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The aim of this study was to synthesize and investigate the in vitro antifungal properties of 23 cinnamyl Schiff bases. In addition, cytotoxic effects of such cinnamyl Schiff bases against human lung, kidney or red blood cells were also checked. The compounds were synthesized in a single-step, 2 min of reaction under microwave irradiation produced up to 97% yield. Six of the 23 cinnamyl Schiff bases possessed antifungal activities against strains of Candida, Aspergillus, Fonsecaea and, particularly, Cryptococcus species. Indeed, cinnamyl Schiff bases 1 and 23 exhibited minimum inhibitory concentration (MIC) values more than twofold lower than fluconazole (FCZ) against all the Cryptococcus neoformans strains (MIC = 1·33, 1·4 and 5·2 µg ml-1 , respectively) and Cryptococcus gattii strains (MIC = 5·3, 2·8 and 9·2 µg ml-1 , respectively) (12 strains of each species) while cinnamyl Schiff base 11 was as potent as FCZ against all strains from both Cryptococcus species. No significant cytotoxic effects were observed for Schiff bases against human lung, kidney or red blood cells, all presenting selective indexes higher than 10. In conclusion, this study revealed cinnamyl Schiff bases, especially 1 and 23, as new lead anticryptococcal agents for the discovery of novel antifungal drugs. SIGNIFICANCE AND IMPACT OF THE STUDY: The occurrence and severity of fungal infections have increased in recent decades due to resistance to available antifungal drugs and the appearance of new emerging pathogens. Thus, the search for new antifungal agents is mandatory. From a series of 23 cinnamyl Schiff bases, two compounds (1 and 23) were interrogated as new anticryptococcal agents without significant cytotoxicity against human lung, kidney or red blood cells. In turns, these new Schiff bases are lead compounds for the discovery of novel antifungal drugs.
Assuntos
Antifúngicos/farmacologia , Micoses/tratamento farmacológico , Bases de Schiff/farmacologia , Antifúngicos/síntese química , Antineoplásicos/farmacologia , Aspergillus/efeitos dos fármacos , Candida/efeitos dos fármacos , Cryptococcus gattii/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacos , Fluconazol/farmacologia , Fonsecaea/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Bases de Schiff/síntese químicaRESUMO
BACKGROUND: An association has been found between lower urinary tract dysfunction (LUTD) and emotional and behavioral problems, particularly in cases of urinary incontinence. Other associated symptoms and the coexistence of functional constipation require further investigation. OBJECTIVE: To assess whether emotional and behavioral problems are more common in children and adolescents with LUTD. STUDY DESIGN: A multicenter, cross-sectional, population-based study conducted in public places. Parents answered questions on urinary and psychological symptoms in their children aged 5-14 years. Children/adolescents with neurological problems or anatomical urinary tract abnormalities were excluded. The Dysfunctional Voiding Scoring System was used for assessing urinary symptoms, the Rome III Diagnostic Criteria for evaluating bowel symptoms, and the Strengths and Difficulties Questionnaire (SDQ) for evaluating emotional and behavioral problems. RESULTS: Of the 806 children/adolescents included, 53% were female. The mean age was 9.1 ± 2.7 years. The prevalence of LUTD was 16.4%. Overall, 26.2% had abnormal scores in the overall SDQ scale, 29.2% in the emotional problems subscale, and 30% in the conduct problems subscale. Of the children with LUTD, 40.5% screened positive for emotional/behavioral problems, with a significant association being found for the overall SDQ scale (P < 0.001) and for the emotional problems (P < 0.001), conduct problems (P < 0.001), and hyperactivity (P = 0.037) subscales. Urinary urgency, urinary incontinence, and voiding postponement were significantly associated with a greater prevalence of abnormalities in the overall SDQ score (P = 0.05; P = 0.004, and P = 0.012, respectively). Bladder and bowel dysfunction was an aggravator of emotional and behavioral problems, with more intense symptoms, both in the overall SDQ scale and in the subscales. In the multivariate analysis, the factors independently associated with the presence of emotional and behavioral problems were LUTD (odds ratio [OR] = 1.91), constipation (OR = 1.7), studying in a government-funded school (OR = 2.2), and poor education of the head of the family (OR = 1.9). CONCLUSIONS: Children and adolescents with LUTD have more emotional and behavioral problems, with bladder and bowel dysfunction being an aggravating factor for this association.
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Constipação Intestinal/psicologia , Sintomas do Trato Urinário Inferior/psicologia , Comportamento Problema/psicologia , Inquéritos e Questionários , Incontinência Urinária/psicologia , Adolescente , Fatores Etários , Brasil , Criança , Constipação Intestinal/diagnóstico , Constipação Intestinal/epidemiologia , Estudos Transversais , Feminino , Humanos , Sintomas do Trato Urinário Inferior/diagnóstico , Sintomas do Trato Urinário Inferior/epidemiologia , Masculino , Testes Neuropsicológicos , Prevalência , Prognóstico , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Estatísticas não Paramétricas , Incontinência Urinária/diagnóstico , Incontinência Urinária/epidemiologiaRESUMO
The aim of this study is to verify the effects of whole-body vibration (WBV) training on the muscle strength of children and adolescents with Down syndrome. We searched MEDLINE, Cochrane, SciELO, Lilacs and PUBMED databases and included manual searches to identify randomised controlled trials to investigate the effects of WBV on the structure and body function of children and adolescents with Down syndrome. Two reviewers independently selected the studies and performed statistical analysis. In total, five studies with 171 patients that compared WBV with exercise and/or control were included. Two studies demonstrated a significant difference between the muscle strength of children and adolescents with Down syndrome who received WBV training and that of those who did not receive the intervention. The studies included in this systematic review showed that WBV training has positive effects on bone mineral density (BMD), body composition and balance. Results of this study showed that WBV training improves muscle strength, BMD, body composition and balance of children and adolescents with Down syndrome, and a more in-depth analysis of its effects on other variables in this population is required, as well as of parameters to be used.
Assuntos
Densidade Óssea/fisiologia , Síndrome de Down/reabilitação , Força Muscular/fisiologia , Vibração/uso terapêutico , Viés , Composição Corporal/fisiologia , Síndrome de Down/fisiopatologia , Humanos , Equilíbrio Postural/fisiologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
UNLABELLED: Cryptococcosis, a fungal infection that affects both immunocompromised and immunocompetent individuals, contributes to increasing indices of mortality and morbidity. The development of resistance by Cryptococcus spp., the limited number of commercial antifungal drugs and the various side effects of these drugs cause the treatment of cryptococcosis to be a challenge. The in vitro anticryptococcal activity of nine hydroxyaldimines was evaluated against 24 strains of Cryptococcus spp. Antifungal susceptibility was evaluated using a broth microdilution assay following the Clinical and Laboratory Standards Institute guidelines, using fluconazole as a positive control. Parameters such as the minimum inhibitory concentration and the minimum fungicidal concentration (MIC and MFC, respectively) were also determined. Antiproliferative activity on the normal cell line VERO was assessed 48 h post-compound exposure to determine the selectivity index (SI) of the hydroxyaldimines and fluconazole. All hydroxyaldimines were active against Cryptococcus spp. strains. Compounds 3A9 and 3B7 were the most potent against the Cryptococcus gattii and Cryptococcus neoformans strains. Selectivity indices also revealed that 3B10, 3C3, 3D3 and 3D9 are good candidates for in vivo studies. The in vitro anticryptococcal activity of hydroxyaldimines against various strains of C. gattii and C. neoformans indicates the potential of this class of molecules as lead compound for the development of selective and efficient anticryptococcal agents. SIGNIFICANCE AND IMPACT OF THE STUDY: The effectiveness of hydroxyaldimines for inhibition of Cryptococcus spp. growth and their low toxicity against healthy monkey kidney epithelial cells makes them promising lead compounds for the design of new anticryptococcal agents.
Assuntos
Antifúngicos/farmacologia , Cryptococcus gattii/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacos , Iminas/farmacologia , Animais , Chlorocebus aethiops , Fluconazol/farmacologia , Iminas/síntese química , Iminas/química , Testes de Sensibilidade Microbiana , Células VeroRESUMO
The aim of the present study was to evaluate the effect of aqueous extract of chinaberry (Melia azedarach) in the control of Plasmopara viticola. For the germination test of sporangia of the oomycete, concentrations of 0, 5, 10, 15, 20 and 25 mL L-1 of aqueous extract of chinaberry (EC) were used, as well as treatments with mancozeb and bordeaux mixture. The experiment in the greenhouse and field involved concentrations of 0, 30, 40 and 50 mL L-1 of EC (1:10 w/v) and a treatment with bordeaux mixture (1:1:100 ). In the second experiment in the field the treatments were: 0, 10, 20, 30, 40 and 50 mL L-1 of EC with an added 2.5 mL L-1 of vegetable oil, the bordeaux mixture and an absolute control. In the germination test, there was highest inhibition of P. viticola at 2 hours after incubation at 20º C, for the 20 and 25 mL L-1 concentrations of the EC, with a reduction of 66.5 and 62.0%, respectively. In the greenhouse conditions, the EC at a concentration of 40 and 50 mL L-1 showed a reduction of 70.0% and 86.0% of the disease, respectively, while the same concentrations in the first cycle of the field experiment showed a decrease of 34.0% and 31.0%, respectively. However, in the second cycle, the use of vegetable oil as an adjunct masked the effect of the EC, and the isolated application of vegetable oil decreased the area under the disease progress curve (ADPC) by 76.3%, similar to results obtained with all concentrations of EC and with the bordeaux mixture.
Este trabalho teve como objetivo avaliar o efeito do extrato aquoso de cinamomo (Melia azederach) no controle de Plasmopara viticola. Para o teste de germinação de esporângios do oomiceto foram utilizadas as concentrações de 0, 5, 10, 15, 20 e 25 mL L-1 de extrato aquoso de cinamomo (EC), além dos tratamentos com mancozebe e calda bordalesa. No experimento em casa de vegetação e a campo foram estudadas as concentrações de 0, 30, 40 e 50 mL L-1 de EC (1:10 p/v), além de um tratamento com calda bordalesa (1:1:100). No segundo experimento, em condições de campo, os tratamentos foram: 0, 10, 20, 30, 40 e 50 mL L-1 de EC, acrescidos de óleo vegetal a 2,5 mL L-1, calda bordalesa e testemunha absoluta. No teste de germinação, verificou-se maior inibição de P. viticola às 2 horas após a incubação, para as concentrações de 20 e 25 mL L-1 de EC com uma redução de 66,5 e 62,0%, respectivamente. Em condições de casa de vegetação o EC a 40 e 50 mL L-¹ apresentou reduções de 70,0% e 86,0% da doença, respectivamente. Enquanto que as mesmas concentrações, no primeiro ciclo do experimento a campo, apresentaram um decréscimo de 34,0% e 31,0%, respectivamente. No segundo ciclo, o uso de óleo vegetal como adjuvante mascarou o efeito do EC e a aplicação isolada de óleo vegetal reduziu em 76,3% a área abaixo da curva de progresso da doença (AACPD), similar aos resultados obtidos com todas as concentrações de EC e com a calda bordalesa.
RESUMO
BACKGROUND: Since July 2006, the Model for End-stage Liver Disease (MELD) score has served as the national basis for allocation of donor livers for transplantation in Brazil. Patients with higher MELD scores receive greater priority for allocation regardless of the time on the waiting list. PURPOSE: To investigate the impact of MELD score implementation on the survival of waiting list patients. METHODS: A retrospective study of patients registered at the national Organ Procurement Organization (OPO) for the liver transplantation waiting list between January 2004 and June 2006 (pre-MELD) and between July 2006 and December 2008 (post-MELD). RESULTS: We included listed patients awaiting liver transplantation in the pre-MELD era (n = 250, 48.4%) and in the post-MELD era (n = 266, 51.6%). The times awaiting transplant prior to and after the MELD system were 487.2 +/- 384.8 days and 183.9 +/- 157.2 days, respectively. Prior to the MELD score, waiting list survivals were greater when compared to rates in the current system. Early posttransplant patient survival rates were significantly reduced in the post-MELD era (83.4%) compared to the period before MELD implementation (93.2%). CONCLUSIONS: MELD score provides a transparent, objective system to drive allocation policy; however, it presents several important limitations. Constant need of changes and reevaluation are needed as an evolutionary process. Future changes in the present system may be addressed by adjusting the MELD system.
Assuntos
Falência Hepática/cirurgia , Transplante de Fígado/estatística & dados numéricos , Listas de Espera , Adolescente , Adulto , Idoso , Cadáver , Criança , Pré-Escolar , Feminino , Humanos , Falência Hepática/mortalidade , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Alocação de Recursos/métodos , Estudos Retrospectivos , Taxa de Sobrevida , Sobreviventes , Doadores de Tecidos/estatística & dados numéricosRESUMO
The purpose of this work was to study the morphology and morphometry of the mental foramen (MF), as well as to evaluate its morphological configuration; in addition to taking measures of its localization using as a parameter the distances of the foramen to the inferior border of the mandible and at the alveolar ridge. 80 dry mandibles were analyzed using the test of Qui-square and T test, with 5 percent of significance. Its average distance, on the right side, at the inferior edge of the mandible (IEM) was of 12.96( +/-1 .57) mm and of the alveolar ridge (AR) was of 12.82(+/-3.4) mm. On the left side it was found distant of IEM 12.96(+/-1.32) mm and of the AR 12.82(+/- 3.22)mm. The largest horizontal diameter found was of 3.32 (+/- 0.91) mm to the right and 3.25 (+/- 0.86) mm to the left side while the largest vertical diameter was of 2.38 (+/- 0.63) mm on the right and of 2.39 (+/- 0.58) mm on the left side. It was predominantly found in the oval form, on the right side, of which 98.3 percent presented as a larger diameter the horizontal (type I). On the left side, all the oval foramens were classified as of type I. 76 (95 percent) appeared single on both sides. As to the localization related to the mandibular dentition, it was localized in similar statistic proportions between the 1st and 2nd premolars and above the 2nd premolar, in 45.17 percent of the mandibles, on the right side. On the left side it was predominantly found between the 1st and 2nd premolars 48.48 percent of the mandibles. The study of the MF is of vital importance to the acupuncture practice, as well as to modern surgical procedures, like anesthesia, requiring a detailed and precise study of the morphology and morphometry of the area.
El objetivo de este trabajo fue estudiar la morfología y morfometría del foramen mentoniano (FM), así como evaluar su configuración morfológica; tomar las medidas de su localization usando como parámetro la distancia del foramen hacia el borde inferior de la mandíbula y el reborde alveolar. 80 mandíbulas secas se analizaron mediante la prueba de Chi-cuadrado y prueba t, con un 5 por ciento de significancia. Su distancia media, en el lado derecho, hasta el borde inferior de la mandíbula (BIM) fue de 12,96 (+/- 1,57) mm y del reborde alveolar (RA) fue de 12,82 (+/- 3,4) mm. En el lado izquierdo se encuentro una distancia del BIM de 12,96 (+/- 1,32) mm y del RA de 12,82 (+/- 3,22) mm. El mayor diámetro horizontal encontrado fue de 3,32 (+/- 0,91) mm a la derecha y 3,25 (+/- 0,86) mm a la izquierda, mientras que el mayor diámetro vertical fue de 2,38 (+/- 0,63) mm a la derecha y de 2,39 (+/- 0,58) mm en el lado izquierdo. Se encuentra principalmente en forma oval en el lado derecho, de los cuales 98,3 por ciento presenta un diámetro mayor horizontal (tipo I). En el lado izquierdo, todos los forámenes ovales fueron clasificados como de tipo I. 76 (95 por ciento) aparecieron solamente en ambos lados. En cuanto a la localization en relación con la dentición mandibular, fue localizado en la misma proporción estadística entre el 1er y 2d° premolar y por encima del 2ª premolar en el 45,17 por ciento de las mandíbulas en el lado derecho. En el lado izquierdo se encuentran principalmente entre los l ros y 2ros premolares en el 48,48 por ciento de las mandíbulas. El estudio del FM, es de vital importancia para la práctica de la acupuntura, así como para los modernos procedimientos quirúrgicos, como la anestesia, que requieren un estudio detallado y preciso de la morfología y morfometría de la zona.
Assuntos
Humanos , Adulto , Mandíbula/anatomia & histologia , Mandíbula/irrigação sanguínea , Mandíbula/ultraestrutura , Queixo/anatomia & histologia , Pontos de Acupuntura , Dentição , Desenvolvimento Maxilofacial/genéticaRESUMO
BACKGROUND AND OBJECTIVE: Interactions between oral bacteria and gingival epithelial cells play an important role in the pathogenesis of periodontal diseases. This study used in situ hybridization with 16 rRNA probes and confocal microscopy to detect the periodontal pathogens Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Tannerella forsythia, and Treponema denticola within epithelial cells from periodontal pockets, gingival crevice, and buccal mucosa collected from subjects with chronic periodontitis (n = 14) and good periodontal health (n = 8). MATERIAL AND METHODS: Each green fluorescent species-specific and universal probe was hybridized with all 58 epithelial samples from the 22 patients. The samples were observed by confocal microscopy to confirm the intracellular localization of oral species of bacteria. The mean frequency of detection and number of intracellular bacteria per epithelial cell were computed for each sample. RESULTS: The frequency of cells with internalized bacteria was higher in samples from the gingival crevice than in samples from the oral mucosa. Epithelial cells from all subjects harbored intracellular bacteria; however, patients with periodontitis presented significantly higher counts of bacteria per cell than periodontally healthy individuals (p < 0.05). Periodontal pathogens showed a trend to be detected in higher numbers in epithelial cells from periodontitis patients. In particular, T. forsythia and T. denticola were significantly more prevalent in periodontal pocket cells than healthy sulci and buccal cell samples in the periodontitis group (p < 0.05). CONCLUSION: Those findings indicate that crevicular and buccal cells present internalized bacteria, regardless of periodontal status. However, higher bacterial loads are detected in cells from subjects with periodontitis.
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Células Epiteliais/microbiologia , Gengiva/citologia , Mucosa Bucal/microbiologia , Periodontite/microbiologia , Adulto , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Doença Crônica , Feminino , Genes de RNAr , Gengiva/microbiologia , Humanos , Hibridização in Situ Fluorescente/métodos , Masculino , Microscopia Confocal/métodos , Bolsa Periodontal/microbiologiaRESUMO
It has been suggested that the measurement of metronidazole clearance is a sensitive method for evaluating liver function. The aim of this study was to evaluate the usefulness of plasma hydroxy-metronidazole/metronidazole ratios as indicators of dynamic liver function to detect changes resulting from the various forms of chronic hepatitis C virus (HCV) infection. A total of 139 individuals were studied: 14 healthy volunteers, 22 healthy, asymptomatic, consecutive anti-HCV-positive HCV-RNA negative subjects, 81 patients with chronic hepatitis C (49 with moderate/severe chronic hepatitis and 34 with mild hepatitis), and 20 patients with cirrhosis of the liver. HCV status was determined by the polymerase chain reaction. Plasma concentrations of metronidazole and its hydroxy-metabolite were measured by reverse-phase high-performance liquid chromatography with ultraviolet detection in a blood sample collected 10 min after the end of a metronidazole infusion. Anti-HCV-positive HCV-RNA-negative individuals demonstrated a significantly reduced capacity to metabolize intravenously infused metronidazole compared to healthy individuals (0.0478 +/- 0.0044 vs 0.0742 +/- 0.0232). Liver cirrhosis patients also had a reduced plasma hydroxy-metronidazole/metronidazole ratio when compared to the other groups of anti-HCV-positive individuals (0.0300 +/- 0.0032 vs 0.0438 +/- 0.0027 (moderate/severe chronic hepatitis) vs 0.0455 +/- 0.0026 (mild chronic hepatitis) and vs 0.0478 +/- 0.0044 (anti-HCV-positive, HCV-RNA-negative individuals)). These results suggest an impairment of the metronidazole metabolizing system induced by HCV infection that lasts after viral clearance. In those patients with chronic hepatitis C, this impairment is paralleled by progression of the disease to liver cirrhosis.
Assuntos
Anti-Infecciosos , Hepacivirus/genética , Hepatite C Crônica/complicações , Cirrose Hepática/diagnóstico , Metronidazol , Adulto , Anti-Infecciosos/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Feminino , Genótipo , Humanos , Cirrose Hepática/etiologia , Testes de Função Hepática , Masculino , Metronidazol/análogos & derivados , Metronidazol/sangue , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Índice de Gravidade de Doença , Carga ViralRESUMO
It is well known that, subsequent to cardiopulmonary bypass, and particularly in children, an inflammatory response within the body can often result in a characteristic syndrome. Recently, it has been suggested that this phenomenon is due to a systemic inflammatory response, with significant involvement of cytokines. With this in mind, we investigated the behavior of tumour necrosis factor-alpha and interleukin-6 during the operative and in the immediate postoperative period in a group of children submitted to open heart surgery. We investigated any possible relation between the levels of these cytokines in the serum and the length of cardiopulmonary bypass, with the serum levels of lactate, and with the extent of use of inotropic drugs in postoperative period. The cytokines were measured in samples withdrawn after induction of anesthesia, after 10 minutes of cardiopulmonary bypass, after re-establishment of circulation, and then 2 and 24 hours after the end of cardiopulmonary bypass. The levels of tumour necrosis factor-alpha and interleukin-6 increased between the beginning and at two hours of the end of cardiopulmonary bypass. There was no correlation between the levels of these cytokines in the serum and the length of cardiopulmonary bypass, although there was a positive relation between levels of interleukin-6 and lactate in samples withdrawn at two hours of the end of bypass, and the measured levels of the cytokines correlated with the extent of inotropic drugs employed in the postoperative period.
Assuntos
Ponte Cardiopulmonar , Cardiopatias Congênitas/imunologia , Cardiopatias Congênitas/cirurgia , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Período Intraoperatório , Masculino , Período Pós-Operatório , Estudos Prospectivos , Fatores de TempoRESUMO
INTRODUCTION: Morbidity due to motor vehicle accidents was analysed in a descriptive study based on reports of hospitals with the objective to characterize their victims, types of injuries, and the health care provided. METHODS: The study was carried out in two municipal hospitals of Rio de Janeiro, Brazil. Motor vehicle accidents were defined as a run over, a collision, and "other traffic accidents". Data was collected from cases seen in May (Hospital 1) and June (Hospital 2) of 1996 by 7 teams that alternated in shifts of 12 hours, covering the collection 24 hours per day. The events were classified according to the victim or, when it was impossible, to the person who helped them or accompanied them to the hospital. RESULTS: In the study period, 320 cases were seen in Hospital 1 and 290 in Hospital 2. Most of the victims were men (69.3%) in both of hospitals and the most affected group was young adults between 20 to 39 years (60.5% in Hospital 1 and 47.5% in Hospital 2). Of all 610 cases, the main cause of injury was being run over (49.3%), followed by collisions (35.6%), and "other traffic accidents" (15.1%). CONCLUSIONS: The analysis of the cases distributions and the type of care required corroborates with the need of a better organization of hospital care teams, more completeness of hospital reports and emphasis on some aspects in prevention campaigns.
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Acidentes de Trânsito/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Acidentes de Trânsito/mortalidade , Acidentes de Trânsito/prevenção & controle , Adulto , Brasil/epidemiologia , Feminino , Humanos , Masculino , MorbidadeRESUMO
BACKGROUND: The effects of Helicobacter pylori infection associated with inhibition of gastric acid secretion on the distribution of medications used for H. pylori eradication are poorly understood. The aim of this study was to investigate the effects of a 7-day administration of 20 mg omeprazole on the transfer of metronidazole from plasma to the gastric juice of individuals with and without H. pylori infection. METHODS: Fourteen H. pylori-positive and 14 H. pylori-negative male volunteers were enrolled in a study with an open, randomized, two-period crossover design with a 21-day washout period between phases. Plasma, salivary, and gastric juice concentrations of metronidazole in subjects with and without omeprazole treatment were measured with reversed-phase high-performance liquid chromatography/liquid chromatography. RESULTS: Metronidazole peak concentration (Cmax) was similar in plasma and saliva and was approximately threefold higher in gastric juice in all groups. Omeprazole treatment increased gastric pH and did not affect metronidazole Cmax or the time required for this to be reached (tmax) in plasma, saliva, or gastric juice. However, omeprazole significantly reduced metronidazole transfer from plasma to gastric juice in H. pylori-positive but not H. pylori-negative subjects, as shown by statistical analysis of AUC(0-2 h). CONCLUSION: Short-term treatment with omeprazole in H. pylori- positive volunteers reduces the amount of metronidazole transferred from plasma to gastric juice. This seems to occur in a pH-independent form.
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Antibacterianos/farmacocinética , Suco Gástrico/química , Infecções por Helicobacter/metabolismo , Helicobacter pylori , Metronidazol/farmacocinética , Adulto , Antibacterianos/uso terapêutico , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Infecções por Helicobacter/tratamento farmacológico , Humanos , Masculino , Metronidazol/uso terapêutico , Saliva/químicaRESUMO
OBJECTIVES: Characterization of beta-galactosidase in leukocytes and fibroblasts of heterozygotes for GM1 type I. DESIGN AND METHODS: Leukocyte and fibroblast beta-galactosidase activity was determined fluorimetrically using 4-methylumbelliferyl-beta-D-galactoside as an artificial substrate. Optimum pH, Km, Vmax and thermostability of the enzyme at 42 degrees C were determined. RESULTS: The leukocyte and fibroblast enzyme of heterozygotes have an optimum pH of 4.0 and 4.2, respectively. In normal subjects, the optimum pH was 4.2 in both cells, according to previous studies. The Km of the enzyme of heterozygotes was determined to be 0.65 mM in leukocytes and 0.59 mM in fibroblasts. The Vmax was determined in 167.21 nmol/h/mg of protein in heterozygotes leukocytes and 541.2 nmol/h/mg of protein in heterozygotes fibroblasts compared to 291.7 and 1768.1 nmol/h/mg of protein in controls leukocytes and fibroblasts, respectively. When leukocyte and fibroblast heterozygote beta-galactosidase was preincubated at 42 degrees C, after 80 min the residual activity was determined to be 25 to 30% of the initial activity. These results are similar to the control group. CONCLUSIONS: We have found significant differences between the two groups in some investigated parameters. Both fibroblasts and leukocytes showed a virtually similar level of reliability as source of enzyme for the detection of heterozygotes.
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Gangliosidose GM1/enzimologia , Gangliosidose GM1/genética , Leucócitos/enzimologia , beta-Galactosidase/metabolismo , Células Cultivadas , Estabilidade Enzimática , Fibroblastos/enzimologia , Gangliosidose GM1/sangue , Triagem de Portadores Genéticos , Temperatura Alta , Humanos , Cinética , Valores de Referência , Pele/enzimologia , beta-Galactosidase/sangueRESUMO
AIMS: To evaluate the usefulness of plasma hydroxy-metronidazole/metronidazole (OH-MET/MET) ratios as a dynamic liver function test in ethanol abusers with or without liver cirrhosis. METHODS: Metronidazole was administered intravenously for 20 min to healthy volunteers, and to patients with alcohol-induced, non-cirrhotic hepatopathy and liver cirrhosis. Plasma concentrations of metronidazole and hydroxy-metronidazole were measured by high performance liquid chromatography in samples collected 5, 10, 20 and 30 min after the metronidazole infusion. RESULTS: Patients with non-cirrhotic alcoholic hepatopathy had significantly elevated aminotransferase levels compared to healthy volunteers and Child A patients. Child-Pugh C patients had significantly prolonged prothrombin times when compared to healthy volunteers and patients with non-cirrhotic hepatopathy. Metronidazole metabolism, as measured by the OH-MET/MET ratio following the intravenous administration of 500 mg of the drug, was significantly impaired in all ethanol-abusing individuals, including patients with non-cirrhotic alcoholic hepatopathy. CONCLUSIONS: Metronidazole metabolism was impaired in ethanol abusers, even in the absence of liver cirrhosis, indicating that ethanol was capable of affecting liver function in the early stages of alcohol-induced liver disease.
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Consumo de Bebidas Alcoólicas/sangue , Anti-Infecciosos/sangue , Cirrose Hepática Alcoólica/fisiopatologia , Hepatopatias/fisiopatologia , Metronidazol/análogos & derivados , Metronidazol/sangue , Adolescente , Adulto , Idoso , Anti-Infecciosos/administração & dosagem , Cromatografia Líquida de Alta Pressão , Humanos , Cirrose Hepática Alcoólica/sangue , Hepatopatias/sangue , Hepatopatias/etiologia , Testes de Função Hepática , Masculino , Metronidazol/administração & dosagem , Pessoa de Meia-IdadeRESUMO
This article presents the results of an evaluation of Orientation and Serological Support Centers, or Anonymous HIV Testing Centers, in the Northeast of Brazil. Methodological triangulation was used to evaluate these health programs and services, including qualitative and quantitative methodology and pointing to the insufficiency of single-discipline reasoning to encompass phenomena in social organizations. The article also shows results from this triangulation experience, seeking to combine Social Sciences and Epidemiology. It describes the structure and dynamics of these services, analyzes the relationships, perceptions, and representations of the actors, presents a self-evaluation by the professionals, expounds on some quantitative results, and discusses some limits and problems, as well as proposals to overcome them.
Assuntos
Síndrome da Imunodeficiência Adquirida/psicologia , Avaliação de Processos em Cuidados de Saúde , Avaliação de Programas e Projetos de Saúde , Grupos de Autoajuda , Síndrome da Imunodeficiência Adquirida/diagnóstico , Brasil , Serviços de Saúde Comunitária/organização & administração , Aconselhamento , Feminino , Humanos , Masculino , Recursos HumanosRESUMO
AIMS: To evaluate plasma hydroxy-metronidazole/metronidazole ratio as a dynamic liver function test in HCV-infected individuals with/without liver disease, in the absence of liver cirrhosis. METHODS: Metronidazole was administered intravenously in healthy volunteers, asymptomatic anti-HCV-positive blood donors, and in chronic hepatitis C patients. Serology to HCV was determined by a second generation assay and confirmed by gelatin particle agglutination test using recombinant antigens C22-3 and C200. Plasma concentration of metronidazole and hydroxy-metronidazole was measured by high performance liquid chromatography in samples collected 5, 10, 20 and 30 min following the end of metronidazole infusion. RESULTS: Chronic hepatitis C patients had abnormal liver enzymes, while healthy volunteers and anti-HCV-positive blood donors had normal liver biochemistry tests. Plasma metronidazole concentration was similar in all groups studied. Plasma hydroxy-metronidazole/metronidazole ratio was significantly reduced in HCV-infected subjects, an effect observed 10 min after the end of drug infusion. CONCLUSIONS: Metronidazole clearance is impaired in anti-HCV-positive blood donors and chronic hepatitis C patients, indicating that HCV is capable of affecting liver function at early stages of the disease. The metronidazole clearance test can detect impaired liver function in HCV-infected individuals even in the absence of liver cirrhosis.
Assuntos
Hepacivirus , Hepatite C/sangue , Fígado/metabolismo , Metronidazol , Adulto , Feminino , Hepacivirus/imunologia , Hepatite C/diagnóstico , Hepatite C/imunologia , Humanos , Testes de Função Hepática , Masculino , Metronidazol/sangue , Metronidazol/metabolismo , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The addition of omeprazole to classical triple therapy for eradication of H. pylori may enhance compliance through reducing ulcer symptoms and side-effects. The aim of this study was to investigate the effects of a 5-day administration of omeprazole on metronidazole pharmacokinetics. METHODS: Fourteen healthy male volunteers were selected. The study had an open, randomized, two-period crossover design with a 21-day washout period between the phases. Plasma concentrations of metronidazole and its hydroxy-metabolite were measured by reversed-phase HPLC with ultraviolet detection. RESULTS: Administration of omeprazole did not affect the pharmacokinetic parameters of orally administered metronidazole. CONCLUSION: Our results indicate that short-term treatment with omeprazole in healthy volunteers does not alter the extent or the rate of metronidazole absorption, and does not affect metronidazole clearance.
Assuntos
Antiulcerosos/farmacologia , Antitricômonas/farmacocinética , Ácido Gástrico/metabolismo , Metronidazol/farmacocinética , Omeprazol/farmacologia , Administração Oral , Adulto , Antiulcerosos/administração & dosagem , Antiulcerosos/uso terapêutico , Antitricômonas/efeitos adversos , Antitricômonas/uso terapêutico , Disponibilidade Biológica , Estudos Cross-Over , Interações Medicamentosas , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Humanos , Masculino , Metronidazol/efeitos adversos , Metronidazol/uso terapêutico , Omeprazol/administração & dosagem , Omeprazol/uso terapêuticoRESUMO
OBJECTIVE: To evaluate whether the addition of bismuth subnitrate to a dual oral therapy regimen with omeprazole plus amoxycillin could improve Helicobacter pylori eradication. METHODS: Fifty consecutive Helicobacter pylori-positive patients were randomly enrolled to receive either (A) bismuth subnitrate (300 mg q.d.s.), omeprazole (20 mg b.d.) and amoxycillin (500 mg q.d.s.), or (B) omeprazole (20 mg b.d.) and amoxycillin (500 mg q.d.s.). Both groups (n=25 each) received the medication for 14 days. H. pylori status was reassessed 30 days after completion of the therapy in order to evaluate eradication rates. RESULTS: Six patients were lost to follow-up and therefore excluded from the study (three patients from each group). One patient from Group B withdrew from the study because of side-effects. The addition of bismuth subnitrate to omeprazole and amoxycillin significantly improved its efficacy in eradicating H. pylori, with 72% (18/25) eradication in Group A and 52% (13/25) in Group B (P=0.027). The addition of bismuth subnitrate to dual oral therapy was also capable of improving the healing of peptic ulcers when compared with dual oral therapy alone (100%, 8/8 vs. 58%, 4/7; P=0.021). CONCLUSION: Our results demonstrate that the addition of bismuth subnitrate to dual oral therapy enhances H. pylori eradication, and improves healing of peptic ulcers.
Assuntos
Amoxicilina/uso terapêutico , Antiulcerosos/uso terapêutico , Bismuto/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Omeprazol/uso terapêutico , Penicilinas/uso terapêutico , Ranitidina/análogos & derivados , Úlcera Gástrica/tratamento farmacológico , Adulto , Idoso , Amoxicilina/administração & dosagem , Amoxicilina/efeitos adversos , Antiulcerosos/administração & dosagem , Antiulcerosos/efeitos adversos , Bismuto/administração & dosagem , Bismuto/efeitos adversos , Quimioterapia Combinada , Feminino , Seguimentos , Gastroscopia , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Omeprazol/administração & dosagem , Omeprazol/efeitos adversos , Penicilinas/administração & dosagem , Penicilinas/efeitos adversos , Ranitidina/administração & dosagem , Ranitidina/efeitos adversos , Ranitidina/uso terapêutico , Úlcera Gástrica/microbiologiaRESUMO
This study presents data on general mortality and mortality from external causes (traffic accidents and homicides) among adolescents 10 to 19 years of age in Rio de Janeiro Municipality, Brazil, from 1980 to 1994. The purpose of the study was to describe and put into context mortality from external causes and to identify areas of the Municipality where the risk of these occurrences is highest. The study also sought to identify trends and seasonal patterns of this mortality and to place violence within the ambit of public health through application of the epidemiologic surveillance approach. Information on mortality was extracted from death certificates provided by the State Health Secretariat of Rio de Janeiro. A total of 20,224 death certificates were studied. The populations used as the denominators for determining rates were estimated from the censuses of 1980 and 1991. For purposes of the analysis; the Municipality was divided into eight programmatic areas, each composed of diverse neighboring districts. A time series analysis was done for traffic accidents and homicides. The results showed that external causes were the leading causes of death in the 10-19 age group, and that during the study period deaths from these causes had increased, especially among males. The results also revealed that mortality was heterogeneously distributed in areas of the Municipality that differed socioeconomically. The study points to the need for better integration of the health sector with other sectors and institutions and for a restructuring of the health system with regard to epidemiologic surveillance of violence.
Assuntos
Acidentes de Trânsito/mortalidade , Adolescente , Homicídio/estatística & dados numéricos , Violência , Brasil/epidemiologia , Causas de Morte , Criança , Atestado de Óbito , Feminino , Humanos , Masculino , Mortalidade/tendências , Neoplasias/mortalidade , Estudos Retrospectivos , Risco , Fatores Socioeconômicos , População Urbana , Violência/tendênciasRESUMO
AIMS: Since patients who regularly take NSAIDS may use sucralfate because of its cytoprotective properties, we examined the influence of this compound on the pharmacokinetics of diclofenac. METHODS: Potassium diclofenac (105 mg) was administered orally to eighteen healthy male volunteers with or without a 5-day pre-treatment with sucralfate (2000 mg twice daily). Blood samples were collected at intervals post-dose and serum concentrations of diclofenac were determined by reverse-phase h.p.l.c. RESULTS: Pre-treatment with sucralfate significantly decreased both the AUC(0,8 h) [2265 ng h ml-1 (geometric mean) (range 1815-2827) vs 1821 ng h ml-1 (1295-2562)] and the Cmax [1135 ng ml-1 (geometric mean) (range 898-1436) 701 ng ml-1 (501-981)] with no significant delay in absorption [tmax 1.0 h (median) (range 0.5-2.0) vs 1.0 h (0.5-4.0)]. CONCLUSIONS: The short-term treatment of healthy male volunteers with sucralfate decreases potassium diclofenac bioavailability. These findings suggest that either an appropriate increase in the diclofenac intake or the use of another gastric mucosa protector must be adopted.