2007. All positive pus samples collected for etiologic diagnosis of SSI were included. RESULTS: In a series of 681 patients who underwent surgery at the hospital, SSI was observed in 159 cases for an incidence of 23.4%. Pus samples for etiologic diagnosis were collected from 112 patients and led to identification of 103 bacterial strains. The most common strains were enterobacteriaceae in 54.0%, gram-positive cocci in 29.0% and non-fermenting Gram-negative bacilli in 16.5%. Escherichia coli was the most common species (30%) followed by Staphylococcus aureus (16.5%) and Pseudomonas aeroginosa (12.0%). Enterobacteriaceae resistance rates were 71% to amoxicillin, 64% to clavulanic acid-amoxicillin and 15% to third generation cephalosporin. Most S. aureus isolates (85%) were sensitive to methicillin. Non-fermenting Gram-negative bacilli resistance rates were 68.5% to carboxypenicillin and 56% to fluoroquinolones. CONCLUSION: These findings indicate that SSI can be treated using third generation cephalosporin-aminosides in combination with oral fluoroquinolones.


Assuntos
Bactérias/isolamento & purificação , Infecção da Ferida Cirúrgica/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Burkina Faso , Criança , Pré-Escolar , Estudos Transversais , Feminino , Hospitais , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
11.
Bull Soc Pathol Exot ; 104(4): 284-7, 2011 Oct.
Artigo em Francês | MEDLINE | ID: mdl-21287372

RESUMO

UNLABELLED: The purpose of this study was to assess the application of national guidelines on the diagnosis and treatment of severe malaria in adults in Burkina Faso. We conducted a retrospective study of medical records of the patients admitted for severe malaria in the emergency service of the regional hospital of Fada N'Gourma in the east of Burkina Faso in the year 2008; 165 records were chosen by simple random sampling. We reported all the severe clinical and biological signs of malaria and its treatment. We compared them with the criteria of severe malaria diagnosis and its treatment according to the national guidelines. The mean age of patients was 38 ± 16.2 and male to female ratio was 0.96. The most frequent period of admissions was between July and October. Fever or recent past of fever was reported in 142 cases (86.1%). According to the two criteria for severe malaria (means existing of at least one of the severe signs associated and positive parasitemia with Falciparum plasmodium), we noted that only 74 cases had at least one of the severe signs (44.8%) which were: anemia (51.3%), cardiovascular collapse (7.9%), jaundice (7.3%), dyspnea (6.7%), impairment of consciousness (5.5%), prostration (5.5%), renal failure (4.8%), hypoglycemia (2.4%), hemorrhage (1.8%) and seizures (1.2%). The biological signs were not systematically searched. Parasitological exam was conducted in 91 cases (55.1%). Only 18 were positive (19.8%). In total, only 18 cases (10.9%) met the guidelines' criteria of severe malaria. The other cases were over-diagnosed; note that the investigation was not complete for 74 of these cases (50.3%). Among the 165 cases, the treatment was appropriate in 146 (88.5%) and 19 cases (11.5%) didn't receive treatment for malaria. CONCLUSION: So much we observed an over diagnosis of severe malaria in adults that we can suggest an under diagnosis of the disease due to the lack of biological investigations.


Assuntos
Malária Falciparum/diagnóstico , Malária Falciparum/tratamento farmacológico , Adulto , Antimaláricos/uso terapêutico , Burkina Faso , Feminino , Febre , Humanos , Malária Falciparum/parasitologia , Masculino , Pessoa de Meia-Idade , Parasitemia , Plasmodium falciparum , Quinina/uso terapêutico
12.
Bull Soc Pathol Exot ; 104(1): 68-73, 2011 Feb.
Artigo em Francês | MEDLINE | ID: mdl-21193981

RESUMO

Meningococcal meningitis remains a periodical threat in the African meningitis belt. The countries concerned, such as Burkina Faso, provided guidelines for its surveillance, diagnosis, treatment, and prevention during outbreaks. The objective of this study is to assess the quality of the surveillance system and case management during an outbreak in Fada N'Gourma district. A retrospective study of the meningitis outbreak in 2007 was conducted by literature review and interviews of health caretakers across 27 health centers (CSPS) and three units in the regional hospital in the district.We reported all data available about surveillance and case management, and then we compared it with the guidelines of the Ministry of Health. The case definition and notification forms were available in all centers and units. During the outbreak, 861 cases were recorded, but only 89% was notified at the upper level and 87% of notification forms were available. The age is marked on all the forms, while the interval between the onset of symptoms and consultation is noted only in 90.7%. The forms were distributed weekly at the district level. Cerebrospinal fluid (CSF) Gram coloration was performed for a limited number of cases (150/349 samples, 42.9%); it showed Gram-negative diplococcus in 86%. Culture was performed for a limited number of patients (7 cases). According to the results of a central level laboratory study, the outbreak was due to Group A Neisseria meningitidis. The case management guidelines were available in all the centers and units which were supervised during the outbreak. Anti-biotherapy was appropriate in 93.6% of the cases. A shortage of antibiotics (free prepositioning) was observed in 7 centers (23.3%). The mortality rate was 3.5%. This assessment shows an under-notification of cases, despite the existence of a surveillance system and supervision, a weak laboratory contribution in germ identification, appropriate case management, and shortage of antibiotics during the outbreak. Management of a meningitis outbreak may become more efficient by improving the notification, the laboratory's capabilities, and the availability of drugs.


Assuntos
Surtos de Doenças , Meningite Meningocócica/epidemiologia , Vigilância da População , Fatores Etários , Antibacterianos/provisão & distribuição , Antibacterianos/uso terapêutico , Anticonvulsivantes/uso terapêutico , Antipiréticos/uso terapêutico , Técnicas Bacteriológicas/estatística & dados numéricos , Burkina Faso/epidemiologia , Gerenciamento Clínico , Notificação de Doenças/normas , Notificação de Doenças/estatística & dados numéricos , Uso de Medicamentos , Controle de Formulários e Registros , Fidelidade a Diretrizes , Instalações de Saúde/estatística & dados numéricos , Hospitais Públicos/estatística & dados numéricos , Humanos , Prontuários Médicos , Meningite Meningocócica/líquido cefalorraquidiano , Meningite Meningocócica/tratamento farmacológico , Guias de Prática Clínica como Assunto , Estudos Retrospectivos
13.
Mali Med ; 26(4): 55-9, 2011.
Artigo em Francês | MEDLINE | ID: mdl-22766171

RESUMO

In Burkina Faso, monitoring of acute meningitis epidemics is difficult to be implemented by routine bacteriology. The Polymerase Chain Reaction (PCR) that freed us from some constraints should allow better documentation of acute bacterial meningitis epidemics [7]. It was about a transverse study with descriptive aim along one year. The recruitment of cases was exhaustive and sample was representative of population at risk. Among the suspected ABM, 87 cases were confirmed by all biological diagnosis methods. Among these 87 confirmed cases, 82.7% were PCR positive. The culture was performed in 82 cases and 54.5% were positive. A statistical difference was observed. The sex ratio was 1.4:1, the average age of patients was 11± 4, 6 years [0-59], 26.4% of cases were observed on less than one year. Meningococcal meningitis ranked first with a rate of 46%. The peak incidence was observed during week 13-2003 or 15, 3%. The weeks pre and per epidemic (week11-week 13) PCR had the highest rate of confirmation for Neisseria meningitidis 78, 8%. The W135 was the most represented or 91%. PCR is thus an excellent alert tool for acute meningitis epidemics.


Assuntos
Meningites Bacterianas/epidemiologia , Meningites Bacterianas/microbiologia , Adolescente , Adulto , Burkina Faso/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Surtos de Doenças , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Vigilância da População , Adulto Jovem
15.
Lett Appl Microbiol ; 41(6): 470-5, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16305672

RESUMO

AIMS: Legionella pneumophila is a contaminant of man-made water systems, including potable water, cooling towers, water systems of large buildings, etc. It is the most common causative agent of legionellosis, a respiratory infection, which may give rise to restricted outbreaks. To survey environmental water samples from hospitals and private habitations in Bologna, we developed a species-specific nested and a TaqMan real-time PCR for the detection of L. pneumophila. We compared the two assays and both to cultural isolation. METHODS AND RESULTS: The targeted gene was macrophage infectivity potentiator (mip), conserved in L. pneumophila, and divergent in other legionellae. One assay was based on a nested PCR and the other on a TaqMan real-time PCR protocol. Their sensitivities were 14 % or 5% higher than that of cultural isolation respectively. The detection limits were 1-2 genome equivalents per 50-microl reaction. Specificity was assessed using DNA from nine target and 20 nontarget organisms. CONCLUSIONS: When applied to water samples, both assays detected L. pneumophila at 80% or higher frequency. SIGNIFICANCE AND IMPACT OF THE STUDY: The species-specific molecular diagnosis of L. pneumophila by means of nested PCR does not require a specific instrumentation, exhibits a high sensitivity, and is advantageous over the cultural isolation and real-time PCR detection. It allows to quickly monitor water samples for the risk assessment of environmental contaminations.


Assuntos
DNA Bacteriano/análise , Legionella pneumophila/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Microbiologia da Água , Abastecimento de Água , Legionella pneumophila/genética , Sensibilidade e Especificidade
16.
Eur J Pharm Sci ; 14(3): 197-200, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11576823

RESUMO

Transdermal therapy receives increasing attention as an attractive alternative to traditional drug delivery. Unfortunately the exact algorithm of transdermal permeation that could guide medicinal chemists towards delivery optimization at an early stage of the drug design process still remains to be decoded. This paper discusses some major hurdles on the way to full understanding of Quantitative Structure-Activity Relationships (QSAR) of skin permeation. From the statistical perspective, a recently published combined data set is found to be inappropriate with respect to the distribution of major molecular descriptors, and therefore should be approached cautiously as a source for QSAR model training and in modelling of occupational and environmental skin exposures.


Assuntos
Portadores de Fármacos , Fenômenos Fisiológicos da Pele , Permeabilidade da Membrana Celular , Portadores de Fármacos/química , Humanos , Técnicas In Vitro , Modelos Estatísticos , Permeabilidade , Absorção Cutânea , Relação Estrutura-Atividade
18.
Drug Des Discov ; 17(1): 34-50, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10928448

RESUMO

A series of 4-(N,N-diarylamino)piperidines are synthesized and evaluated for high affinity binding and selectivity to the delta-opioid receptor using a combination of 3D-QSAR and molecular docking techniques. Based on experimental ligand binding data to both mu- and delta- opioid receptors, CoMFA fields are generated and applied to identify potential ligand modifications to further optimize lead compounds. Molecular docking experiments to the delta-receptor are also reported that explain the CoMFA trends predicted as well as the differential binding and selectivity displayed by various compounds in the series. An analysis of the binding site model proposed indicates the piperidines take advantage of 3 key sites or binding domains within the delta-receptor. These include an aromatic pocket (approximately 1/3 into the receptor cavity), an aspartic acid residue (which serves as a docking point for the piperidinyl cationic amine) and a hydrophobic pocket at the extracellular boundary of the receptor cavity. Links are established between ligand modification and amino acid composition at these sites in mu and delta, providing new insight to the structural basis to binding and selectivity across the series and for related piperazines (i.e. SNC80 and BW373U86). Results are also presented that indicate delta- and mu-selectivity may be determined at alternate sites, suggesting opioid receptors may display multiple binding domains. The model is further supported by comparisons with opiate binding modes and site directed mutagenesis studies and is finally applied to suggest new strategies in ligand design.


Assuntos
Piperidinas/síntese química , Relação Quantitativa Estrutura-Atividade , Receptores Opioides delta/metabolismo , Sequência de Aminoácidos , Animais , Ligantes , Masculino , Dados de Sequência Molecular , Piperidinas/metabolismo , Ratos , Ratos Wistar , Receptores Opioides delta/química , Receptores Opioides mu/química , Receptores Opioides mu/metabolismo
19.
Protein Eng ; 11(12): 1163-79, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9930666

RESUMO

The opioid receptor like (ORL1) receptor is a G-protein coupled receptor superfamily, and regulates a plethora of neurophysiological functions. The structural requirements for receptor activation by its endogenous agonist, nociceptin (FGGFTGARKSARKLANQ), differ markedly from those of the kappa-opioid receptor and its putative peptide agonist, dynorphin A (YGGFLRRIRPKLKWDNQ). In order to probe the functional architecture of the ORL1 receptor, a molecular model of the receptor has been built, including the TM domain and the extra- and intracellular loops. An extended binding site able to accommodate nociceptin-(1-13), the shortest fully active analogue of nociceptin, has been characterized. The N-terminal FGGF tetrapeptide is proposed to bind in a highly conserved region, comprising two distinct hydrophobic pockets in a cavity formed by TM helices 3, 5, 6 and 7, capped by the acidic second extracellular (EL2) loop controlling access to the TM elements of the peptide binding site. The nociceptin conformation provides for the selective preference of the ORL1 receptor for nociceptin over dynorphin A, conferred by residue positions 5 and 6 (TG versus LR), and the favourable interaction of its highly positively charged core (residues 8-13) with the EL2 loop, thought to mediate receptor activation. The functional roles of the EL2 loop and the conserved N-terminal tetrapeptide opioid 'message' binding site are discussed in the context of the different structural requirements of the ORL1 and kappa-opioid receptors for activation.


Assuntos
Modelos Moleculares , Peptídeos Opioides/metabolismo , Receptores Opioides/química , Receptores Opioides/metabolismo , Sequência de Aminoácidos , Animais , Sítios de Ligação , Bovinos , Simulação por Computador , Sequência Conservada , Dinorfinas/metabolismo , Humanos , Dados de Sequência Molecular , Peptídeos Opioides/química , Conformação Proteica , Estrutura Secundária de Proteína , Receptores Opioides/agonistas , Alinhamento de Sequência , Receptor de Nociceptina , Nociceptina
20.
Epidemiol Infect ; 117(3): 429-36, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8972666

RESUMO

An outbreak of gastroenteritis occurred in Italy among 39 persons who had attended a private supper. All guests were previously healthy, young, non-pregnant adults; 18 (46%) had symptoms, mostly gastrointestinal (78%), with a short incubation period. Four were hospitalized with acute febrile gastroenteritis, two of whom had blood cultures positive for Listeria monocytogenes. No other microorganisms were recovered from the hospitalized patients' specimens. Epidemiological investigation identified rice salad as the most likely vehicle of the food-borne outbreak. L. monocytogenes was isolated from three leftover foods, the kitchen freezer and blender. Isolates from the patients, the foods and the freezer were indistinguishable: serotype 1/2b, same phage type and multilocus enzyme electrophoretic type. Eight (36%) of 22 guests tested were found to have antibodies against L. monocytogenes, compared with none of 11 controls from the general population. This point source outbreak was probably caused by infection with L. monocytogenes. Unusual features included the high attack rate among immunocompetent adults and the predominance of gastrointestinal symptoms.


Assuntos
Surtos de Doenças , Doenças Transmitidas por Alimentos/epidemiologia , Doenças Transmitidas por Alimentos/microbiologia , Gastroenterite/epidemiologia , Gastroenterite/microbiologia , Listeria monocytogenes/isolamento & purificação , Adolescente , Adulto , Métodos Epidemiológicos , Feminino , Microbiologia de Alimentos , Doenças Transmitidas por Alimentos/fisiopatologia , Gastroenterite/fisiopatologia , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Sorotipagem
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