RESUMO
OBJECTIVE: Controlling vaccine-preventable infectious diseases is a public health priority in French Guiana but there is currently no epidemiological data on pediatric bacterial meningitis in this overseas department. Our aim was to describe data related to pediatric bacterial meningitis in French Guiana and compare it with that of metropolitan France. METHODS: We conducted a multicenter retrospective study from 2000 to 2010 to describe the clinical picture, biological data, epidemiology, and outcome of pediatric bacterial meningitis case patients in French Guiana. RESULTS: The median age of bacterial meningitis patients was 6months [0-15] and the sex ratio 1.06. We observed a total of 60 bacterial meningitis case patients. Most presented with pneumococcal meningitis (24 patients; 40%); 11 with Haemophilus influenzae type b meningitis (23%), five with group B streptococcal meningitis (8.5%), and five others (8.5%) with staphylococcal meningitis (three patients presented with coagulase-negative staphylococci and two with Staphylococcus aureus). Only one patient presented with group B meningococcal meningitis, an 18-month-old infant. We recorded 14 deaths (overall case fatality: 23%); eight were due to Streptococcus pneumoniae (case fatality: 33%). The overall sequelae rate was 28%. It was 32% for patients presenting with pneumococcal meningitis. We observed that 38% of children who had never been vaccinated were infected by a vaccine-preventable bacterium. We observed many differences in the distribution of the bacteria and in the patients' prognosis when comparing the French Guiana data with that of metropolitan France. CONCLUSION: Improving vaccination coverage would decrease the incidence of H. influenzae meningitis.
Assuntos
Meningites Bacterianas/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , França/epidemiologia , Guiana Francesa/epidemiologia , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
Beraprost sodium (BPS) is a prostaglandin analogue. We investigated its effects on rats with diabetic nephropathy. There were 20 rats each in the normal control group (NC), the diabetic nephropathy group (DN), and the BPS treatment group. The rats in DN and BPS groups were given a high-fat diet combined with low-dose streptozotocin intraperitoneal injections. The rats in the BPS group were given daily 0.6 mg/kg intraperitoneal injections of this drug. After 8 weeks, blood glucose, 24-h UAlb, Cr, BUN, hs-CRP, and IL-6 levels increased significantly in the DN group compared with the NC group; however, the body mass was significantly reduced in the DN group compared with the NC group. Blood glucose, urine output, 24-h UAlb, Cr, hs-CRP, and IL-6 levels were significantly lower in the BPS group than in the DN group; the body mass was significantly greater in the DN group. Therefore, we concluded that BPS can improve renal function and protect the kidneys of DN rats by reducing oxidative stress and generation of inflammatory cytokines; it also decreases urinary protein excretion of rats with diabetic nephropathy.
Assuntos
Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/tratamento farmacológico , Epoprostenol/análogos & derivados , Rim/efeitos dos fármacos , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Dieta Hiperlipídica , Epoprostenol/administração & dosagem , Epoprostenol/uso terapêutico , Interleucina-6/análise , Testes de Função Renal , Masculino , Ratos , Ratos Sprague-Dawley , EstreptozocinaRESUMO
MicroRNAs (miRNAs) are small RNA molecules that modulate gene expression implicated in cancer, which play crucial roles in diverse biological processes, such as development, differentiation, apoptosis, and proliferation. The aim of this study was to investigate whether miR-30c mediated the resistance of breast cancer cells to the chemotherapeutic agent doxorubicin (ADR) by targeting tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ). miR-30c was downregulated in the doxorubicin-resistant human breast cancer cell lines MCF-7/ADR and MDA-MB-231/ADR compared with their parental MCF-7 and MDA-MB-231 cell lines, respectively. Furthermore, we observed that transfection of an miR-30c mimic significantly suppressed the ability of MCF-7/ADR to resist doxorubicin. Moreover, the anti-apoptotic gene YWHAZ was confirmed as a target of miR-30c by luciferase reporter assay, and further studies indicated that the mechanism for miR-30c on the sensitivity of breast cancer cells involved YWHAZ and its downstream p38 mitogen-activated protein kinase (p38MAPK) pathway. Together, our findings provided evidence that miR-30c was one of the important miRNAs in doxorubicin resistance by regulating YWHAZ in the breast cancer cell line MCF-7/ADR.
Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos , MicroRNAs/fisiologia , Animais , Resistencia a Medicamentos Antineoplásicos/genética , Ativação Enzimática/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Células MCF-7 , Camundongos , MicroRNAs/genética , Triptofano Hidroxilase/efeitos dos fármacos , Tirosina 3-Mono-Oxigenase/efeitos dos fármacosRESUMO
MicroRNAs (miRNAs) are small RNA molecules that modulate gene expression implicated in cancer, which play crucial roles in diverse biological processes, such as development, differentiation, apoptosis, and proliferation. The aim of this study was to investigate whether miR-30c mediated the resistance of breast cancer cells to the chemotherapeutic agent doxorubicin (ADR) by targeting tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ). miR-30c was downregulated in the doxorubicin-resistant human breast cancer cell lines MCF-7/ADR and MDA-MB-231/ADR compared with their parental MCF-7 and MDA-MB-231 cell lines, respectively. Furthermore, we observed that transfection of an miR-30c mimic significantly suppressed the ability of MCF-7/ADR to resist doxorubicin. Moreover, the anti-apoptotic gene YWHAZ was confirmed as a target of miR-30c by luciferase reporter assay, and further studies indicated that the mechanism for miR-30c on the sensitivity of breast cancer cells involved YWHAZ and its downstream p38 mitogen-activated protein kinase (p38MAPK) pathway. Together, our findings provided evidence that miR-30c was one of the important miRNAs in doxorubicin resistance by regulating YWHAZ in the breast cancer cell line MCF-7/ADR.
Assuntos
Animais , Feminino , Humanos , Camundongos , Antibióticos Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Doxorrubicina/farmacologia , MicroRNAs/fisiologia , Resistencia a Medicamentos Antineoplásicos/genética , Ativação Enzimática/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , MicroRNAs/genética , Triptofano Hidroxilase/efeitos dos fármacos , /efeitos dos fármacosRESUMO
Methylenetetrahydrofolate reductase (MTHFR) plays an important role in folate metabolism and is involved in DNA synthesis, DNA repair and DNA methylation. The two common functional polymorphisms of MTHFR, C677T and A1298C have been associated with several diseases, including cancer. We made a case-control study to analyze a possible association of MTHFR gene polymorphisms C677T and A1298C with risk for colorectal cancer in an eastern Chinese Han population of 137 patients with a confirmed histopathological diagnosis of CRC and 145 age- and gender-matched controls with no history of cancer. DNA was isolated from peripheral blood samples and the genotypes were determined by PCR-RFLP. The concentrations of folate in plasma were measured by chemiluminescence immunoassay. The MTHFR 677TT genotype had a protective effect against colorectal cancer, with an odds ratio (OR) = 0.467 (95% confidence interval (CI) = 0.225-0.966). The 1298CC genotype was significantly correlated with a reduced risk of colorectal cancer (OR = 0.192; 95%CI = 0.040-0.916). Compared with the MTHFR 677CC and MTHFR 1298 AA genotypes, for individuals who carried both MTHFR 677CC and 1298CC genotypes, the OR of colorectal cancer was 0.103 (95%CI = 0.012-0.900); among individuals who carried both MTHFR 677TT and 1298AC genotypes, the OR for risk of colorectal cancer was 0.169 (95%CI = 0.044-0.654). MTHFR 677TT+CT genotypes had a significantly lower plasma folate concentration than those with the MTHFR 677CC genotype. MTHFR 1298AC+CC genotypes had a lower plasma folate concentration than those with the MTHFR 1298AA genotype (P < 0.05). In conclusion, subjects with the MTHFR 677TT and MTHFR 1298CC genotypes appeared to have a significantly lower risk for colorectal cancer. MTHFR haplotypes 677CC/1298CC and 677TT/1298AC were less common in cases than in controls. These haplotypes, when compared to the most common haplotype 677CC/1298AA, were associated with a decreased risk for colorectal cancer. We conclude that plasma folate level is influenced by MTHFR genotypes.
Assuntos
Povo Asiático/genética , Neoplasias Colorretais/genética , Etnicidade/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Idoso , China , Neoplasias Colorretais/sangue , Neoplasias Colorretais/enzimologia , Feminino , Ácido Fólico/sangue , Genética Populacional , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de RestriçãoRESUMO
Apoptosis is an essential physiological process that regulates cellular proliferation. Here, we explored the effect of DNA sequence variation within the BCL-2 gene on prostate cancer susceptibility in three clinical populations, consisting of 428 African Americans, 214 Jamaicans and 218 European Americans. We observed a 70% reduced risk for prostate cancer among the European Americans who had possessed two copies of a promoter variant -938C/A. Additionally, common BCL-2 haplotypes appeared to influence prostate cancer risk; however, studies in larger data sets are needed to confirm our findings. Our data suggest that inherited BCL-2 variants may be associated with a decrease in prostate cancer susceptibility.
Assuntos
Carcinoma/genética , Predisposição Genética para Doença , Variação Genética , Mutação em Linhagem Germinativa , Neoplasias da Próstata/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Adulto , Negro ou Afro-Americano/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Frequência do Gene , Genótipo , Haplótipos , Humanos , Padrões de Herança , Jamaica/etnologia , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Fases de Leitura Aberta , Elementos Reguladores de Transcrição , População Branca/genéticaRESUMO
Approximately 15 human papillomavirus (HPV) types cause virtually all cervical cancer whereas other HPV types are unrelated to cancer. We were interested in whether some noncarcinogenic types differ from carcinogenic in their affinity for the cervical transformation zone, where nearly all HPV-induced cancers occur. To examine this possibility, we tested cervical specimens from 8,374 women without cervical precancer and cancer participating in a population-based study in Guanacaste for >40 HPV types using PCR. We compared age-group specific prevalences of HPV types of the alpha9 species, which are mainly carcinogenic and include HPV16, to the genetically distinct types of the alpha3/alpha15 species (e.g., HPV71), which are noncarcinogenic and common in vaginal specimens from hysterectomized women. We related HPV detection of each group to the location of the junction between the squamous epithelium of the ectocervix and vagina and the columnar epithelium of the endocervical canal. Models evaluated the independent effects of amount of exposed columnar epithelium (ectopy) and age on the presence of alpha9 or alpha3/alpha15 types. Prevalence of alpha9 types (7.6%) peaked in the youngest women, declined in middle-aged women, and then increased slightly in older women. By contrast, prevalence of alpha3/alpha15 types (7.6%) tended to remain invariant or to increase with increasing age. Detection of alpha9 infections increased (P(trend) < 0.0005) but alpha3/alpha15 infections decreased (P(trend) < 0.0005) with increasing exposure of the columnar epithelia. Older age and decreasing cervical ectopy were independently positively associated with having an alpha3/alpha15 infection compared with having an alpha9 infection. These patterns need to be confirmed in other studies and populations. We suggest that these genetically distinct groups of HPV types may differ in tissue preferences, which may contribute to their differences in carcinogenic potential.
Assuntos
Papillomaviridae/genética , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/virologia , Adulto , Fatores Etários , Idoso , Transformação Celular Neoplásica , Costa Rica/epidemiologia , DNA Viral/análise , Estudos Epidemiológicos , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Lesões Pré-Cancerosas , Prevalência , Vagina/virologiaRESUMO
Osteoarthritis is a common rheumatic disease. Limitations of conventional medical management of this condition indicate a real need for safe and effective treatment of osteoarthritic patients. The authors review the clinical evidence for and against the effectiveness of homeopathic medicines in the... (AU)
Assuntos
Humanos , Osteoartrite/terapia , HomeopatiaRESUMO
Turner syndrome is associated with insulin resistance, increased incidence of type II diabetes, and hypertension, all of which are cardiovascular risk factors. The purpose of this study was to evaluate the lipid profile of girls with untreated Turner syndrome, (aged 5 to 14 years; 68% 45,XO) and age-matched, normal girls. A total of 137 girls with Turner syndrome and 70 normal girls had lipid profile measurements, including cholesterol, high-density lipoprotein cholesterol, and triglycerides. Older girls with Turner syndrome (> 11.0 years) had increased cholesterol levels (p < 0.01), compared with control values (190 +/- 38 vs 165 +/- 26 mg/dl). Cholesterol levels were elevated in older subjects with Turner syndrome versus normal subjects, after adjustment for age, karyotype, and body mass index z score effects (p = 0.01). In the subjects with Turner syndrome but not the normal subjects, serum cholesterol values correlated with age, weight, and body mass index z score (p < 0.02). We conclude that adolescent girls with untreated Turner syndrome have significantly increased cholesterol levels, independent of age, body mass index z score, or karyotype, and that these precede any treatment with exogenous estrogen or growth hormone.
Assuntos
Lipídeos/sangue , Síndrome de Turner/sangue , Adolescente , Envelhecimento/sangue , Análise de Variância , Antropometria , Criança , Pré-Escolar , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Análise de Regressão , Triglicerídeos/sangueRESUMO
We randomly assigned 16 girls with Turner syndrome, age 5 to 15 years, to receive treatment with 100 ng/kg/day ethinyl estradiol or placebo for 6 months, with crossover after a 2-month interim period. We assessed growth by measurement of the 4-week lower leg growth rate and by height velocity. Bone age was determined at the beginning and end of treatment. Growth rate during ethinyl estradiol treatment was approximately 70% greater than during placebo (P less than 0.001), without any bone age advancement relative to that with placebo. The change in predicted height was significantly greater after 6 months treatment with ethinyl estradiol than after treatment with placebo (mean +/- SEM, +0.35 +/- 0.38 cm vs. -0.85 +/- 0.32 cm, P less than 0.03). Breast budding occurred in six patients. We conclude that it may be feasible to begin low-dose estrogen therapy to promote growth at an earlier age than would be conventionally used to induce pubertal development. These data are still relatively short term, however; until long-term data are available, it would be premature to make definitive recommendations regarding the dose and timing of estrogen treatment in Turner syndrome.
Assuntos
Estatura/efeitos dos fármacos , Etinilestradiol/uso terapêutico , Crescimento/efeitos dos fármacos , Síndrome de Turner/tratamento farmacológico , Adolescente , Determinação da Idade pelo Esqueleto , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Etinilestradiol/administração & dosagem , Feminino , Humanos , Perna (Membro) , Distribuição AleatóriaRESUMO
We investigated whether a decrease in serum growth hormone contributes to the short stature of adults with Turner syndrome by measuring the 24-hour profile of serum growth hormone in 30 patients aged 2 to 20 years. Growth hormone pulses were defined as a rise from nadir to peak that exceeded three times the intraassay coefficient of variation. Girls with Turner syndrome aged 2 to 8 years did not have statistically different growth hormone levels, peak amplitudes, and peak frequencies compared with those in age-matched controls. By contrast, girls with Turner syndrome aged 9 to 20 years had significantly decreased mean 24-hour growth hormone levels, peak amplitudes, and peak frequencies compared with those in age-matched normal girls. Patients with Turner syndrome of all ages had decreased serum somatomedin-C concentrations and delayed bone ages. We conclude that a relative deficiency of growth hormone in pubertal patients with Turner syndrome may contribute to their adult short stature.