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1.
Vaccine ; 33(38): 4820-6, 2015 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-26241948

RESUMO

BACKGROUND: Many areas with endemic and epidemic cholera report significant levels of HIV transmission. According to the World Health Organization (WHO), over 95% of reported cholera cases occur in Africa, which also accounts for nearly 70% of people living with HIV/AIDS globally. Peru-15, a promising single dose live attenuated oral cholera vaccine (LA-OCV), was previously found to be safe and immunogenic in cholera endemic areas. However, no data on the vaccine's safety among HIV-seropositive adults had been collected. METHODS: This study was a double-blinded, individually randomized, placebo-controlled trial enrolling HIV-seropositive adults, 18-45 years of age, conducted in Bangkok, Thailand, to assess the safety of Peru-15 in a HIV-seropositive cohort. RESULTS: 32 HIV infected subjects were randomized to receive either a single oral dose of the Peru-15 vaccine with a buffer or a placebo (buffer only). No serious adverse events were reported during the follow-up period in either group. The geometric mean fold (GMF) rise in V. cholerae O1 El Tor specific antibody titers between baseline and 7 days after dosing was 32.0 (p<0.001) in the vaccine group compared to 1.6 (p<0.14) in the placebo group. Among the 16 vaccinees,14 vaccinees (87.5%) had seroconversion compared to 1 of 16 placebo recipients (6.3%). V. cholerae was isolated from the stool of one vaccinee, and found to be genetically identical to the Peru-15 vaccine strain. There were no significant changes in HIV viral load or CD4 T-cell counts between vaccine and placebo groups. CONCLUSION: Peru-15 was shown to be safe and immunogenic in HIV-seropositive Thai adults.


Assuntos
Vacinas contra Cólera/efeitos adversos , Vacinas contra Cólera/imunologia , Cólera/prevenção & controle , Infecções por HIV/complicações , Administração Oral , Adolescente , Adulto , Anticorpos Antibacterianos/sangue , Vacinas contra Cólera/administração & dosagem , Método Duplo-Cego , Feminino , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Tailândia , Resultado do Tratamento , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Adulto Jovem
2.
Epidemiol Infect ; 138(2): 199-209, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19698213

RESUMO

The epidemiology, symptomology, and viral aetiology of endemic influenza remain largely uncharacterized in Cambodia. In December 2006, we established passive hospital-based surveillance to identify the causes of acute undifferentiated fever in patients seeking healthcare. Fever was defined as tympanic membrane temperature >38 degrees C. From December 2006 to December 2008, 4233 patients were screened for influenza virus by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR). Of these patients, 1151 (27.2%) were positive for influenza. Cough (68.8% vs. 50.5%, P < 0.0001) and sore throat (55.0% vs. 41.9%, P < 0.0001) were more often associated with laboratory-confirmed influenza-infected patients compared to influenza-negative enrollees. A clear influenza season was evident between July and December with a peak during the rainy season. Influenza A and B viruses were identified in 768 (66.3%) and 388 (33.7%) of the influenza-positive population (n = 1153), respectively. In December 2008, passive surveillance identified infection of the avian influenza virus H5N1 in a 19-year-old farmer from Kandal province who subsequently recovered. From a subset of diagnostic samples submitted in 2007, 15 A(H1N1), seven A(H3N2) and seven B viruses were isolated. The predominant subtype tested was influenza A(H1N1), with the majority antigenically related to the A/Solomon Island/03/2006 vaccine strain. The influenza A(H3N2) isolates and influenza B viruses analysed were closely related to A/Brisbane/10/2007 or B/Ohio/01/2005 (B/Victoria/2/87-lineage) vaccine strains, respectively. Phylogenetic analysis of the HA1 region of the HA gene of influenza A(H1N1) viruses demonstrated that the Cambodian isolates belonged to clade 2C along with representative H1N1 viruses circulating in SE Asia at the time. These viruses remained sensitive to oseltamivir. In total, our data suggest that viral influenza infections contribute to nearly one-fifth of acute febrile illnesses and demonstrate the importance of influenza surveillance in Cambodia.


Assuntos
Febre/etiologia , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Vírus da Influenza B/isolamento & purificação , Influenza Humana/epidemiologia , Influenza Humana/virologia , Adolescente , Adulto , Camboja/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza B/genética , Influenza Humana/complicações , Masculino , Filogenia , População Rural , População Suburbana , Adulto Jovem
3.
J Clin Microbiol ; 47(1): 189-97, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18971368

RESUMO

Hospital surveillance was established in the Nile River Delta to increase the understanding of the epidemiology of diarrheal disease among Egyptian children. Between September 2000 and August 2003, samples obtained from children less than 5 years of age who had diarrhea and who were seeking hospital care were cultured for enteric bacteria. Colonies from each culture with a morphology typical of that of Escherichia coli were tested for the heat-labile (LT) and heat-stable (ST) toxins by a GM-1-specific enzyme-linked immunosorbent assay and colonization factor (CF) antigens by an immunodot blot assay. Enterotoxigenic E. coli (ETEC) isolates were recovered from 320/1,540 (20.7%) children, and ETEC isolates expressing a known CF were identified in 151/320 (47%) samples. ST CFA/I, ST CS6, ST CS14, and LT and ST CS5 plus CS6 represented 75% of the CFs expressed by ETEC isolates expressing a detectable CF. Year-to-year variability in the proportion of ETEC isolates that expressed a detectable CF was observed (e.g., the proportion that expressed CFA/I ranged from 10% in year 1 to 21% in year 3); however, the relative proportions of ETEC isolates expressing a CF were similar over the reporting period. The proportion of CF-positive ETEC isolates was higher among isolates that expressed ST. ETEC isolates expressing CS6 were isolated significantly less often (P < 0.001) than isolates expressing CFA/I in children less than 1 year of age. Macrorestriction profiling of CFA/I-expressing ETEC isolates by using the restriction enzyme XbaI and pulsed-field gel electrophoresis demonstrated a wide genetic diversity among the isolates that did not directly correlate with the virulence of the pathogen. The genome plasticity demonstrated in the ETEC isolates collected in this work suggests an additional challenge to the development of a globally effective vaccine for ETEC.


Assuntos
Diarreia/microbiologia , Escherichia coli Enterotoxigênica/genética , Escherichia coli Enterotoxigênica/metabolismo , Infecções por Escherichia coli/microbiologia , Toxinas Bacterianas/biossíntese , Pré-Escolar , Análise por Conglomerados , Impressões Digitais de DNA , DNA Bacteriano/metabolismo , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Diarreia/epidemiologia , Egito/epidemiologia , Eletroforese em Gel de Campo Pulsado , Escherichia coli Enterotoxigênica/classificação , Escherichia coli Enterotoxigênica/isolamento & purificação , Enterotoxinas/biossíntese , Infecções por Escherichia coli/epidemiologia , Proteínas de Escherichia coli/biossíntese , Proteínas de Fímbrias/biossíntese , Variação Genética , Hospitais , Humanos , Lactente , Recém-Nascido , Epidemiologia Molecular , Polimorfismo de Fragmento de Restrição
4.
Epidemiol Infect ; 134(6): 1237-48, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16690004

RESUMO

Ninety-seven isolates of Shigella flexneri from children seeking medical care from three sites in Egypt were characterized. Overall, 46.4% of children (median age 17 months) were febrile or reported blood in their stools, 25.8% were dehydrated and 16.5% were admitted to hospital. Serotypes 2a (37.1%), 1b (18.6%), 1c (17.5%), and 6 (15.5%) comprised over 88.7% of the total isolates. We observed marked resistance to ampicillin (87.6%), tetracycline (84.5%) and trimethoprim-sulfamethoxazole (63.9%). Pulsed-field electrophoresis grouped the majority of isolates within a serotype together, separately from isolates of an alternative serotype. The set gene was present in all serogroup 2a isolates, however, the sen gene was detected in every isolate. Our results show S. flexneri 1c has emerged as a dominant S. flexneri serotype in Egypt. Development and application of a Shigella vaccine should consider the diversity of Shigella serotypes within a geographical region prior to administration.


Assuntos
Disenteria Bacilar/epidemiologia , Shigella flexneri/genética , Shigella flexneri/isolamento & purificação , Antibacterianos/farmacologia , Pré-Escolar , Coleta de Dados/métodos , Farmacorresistência Bacteriana/genética , Disenteria Bacilar/microbiologia , Egito/epidemiologia , Eletroforese em Gel de Campo Pulsado , Enterotoxinas/análise , Enterotoxinas/genética , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Filogenia , Sorotipagem , Shigella flexneri/classificação , Shigella flexneri/efeitos dos fármacos , Shigella flexneri/fisiologia
5.
J Physiol Pharmacol ; 57 Suppl 10: 115-31, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17242495

RESUMO

Exercise induces extensive generation of reactive oxygen species, which are responsible for tissue damage: enzymes inactivation, lipid peroxidation and single strand breaks in DNA. Defense system against free radicals is consisting of enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and numerous non-enzymatic antioxidants. The study was performed to evaluate the effect of a single bout of submaximal running exercise, on the lymphocyte DNA strand breaks and also to test how supplementation with tempol - a membrane-permeable SOD-mimetic (0.2 mmol/kg/day) influences the eventually evoked damage. Male, Wistar rats were challenged with graded 50 min. running on treadmill at intensity up to 75-85% of predicted VO(2)max. The DNA strand breaks in individual lymphocytes were determined by using a gel electrophoretic technique - "comet" assay. We found substantial lymphocyte DNA damage 60 min. after the exercise. Tempol failed to prevent from oxidative damage in rats challenged with exercise. Moreover tempol by itself induced higher DNA damage than the exercise bout.


Assuntos
Antioxidantes/efeitos adversos , Óxidos N-Cíclicos/efeitos adversos , Quebras de DNA , Linfócitos/metabolismo , Condicionamento Físico Animal/fisiologia , Animais , Ensaio Cometa , Teste de Esforço , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio , Corrida/fisiologia , Marcadores de Spin , Fatores de Tempo
7.
Clin Microbiol Infect ; 10(9): 804-10, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15355411

RESUMO

Antimicrobial susceptibility testing was performed on 3,627 isolates of Escherichia coli and 180 isolates of Shigella spp. collected in rural locations from 875 Egyptian children with diarrhoea between 1995 and 2000. The cumulative rates of resistance for E. coli and Shigella spp. were high (respectively, 68.2% and 54.8% for ampicillin, 24.2% and 23.5% for ampicillin-sulbactam, 57.2% and 42.5% for trimethoprim-sulphamethoxazole, and 50.9% and 75.4% for tetracycline). Non-enterotoxigenic E. coli (NETEC) isolates had a consistently higher level of antimicrobial resistance than did enterotoxigenic E. coli (ETEC) isolates. Trend testing showed significant decreases in resistance to ampicillin, ampicillin-sulbactam and tetracycline among all E. coli isolates. Increasing rates of resistance were observed for trimethoprim-sulphamethoxazole in ETEC isolates and Shigella spp., but not in NETEC isolates. Low levels of resistance were observed for all other antimicrobial agents tested. Overall, high levels, but decreasing trends, of resistance to commonly used antimicrobial agents were detected among isolates of E. coli and Shigella spp. from children in rural Egypt.


Assuntos
Antibacterianos/farmacologia , Diarreia/microbiologia , Escherichia coli/efeitos dos fármacos , População Rural , Shigella/efeitos dos fármacos , Criança , Pré-Escolar , Farmacorresistência Bacteriana , Disenteria Bacilar/microbiologia , Egito , Enterotoxinas/metabolismo , Escherichia coli/imunologia , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/prevenção & controle , Vacinas contra Escherichia coli/administração & dosagem , Feminino , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Shigella/isolamento & purificação
8.
Trans R Soc Trop Med Hyg ; 98(6): 331-6, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15099987

RESUMO

In Egypt, the etiology of chronic renal failure (CRF) is not well defined. A hospital-based case-control study was initiated in February 1998, to determine whether hantavirus infection is involved in chronic renal disease (CRD) in Egypt. The study enrolled 350 study patients with a history of CRF and 695 matched controls with CRD due to renal calculus or renal cancer, but with normal renal functions. Sera from cases and controls were tested for anti-hantavirus IgG using ELISA with a cell-lysate antigen from Hantaan virus prototype strain 76-118. A demographic questionnaire was completed for each study participant. Five of the 350 cases (1.4%), and seven of the 695 controls (1.0%) were antibody-positive to hantavirus, with a titer > or =1:400. The difference in antibody prevalence between the study cases and the control cases was not statistically significant (P = 0.48). All antibody-positive study cases and controls had been exposed to rodents. Data indicated that in Egypt, hantavirus seroprevalence in CRD patients is low, and hantavirus infections do not appear to be a significant cause of CRF.


Assuntos
Anticorpos Antivirais/sangue , Infecções por Hantavirus/complicações , Falência Renal Crônica/virologia , Orthohantavírus/imunologia , Adulto , Estudos de Casos e Controles , Egito/epidemiologia , Feminino , Infecções por Hantavirus/epidemiologia , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estudos Soroepidemiológicos
9.
J Pept Res ; 63(1): 29-35, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14984571

RESUMO

Two new analogues of a previously designed bradykinin (BK) antagonist, d-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-d-Phe-Thi-Arg, substituted in position 8 by N-benzylglycine and N-benzyl-l-alanine were designed, synthesized and bioassayed. The results show an impressive enhancement of B2 antagonistic potencies of both peptides in comparison with the model. In two further analogues these modifications were combined with acylation of the N-terminus with 1-adamantanacarboxylic acid. Acylated analogues exhibited higher antagonistic potency in comparison with the parent compounds, however, the range of effect was not as high as in previously described cases. The activity of analogues was assessed by their ability to inhibit vasodepressor response to exogenous BK (rat blood pressure test). Our results may be of value in the design of more potent BK antagonists.


Assuntos
Alanina/química , Bradicinina/antagonistas & inibidores , Glicina/análogos & derivados , Glicina/química , Oligopeptídeos/síntese química , Oligopeptídeos/farmacologia , Alanina/análogos & derivados , Animais , Pressão Sanguínea/efeitos dos fármacos , Bradicinina/análogos & derivados , Masculino , Oligopeptídeos/química , Ratos , Ratos Wistar
10.
Am J Epidemiol ; 154(2): 166-73, 2001 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-11447051

RESUMO

Campylobacter infection in developing countries has not received much public health attention because of the observation that infections are not associated with disease beyond the first 6 months of life. A cohort of 397 Egyptian children aged less than 3 years, who were observed twice weekly during 1995--1998, experienced an incidence of 0.6 episodes of Campylobacter diarrhea per child-year. A total of 13% of the Campylobacter diarrheal episodes were characterized by severe dehydration. Age-specific incidence rates (episodes per year) were 0.9 in infants aged less than 6 months, 1.5 in those 6--12 months, and 0.4 and 0.2 in the second and third years of life, respectively. Convalescent excretion of Campylobacter after a diarrheal episode might be enhancing transmission and contributing to this high incidence. Observed risk factors for Campylobacter diarrhea were poor hygienic conditions and the presence of animals in the house. Regardless of the child's age, a first infection by Campylobacter was associated with diarrhea (odds ratio = 2.45; 95% confidence interval: 1.61, 3.71); however, subsequent infections were associated with diarrhea only in children aged less than 6 months. This observation that natural infection did not confer protection during the first 6 months of life poses a challenge to vaccine development.


Assuntos
Infecções por Campylobacter/microbiologia , Infecções por Campylobacter/transmissão , Convalescença , Diarreia/microbiologia , Fezes/microbiologia , Saúde da População Rural/estatística & dados numéricos , Distribuição por Idade , Animais , Animais Domésticos/microbiologia , Campylobacter/patogenicidade , Infecções por Campylobacter/epidemiologia , Estudos de Casos e Controles , Pré-Escolar , Países em Desenvolvimento , Diarreia/epidemiologia , Egito/epidemiologia , Humanos , Higiene , Incidência , Lactente , Estudos Longitudinais , Vigilância da População , Fatores de Risco , Estações do Ano , Inquéritos e Questionários , Fatores de Tempo
11.
J Pediatr Gastroenterol Nutr ; 32(2): 189-96, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11321391

RESUMO

BACKGROUND: In the developing world, children are often observed to have both diarrhea and malnutrition. This observation has led many researchers to speculate that diarrhea may produce malnutrition and that malnutrition may predispose to diarrhea. In this study, the interrelationship between diarrhea and malnutrition was investigated among 143 Egyptian children less than 3 years of age. METHODS: For 22 months, children were followed for diarrhea at twice weekly home visits and measured for nutritional status at approximately 3-month intervals. Nutritional measurements were converted to z-scores based on the National Center for Health Statistics/World Health Organization (NCHS/WHO) reference population. RESULTS: Three hundred fifty-eight diarrheal episodes were reported with only 1% of episodes lasting 14 days or more. Stunting, wasting, and low weight-for-age were found in 19%, 3%, and 7%, of these children, respectively. When testing whether malnutrition predisposes to diarrhea, a weight-for-age z-score of <-2 standard deviations was associated with increased incidence of diarrhea (RR = 1.7, P < 0.01) but not height-for-age or weight-for-height. Diarrhea itself was associated with a subsequent attack of diarrhea (RR = 2.1, P < 0.001). During short intervals of follow-up (approximately 3 months), an association was detected between diarrhea episodes and growth faltering for height-for-age z-score (-0.16, P < 0.05). This association was reduced, however, when analyzed during 6-month intervals, if no diarrhea was reported in either the first or second half of this interval. CONCLUSIONS: In a population with moderate malnutrition, both low weight-for-age and diarrhea itself are associated with increased diarrhea risk. Diarrhea alone does not appear to contribute substantially to malnutrition when children have diarrhea-free time for catch-up growth.


Assuntos
Transtornos da Nutrição Infantil/etiologia , Diarreia/etiologia , Transtornos da Nutrição do Lactente/etiologia , Estado Nutricional , Estatura , Peso Corporal , Transtornos da Nutrição Infantil/prevenção & controle , Pré-Escolar , Diarreia/prevenção & controle , Egito , Feminino , Crescimento , Humanos , Incidência , Lactente , Transtornos da Nutrição do Lactente/prevenção & controle , Estudos Longitudinais , Masculino , Fatores de Risco , Saúde da População Urbana
12.
Infect Immun ; 69(5): 2853-7, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11292698

RESUMO

We assessed serologic responses to an oral, killed whole-cell enterotoxigenic Escherichia coli plus cholera toxin B-subunit (ETEC-rCTB) vaccine in 73 Egyptian adults, 105 schoolchildren, and 93 preschool children. Each subject received two doses of vaccine or placebo 2 weeks apart, giving blood before immunization and 7 days after each dose. Plasma antibodies to rCTB and four vaccine-shared colonization factors (CFs) were measured by enzyme-linked immunosorbent assay. Immunoglobulin A (IgA) antibodies to rCTB and CFA/I were measured in all subjects, and those against CS1, CS2, and CS4 were measured in all children plus a subset of 33 adults. IgG antibodies to these five antigens were measured in a subset of 30 to 33 subjects in each cohort. Seroconversion was defined as a >2-fold increase in titer after vaccination. IgA and IgG seroconversion to rCTB was observed in 94 to 95% of adult vaccinees, with titer increases as robust as those previously reported for these two pediatric cohorts. The proportion showing IgA seroconversion to each CF antigen among vaccinated children (range, 70 to 96%) and adults (31 to 69%), as well as IgG seroconversion in children (44 to 75%) and adults (25 to 81%), was significantly higher than the corresponding proportion in placebo recipients, except for IgA responses to CS2 in adults. IgA anti-CF titers peaked after one dose in children, whereas in all age groups IgG antibodies rose incrementally after each dose. Independently, both preimmunization IgA titer and age were inversely related to the magnitude of IgA responses. In conclusion, serologic responses to the ETEC-rCTB vaccine may serve as practical immune outcome measures in future pediatric trials in areas where ETEC is endemic.


Assuntos
Anticorpos Antibacterianos/sangue , Proteínas de Bactérias/imunologia , Vacinas Bacterianas/imunologia , Toxina da Cólera/imunologia , Escherichia coli/imunologia , Proteínas de Fímbrias , Vacinas Sintéticas/imunologia , Administração Oral , Adulto , Criança , Pré-Escolar , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Pessoa de Meia-Idade
13.
J Pept Res ; 57(1): 11-8, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11168884

RESUMO

The present paper describes the synthesis and some pharmacological properties of two new bradykinin analogues containing the ethylene-bridged dipeptide Phe-Phe in their molecules. In a further two peptides this modification was combined with acylation of the N-terminus with 1-adamantaneacetic acid. Finally, we synthesized four analogues by removing the Ser6 residue from the four peptides mentioned above. The activity of the new analogues was assayed on isolated rat uterus (RUT) and in rat blood pressure tests (BPT). The results clearly indicate that the proposed modification, alone or in combination with other changes, resulted in either a drop in antiuterotonic activity or even in conversion to an agonism. Although this tendency is not so distinct in blood pressure assays, the antagonistic potency of the new analogues is also diminished. Nevertheless, it was demonstrated that the D-amino acid in position 7 which, until recently, was considered necessary for antagonism, may be replaced, together with the amino acid occupying position 8, by a suitable, sterically restricted L,L-dipeptide unit.


Assuntos
Adamantano/análogos & derivados , Adamantano/síntese química , Bradicinina/análogos & derivados , Bradicinina/síntese química , Peptídeos/química , Ácido Acético/química , Adamantano/farmacologia , Sequência de Aminoácidos , Aminoácidos/química , Animais , Pressão Sanguínea/efeitos dos fármacos , Bradicinina/farmacologia , Feminino , Masculino , Dados de Sequência Molecular , Fenilalanina/química , Conformação Proteica , Ratos , Ratos Wistar , Útero/efeitos dos fármacos
14.
Anticancer Res ; 20(5B): 3583-90, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11131666

RESUMO

BACKGROUND: The incidence of cancers of the digestive tract has been high among all of the cancers in Japan and the western hemisphere. The poor prognosis of patients, especially those with liver metastases, has become a great challenge for the development of a new drug to cope with this problem. MATERIALS AND METHODS: Mice implanted by intrasplenic injection of TMK-1, human gastric carcinoma cells, were used to examine the life-prolonging effect of TAC-101. To elucidate a mechanism of action of TAC-101, the drug-induced apoptosis was assessed by DNA ladder formation whilst the prevention of transcription factor AP-1 binding to its DNA recognition sequence was assessed by gel shift assay. RESULTS: TAC-101 showed the life prolonging effect in a model of experimental liver metastasis of TMK-1. The antitumor effect, expressed as T/C (%), was 201, 141 and 112%, for TAC-101 (2 mg/kg), ATRA (8 mg/kg) and 5-FU (19 mg/kg), respectively. The in vitro experiments revealed that the anticancer activity of TAC-101 is related to its ability to induce apoptosis within a short period of time in TMK-1 cells and human leukemic cells, HL-60. TAC-101-induced apoptosis was suppressed by the inhibitors of proteases, specifically by Z-Val-Ala-DL-Asp-fluoromethylketone, indicating the involvement of caspase activation. TAC-101 also inhibited, in a concentration-dependent manner, the binding of AP-1 to its DNA binding sites present in the promoter region of the genes involved in the control of cell migration, invasion, and angiogenesis. CONCLUSION: TAC-101 may suppress liver metastasis by the induction of an apoptotic mechanism(s) in cancer cells and possibly by controlling transcriptional activity of AP-1.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Benzoatos/farmacologia , Fator de Transcrição AP-1/antagonistas & inibidores , Compostos de Trimetilsilil/farmacologia , Animais , Divisão Celular/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/prevenção & controle , Neoplasias Hepáticas Experimentais/secundário , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Int J Epidemiol ; 29(5): 928-32, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11034980

RESUMO

BACKGROUND: To describe the seroepidemiology of Helicobacter pylori infection in a population of Egyptian children under 3 years. METHODS: A cohort of children under 36 months, residing in Abu Homos, Egypt, were visited at home twice weekly. Information regarding the child's breastfeeding status was obtained, and periodic anthropometric and household hygiene surveys were performed. In June 1997, a serosurvey was conducted on 187 study participants over 6 months old. The serosurvey was repeated in October 1997. All sera were tested for IgG antibodies to H. pylori. RESULTS: The June prevalence of H. pylori infection was 10%, and the incidence from June to October was 15%. Between June and October, 8 (42%) of 19 children that were positive for H. pylori infection seroreverted to negative. All seroreversions occurred in children 6-17 months. Other than age, no sociodemographic or environmental factor was significantly associated with incident H. pylori infection. There was no significant differences in the weight-for-age, weight-for-height, and height-for-age z-scores between children with and without prevalent H. pylori infection. CONCLUSIONS: Infection with H. pylori is common in Egyptian children under 3 years old and is not associated with malnutrition. No predictors for H. pylori infection were found. Our preliminary evidence for transient H. pylori infections in young children needs to be confirmed in a prospective cohort study, and predictors for persistent infection should be sought, since only these may be relevant to the known sequellae of infection.


Assuntos
Infecções por Helicobacter/epidemiologia , Helicobacter pylori , Antropometria , Pré-Escolar , Estudos de Coortes , Egito/epidemiologia , Feminino , Infecções por Helicobacter/sangue , Humanos , Higiene , Incidência , Lactente , Masculino , Prevalência , Estudos Soroepidemiológicos
16.
J Infect Dis ; 182(3): 685-90, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10950760

RESUMO

This study describes the epidemiology of astrovirus diarrhea among a population-based cohort of 397 children aged <3 years residing in rural Egypt from 1995 to 1998. The age-specific incidence rates of astrovirus diarrheal episodes per person-year were 0.38 for infants aged <6 months, 0.40 for those aged 6-11 months, 0.16 for those aged 12-23 months, and 0.05 for those aged 24-35 months. The overall incidence rate of astrovirus diarrhea was the same as that of rotavirus diarrhea, 0.19 episodes per person-year. Astrovirus infection was pathogenic and associated with severe dehydration in 17% of the cases. The most frequent serotype was HAstV-1, and, in order of decreasing frequency, HAstV-5, HAstV-8 and HAstV-3, HAstV-6, HAstV-4, and HAstV-2. In determining whether astrovirus diarrhea was associated with a reduced incidence of subsequent disease, there was evidence to suggest HAstV-1 homotypic immunity but not heterotypic immunity. Because we observed 38% of the incidence of astrovirus diarrhea to occur in infants aged <6 months, a candidate astrovirus vaccine would have to confer immunity very early in life.


Assuntos
Infecções por Astroviridae/epidemiologia , Diarreia/epidemiologia , Diarreia/virologia , Pré-Escolar , Estudos de Coortes , Egito/epidemiologia , Feminino , Humanos , Incidência , Lactente , Masculino , Mamastrovirus/classificação , Sorotipagem
17.
Am J Epidemiol ; 150(7): 770-7, 1999 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-10512431

RESUMO

Reliable epidemiologic data are essential for formulating effective policy to control rotavirus disease through immunization. The objective of this study was to describe the epidemiology of rotavirus diarrhea in a population-based cohort of children under 3 years of age residing in Abu Homos, Egypt, in 1995-1996. Rotavirus diarrhea incidence rates (episodes per person-year) were 0.13 for infants aged <6 months, 0.61 for those aged 6-11 months, 0.17 for those aged 12-23 months, and 0.15 for those aged 24-35 months. Fifty-six percent of children with rotavirus diarrhea had clinical dehydration; 90% of rotavirus diarrheal episodes occurred between July and November. In infants under 1 year of age, receipt of breast milk was associated with a lower incidence of rotavirus diarrhea. No other sociodemographic or environmental factor was found to be significantly associated with rotavirus diarrhea. Of 46 rotavirus isolates with strains identified, 41 (89%) were G serotypes 1 and 2. Rotavirus diarrhea was a major cause of morbidity in this cohort. Promotion of breastfeeding may exert a protective effect in young infants in this setting, but improvements in water and sanitation are unlikely to be effective preventive measures. The use of effective immunization against rotavirus in early infancy should be considered a public health priority.


PIP: This study describes the epidemiology of rotavirus diarrhea in a population-based cohort of children under 3 years of age residing in Abu Homos, Egypt, during 1995-96. Samples consisted of a cohort of children under the age of 24 months assembled from two villages in the vicinity of Abu Homos. The age-specific incidence rates of rotavirus diarrheal episodes per person-year were 0.13 for infants aged 6 months, 0.61 for those aged 6-11 months, 0.17 for those aged 12-23 months, and 0.15 for those aged 24-35 months. No rotavirus diarrheal incidence occurred in infants under 20 weeks of age. The monthly incidence rates of rotavirus diarrhea demonstrate that 90% of the disease episodes occurred during the warmer months of July-November, with a peak incidence in August. In infants under 1 year of age, breast-feeding was associated with a lower incidence of rotavirus diarrhea. Promotion of breast-feeding may employ a protective effect in young infants in this setting, but improvements in water and sanitation are unlikely to be effective preventive measures.


Assuntos
Diarreia Infantil/epidemiologia , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/prevenção & controle , Distribuição por Idade , Aleitamento Materno , Infecções por Campylobacter/epidemiologia , Estudos de Coortes , Diarreia Infantil/prevenção & controle , Diarreia Infantil/virologia , Disenteria Bacilar/epidemiologia , Egito/epidemiologia , Infecções por Escherichia coli/epidemiologia , Fezes/microbiologia , Fezes/virologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Fatores de Risco , Rotavirus/isolamento & purificação , Estações do Ano
18.
J Clin Microbiol ; 37(9): 2974-8, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10449484

RESUMO

No past studies of diarrhea in children of the Middle East have examined in detail the phenotypes of enterotoxigenic Escherichia coli (ETEC) strains, which are important pathogens in this setting. During a prospective study conducted from November 1993 to September 1995 with 242 children under 3 years of age with diarrhea living near Alexandria, Egypt, 125 episodes of diarrhea were positive for ETEC. ETEC strains were available for 98 of these episodes, from which 100 ETEC strains were selected and characterized on the basis of enterotoxins, colonization factors (CFs), and O:H serotypes. Of these representative isolates, 57 produced heat-stable toxin (ST) only, 34 produced heat-labile toxin (LT) only, and 9 produced both LT and ST. Twenty-three ETEC strains expressed a CF, with the specific factors being CF antigen IV (CFA/IV; 10 of 23; 43%), CFA/II (5 of 23; 22%), CFA/I (3 of 23; 13%), PCFO166 (3 of 23; 13%), and CS7 (2 of 23; 9%). No ETEC strains appeared to express CFA/III, CS17, or PCFO159. Among the 100 ETEC strains, 47 O groups and 20 H groups were represented, with 59 O:H serotypes. The most common O serogroups were O159 (13 strains) and O43 (10 strains). O148 and O21 were each detected in five individual strains, O7 and O56 were each detected in four individual strains, O73, O20, O86, and O114 were each detected in three individual strains, and O23, O78, O91, O103, O128, and O132 were each detected in two individual strains. The most common H serogroups were H4 (16 strains), 12 of which were of serogroup O159; H2 (9 strains), all of which were O43; H18 (6 strains); H30 (6 strains); and H28 (5 strains); strains of the last three H serogroups were all O148. Cumulatively, our results suggest a high degree of clonal diversity of disease-associated ETEC strains in this region. As a low percentage of these strains expressed a CF, it remains possible that other adhesins for which we either did not assay or that are as yet undiscovered are prevalent in this region. Our findings point out some potential barriers to effective immunization against ETEC diarrhea in this population and emphasize the need to identify additional protective antigens commonly expressed by ETEC for inclusion in future vaccine candidates.


Assuntos
Diarreia/microbiologia , Escherichia coli/classificação , Proteínas de Fímbrias , Proteínas de Bactérias/análise , Pré-Escolar , Escherichia coli/patogenicidade , Humanos , Lactente , Recém-Nascido , Fenótipo , Estudos Prospectivos , Sorotipagem
19.
Am J Trop Med Hyg ; 61(1): 37-40, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10432052

RESUMO

Helicobacter pylori is one of the most common human bacterial infections in the world and children in the developing countries acquire H. pylori infection early in life. We prospectively evaluated the prevalence of serum antibodies to H. pylori in a cohort of pregnant women and their offspring. Mothers' sera were collected during the third trimester of pregnancy and sera from their offspring were collected when they were 7-9 months and 18 months of age. Pylori-Stat, a commercially available ELISA kit, was used to detect antibodies to H. pylori in the serum of the subjects tested. Sera from 169 mothers were available for testing and 88% of these samples were positive for anti-H. pylori IgG. Of the 169 children tested, 13% of the infants 7-9 months of age and 25% of the children 18 months of age had serologic evidence of H. pylori infection. These data indicate that infection with H. pylori is common in Egypt and acquisition of infection occurs at a very young age.


Assuntos
Infecções por Helicobacter/epidemiologia , Helicobacter pylori/isolamento & purificação , Mães , Adolescente , Adulto , Anticorpos Antibacterianos/sangue , Estudos de Coortes , Escolaridade , Egito/epidemiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Humanos , Lactente , Análise Multivariada , Gravidez , Terceiro Trimestre da Gravidez/sangue , Estudos Prospectivos , Análise de Regressão , Estudos Soroepidemiológicos , Inquéritos e Questionários
20.
Pediatrics ; 104(1): e3, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10390289

RESUMO

BACKGROUND: Initiation of breastfeeding shortly after delivery may enhance breastfeeding's protective effect against diarrhea because of the protective properties of human colostrum contained in early breast milk. OBJECTIVE: To evaluate whether initiation of breastfeeding within the first 3 days of life, when breast milk contains colostrum, was associated with a lower rate of diarrhea in rural Egyptian infants during the first 6 months of life. METHODS: Infants initially breastfed (n = 198) were monitored prospectively with twice-weekly home visits to ascertain dietary practices and diarrheal illnesses. RESULTS: The burden of diarrhea during the first 6 months of life in the cohort was high: seven episodes per child-year of follow-up. Only 151 (76%) infants initiated breastfeeding during the first 3 days of life ("early initiation"). Infants in whom breastfeeding was initiated early had a 26% (95% CI: 2%,44%) lower rate of diarrhea than those initiated late. The protective association between early initiation and diarrhea was independent of the pattern of postinitiation dietary practices and was evident throughout the first 6 months of life. CONCLUSIONS: Early initiation of breastfeeding was associated with a marked reduction of the rate of diarrhea throughout the first 6 months of life, possibly because of the salutary effects of human colostrum. These data highlight the need for interventions to encourage early initiation of breastfeeding in less developed settings.


Assuntos
Aleitamento Materno , Diarreia Infantil/prevenção & controle , Aleitamento Materno/estatística & dados numéricos , Estudos de Coortes , Colostro/imunologia , Diarreia Infantil/epidemiologia , Egito , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Análise Multivariada , Saúde da População Rural , Análise de Sobrevida , Fatores de Tempo
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