RESUMO
OBJECTIVE: This study aimed to analyze the prognostic factors for overall and progression-free survival in patients with vulvar cancer. METHODS: This international, multicenter, retrospective study included 2453 patients diagnosed with vulvar cancer at 100 different institutions. Inclusion criteria were institutional review board approval from each collaborating center, pathologic diagnosis of invasive carcinoma of the vulva, and primary treatment performed at the participating center. Patients with intraepithelial neoplasia or primary treatment at non-participating centers were excluded. Global survival analysis and squamous cell histology subanalysis was performed. RESULTS: After excluding patients due to incomplete data entry, 1727 patients treated for vulvar cancer between January 2001 and December 2005 were registered for analysis (1535 squamous, 42 melanomas, 38 Paget's disease and 112 other histologic types). Melanomas had the worse prognosis (p=0.02). In squamous vulvar tumors, independent factors for increase in local recurrence of vulvar cancer were: no prior radiotherapy (p<0.001) or chemotherapy (p=0.006), and for distant recurrence were the number of positive inguinal nodes (p=0.025), and not having undergone lymphadenectomy (p=0.03) or radiotherapy (p<0.001), with a HR of 1.1 (95% CI 1.2 to 1.21), 2.9 (95% CI 1.4 to 6.1), and 3.1 (95% CI 1.7 to 5.7), respectively. Number of positive nodes (p=0.008), FIGO stage (p<0.001), adjuvant chemotherapy (p=0.001), tumor resection margins (p=0.045), and stromal invasion >5 mm (p=0.001) were correlated with poor overall survival, and large case volume (≥9 vs <9 cases per year) correlated with more favorable overall survival (p=0.05). CONCLUSIONS: Advanced patient age, number of positive inguinal lymph nodes, and lack of adjuvant treatment are significantly associated with a higher risk of relapse in patients with squamous cell vulvar cancer. Case volume per treating institution, FIGO stage, and stromal invasion appear to impact overall survival significantly. Future prospective trials are warranted to establish these prognostic factors for vulvar cancer.
Assuntos
Neoplasias Vulvares/epidemiologia , Neoplasias Vulvares/mortalidade , Idoso , Feminino , Humanos , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
BACKGROUND: The frequency of deficient variants of glucose-6-phosphate dehydrogenase (G6PDd) is particularly high in areas where malaria is endemic. The administration of antirelapse drugs, such as primaquine, has the potential to trigger an oxidative event in G6PD-deficient individuals. According to Honduras´ national scheme, malaria treatment requires the administration of chloroquine and primaquine for both Plasmodium vivax and Plasmodium falciparum infections. The present study aimed at investigating for the first time in Honduras the frequency of the two most common G6PDd variants. METHODS: This was a descriptive study utilizing 398 archival DNA samples of patients that had been diagnosed with malaria due to P. vivax, P. falciparum, or both. The most common allelic variants of G6PD: G6PD A+(376G) and G6PD A-(376G/202A) were assessed by two molecular methods (PCR-RFLP and a commercial kit). RESULTS: The overall frequency of G6PD deficient genotypes was 16.08%. The frequency of the "African" genotype A- (Class III) was 11.9% (4.1% A- hemizygous males; 1.5% homozygous A- females; and 6.3% heterozygous A- females). A high frequency of G6PDd alleles was observed in samples from malaria patients residing in endemic regions of Northern Honduras. One case of Santamaria mutation (376G/542T) was detected. CONCLUSIONS: Compared to other studies in the Americas, as well as to data from predictive models, the present study identified a higher-than expected frequency of genotype A- in Honduras. Considering that the national standard of malaria treatment in the country includes primaquine, further research is necessary to ascertain the risk of PQ-triggered haemolytic reactions in sectors of the population more likely to carry G6PD mutations. Additionally, consideration should be given to utilizing point of care technologies to detect this genetic disorder prior administration of 8-aminoquinoline drugs, either primaquine or any new drug available in the near future.
Assuntos
Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Feminino , Frequência do Gene , Deficiência de Glucosefosfato Desidrogenase/sangue , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Deficiência de Glucosefosfato Desidrogenase/genética , Honduras/epidemiologia , Humanos , Malária Falciparum/parasitologia , Malária Vivax/parasitologia , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , PrevalênciaRESUMO
Only one fourth of Texas counties have a local health authority (LHA) or health district. Primary care physicians in the remaining counties could be trained in public health basics by providing an online LHA training course and courses at annual meetings of the Texas Medical Association and the Texas Academy of Family Physicians. The Texas Department of State Health Services should develop a web portal for LHAs. The Texas Association of Local Health Officials should also provide automatic limited membership for LHAs. These initiatives would provide public health training to primary care physicians and would greatly improve availability of public health services for the citizens of Texas.
Assuntos
Governo Local , Médicos de Atenção Primária/educação , Saúde Pública , Certificação , Humanos , Papel do Médico , Administração em Saúde Pública , Serviços de Saúde Rural , Texas , Recursos HumanosRESUMO
Parents of children who attend Head Start Centers are key participants in the health promotion and care of their own children. This non-randomized, longitudinal study aimed to test the effectiveness of an educational intervention based on the asthma and healthy homes curriculum targeting parents of Head Start children with or without an asthma diagnosis. One hundred and fifteen parents of children in Head Start Centers received an educational intervention at their corresponding sites, additionally pre- and post-test surveys were administered to measure educational intervention outcomes. A follow-up survey was conducted 6 months after the educational intervention was offered. Results showed a statistically significant increase in asthma and healthy home-knowledge (p < 0.001) in several areas. At 6 months post-intervention (54.4 %) (61 participants) were contacted and 98.4 % of made changes in their households as a result of their training. This study suggests that education can improve knowledge and change behaviors for the well-being of the residents of that household.
Assuntos
Asma/prevenção & controle , Educação em Saúde , Conhecimentos, Atitudes e Prática em Saúde , Promoção da Saúde/métodos , Pais/educação , Asma/diagnóstico , Creches , Pré-Escolar , Currículo , Avaliação Educacional , Feminino , Seguimentos , Habitação , Humanos , Masculino , Pais/psicologia , TexasRESUMO
The pharmaceuticals industry is one of the main industries in Jordan. Jordanian pharmaceuticals rank third in the export industry of this country. This study aims to examine the strengths that Jordanian pharmaceutical companies have, which, in turn, form their competitiveness base. In addition, this study aims to identify their weaknesses and the effects of marketing their products in the local market. What is the relationship between Jordanian pharmaceutical product quality, price and value, and the competitiveness of pharmaceutical companies in the local market? Our study aims to answer this and other questions. Our results and practical implications are discussed.
Assuntos
Indústria Farmacêutica/organização & administração , Competição Econômica/organização & administração , Marketing/organização & administração , Comércio/organização & administração , Escolaridade , Feminino , Humanos , Renda , Jordânia , MasculinoRESUMO
Anopheles albitarsis F is a putative species belonging to the Albitarsis Complex, recognized by rDNA, mtDNA, partial white gene, and microsatellites sequences. It has been reported from the island of Trinidad, Venezuela and Colombia, and incriminated as a vector of malaria parasites in the latter. This study examined mitochondrially encoded cytochrome c oxidase I (MT-CO1) sequences of An. albitarsis F from malaria-endemic areas in Colombia and Venezuela to understand its relations with other members of the Complex, revised and update the geographical distribution and bionomics of An. albitarsis F and explore hypotheses to explain its phylogenetic relationships and geographical expansion. Forty-five MT-CO1 sequences obtained in this study were analyzed to estimate genetic diversity and possible evolutionary relationships. Sequences generated 37 haplotypes clustered in a group where the genetic divergence of Venezuelan populations did not exceed 1.6% with respect to Colombian samples. Anopheles albitarsis F (π = 0.013) represented the most recent cluster located closer to An. albitarsis I (π = 0.009). Barcode gap was detected according to Albitarsis Complex lineages previously reported (threshold 0.014-0.021). Anopheles albitarsis F has a wide distribution in northern South America and might play an important role in the transmission dynamics of malaria due to its high expansion capacity. Future studies are required to establish the southern distribution of An. albitarsis F in Venezuela, and its occurrence in Guyana and Ecuador.
Assuntos
Distribuição Animal , Anopheles/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Variação Genética , Haplótipos , Animais , DNA Mitocondrial/genética , Mosquitos Vetores , Filogenia , América do SulRESUMO
OBJECTIVE: Identify racial/ethnic differences among people with multiple sclerosis (MS) in demographics, MS disease characteristics, and health services received. PARTICIPANTS: We analyzed enrollment data from the Registry of the North American Research Committee on Multiple Sclerosis (NARCOMS) Project to compare 26,967 Caucasians, 715 Latinos, and 1,313 African Americans with MS. DESIGN: Racial/ethnic analyses of NARCOMS data focused on descriptive characteristics, using ANOVA and chi-square tests to identify significant differences in means and frequencies among Caucasians, Latinos, and African Americans. RESULTS: We identified significant racial/ethnic differences in demographics, MS disease characteristics, and treatments. Caucasians were older when first MS symptoms were experienced (30.1 years) and at MS diagnosis (37.4 years) than Latinos (28.6 years and 34.5 years) or African Americans (29.8 years and 35.8 years). Larger proportions of Latinos reported normal function for mobility and bladder/bowel function compared to Caucasians. Larger proportions of Latinos (44.2 percent) and African Americans (45.8 percent) reported at least mild depression compared to only 38.7 percent of Caucasians. Larger proportions of Latinos never received mental health care or care from rehabilitation specialists than Caucasians or African Americans. A larger proportion of African Americans had never been treated by a neurologist specializing in MS and a smaller proportion of African Americans received care at a MS clinic than Caucasians or Latinos. CONCLUSIONS: Our findings highlight the need for future analyses to determine if age, disease duration, MS symptoms, and disability levels provide additional insights into racial/ethic differences in the use of MS-related providers.
Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , Esclerose Múltipla/etnologia , População Branca/estatística & dados numéricos , Análise de Variância , Distribuição de Qui-Quadrado , Pessoas com Deficiência/estatística & dados numéricos , Progressão da Doença , Feminino , Serviços de Saúde/estatística & dados numéricos , Humanos , Masculino , Projetos Piloto , Sistema de Registros , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: This paper proposes an analytical approach to the assessment of geographic population health disparities that are measured as the consolidation of public health related indicators into geographic-specific scores, and are representative of the level of public health capability within counties in the state of Mississippi. STUDY DESIGN: A multi-criteria decision model was employed to develop an additive scoring system that assigns a numerical score of public health capability disparities for a geographical area (county). METHODS: Routinely collected indicators were used to measure each county's current public health related concerns. These indicators include access, risks, health care quality, and outcomes data. Public health experts rated and ranked indicators to generate indicator weight. RESULTS: A county score was developed to rank Mississippi counties based on relative public health capability. This scoring system depicts population health disparities among Mississippi counties. CONCLUSIONS: The model is useful and ideal for establishing expectations and benchmarks for reduction or equalization of disparities. This information can be used to manage geographic population health disparities by guiding policy formulation and implementation.
Assuntos
Planejamento em Saúde Comunitária/métodos , Técnicas de Apoio para a Decisão , Disparidades nos Níveis de Saúde , Indicadores Básicos de Saúde , Saúde Pública/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde , Humanos , Mississippi , Qualidade da Assistência à Saúde , Medição de RiscoRESUMO
BACKGROUND: We investigated the relationship between Body Mass Index (BMI) and health-related quality of life (HRQOL) indicated by baseline health status in elementary school children. METHODS: Data were obtained via parents whose children enrolled in an elementary school, kindergarten to fourth grade, in southern Mississippi in spring 2004. Parents completed the SF-10 for Children, a brief 10-item questionnaire designed to measure children's HRQOL on a voluntary basis. RESULTS: A total of 279 parents completed the questionnaires for their children. On average, physical and psychosocial summary scores, major indicators for HRQOL, were significantly higher among the elementary school children in our study relative to those from U.S. children overall (p < 0.0001 and p = 0.0007, respectively). Males tended to have better physical functioning than their female classmates, whereas females had better psychosocial health. Overall, except for third graders, the physical summary scores increased as grade level increased. The means for psychosocial score fluctuated without a clear pattern over the five grade levels. High level of BMI was significantly associated with children's physical summary scores below 50, a norm used for U.S. children (p = 0.003). Gender and grade were not significant predictors of children's physical and psychosocial scores. DISCUSSION: This study can be used as baseline information to track changes over time, in BMI and health status among the elementary school children. In addition, this study can be used to investigate relationships between BMI, health status, intellectual ability, and performance in school. CONCLUSION: The findings suggest that programs designed to encourage children to lose weight in a healthy manner, thus reducing their BMI, could improve the physical and psychosocial health, and subsequently increase HRQOL.
Assuntos
Índice de Massa Corporal , Indicadores Básicos de Saúde , Sobrepeso/psicologia , Psicologia da Criança , Qualidade de Vida , Magreza/psicologia , Peso Corporal , Criança , Pré-Escolar , Feminino , Nível de Saúde , Humanos , Masculino , Mississippi , Relações Pais-Filho , Pais , Projetos Piloto , Procurador , Psicometria , Instituições Acadêmicas , Ajustamento Social , Inquéritos e QuestionáriosRESUMO
Many patients previously using darunavir/ritonavir (DRV/r) (800/100mg) have switched to darunavir/cobicistat (DRV/C) (800/150 mg) either as part of triple therapy (ART) or as monotherapy with DRV (mDRV). The latter approach continues to be used in some countries for patients receiving long-term treatment. However, to date, the behaviour of DRV/C in the seminal compartment has not been analysed. This study explores how the combination behaves in monotherapy, with respect to the control of viral load and seminal quality. To this end, we studied 20 patients who were treated with mDRV/C after previous treatment with mDRV/r for at least 24 weeks. A viral load control in seminal plasma similar to that published in the literature was observed after 24 weeks of treatment with mDRV/C (viral load positivity in 20% of patients). Similarly, semen quality was confirmed (70% normozoospermic) in patients treated with this formulation, as has previously been reported for ART and mDRV/r. The DRV levels measured in seminal plasma were above EC50, regardless of whether the seminal viral load was positive or negative. We conclude that this mDRV/C co-formulation behaves like mDRV/r in seminal plasma in terms of viral load control and semen quality.
Assuntos
Cobicistat/administração & dosagem , Darunavir/administração & dosagem , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/administração & dosagem , Sêmen/efeitos dos fármacos , Carga Viral/efeitos dos fármacos , Adulto , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Cobicistat/efeitos adversos , Estudos de Coortes , Darunavir/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Infecções por HIV/virologia , Inibidores da Protease de HIV/efeitos adversos , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Sêmen/virologia , Análise do SêmenRESUMO
BACKGROUND: Previous medication management research has focused on hospital and long-term care facility settings, where drug-utilization reviews are used to reduce medication errors. Patients receiving home health care (HHC) are without the benefit of systematic drug-utilization reviews. OBJECTIVE: The purpose of this study was to review medication use in elderly patients receiving HHC to identify the prevalence of potentially inappropriate medication (PIM) use, dangerous drug interactions (DDIs), and other patterns of medication use. METHODS: This retrospective chart review was conducted using data from Medicare recipients aged > or =65 years who were patients of Scott & White Memorial Hospital and Clinic, Scott, Sherwood and Brindley Foundation, Temple, Texas, in 2002. Pharmacists compiled medication profiles based on admissions data. PIM use was identified using the Beers criteria. DDIs were identified using the Multidisciplinary Medication Management Project criteria. Polyphsarmsacy was identified in patients receiving > or =9 medications. RESULTS: Data from 786 patients were included (mean [SD] age, 78 [7] years [range, 65-100 years; median, 78 years]; 36% men; 86% white; and 53% admitted to HHC after a hospital stay). The mean (SD) number of medications was 8.0 (3.7), with 39% of patients receiving polypharmacy. PIM use was identified in 31% of patients. DDIs were identified in 10% of patients, with a significantly higher prevalence in men (P < 0.01). Rates of PIM use and DDIs were 37% and 20%, respectively, in patients receiving polypharmacy. CONCLUSION: In this retrospective data analysis in this population of elderly patients receiving HHC in 2002, PIM and DDI were prevalent, and polypharmacy was associated with increased rates of PIM use and DDIs.
Assuntos
Tratamento Farmacológico/estatística & dados numéricos , Revisão de Uso de Medicamentos , Serviços de Assistência Domiciliar/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Interações Medicamentosas , Feminino , Humanos , Masculino , Polimedicação , Estudos RetrospectivosRESUMO
Patients with human immunodeficiency virus type 1 (HIV-1) who receive antiretroviral therapy (ART) often achieve increased survival and improved quality of life. In this respect, monotherapy with darunavir/ritonavir (mDRV/r) can be a useful treatment strategy. This prospective study analyses the effect of mDRV/r on sperm quality and viral load in a group of 28 patients who had previously been given conventional ART and who had recorded a viral load <20 copies/mL for at least six months. These patients were given mDRV/r at a dose of 800/100 mg for 48 weeks. At baseline (V0), CD4, CD8, FSH, LH and testosterone levels were measured, together with HIV-1 viral load in plasma and semen. In addition, seminal fluid quality was studied before mDRV/r treatment was prescribed. At week 48 (V1), HIV-1 viral load in plasma and semen and the quality of the seminal fluid were again measured. The results obtained indicate that at V0, 10% of the patients with ART had a positive viral load in seminal fluid (>20 copies/ml), and that at V1, after mDRV/r treatment, this figure had fallen to 3%. The quality of seminal fluid was close to normal in 57% of patients at V0 and in 62% at V1. We conclude that, similar to ART, mDRV/r maintains HIV-1 viral load in most patients, and that there is no worsening in seminal fluid quality.
Assuntos
Darunavir/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Ritonavir/uso terapêutico , Sêmen/virologia , Adulto , Terapia Antirretroviral de Alta Atividade , Darunavir/farmacologia , Quimioterapia Combinada , Humanos , Masculino , Ritonavir/farmacologia , Sêmen/efeitos dos fármacos , Carga Viral/efeitos dos fármacosRESUMO
BACKGROUND: This study was conducted to assess the presence and/or absence of cross-cultural differences or similarities between Korean and United States cataract patients. A systematic assessment was performed using utility and psychometric measures in the study population. RESEARCH DESIGN: A cross-sectional study design was used to examine the comparison of preoperative outcomes measures in cataract patients in Korea and the United States. Study subjects were selected using non-probabilistic methods and included 132 patients scheduled for cataract surgery in one eye. PARTICIPANTS: Subjects were adult cataract patients at Samsung and Kunyang General Hospital in Seoul, Korea, and Tulane University Hospital and Clinics in New Orleans, Louisiana. MEASUREMENTS: Preoperative utility was assessed using the verbal rating scale and standard reference gamble techniques. Current preoperative health status was assessed using the SF-36 and VF-14 surveys. Current preoperative Snellen visual acuity was used as a clinical measure of vision status. RESULTS: Korean patients were more likely to be younger (p = 0.001), less educated (p = 0.001), and to have worse Snellen visual acuity (p = 0.002) than United States patients. Multivariate analysis of variance (MANOVA) revealed that in contrast to Korean patients, United States patients were assessed to have higher scoring in general health, vitality, VF-14, and verbal rating for visual health. This higher scoring trend persisted after controlling for age, gender, education and Snellen visual acuity. The difference in health-related quality of life (HRQOL) between the two countries was quite clear, especially in the older age and highly educated group. CONCLUSIONS: Subjects in Korea and the United States were significantly different in quality of life, functional status and clinical outcomes. Subjects in the United States had more favorable health outcomes than those in Korea. These differences may be caused by multiple factors, including country-specific differences in economic status, health care system, cultural value system, and health policy. Cross-cultural differences should be considered when making international comparisons of quality of life.
Assuntos
Catarata/epidemiologia , Comparação Transcultural , Indicadores Básicos de Saúde , Qualidade de Vida , Idoso , Estudos Transversais , Características Culturais , Feminino , Humanos , Coreia (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Psicometria/métodos , Anos de Vida Ajustados por Qualidade de Vida , Inquéritos e Questionários , Estados Unidos/epidemiologia , Acuidade VisualRESUMO
This study identifies characteristics associated with health-related quality of life (HRQOL) among Latinos with multiple sclerosis (MS). Data were collected from 99 Latinos with MS, with multiple linear regression models utilized to analyze these data. Marital status, MS symptoms, depressive symptoms, treatment at MS clinics, and satisfaction with insurance coverage of MS-related care were significantly linked with physical HRQOL. Marital status, employment, access to MS-focused care, and need for mental health care were significantly associated with mental health dimensions of HRQOL. Identifying characteristics associated with better HRQOL among Latinos with MS should facilitate approaches that address the health needs of this community.
Assuntos
Hispânico ou Latino , Esclerose Múltipla/psicologia , Qualidade de Vida , Depressão/epidemiologia , Emprego , Acessibilidade aos Serviços de Saúde , Humanos , Cobertura do Seguro , Seguro Saúde , Entrevistas como Assunto , Modelos Lineares , Estado Civil , Serviços de Saúde Mental , Esclerose Múltipla/epidemiologia , Avaliação das Necessidades , Sistema de Registros , Estados Unidos/epidemiologiaRESUMO
Several different approaches have been taken to development of homogeneous fluorescent aptamer assays including end-labeled beacons and signaling aptamers which are intrinsically quenched by nucleotides. Two new strategies dubbed "intrachain" and "competitive" FRET-aptamer assays are summarized in this review. Intrachain and competitive FRET-aptamers can be engineered on the molecular level through a series exploratory experiments involving prior knowledge of aptamer secondary or tertiary structures and hypotheses about aptamer conformational changes. However, there is an intrinsic risk of altering aptamer affinity or specificity associated with chemical modifications of an aptamer. Natural selection methods for FRET-aptamers have also been devised to potentially obviate the chemical modification problem. The naturally selected aptamers are subjected to fluorophore (F)- and or quencher (Q)-conjugated nucleotide triphosphate (NTP) incorporation by polymerase chain reaction (PCR) with permissive polymerases such as Deep Vent exo-, but still demonstrate sensitive and specific assay performance despite modified bases, because they are ultimately selected after decoration with F and Q. This paper summarizes work in this area and presents some new examples of the engineered and naturally selected FRET-aptamers for detection of vitamin D.
Assuntos
Aptâmeros de Nucleotídeos/síntese química , Aptâmeros de Nucleotídeos/isolamento & purificação , Aptâmeros de Nucleotídeos/química , Ligação Competitiva , Transferência Ressonante de Energia de Fluorescência , Ensaios de Triagem em Larga Escala , Técnica de Seleção de AptâmerosRESUMO
In this study the authors present results from a survey of 99 Latinos with multiple sclerosis (MS), including demographic, disease, and mental health characteristics. Four in 10 respondents reported depressive symptoms; half thought they had more worries than other people due to their MS; and about 29 % thought they needed mental health care in the past year. Whereas 76 % of respondents were highly satisfied with their access to MS-focused care, only 61% were highly satisfied with their access to mental health care. These findings highlight the role of mental health and social services in the comprehensive care needed by Latinos with MS.
Assuntos
Atitude Frente a Saúde , Transtorno Depressivo/epidemiologia , Hispânico ou Latino/psicologia , Hispânico ou Latino/estatística & dados numéricos , Esclerose Múltipla/psicologia , Adulto , Idoso , Atitude Frente a Saúde/etnologia , Demografia , Feminino , Humanos , Entrevistas como Assunto , Masculino , Saúde Mental , Serviços de Saúde Mental , Pessoa de Meia-Idade , Esclerose Múltipla/terapia , Relações Médico-Paciente , Projetos Piloto , Qualidade de Vida/psicologia , Sistema de Registros , Estados Unidos/epidemiologiaRESUMO
We recently reported the protective effect of 2-hydroxy- cis-terpenone (HCT) against aflatoxin B 1 (AFB1)-induced cytotoxicity in human HepG2 liver cells ( Zhou et al. Chem. Res. Toxicol. 2006, 19, 1415-1419 ); however, the mechanism was not clear. In this paper, the chemoprotective mechanism was investigated with liver microsomes and purified P450 3A4 enzyme. HCT showed effective inhibition of the metabolic conversion of AFB1 in liver microsomes at 40 microM, and more importantly, the inhibition of the carcinogenic exo-AFB1-epoxide formation from AFB1. Further study indicated the direct inhibition of purified P450 3A4 enzyme activity by HCT with an IC 50 value of 20 microM. Under aqueous conditions, HCT was slowly converted to an oxidized product OHCT, which exhibits similar inhibitory effects on both P450 3A4 and the metabolic conversion and carcinogenic activation of AFB1 with liver microsomes as those of HCT. Enzyme mechanism studies revealed that OHCT acted as a mixed inhibitor of P450 3A4 with K i and K i' at 17.6 +/- 5.6 and 7.6 +/- 1.5 microM, respectively. Finally, OHCT showed no cytotoxicity at 60 microM in HepG2 liver cells and effective chemoprotection at 40 and 60 microM against AFB1 (2 microM) induced cytotoxicity. In contrast, ketoconazole alone exhibited 20% cell mortality at 20 microM, while chemoprotection with ketoconazole against 2 microM AFB1 in HepG2 was observed at 10 and 20 microM, which was much higher than the 1 microM concentration used in the inhibitory assays of P450 3A4 activity and AFB1 metabolism with liver microsomes.
Assuntos
Aflatoxina B1/antagonistas & inibidores , Aflatoxina B1/toxicidade , Anticarcinógenos/farmacologia , Carcinógenos/antagonistas & inibidores , Carcinógenos/toxicidade , Inibidores do Citocromo P-450 CYP3A , Inibidores Enzimáticos/farmacologia , Fenantrenos/farmacologia , Algoritmos , Células Cultivadas , Citocromo P-450 CYP3A , Glutationa/metabolismo , Humanos , Hidrólise , Técnicas In Vitro , Indicadores e Reagentes , Cetoconazol/toxicidade , Cinética , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologiaRESUMO
OBJECTIVES: To examine physical and mental health domains of health-related quality of life (HRQL) in a binational adult population with type 2 diabetes at the Texas-Mexico border, and to explore individual and social correlates to physical and mental health status. METHODS: Adults 18 years and older with type 2 diabetes residing in the South Texas Lower Rio Grande Valley and in Reynosa, Tamaulipas, Mexico, were recruited using a convenience sampling technique and interviewed face-to-face with a structured survey. HRQL was measured using physical and mental health summary components of the Medical Outcomes Study Short Form. HRQL correlates included demographic characteristics, health factors, access to healthcare, and family support. Samples characteristics were compared using the Student's t-test or Mann-Whitney U test. Associations between dependent and independent variables were examined using unadjusted and adjusted (multiple variable) logistic regression models. RESULTS: There were no significant differences between Valley and Reynosa respondents in physical or mental health status scores. Valley participants with lower socioeconomic status and those perceiving their supportive relative's level of diabetes-related knowledge as "low" were more likely to report worse physical health than those lacking those characteristics. In the Reynosa group, lower physical health status was associated with duration of diabetes and insulin use. Both sample populations with clinical depressive symptoms were more likely to have worse physical and mental health than those without such symptoms. CONCLUSIONS: HRQL is an important outcome in monitoring health status. Understanding the levels and influences of HRQL in U.S.-Mexico border residents with diabetes may help improve diabetes management programs.
Assuntos
Diabetes Mellitus Tipo 2 , Nível de Saúde , Qualidade de Vida , Adolescente , Adulto , Idoso , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/psicologia , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Entrevistas como Assunto , Modelos Logísticos , Masculino , Americanos Mexicanos , México , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Qualidade de Vida/psicologia , Fatores de Risco , Fatores Socioeconômicos , Estatísticas não Paramétricas , TexasRESUMO
BACKGROUND: Depression affects more Hispanics with type 2 diabetes than other ethnic groups. This exploratory, binational study examined the prevalence and correlates of clinical depressive symptoms in Hispanics of Mexican origin with type 2 diabetes living on both sides of the Texas Mexico border. METHODS: Two binational samples, consisting of 172 adult patients of Mexican origin with type 2 diabetes in South Texas and 200 from the Northeastern region of Mexico, were compared. Logistic regression analyses were used to test personal and social correlates to clinical depressive symptoms. RESULTS: The rate of clinical depressive symptoms was similar in both South Texas and Northeastern Mexico patients (39% and 40.5%, respectively). Gender, education, emergency department visits, and burden of diabetes symptoms were predictors of clinical depressive symptoms in the South Texas sample. Among respondents in the Northeastern Mexico sample, the only statistically significant correlate to clinical depressive symptoms was the burden of diabetes symptoms. CONCLUSIONS: Diabetes and depression must be addressed as priorities in diabetes initiatives at the US Mexico border region. Further research is warranted to examine the extent and impact of involving family practice physicians from both sides of the border in depression screenings among patients with type 2 diabetes.
Assuntos
Depressão/etnologia , Diabetes Mellitus Tipo 2/etnologia , Comorbidade , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Modelos Logísticos , Masculino , Americanos Mexicanos/estatística & dados numéricos , México/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Texas/epidemiologiaRESUMO
Natural terpene quinone methides (QM) and their derivatives have been investigated as therapeutics due to their broad antifungal, antibacterial, and antitumor activities. Recently, we reported that a terpene QM was formed from the catechol precursor through the disproportionation of Cu(II)/(I) redox cycle, and extensive DNA damage was observed throughout the oxidation process. In this paper, we investigate DNA damage with a series of terpene catechols as analogues of natural QM precursors and suggest that reactive oxygen species (ROS) are responsible for the observed DNA damage in the Cu(2+)-induced oxidation despite the stereo- and structural difference of these catechol or subsequent oxidation products. In addition, the presence of NADH significantly enhanced the extent of DNA damage by oxidation of these catechols. Especially with alkene catechols 6-7, the extent of DNA damage was independent of the concentration of catechols, implying that NADH enables the continuous production of ROS through the redox cycle of catechols/quinones.