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2.
Am J Transplant ; 16(3): 960-7, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26731613

RESUMO

Solid organ transplant recipients have increased colorectal cancer (CRC) risk. We assessed CRC risk among transplant recipients and identified factors contributing to this association. The US transplant registry was linked to 15 population-based cancer registries (1987-2010). We compared CRC risk in recipients to the general population by using standardized incidence ratios (SIRs) and identified CRC risk factors by using Poisson regression. Based on 790 cases of CRC among 224 098 transplant recipients, the recipients had elevated CRC risk (SIR 1.12, 95% confidence interval [CI] 1.04 to 1.20). The increase was driven by an excess of proximal colon cancer (SIR 1.69, 95% CI 1.53 to 1.87), while distal colon cancer was not increased (SIR 0.93, 95% CI 0.80 to 1.07), and rectal cancer was reduced (SIR 0.64, 95% CI 0.54 to 0.76). In multivariate analyses, CRC was increased markedly in lung recipients with cystic fibrosis (incidence rate ratio [IRR] 12.3, 95% CI 6.94 to 21.9, vs. kidney recipients). Liver recipients with primary sclerosing cholangitis and inflammatory bowel disease also had elevated CRC risk (IRR 5.32, 95% CI 3.73 to 7.58). Maintenance therapy with cyclosporine and azathioprine was associated with proximal colon cancer (IRR 1.53, 95% CI 1.05 to 2.23). Incidence was not elevated in a subgroup of kidney recipients treated with tacrolimus and mycophenolate mofetil, pointing to the relevance of the identified risk factors. Transplant recipients have increased proximal colon cancer risk, likely related to underlying medical conditions (cystic fibrosis and primary sclerosing cholangitis) and specific immunosuppressive regimens.


Assuntos
Neoplasias Colorretais/etiologia , Rejeição de Enxerto/etiologia , Transplante de Órgãos/efeitos adversos , Complicações Pós-Operatórias , Sistema de Registros , Adulto , Idoso , Neoplasias Colorretais/epidemiologia , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Fatores de Risco , Transplantados , Estados Unidos/epidemiologia
3.
Br J Cancer ; 109(5): 1352-9, 2013 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-23907431

RESUMO

BACKGROUND: Coffee and tea are commonly consumed and carry potential anticancer components that could reduce the risk of colorectal cancer; however, their relationships with colorectal cancer risk remain inconsistent. METHODS: A prospective analysis was carried out to examine the relationships of coffee and tea intake with colorectal cancer risk in 57,398 men and women in the intervention arm of the National Cancer Institute-Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, a national screening study that limits differential detection biases. Coffee and tea intakes were assessed by food frequency questionnaire. RESULTS: Six hundred and eighty-one incident colorectal cancer cases were ascertained during a median follow-up of 11.4 years. Greater coffee intake was not associated with risk of colorectal cancer (relative risk (RR)=1.08, 95% confidence interval (CI)=0.79-1.48, Ptrend=0.23). Stratifying by cancer site (Pheterogeneity=0.48) or stage (Pheterogeneity=0.83) did not alter the relationship. Associations remained unchanged in subsets of participants for either caffeinated or decaffeinated coffee or when stratifying by several colorectal cancer risk factors. Similarly, greater tea intake was not associated with colorectal cancer risk overall (RR=0.77, 95% CI=0.55-1.09, Ptrend=0.17) or by cancer site (Pheterogeneity=0.14) or stage (Pheterogeneity=0.60). These associations were not modified by several colorectal cancer risk factors. CONCLUSION: The findings of this study do not provide evidence to suggest that drinking coffee or tea is beneficial in protecting against colorectal cancer.


Assuntos
Cafeína , Café/efeitos adversos , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/mortalidade , Chá , Comportamento Alimentar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários
4.
Br J Cancer ; 108(6): 1378-86, 2013 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-23361049

RESUMO

BACKGROUND: The chromosome 9p21.3 region has been implicated in the pathogenesis of multiple cancers. METHODS: We systematically examined up to 203 tagging SNPs of 22 genes on 9p21.3 (19.9-32.8 Mb) in eight case-control studies: thyroid cancer, endometrial cancer (EC), renal cell carcinoma, colorectal cancer (CRC), colorectal adenoma (CA), oesophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma and osteosarcoma (OS). We used logistic regression to perform single SNP analyses for each study separately, adjusting for study-specific covariates. We combined SNP results across studies by fixed-effect meta-analyses and a newly developed subset-based statistical approach (ASSET). Gene-based P-values were obtained by the minP method using the Adaptive Rank Truncated Product program. We adjusted for multiple comparisons by Bonferroni correction. RESULTS: Rs3731239 in cyclin-dependent kinase inhibitors 2A (CDKN2A) was significantly associated with ESCC (P=7 × 10(-6)). The CDKN2A-ESCC association was further supported by gene-based analyses (Pgene=0.0001). In the meta-analyses by ASSET, four SNPs (rs3731239 in CDKN2A, rs615552 and rs573687 in CDKN2B and rs564398 in CDKN2BAS) showed significant associations with ESCC and EC (P<2.46 × 10(-4)). One SNP in MTAP (methylthioadenosine phosphorylase) (rs7023329) that was previously associated with melanoma and nevi in multiple genome-wide association studies was associated with CRC, CA and OS by ASSET (P=0.007). CONCLUSION: Our data indicate that genetic variants in CDKN2A, and possibly nearby genes, may be associated with ESCC and several other tumours, further highlighting the importance of 9p21.3 genetic variants in carcinogenesis.


Assuntos
Biomarcadores Tumorais/genética , Cromossomos Humanos Par 9/genética , Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Neoplasias/genética , Polimorfismo de Nucleotídeo Único/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos , Metanálise como Assunto , Prognóstico
5.
Am J Physiol Endocrinol Metab ; 303(8): E950-8, 2012 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-22811468

RESUMO

Human chorionic gonadotropin (hCG) displays a major role in pregnancy initiation and progression and is involved in trophoblast differentiation and fusion. However, the site and the type of dimeric hCG production during the first trimester of pregnancy is poorly known. At that time, trophoblastic plugs present in the uterine arteries disappear, allowing unrestricted flow of maternal blood to the intervillous space. The consequence is an important modification of the trophoblast environment, including a rise of oxygen levels from about 2.5% before 10 wk of amenorrhea (WA) to ∼8% after 12 WA. Two specific ß-hCG proteins that differ from three amino acids have been described: type 1 (CGB7) and type 2 (CGB3, -5, and -8). Here, we demonstrated in situ and ex vivo on placental villi and in vitro in primary cultures of human cytotrophoblasts that type 1 and 2 ß-hCG RNAs and proteins were expressed by trophoblasts and that these expressions were higher before blood enters in the intervillous space (8-9 vs. 12-14 WA). hCG was immunodetected in villous mononucleated cytotrophoblasts (VCT) and syncytiotrophoblast (ST) at 8-9 WA but only in ST at 12-14 WA. Furthermore, hCG secretion was fourfold higher in VCT cultures from 8-9 WA compared with 12-14 WA. Interestingly, VCT from 8-9 WA placentas were found to exhibit more fusion features. Taken together, we showed that type 1 and type 2 ß-hCG are highly expressed by VCT in the early first trimester, contributing to the high levels of hCG found in maternal serum at this term.


Assuntos
Gonadotropina Coriônica Humana Subunidade beta/biossíntese , Placenta/metabolismo , Primeiro Trimestre da Gravidez/genética , Primeiro Trimestre da Gravidez/metabolismo , Trofoblastos/metabolismo , Animais , Western Blotting , Fusão Celular , Separação Celular , Células Cultivadas , Gonadotropina Coriônica Humana Subunidade beta/genética , Vilosidades Coriônicas/metabolismo , Feminino , Expressão Gênica/fisiologia , Humanos , Imuno-Histoquímica , Consumo de Oxigênio/fisiologia , Gravidez , RNA/biossíntese , RNA/genética , Reação em Cadeia da Polimerase em Tempo Real
6.
Br J Cancer ; 106(3): 608-16, 2012 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-22166801

RESUMO

BACKGROUND: Most studies of meat and colorectal adenoma have investigated prevalent events from a single screening, thus limiting our understanding of the role of meat and meat-related exposures in early colorectal carcinogenesis. METHODS: Among participants in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who underwent baseline and follow-up sigmoidoscopy (n=17,072), we identified 1008 individuals with incident distal colorectal adenoma. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between meat and meat-related components and incident distal colorectal adenoma using multivariate logistic regression. RESULTS: We observed suggestive positive associations for red meat, processed meat, haeme iron, and nitrate/nitrite with distal colorectal adenoma. Grilled meat (OR=1.56, 95% CI=1.04-2.36), well or very well-done meat (OR=1.59, 95% CI=1.05-2.43), 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) (OR=1.75, 95% CI=1.17-2.64), benzo[a]pyrene (OR=1.53, 95% CI=1.06-2.20), and total mutagenic activity (OR=1.57, 95% CI=1.03-2.40) were positively associated with rectal adenoma. Total iron (diet and supplements) (OR=0.69, 95% CI=0.56-0.86) and iron from supplements (OR=0.65, 95% CI=0.44-0.97) were inversely associated with any distal colorectal adenoma. CONCLUSION: Our findings indicate that several meat-related components may be most relevant to early neoplasia in the rectum. In contrast, total iron and iron from supplements were inversely associated with any distal colorectal adenoma.


Assuntos
Adenoma/epidemiologia , Neoplasias Colorretais/epidemiologia , Carne , Adenoma/etiologia , Idoso , Colo/patologia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/prevenção & controle , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Sigmoidoscopia , Estados Unidos/epidemiologia
7.
Br J Cancer ; 100(5): 822-8, 2009 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-19259097

RESUMO

Autoimmune conditions are associated with an elevated risk of lymphoproliferative malignancies, but few studies have investigated the risk of myeloid malignancies. From the US Surveillance Epidemiology and End Results (SEER)-Medicare database, 13 486 myeloid malignancy patients (aged 67+ years) and 160 086 population-based controls were selected. Logistic regression models adjusted for gender, age, race, calendar year and number of physician claims were used to estimate odds ratios (ORs) for myeloid malignancies in relation to autoimmune conditions. Multiple comparisons were controlled for using the Bonferroni correction (P<0.0005). Autoimmune conditions, overall, were associated with an increased risk of acute myeloid leukaemia (AML) (OR 1.29) and myelodysplastic syndrome (MDS, OR 1.50). Specifically, AML was associated with rheumatoid arthritis (OR 1.28), systemic lupus erythematosus (OR 1.92), polymyalgia rheumatica (OR 1.73), autoimmune haemolytic anaemia (OR 3.74), systemic vasculitis (OR 6.23), ulcerative colitis (OR 1.72) and pernicious anaemia (OR 1.57). Myelodysplastic syndrome was associated with rheumatoid arthritis (OR1.52) and pernicious anaemia (OR 2.38). Overall, autoimmune conditions were not associated with chronic myeloid leukaemia (OR 1.09) or chronic myeloproliferative disorders (OR 1.15). Medications used to treat autoimmune conditions, shared genetic predisposition and/or direct infiltration of bone marrow by autoimmune conditions, could explain these excess risks of myeloid malignancies.


Assuntos
Doenças Autoimunes/complicações , Síndromes Mielodisplásicas/etiologia , Doenças Mieloproliferativas-Mielodisplásicas/etiologia , Transtornos Mieloproliferativos/etiologia , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/epidemiologia , Feminino , Humanos , Masculino , Síndromes Mielodisplásicas/epidemiologia , Doenças Mieloproliferativas-Mielodisplásicas/epidemiologia , Transtornos Mieloproliferativos/epidemiologia , Razão de Chances , Fatores de Risco , Fatores de Tempo
8.
Occup Environ Med ; 66(12): 848-53, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19773279

RESUMO

INTRODUCTION: Benzene is an established human haematotoxin, with substantial interindividual variation in benzene-induced toxicity. METHODS: To further examine if genetic variation contributes to benzene haematotoxicity, we analysed 1023 tagSNPs in 121 gene regions important for benzene metabolism, haematopoiesis, leukaemia and lymphoma among 250 workers exposed to benzene and 140 unexposed controls in a cross-sectional study carried out in China. Linear regression was used to analyse the relationship between genetic polymorphisms and total white blood cell (WBC) count and its subtypes, adjusting for potential confounders and occupational exposure to benzene and toluene among exposed workers. The minp test assessed the association on the gene region level. The false discovery rate method was used to control for multiple comparisons. RESULTS: VEGF (minp = 0.0030) and ERCC3 (minp = 0.0042) were the most significantly associated gene regions with altered WBC counts among benzene-exposed workers, after accounting for multiple comparisons. Highly significant changes were also found for WBC subtype counts, including granulocytes, CD4+ T cells and lymphocytes for VEGF and granulocytes and NK cells for ERCC3. Further, in workers exposed to <1 ppm, a SNP in VEGF was associated with changes in WBC and granulocyte counts, and SNPs in ERCC3 were associated with changes in WBC, NK cell and granulocyte counts. DISCUSSION: Our findings suggest that genetic variation in VEGF, which plays an important role in blood vessel growth, and ERCC3, which is a member of the DNA repair pathway and is responsible for repairing bulky DNA adducts formed by chemicals, may contribute to individual susceptibility to benzene-induced haematotoxicity at relatively low levels of benzene exposure.


Assuntos
Benzeno/toxicidade , DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Doenças Hematológicas/induzido quimicamente , Doenças Profissionais/induzido quimicamente , Fator A de Crescimento do Endotélio Vascular/genética , Feminino , Predisposição Genética para Doença , Doenças Hematológicas/sangue , Doenças Hematológicas/genética , Humanos , Contagem de Leucócitos , Leucócitos/efeitos dos fármacos , Masculino , Doenças Profissionais/sangue , Doenças Profissionais/genética , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Polimorfismo de Nucleotídeo Único
9.
Gynecol Obstet Invest ; 64(3): 156-60, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17934312

RESUMO

The specific interaction of blastocyst-derived human chorionic gonadotropin (hCG) and endometrial LH/hCG-R constitutes a fundamental component of the molecular dialogue at the materno-fetal interface. From our observations and studies from other groups, hCG was indeed shown to play a significant role in implantation and tolerance of the embryo, decidual differentiation and remodeling, as well as in placentation. The profile pattern of LH/hCG-R expression by endometrial epithelium correlates with the theoretical timing of the implantation window. Studies are currently being conducted in assisted medical procreation and in an animal model of implantation to establish the index of LH/hCG-R expression as a new biomarker of uterine receptivity for embryo implantation.


Assuntos
Blastocisto/fisiologia , Gonadotropina Coriônica/fisiologia , Implantação do Embrião/fisiologia , Endométrio/fisiologia , Gravidez/fisiologia , Receptores do LH/fisiologia , Feminino , Humanos , Hormônio Luteinizante/fisiologia
10.
Ophthalmologe ; 104(10): 875-9, 2007 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-17653725

RESUMO

OBJECTIVE: The critical dose of chloroquine/hydroxychloroquine leading to a maculopathy or generalised retinopathy remains undetermined. In the literature, 100 g is considered the dose at which regular vision checks should be performed. Generally, chloroquine is said to be more toxic than hydroxychloroquine. A young patient presenting with toxic maculopathy after 57 g of hydroxychloroquine and a daily dosage of 2 mg/kg body weight prompted us to retrospectively look at our patients examined in this respect over about 1 year. METHODS: The data of patients who were examined because of chloroquine/hydroxychloroquine intake or a respective maculopathy/retinopathy were retrospectively analysed. The time period was January 2005 until March 2006. Retinal damage was defined by fundus changes and alteration of the multifocal electroretinogram (ERG). RESULTS: Twenty-one patients--18 women and three men--were examined. The mean age was 51 years (range 6-71). Five of the nine chloroquine-treated patients developed a maculopathy, and one of them developed an additional generalised retinopathy. Of the patients treated by hydroxychloroquine, three of 12 suffered from a maculopathy and one from an additional generalised retinopathy. The cumulative doses leading to retinal damage ranged from 170 g to 1650 g for chloroquine and from 57 g to 1190 g for hydroxychloroquine. The highest cumulative doses without leading to signs of retinopathy were 790 g for chloroquine and 1200 g for hydroxychloroquine. CONCLUSIONS: There is a high variability of cumulative doses of chloroquine/hydroxychloroquine that lead to a toxic retinopathy. Therefore, early and regular ophthalmologic examinations are recommended. Electrophysiological testing should be performed once a year, corresponding to about 60 g of base with one tablet a day. For electrophysiology, the multifocal ERG has turned out to be the most important test in this regard. However, visual acuity and funduscopy should be performed more frequently.


Assuntos
Antirreumáticos/toxicidade , Cloroquina/toxicidade , Hidroxicloroquina/toxicidade , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Retina/efeitos dos fármacos , Doenças Retinianas/induzido quimicamente , Adolescente , Adulto , Idoso , Azatioprina/administração & dosagem , Azatioprina/toxicidade , Criança , Cloroquina/administração & dosagem , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Eletrorretinografia/efeitos dos fármacos , Feminino , Fundo de Olho , Humanos , Hidroxicloroquina/administração & dosagem , Assistência de Longa Duração , Macula Lutea/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Oftalmoscopia , Prednisolona/administração & dosagem , Prednisolona/toxicidade , Doenças Retinianas/diagnóstico , Campos Visuais/efeitos dos fármacos
11.
Oncogene ; 36(15): 2172-2183, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27819678

RESUMO

Genetic alterations associated with prostate cancer (PCa) may be identified by sequencing metastatic tumour genomes to identify molecular markers at this lethal stage of disease. Previously, we characterized somatic alterations in metastatic tumours in the methylcytosine dioxygenase ten-eleven translocation 2 (TET2), which is altered in 5-15% of myeloid, kidney, colon and PCas. Genome-wide association studies previously identified non-coding risk variants associated with PCa and melanoma. We perform fine-mapping of PCa risk across TET2 using genotypes from the PEGASUS case-control cohort and identify six new risk variants in introns 1 and 2. Oligonucleotides containing two risk variants are bound by the transcription factor octamer-binding protein 1 (Oct1/POU2F1) and TET2 and Oct1 expression are positively correlated in prostate tumours. TET2 is expressed in normal prostate tissue and reduced in a subset of tumours from the Cancer Genome Atlas (TCGA). Small interfering RNA-mediated TET2 knockdown (KD) increases LNCaP cell proliferation, migration and wound healing, verifying loss drives a cancer phenotype. Endogenous TET2 bound the androgen receptor (AR) and AR-coactivator proteins in LNCaP cell extracts, and TET2 KD increases prostate-specific antigen (KLK3/PSA) expression. Published data reveal TET2 binding sites and hydroxymethylcytosine proximal to KLK3. A gene co-expression network identified using TCGA prostate tumour RNA-sequencing identifies co-regulated cancer genes associated with 2-oxoglutarate (2-OG) and succinate metabolism, including TET2, lysine demethylase (KDM) KDM6A, BRCA1-associated BAP1, and citric acid cycle enzymes IDH1/2, SDHA/B, and FH. The co-expression signature is conserved across 31 TCGA cancers suggesting a putative role for TET2 as an energy sensor (of 2-OG) that modifies aspects of androgen-AR signalling. Decreased TET2 mRNA expression in TCGA PCa tumours is strongly associated with reduced patient survival, indicating reduced expression in tumours may be an informative biomarker of disease progression and perhaps metastatic disease.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores Androgênicos/metabolismo , Proliferação de Células/fisiologia , Proteínas de Ligação a DNA/genética , Dioxigenases , Células HEK293 , Humanos , Íntrons , Calicreínas/genética , Calicreínas/metabolismo , Ácidos Cetoglutáricos/metabolismo , Masculino , Polimorfismo de Nucleotídeo Único , Antígeno Prostático Específico/genética , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas/genética , Receptores Androgênicos/genética , Succinatos/metabolismo
12.
J Control Release ; 224: 199-207, 2016 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-26780173

RESUMO

Transarterial chemoembolization (TACE) is used to treat various types of hypervascular tumors such as hepatocellular carcinoma and renal cancer. However, embolization and blocking of blood vessels nourishing a tumor mass evokes an angiogenic response due to the secretion of vascular endothelial growth factor (VEGF), which results in the formation of new blood vessels and eventually limitation in therapeutic efficacy. The presented work investigates the feasibility of loading the clinically used embolic beads (DC Bead®) with Bevacizumab (BEV), an anti-VEGF antibody, and control its release kinetics via Layer-by-Layer (LbL) coating. This strategy has the aim to achieve high, localized and sustained concentrations of BEV at the tumor site and reduce drug exposure in the systemic circulation. High loading of BEV on lyophilized beads of about 76mg BEV/bead vial was achieved. LbL coating was carried out by depositing alternating layers of the biocompatible polymers alginate and poly-L-lysine. Coating was proven successful by monitoring the reversal of zeta potential after addition of each layer. Morphological changes of the bead surface before and after coating were illustrated using SEM imaging. Moreover, release profiles from different formulations were studied and results showed that optimizing the number of deposited layers effectively slows the release of BEV for three days. Activity of released BEV was studied in different 2D and 3D cell based assays. Released BEV fractions showed comparable activity to fresh BEV solution used as control after 3days. In conclusion, our results suggest the opportunity for loading anti-VEGF antibodies on commercially available embolic beads to increase the efficacy of TACE of hypervascular tumors.


Assuntos
Anticorpos Bloqueadores/administração & dosagem , Anticorpos Bloqueadores/farmacologia , Quimioembolização Terapêutica/métodos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Alginatos , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/administração & dosagem , Bevacizumab/uso terapêutico , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Excipientes , Humanos , Tamanho da Partícula , Polilisina/química , Fator A de Crescimento do Endotélio Vascular/imunologia
13.
Naunyn Schmiedebergs Arch Pharmacol ; 294(3): 271-5, 1976 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-187961

RESUMO

The correlations between the relaxing effect of papaverine derivatives, inhibition of low Km-phosphodiesterase (cAMP-PDE = EC 3.1.4.17) activity and cyclic 3',5'-AMP (cAMP) levels in isolated rabbit ileum were investigated. There was a strong correlation between the relaxing effect, inhibition of PDE activity and cAMP content for eupaverine, ethylpapaverine and papaverine. Eupaverine was the most effective relaxing agent (I50 = 7.5 muM) and the most potent inhibitor of PDE activity (Ki = 0.6 muM), followed by ethylpapaverine (I50 = 10 muM;Ki 0.8 muM) and papaverine (I50 = 20 muM;Ki = 2 muM). In contrast, there was a strong relaxing effect (I50 = 6 muM) but only slight inhibition of PDE activity (Ki = 350 muM) by tetrahydropapaveroline (THP). The adenylate cyclase stimulating effect of THP which was shown by others is most likely the reason for comparatively higher cAMP levels, which were found to be elevated about seven times over basal levels of 0.35 nmoles/g wet weight, and effective relaxation. Relaxation could be induced by exogenously added cAMP (I50 = 45 muM) and dibutyryl-cAMP (I50 = 450 muM). Our results support the assumption that smooth muscle relaxation in rabbit ileum is mediated by cAMP. Some of these observations have been published in abstract form (Schulz and Berndt, 1972).


Assuntos
3',5'-AMP Cíclico Fosfodiesterases/antagonistas & inibidores , AMP Cíclico/metabolismo , Músculo Liso/efeitos dos fármacos , Papaverina/análogos & derivados , Inibidores de Fosfodiesterase , Diester Fosfórico Hidrolases/metabolismo , Animais , Bucladesina/farmacologia , AMP Cíclico/farmacologia , Feminino , Íleo/efeitos dos fármacos , Íleo/enzimologia , Cinética , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso/enzimologia , Músculo Liso/metabolismo , Papaverina/farmacologia , Coelhos
14.
Clin J Pain ; 6(4): 271-5, 1990 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-2135026

RESUMO

This study examined profiles of self-reported depressive symptoms in chronic pain patients (n = 51), family practice outpatients (n = 52), and controls (n = 53) who were receiving neither psychological nor medical treatment and were pain free. Subjects in the three groups were matched for age and sex. The short form of the Multiscore Depression Inventory (SMDI) was used. Chronic pain and family practice groups had similar SMDI profiles, with significant elevations on Low Energy, Pessimism, Sad Mood, and Low Self-Esteem subscales compared with controls. Although both groups of medical patients were depressed compared with control subjects, their SMDI profiles were different from those previously reported for psychiatric inpatients with a diagnosis of depression.


Assuntos
Depressão/psicologia , Dor/psicologia , Adulto , Doença Crônica , Depressão/complicações , Depressão/diagnóstico , Medicina de Família e Comunidade , Feminino , Humanos , Masculino , Dor/complicações , Escalas de Graduação Psiquiátrica
15.
Reprod Toxicol ; 15(5): 545-50, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11780962

RESUMO

In order to study the possible placental transfer of the Fusarium mycotoxin zearalenone (ZON), Sprague Dawley rats were treated with a single dose (0.74 mg/kg b.w.) of ZON i.v. on day 12 or day 18 of pregnancy, or intragastrically (i.g.) on day 18 of pregnancy. Samples of placenta, foetus, and maternal liver and spleen were collected for chemical analyses 0.3 h after treatment on day 12, and 0.3, 4, and 24 h after treatment on day 18. Three rats were used for each pregnancy day, administration route, and exposure time. The concentrations of ZON and its metabolites alpha- and beta-zearalenol (-ZOL) were determined quantitatively by high-performance liquid chromatography (HPLC) after incubation with beta-glucuronidase and purification on immunoaffinity columns. Tissue distribution was studied by means of whole body autoradiography at 4 and 24 h after treatment with tritiated ZON (750 microCi/kg b.w; 7.4 mg/kg b.w.) on day 18 of pregnancy. ZON and alpha-ZOL were transferred into the foetus on both gestational days. However, a delay in distribution into the foetus, relative to the maternal tissue, was observed. Beta-ZOL was below the detection limit in the foetus. No specific site of foetal accumulation of ZON or its metabolites was apparent. In the maternal tissues, the highest levels of ZON and of alpha- and beta-ZOL were found in the liver.


Assuntos
Estrogênios não Esteroides/farmacocinética , Troca Materno-Fetal , Placenta/metabolismo , Zearalenona/farmacocinética , Administração Oral , Animais , Autorradiografia , Cromatografia Líquida de Alta Pressão , Estrogênios não Esteroides/administração & dosagem , Feminino , Feto/efeitos dos fármacos , Feto/metabolismo , Injeções Intravenosas , Fígado/efeitos dos fármacos , Fígado/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley , Baço/efeitos dos fármacos , Baço/metabolismo , Distribuição Tecidual , Trítio , Zearalenona/administração & dosagem
16.
Vet Res Commun ; 28(3): 225-34, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15074768

RESUMO

Thirty-nine leaf samples of Narthecium ossifragum collected from eight sites in Møre og Romsdal County, Norway, during June-September 1997 and 41 leaf samples collected at five sites in the same county during June-August 1998 were analysed for the concentrations of steroidal sapogenins using GC-MS. The 1998 samples were also examined for fungal elements (conidia and hyphae) after incubation in a moist chamber for 10-14 days. The highest 1997 and 1998 leaf sapogenin concentrations (4881 and 7115 mg/kg dry matter, respectively) were 13-14 times greater than the lowest sapogenin concentrations found (344 and 531 mg/kg dry matter, respectively). The results did not reveal systematic differences in sapogenin concentrations between the two seasons, or between samples harvested early or late in the same seasons, or between sapogenin concentrations in plants harvested at different sites. Cladosporium magnusianum was the predominant fungus found in the samples. The degree of fungal infection on the samples was in generally low, but the number of C. magnusianum colonies in the moist chamber preparations and fungal elements (conidia and hyphae) in leaf washings and on leaves tended to increase with time. Factor analysis and multiple regression analysis performed on the chemical and fungal results suggest that sporulation may have occurred in the fungi in response to increase in sapogenin concentrations.


Assuntos
Cladosporium/crescimento & desenvolvimento , Liliaceae/metabolismo , Liliaceae/microbiologia , Doenças das Plantas/microbiologia , Plantas Tóxicas/microbiologia , Sapogeninas/metabolismo , Análise Fatorial , Noruega , Folhas de Planta/microbiologia , Análise de Regressão , Estações do Ano
17.
Pediatr Nurs ; 17(6): 607-11, 621, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1754290

RESUMO

Oxygen-dependent infants with BPD are routinely sent home as soon as their conditions have stabilized. This article presents a prospective case study examining one family's adaptation to the birth, prolonged hospitalization, and home oxygen management of an infant with severe BPD.


Assuntos
Adaptação Psicológica , Displasia Broncopulmonar/enfermagem , Cuidadores/psicologia , Família/psicologia , Adulto , Displasia Broncopulmonar/terapia , Feminino , Assistência Domiciliar , Hospitalização , Humanos , Recém-Nascido , Estudos Longitudinais
18.
J Fam Pract ; 16(1): 83-7, 1983 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-6848640

RESUMO

Depression among outpatients of three descriptively and geographically dissimilar family practice residency programs was studied. The Beck Depression Inventory, the Popoff Index of Depression, and the Multiscore Depression Inventory (MDI) were compared. Reliabilities of all three instruments were high, as were correlations among the instruments. The only significant differences among the three populations were on the social introversion and sad mood subscales of the MDI. Regression analyses were then performed to compute equivalent scores on the Beck Depression Inventory short form from the MDI and Popoff instruments. This allowed approximate conversion of scores to the four levels of severity of depression described by Beck and Beck. This study provides the first extensive normative data for family practice on these measures, thus providing family physicians with a comparison group appropriate for a family practice rather than a psychiatric population.


Assuntos
Depressão/epidemiologia , Escalas de Graduação Psiquiátrica , Adolescente , Adulto , Fatores Etários , Idoso , Medicina de Família e Comunidade , Feminino , Humanos , Illinois , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores Sexuais , Fatores Socioeconômicos , South Carolina , População Urbana
19.
Free Radic Res ; 48(3): 380-6, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24437375

RESUMO

Both endogenous factors (genomic variations) and exogenous factors (environmental exposures, lifestyle) impact the balance of reactive oxygen species (ROS). Variants of the ND3 (rs2853826; G10398A) gene of the mitochondrial genome, manganese superoxide dismutase (MnSOD; rs4880 Val16Ala) and glutathione peroxidase (GPX-1; rs1050450 Pro198Leu), are purported to have functional effects on regulation of ROS balance. In this study, we examined associations of breast and prostate cancer risks and survival with these variants, and interactions between rs4880-rs1050450, and alcohol consumption-rs2853826. Nested case-control studies were conducted in the Breast and Prostate Cancer Cohort Consortium (BPC3), consisting of nine cohorts. The analyses included over 10726 post-menopausal breast and 7532 prostate cancer cases with matched controls. Logistic regression models were used to evaluate associations with risk, and proportional hazard models were used for survival outcomes. We did not observe significant interactions between polymorphisms in MnSOD and GPX-1, or between mitochondrial polymorphisms and alcohol intake and risk of either breast (p-interaction of 0.34 and 0.98, respectively) or prostate cancer (p-interaction of 0.49 and 0.50, respectively). We observed a weak inverse association between prostate cancer risk and GPX-1 Leu198Leu carriers (OR 0.87, 95% CI 0.79-0.97, p = 0.01). Overall survival among women with breast cancer was inversely associated with G10398 carriers who consumed alcohol (HR 0.66 95% CI 0.49-0.88). Given the high power in our study, it is unlikely that interactions tested have more than moderate effects on breast or prostate cancer risk. Observed associations need both further epidemiological and biological confirmation.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Estresse Oxidativo/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Estresse Oxidativo/fisiologia , Polimorfismo de Nucleotídeo Único , Espécies Reativas de Oxigênio/metabolismo , Análise de Sobrevida
20.
Ophthalmologe ; 109(1): 54-8, 2012 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-22130724

RESUMO

BACKGROUND: As techniques for cataract surgery have evolved, spontaneous intraocular lens (IOL) dislocation in patients with no ocular pathology arises less frequently. We present seven consecutive cases of uncomplicated cataract surgery with early in-the-bag spontaneous intraocular lens dislocation for which the same type of hydrophilic single piece lens was used. MATERIAL AND METHODS: A retrospective analysis was conducted on seven cases involving patients with IOL dislocation who underwent uncomplicated cataract surgery within a period of 4 months (October 2010 to January 2011) using the same type of single piece IOL. The median age of the 7 patients was 73 years and IOL repositioning was performed after an average of 10 weeks. RESULTS: Sulcus repositioning could be carried out in only five of the seven patients and IOL repositioning within the capsule was achieved in one patient. A second patient exhibited IOL dislocation after yttrium aluminium garnet (YAG) laser capsulotomy. Explantation of the IOL and sulcus implantation of another IOL type (Acrysof MA50 MB) was necessary for a third patient. A fourth case presented an angled IOL haptic and dislocation of the IOL in the sulcus position. DISCUSSION: Even after uncomplicated cataract surgery, spontaneous in-the-bag IOL dislocation in patients with no ocular pathology may occur due to a hydrophilic lens material which induces stronger anterior capsular phimosis (ACP) in comparison to alternative materials. In combination with a thin lens design this may result in angled IOL haptics and IOL dislocation. CONCLUSIONS: Careful selection of suitable lens design and material according to individual predisposing factors is necessary. This retrospective case study demonstrates that the combination of hydrophilic lens material and a thin lens design may result in early spontaneous IOL dislocation. Furthermore, as established in one case, YAG laser capsulotomy may induce IOL dislocation if the lens design cannot withstand capsular fibrosis.


Assuntos
Remoção de Dispositivo/métodos , Migração de Corpo Estranho/etiologia , Migração de Corpo Estranho/cirurgia , Lentes Intraoculares/efeitos adversos , Facoemulsificação/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Catarata/complicações , Feminino , Humanos , Masculino , Falha de Tratamento
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