RESUMO
OBJECTIVES: High-risk human papillomavirus (HR-HPV) is an important risk factor for esophageal cancer. Macrophages constitute a crucial immune medium for regulating HPV-related tumors; however, the specific regulatory mechanisms remain unknown. Therefore, the purpose of our current study was to investigate the mechanism by which HPV16E6 regulates macrophages to promote the invasion and metastasis of esophageal cancer. METHODS: HPV16E6 infection was detected by polymerase chain reaction. Immunohistochemistry was used to verify the distribution of tumor-associated macrophages (TAMs) and MMP-9 expression in esophageal squamous cell carcinoma tissues (ESCCs), and cancer adjacent normal tissues (CANs) from Kazakh patients. ESCC cells were transfected with a plasmid over-expressing HPV16E6 and non-contact cocultured with macrophages. RESULTS: The infection rate of HPV16E6 in Kazakh ESCCs was clearly higher than that in CANs (P < 0.05). The density of CD163-positive TAMs was significantly positively correlated with HPV16E6 infection in ESCCs (P < 0.05). After coculturing macrophages and EC9706 cells transfected with the HPV16E6 plasmid, the phenotype of macrophages transformed into M2 macrophages. The migration and invasion ability of ESCC cells were higher in the HPV16E6-transfected and coculture group than in the HPV16E6 empty vector-transfected and non-cocultured HPV16E6-transfected groups (all P < 0.05). The density of M2-like TAMs in ESCCs was positively correlated with the level of MMP-9 expression. MMP-9 expression in the HPV16E6-ESCC coculture macrophages group was substantially higher than that in controls (all P < 0.05). CONCLUSIONS: HPV16 infection mediates tumor-associated macrophages to promote ESCC invasion and migration.
Assuntos
Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Papillomavirus Humano 16 , Proteínas Oncogênicas Virais/metabolismo , Infecções por Papillomavirus/complicações , Proteínas Repressoras/metabolismo , Macrófagos Associados a Tumor/patologia , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Diferenciação Celular , China/etnologia , Técnicas de Cocultura , Neoplasias Esofágicas/etnologia , Neoplasias Esofágicas/virologia , Carcinoma de Células Escamosas do Esôfago/etnologia , Carcinoma de Células Escamosas do Esôfago/virologia , Humanos , Metaloproteinase 9 da Matriz/metabolismo , Invasividade Neoplásica , Proteínas Oncogênicas Virais/genética , Infecções por Papillomavirus/etnologia , Fenótipo , Receptores de Superfície Celular/metabolismo , Proteínas Repressoras/genética , Microambiente Tumoral , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/virologiaRESUMO
We explored the protective effect of ischemia preconditioning (IP) on ischemia-reperfusion injury in rat liver transplantation. An orthotopic liver transplantation model was utilized in the study. A total of 54 Sprague-Dawley rats were divided into a control group (group A, no liver transplantation), liver transplantation group (group B, heparin Ringer's lactate solution was perfused via the portal vein before donor liver collection), and liver transplantation with IP group (group C, IP was performed for different time periods before donor liver collection). Liver function, B-cell lymphoma 2 expression in hepatic cells, cell apoptosis, and cellular ultrastructure changes were detected after surgery. After surgery, serum alanine aminotransferase activity was significantly higher in group B than in group A, while it was not clearly enhanced in group C and decreased progressively with increasing cycles of IP as bile capacity gradually increased. Compared with group B, group C showed alleviated injury of hepatic cells, increased B-cell lymphoma 2 expression, and a lower apoptosis index. IP had a protective effect on ischemia-reperfusion injury in rat liver transplantation, and the mechanism correlated with increased B-cell lymphoma 2 expression in hepatic cells and inhibition of cell apoptosis.
Assuntos
Precondicionamento Isquêmico/métodos , Transplante de Fígado/métodos , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/terapia , Animais , Estudos de Casos e Controles , Fígado/metabolismo , Fígado/patologia , Testes de Função Hepática , Masculino , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
Mitochondrial DNA mutations have been found to play important roles in carcinogenesis. The most common G10398A mutation, a non-conservative amino acid substitution from Thr to Ala, seems to be involved in the tumorigenesis of breast cancer. Results from studies concerning this mutation remain inconclusive. In the current study, we first took clinical and molecular datasets from case-control studies to determine the association between the G10398A mutation and breast cancer. We further used the Phylotree to determine the haplogroups of this mutation. The frequencies of this mutation in 500 unrelated healthy controls were also screened. We found that this mutation is very common in the human population, and may be a polymorph.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Carcinogênese , Complexo I de Transporte de Elétrons/genética , Substituição de Aminoácidos/genética , Neoplasias da Mama/patologia , Estudos de Casos e Controles , DNA Mitocondrial/genética , Feminino , Humanos , MutaçãoRESUMO
Since Paracoccidioides brasiliensis and Histoplasma capsulatum are known to be present in similar environments, there have been many epidemiologic investigations regarding the prevalences of these two organisms. However, cross-reactivity can occur in paracoccidioidin and histoplasmin skin tests, and this usually results in the overestimation of the prevalence of P. brasiliensis. The prevalence of infection with P. brasiliensis was evaluated in a cross-sectional study of 298 asymptomatic school children in the Brazilian Amazon region (Mato Grosso State). In this investigation, the reactivity of children to two different P. brasiliensis antigen preparations, paracoccidioidin and a purified 43-kD glycoprotein (gp43), was compared with or without the co-administration of histoplasmin. In the group of individuals receiving paracoccidioidin who had a positive histoplasmin skin test result, the prevalence of exposure to P. brasiliensis was 44% (16 of 36). This reactivity to P. brasiliensis was significantly higher than that observed in other groups, which ranged from 4% to 6% (P < 5 x 10(-4) for each). Overall prevalence was 4.6% (95% confidence interval = 2.5-7.7%). These data suggest that gp43 provides a better estimate of exposure to P. brasiliensis when the co-administration of histoplasmin is desired.
Assuntos
Antígenos de Fungos/análise , Proteínas Fúngicas , Glicosaminoglicanos/análise , Histoplasmina/análise , Paracoccidioides/imunologia , Paracoccidioidomicose/epidemiologia , Adolescente , Brasil/epidemiologia , Criança , Feminino , Proteínas Fúngicas/imunologia , Glicoproteínas/imunologia , Glicosaminoglicanos/imunologia , Histoplasmina/imunologia , Humanos , Testes Intradérmicos , Masculino , Paracoccidioidomicose/diagnóstico , Paracoccidioidomicose/imunologia , Prevalência , Testes CutâneosRESUMO
The ring-infected erythrocyte surface antigen (RESA), is one of the falciparum malaria vaccine candidates rarely studied in Brazil. Fieldwork logistics to conduct serology studies is simplified when eluates from whole blood dried on filter paper can be used. Therefore, this study aimed to assess the inter-test reliability for the anti-RESA ELISA-based indices using eluates from filter paper and from serum samples. The study population consisted of 210 individuals (Brazil) from whom matched samples were collected. Anti-RESA ELISA-based index means (+/- S.D.) were 15.29% (+/-28.13%) for filter paper and 11.79% (+/-23.67%) for serum samples. The intra-class correlation coefficient was estimated to be 82.38%, indicating high test reliability. However, there was a significant tendency for filter paper test results to have higher values than serum sample test results (P < 0.001). Explanations for this finding may be the presence of haemoglobin in the eluates from filter paper, which may interfere with ELISA testing.
Assuntos
Anticorpos Antiprotozoários/sangue , Plasmodium falciparum/imunologia , Proteínas de Protozoários/imunologia , Adolescente , Adulto , Animais , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Filtração , Humanos , Lactente , Masculino , Pessoa de Meia-IdadeRESUMO
This study evaluated the cure rate of the standard recommended regimen for Plasmodium vivax malaria in Brazil and assessed risk factors for failures. Fifty patients with vivax malaria given supervised medical treatment (standard dose of chloroquine: total dose = 1.5 g over a three-day period plus primaquine: total dose = 210 mg over a 14-day period) were followed for six months in a non-endemic area. Cox's regression was used to identify predictors of relapses. Among the 289 patient-months of follow-up, seven relapses were identified (2.4 relapses per 100 person-months) between 33 and 137 days after treatment initiation. Risk factors for relapses (P < or = 0.05) were female sex, higher parasitemia at baseline, shorter number of days with symptoms prior to baseline, and lower mg/kg dose of primaquine. Relapses following supervised vivax treatment is in principle a necessary, but not sufficient, component of in vivo parasite resistance. Results indicate that other factors, principally sub-therapeutic primaquine doses, may explain the occurrence of vivax treatment failures.
Assuntos
Antimaláricos/administração & dosagem , Cloroquina/administração & dosagem , Malária Vivax/tratamento farmacológico , Primaquina/administração & dosagem , Adolescente , Adulto , Idoso , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Risco , Falha de TratamentoRESUMO
In areas of drug-resistant malaria, control programs may restrict chemotherapy until malaria has been confirmed via microscopy to contain costs and toxicity. In Brazil, patients travel to centralized laboratory posts (FNS) at great cost for diagnosis and treatment. A program was established through the bars of a mining town offering free dipstick diagnosis and mefloquine treatment on a 24-hr basis; falciparum malaria dipstick tests are accurate and easy to use. Outcomes were compared with historical data and results of a neighboring non-intervention village. Guidelines for dipstick use and treatment were followed for 98% of visits. The number of FNS visits was reduced from 2,316 (expected) to 1,097 (observed) with 626 dipstick tests applied. Ninety-five percent of those who visited the FNS experienced onset of malaria symptoms in the town where the FNS was located. There was an unexpected doubling of the malaria hospital admission rate. We demonstrate that dipstick testing can be used in a sustainable, community-based program that should be applicable in a wide variety of settings.
Assuntos
Antígenos de Protozoários/sangue , Serviços de Saúde Comunitária/normas , Malária Falciparum/diagnóstico , Malária Falciparum/prevenção & controle , Plasmodium falciparum/imunologia , Serviços Preventivos de Saúde/normas , Animais , Antimaláricos/uso terapêutico , Brasil/epidemiologia , Serviços de Saúde Comunitária/estatística & dados numéricos , Humanos , Malária Falciparum/epidemiologia , Malária Falciparum/urina , Mefloquina/uso terapêutico , Serviços Preventivos de Saúde/estatística & dados numéricos , Avaliação de Programas e Projetos de SaúdeRESUMO
In the Brazilian Amazon, travel costs to centralized malaria clinics for diagnosis and treatment can approach 20% of one's monthly salary. A program was established in a mining town for community-based dipstick test diagnosis and treatment. An economic analysis was performed that compared expected costs under the old program to the observed costs of the new one. Data were obtained through interviews, government reports, clinic and hospital records, and community records. There was a 53% reduction (by 1,219 visits) of clinic visits but a doubling of malaria hospitalization admissions (to 191). The new program had an overall annual savings of $60,900 ($11.8K-$160K, sensitivity limits), a 77% reduction of the old program's cost. The benefit-to-cost ratio was 9:1, where benefits were patients' savings from travel and lost wages and costs were government drug, diagnostic, training, and monitoring expenses. A community-based program incorporating dipstick tests for malaria management can have economic advantages.
Assuntos
Antígenos de Protozoários/sangue , Serviços de Saúde Comunitária/economia , Testes Diagnósticos de Rotina/economia , Malária/diagnóstico , Malária/prevenção & controle , Plasmodium/imunologia , Animais , Brasil/epidemiologia , Análise Custo-Benefício , Humanos , Prontuários Médicos , Visita a Consultório Médico/estatística & dados numéricos , Admissão do Paciente/estatística & dados numéricos , Estudos RetrospectivosRESUMO
Objective: To determine the extent to which two homeopaths agree on whether symptoms reported by patients in a proving are possibly associated with Mercurius solubilis. Design: Blinded, inter-rater reliability study. Participants: 104 subjects in a... (AU)
Assuntos
Humanos , Homeopatia/métodos , Mercurius Solubilis , Repertorização , Princípio da SimilitudeAssuntos
Infecções Oportunistas Relacionadas com a AIDS/imunologia , Soropositividade para HIV/imunologia , Malária Falciparum/imunologia , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Adolescente , Adulto , Animais , Anticorpos Antiprotozoários/análise , Western Blotting , Brasil/epidemiologia , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Anticorpos Anti-HIV/análise , Soropositividade para HIV/diagnóstico , Soropositividade para HIV/epidemiologia , Humanos , Malária Falciparum/diagnóstico , Malária Falciparum/epidemiologia , Masculino , Pessoa de Meia-Idade , Plasmodium falciparum/imunologia , Reação em Cadeia da Polimerase/métodosRESUMO
BACKGROUND: Malaria represents one of the most important infectious disease threats to deployed military forces; most personnel from developed countries are nonimmune personnel and are at high risk of infection and clinical malaria. This is especially true for forces deployed to highly-endemic areas in Africa and Southeast Asia where drug-resistant malaria is common. METHODS: We conducted an outbreak investigation of malaria cases in Angola where a total of 439 nonimmune Brazilian troops were deployed for a 6-month period in 1995-1996. A post-travel medical evaluation was also performed on 338 (77%) of the 439 soldiers upon return to Brazil. Questionnaire, medical record, thick/thin smear, and serum anti-Plasmodium falciparum antibody titer (by IFA) data were obtained. Peak serum mefloquine (M) and methylmefloquine (MM) metabolite levels were measured in a subsample of 66 soldiers (42 cases, 24 nonmalaria controls) who were taking weekly mefloquine prophylaxis (250 mg). RESULTS: Seventy-eight cases of malaria occurred among the 439 personnel initially interviewed in Angola (attack rate = 18%). Four soldiers were hospitalized, and 3 subsequently died of cerebral malaria. Upon return to Brazil, 63 (19%) of 338 soldiers evaluated were documented to have had clinical symptoms and a diagnosis of malaria while in Angola. In addition, 37 (11%) asymptomatically infected individuals were detected upon return (< 1% parasitemia). Elevated, post-travel anti-P. falciparum IFA titers (> or = 1:64) were seen in 101 (35%) of 292 soldiers tested, and was associated with a prior history of malaria in-country (OR = 3.67, 95% CI 1.98-6.82, p <.001). Noncompliance with weekly mefloquine prophylaxis (250 mg) was associated with a malaria diagnosis in Angola (OR = 3.75, 95% CI 0.97-17.41, p =.03) but not with recent P. falciparum infection (by IFA titer). Mean peak levels (and ratios) of serum M and MM were also found to be lower in those who gave a history of malaria while in Angola. CONCLUSIONS: Malaria was a significant cause of morbidity among Brazilian Army military personnel deployed to Angola. Mefloquine prophylaxis appeared to protect soldiers from clinical, but not subclinical, P. falciparum infections. Mefloquine noncompliance and an erratic chemoprophylaxis prevention policy contributed to this large outbreak in nonimmune personnel. This report highlights the pressing need for development of newer, more efficacious and practical, prophylactic drug regimens that will reduce the malaria threat to military forces and travelers.
Assuntos
Surtos de Doenças , Malária Falciparum/epidemiologia , Militares , Angola/epidemiologia , Animais , Anticorpos Antiprotozoários/sangue , Antimaláricos/uso terapêutico , Brasil , Humanos , Malária Falciparum/diagnóstico , Malária Falciparum/prevenção & controle , Mefloquina/uso terapêutico , Cooperação do Paciente , Plasmodium falciparum/imunologiaRESUMO
From March 1996 to August 1997, a study was carried out in a malaria endemic area of the Brazilian Amazon region. In vivo sensitivity evaluation to antimalarial drugs was performed in 129 patients. Blood samples (0.5 ml) were drawn from each patient and cryopreserved to proceed to in vitro studies. In vitro sensitivity evaluation performed using a radioisotope method was carried out with the cryopreserved samples from September to December 1997. Thirty-one samples were tested for chloroquine, mefloquine, halofantrine, quinine, arteether and atovaquone. Resistance was evidenced in 96.6% (29/30) of the samples tested for chloroquine, 3. 3% (1/30) for quinine, none (0/30) for mefloquine and none for halofantrine (0/30). Overall low sensitivity was evidenced in 10% of the samples tested for quinine, 22.5% tested for halofantrine and in 20% tested for mefloquine. Means of IC 50 values were 132.2 (SD: 46. 5) ng/ml for chloroquine, 130.6 (SD: 49.6) ng/ml for quinine, 3.4 (SD: 1.3) ng/ml for mefloquine, 0.7 (SD: 0.3) ng/ml for halofantrine, 1 (SD: 0.6) ng/ml for arteether and 0.4 (SD: 0.2) ng/ml for atovaquone. Means of chloroquine IC 50 of the tested samples were comparable to that of the chloroquine-resistant strain W2 (137.57 ng/ml) and nearly nine times higher than that of the chloroquine-sensitive strain D6 (15.09 ng/ml). Means of quinine IC 50 of the tested samples were 1.7 times higher than that of the low sensitivity strain W2 (74.84 ng/ml) and nearly five times higher than that of the quinine-sensitive strain D6 (27.53 ng/ml). These results disclose in vitro high resistance levels to chloroquine, low sensitivity to quinine and evidence of decreasing sensitivity to mefloquine and halofantrine in the area under evaluation.
Assuntos
Antimaláricos/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Animais , Brasil , Resistência a Medicamentos , Parasitologia/métodos , RadioisótoposRESUMO
Ninety-four patients with falciparum malaria were treated with mefloquine (1000-mg single dose) and remained hospitalized in a malaria-free area for a minimum of 28 days. There was 1 parasitologic failure (grade I resistance [RI]) for a 99% cure rate (95% confidence interval, 94.2%-99.7%). Mean parasite clearance time by thick smear was 45.7 h (SD, 11.4 h). The subject in whom therapy failed had a parasite clearance time (71 h) >2 SD above the population mean. His plasma mefloquine level 48 h after administration was lower (578 ng/mL) than the range of levels from 8 randomly selected cured subjects (834-2360 ng/mL). The IC50 to mefloquine for the recrudescent strain of the RI failure was in the upper 90th percentile of IC50 values from 30 cured subjects. These results show a high mefloquine cure rate but document the onset and mechanism of the emergence of resistance.
Assuntos
Antimaláricos/uso terapêutico , Malária Falciparum/tratamento farmacológico , Mefloquina/uso terapêutico , Adolescente , Adulto , Animais , Antimaláricos/farmacologia , Brasil , Resistência a Medicamentos , Humanos , Masculino , Mefloquina/farmacologia , Pessoa de Meia-Idade , Plasmodium falciparum/efeitos dos fármacos , Resultado do TratamentoRESUMO
Reported are the results of a study to determine the efficacy and safety of liposomal amphotericin B (AmBisome) for treating visceral leishmaniasis (kala-azar) in several developing countries where the disease is endemic (Brazil, India, and Kenya). At each study site, sequential cohorts of 10 patients each were treated with AmBisome at a dose of 2 mg.kg-1.day-1 (2 MKD). The first cohort received regimen 1:2 MKD on days 1-6 and day 10 (total dose: 14 mg/kg). If the efficacy with this regimen was satisfactory, a second cohort received regimen 2:2 MKD on days 1-4 and 10 (total dose: 10 mg/kg); and a third cohort received regimen 3:2 MKD on days 1, 5, and 10 (total dose: 6 mg/kg). In India, regimens 1, 2, and 3 (which were studied concurrently) each cured 100% of 10 patients. In Kenya, regimen 1 cured all 10 patients, regimen 2 cured 90% of 10 patients, but regimen 3 cured only 20% of 5 patients. In Brazil, regimen 1 was only partially curative: 5 of 13 patients (62%). Therefore, 15 patients were administered regimen 4 (2 MKD for 10 consecutive days; total dose, 20 mg/kg) and 13 patients were cured (83%). These results suggest that for the treatment of kala-azar the following doses of AmBisome should be administered: in India and Kenya, 2 mg/kg on days 1-4 and day 10; and in Brazil, 2 mg/kg on days 1-10.
PIP: The efficacy and safety of liposomal amphotericin B (AmBisome) for the treatment of visceral leishmaniasis (kala-azar) were evaluated in a phase II clinical trial conducted in Brazil, India, and Kenya--countries where kala-azar is endemic. At each study site, sequential cohorts of 10 patients each received three different dosage regimens of AmBisome. The first cohort received 2 mg/kg/day (MKD) on days 1-6 and day 10 (total dose, 14 mg/kg). If the efficacy of this regimen was satisfactory, the second cohort received 2 MKD on days 1-4 and day 10 (total dose, 10 mg/kg) and a third cohort was administered 2 MKD on days 1, 5, and 10 (total dose, 6 mg/kg). In India, all three regimens (studied concurrently) cured 100% of the total of 30 patients. In Kenya, the first regimen cured all 10 patients (100%), the second cured 9 of 10 patients (90%), and the third cured only 1 of 5 patients (20%). In Brazil, since the first regimen cured only 5 of 13 patients (62%), the next 15 patients were given 2 MKD for 10 consecutive days (total dose, 20 mg/kg); this intensified regimen cured 13 of the 15 patients (83%). Adverse effects were minor, primarily fever and chills associated with infusion and irregular pulse. These findings suggest that leishmaniasis patients in India and Kenya should receive 2 mg/kg of AmBisome on days 1-4 and day 10, while those in Brazil should be given 2 mg/kg on days 1-10. AmBisome treatment is especially recommended for those for whom standard agents are likely to be ineffective, toxic, or difficult to administer.
Assuntos
Anfotericina B/uso terapêutico , Antiprotozoários/uso terapêutico , Países em Desenvolvimento , Doenças Endêmicas , Leishmaniose Visceral/tratamento farmacológico , Adolescente , Adulto , Brasil , Criança , Relação Dose-Resposta a Droga , Esquema de Medicação , Humanos , Índia , Quênia , Leishmaniose Visceral/epidemiologia , Resultado do TratamentoRESUMO
The prevalence and severity of drug-resistant malaria is emerging rapidly in the Amazon basin of Brazil. In support of clinical trials using the new antimalarial drug combination of atovaquone and proguanil, we performed in vitro drug sensitivities, molecular characterization of parasite populations using the circumsporozoite protein, merozoite surface antigen-1 (MSA-1), and MSA-2 markers, and an analysis of the Plasmodium falciparum multidrug resistance (pfmdr1) gene sequence and copy number in 26 isolates of P. falciparum obtained in a gold-mining endemic area in Peixoto de Azevedo, Mato Grosso State. All 26 isolates were found to be resistant to chloroquine (50% inhibitory concentration [IC50] = 100-620 nM) and sensitive to mefloquine (IC50 < 23 nM) and halofantrine (IC50 < 6 nM). The isolates also show reduced susceptibility to quinine (IC50 = 48-280 nM). Sequence analysis of the pfmdr1 gene revealed Asn, Phe, Cys, Asp, and Tyr in positions 86, 184, 1034, 1042, and 1246, respectively. These point mutations were similar to that previously described in other Brazilian isolates. Southern blot analysis revealed no amplification of the pfmdr1 gene. These results suggest that three different mechanisms for drug resistance exist for chloroquine, mefloquine, and quinine.
Assuntos
Transportadores de Cassetes de Ligação de ATP , Antimaláricos/farmacologia , DNA de Protozoário/análise , Plasmodium falciparum/efeitos dos fármacos , Proteínas de Protozoários/genética , Animais , Brasil/epidemiologia , Resistência a Medicamentos , Resistência a Múltiplos Medicamentos/genética , Quimioterapia Combinada , Genes de Protozoários/genética , Humanos , Malária Falciparum/epidemiologia , Malária Falciparum/metabolismo , Mefloquina/farmacologia , Plasmodium falciparum/classificação , Plasmodium falciparum/isolamento & purificação , Mutação Puntual , Quinina/farmacologiaRESUMO
The purpose of this study was to compare an experimental regimen of atovaquone plus proguanil with the standard regimen of quinine plus tetracycline for the treatment of uncomplicated falciparum malaria. The study was designed as an open, randomized study of men presenting with symptoms of uncomplicated malaria and thick-smear slide confirmation of parasitemia (1000-100,000 ring forms/microL). Subjects were hospitalized for 28 days to insure medication compliance and to rule out the possibility of reinfections. With 77 patients in each group, the cure rates were 98.7% and 100% for atovaquone plus proguanil and quinine plus tetracycline, respectively. The parasite clearance times (mean, 56 h) and fever clearance times (mean, 19 h) were significantly shorter in the atovaquone plus proguanil group, and there were significantly fewer side effects in the atovaquone plus proguanil group. Atovaquone plus proguanil is an efficacious, easily administered, safe regimen for the treatment of uncomplicated, multidrug-resistant falciparum malaria in Brazil.
Assuntos
Antimaláricos/administração & dosagem , Malária/tratamento farmacológico , Naftoquinonas/administração & dosagem , Proguanil/administração & dosagem , Adolescente , Adulto , Idoso , Antimaláricos/efeitos adversos , Atovaquona , Brasil , Quimioterapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Naftoquinonas/efeitos adversos , Proguanil/efeitos adversos , Quinina/administração & dosagem , Quinina/efeitos adversos , Tetraciclina/administração & dosagem , Tetraciclina/efeitos adversosRESUMO
This is the first report of serologic evidence of hepatitis E infection in Brazil. During a community-based survey of healthy individuals, six of 97 gold miners in the Amazon region of Mato Grosso had antibody to the virus. The mining camps have poor sanitation with a great potential for fecal-oral transmission of disease. Since levels of hepatitis E antibodies may quickly wane, studies to directly measure the incidence of seroconversion are planned to determine the intensity of transmission in this area.
Assuntos
Hepatite E/epidemiologia , Mineração , Doenças Profissionais/epidemiologia , Adulto , Brasil/epidemiologia , Feminino , Anticorpos Anti-Hepatite/sangue , Vírus da Hepatite E/imunologia , Humanos , MasculinoAssuntos
Ouro , Malária Falciparum/epidemiologia , Mineração , Brasil/epidemiologia , Humanos , PrevalênciaRESUMO
Clusters of rat carotid body glomus cells were cultured for 1 to 12 days. Preparations were exposed to a control PO2 of 134.9 +/- 1.1 torr (mean +/- SE), and an external chloride activity, ao(Cl), of 105.6 +/- 2 mM. Thirty-six cells had a resting potential (Em) of -25.2 +/- 0.9 mV. The intracellular chloride activity, ai(Cl), was 32.8 +/- 1.1 mM, and the calculated chloride equilibrium potential (ECl) was -30.9 +/- 0.9 mV. ECl was more negative than Em, indicating that Cl- ions are not passively distributed. Hypoxia (5.4 +/- 0.8 torr), induced by Na-dithionite (Na2S2O4) 1.25 mM, elicited cell depolarization, increased ai(Cl) and a less negative ECl in about 80% of the cells. Fourteen per cent of the cells showed opposite effects. It is hypothesized that the increased ai(Cl) occurs because an outward-directed chloride pump is blocked by hypoxia. This effect is aided by depolarization of the cell. Decreased ai(Cl) may be due to cell hyperpolarization.