RESUMO
CONTEXT: Anti-müllerian hormone (AMH) is an accurate marker of ovarian reserve. However, sufficiently large sets of normative data from infancy to the end of reproductive life are scarce. OBJECTIVE: This study was an assessment of serum AMH levels in healthy females. SUBJECTS: In 804 healthy females ranging from infancy until the end of the reproductive period, serum AMH levels were measured with an enzyme-linked immunometric assay. All adults had regular menstrual cycles. The majority was proven fertile and none of them had used oral contraceptive pills prior to study inclusion. RESULTS: In the total cohort, AMH was inversely correlated with age (r = -0.24; P < 0.001). The age at which the maximum AMH value was attained was at 15.8 yr. In girls younger than 15.8 yr, serum AMH and age were positively correlated (r = +0.18; P = 0.007). Thereafter AMH levels remained stable (r = -0.33; P = 0.66), whereas from the age of 25.0 yr onward, an inverse correlation between AMH and age (r = -0.47; P < 0.001) was observed. At any given age, considerable interindividual differences in serum AMH levels were observed. CONCLUSION: During infancy AMH levels increase, whereas during adolescence, a plateau until the age of 25 yr was observed. From the age of 25 yr onward, serum AMH levels correlate inversely with age, implying that AMH is applicable as a marker of ovarian reserve only in women of 25 yr old and older. Our nomogram may facilitate counseling women on their reproductive potential.
Assuntos
Hormônio Antimülleriano/sangue , Saúde , Nomogramas , Adolescente , Adulto , Envelhecimento/sangue , Hormônio Antimülleriano/análise , Biomarcadores/análise , Biomarcadores/sangue , Criança , Pré-Escolar , Estudos de Coortes , Técnicas de Diagnóstico Endócrino/normas , Técnicas de Diagnóstico Obstétrico e Ginecológico/normas , Feminino , Humanos , Lactente , Recém-Nascido , Ciclo Menstrual/sangue , Ciclo Menstrual/fisiologia , Pessoa de Meia-Idade , Valores de Referência , Adulto JovemRESUMO
Colorectal cancer (CRC) is one of the most common malignancies in the Western world. CRC is strongly associated with lifestyle factors. Susceptibility to CRC may be partly due to deficient detoxification capacity in the gastrointestinal tract. Genetic polymorphisms in detoxification enzymes result in variations in detoxification activities, which might influence the levels of carcinogens in the gastrointestinal tract, influencing the risk for CRC. To determine whether a genetic polymorphism in the detoxification enzyme UDP-glucuronosyltransferase 2B7 (UGT2B7) predisposes to CRC, 411 Caucasian patients with sporadic CRC and 600 Caucasian controls recruited from the same geographic area were genotyped for the functional UGT2B7 H268Y polymorphism. DNA was isolated and tested by a dual-color real-time polymerase chain reaction assay. Overall, no differences in genotype distributions between patients with CRC and controls were observed. When analyzed with respect to tumor location, a shift from the UGT2B7*I *2 into the UGT2B7*2*2 genotype was seen in patients with proximal CRC (OR 1.80, 95% CI 1.11-2.89). In the male patient subpopulation an even stronger association was observed (*1*1 + *1*2 vs. *2*2: OR 2.17, 95% CI 1.11-4.04; *1*2 vs. *2*2: OR 2.19, 95% CI 1.10-4.37). No associations with respect to tumor stage were seen. In conclusion, the frequency of the UGT2B7*2*2 genotype is higher in CRC patients with proximal location of the tumor, especially in males, which suggests that this genotype is associated with an increased risk for proximal CRC.
Assuntos
Neoplasias Colorretais/genética , Glucuronosiltransferase/genética , Polimorfismo Genético/genética , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , DNA/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Fatores de RiscoRESUMO
Hepatocellular toxicity is a putative side-effect of amiodarone. The hepatic detoxification enzyme glutathione S-transferase-A1-1 (GSTA1-1) is a sensitive indicator of hepatocellular damage. We investigated the occurrence of subclinical liver injury, as measured by plasma GSTA1-1 in intensive care unit patients with atrial fibrillation receiving amiodarone. Sixteen haemodynamically stable intensive care unit patients with atrial fibrillation were treated with amiodarone intravenously. Patients were given a loading dose of 150 mg followed by another 150 mg followed by a continuous infusion of 1200 mg/hour if atrial fibrillation persisted. Blood samples for GSTA1-1 (measured by an enzyme-linked immunosorbent assay) were taken at zero, one, three, six, 12 and 24 hours, transaminases and bilirubin at zero, six, 12 and 24 hours. Blood pressure and heart rate were continuously monitored. Effects were analysed for time-dependent changes (one-way analysis of variance for repeated measures). Blood pressure increased from 125 +/- 8/60 +/- 3 mmHg at t = 0 to 144 +/- 9/66 +/- 4 mmHg at t = 24 hours (P < 0.05), heart rate decreased from atrial fibrillation 124 +/- 5 to sinus rhythm 86 +/- 6 beats per minute (P < 0.05). There was no significant elevation of GSTA1-1, transaminases or bilirubin during the observation period of 24 hours. Amiodarone does not cause elevation of GSTA1-1 as a marker of subclinical liver injury in haemodynamically stable intensive care unit patients with atrial fibrillation.
Assuntos
Amiodarona/efeitos adversos , Antiarrítmicos/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Glutationa Transferase/sangue , Fígado/efeitos dos fármacos , Adulto , Idoso , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Pressão Sanguínea/efeitos dos fármacos , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Patients with familial adenomatous polyposis (FAP) are at high risk of developing duodenal adenomas and carcinomas. Besides germline mutations in the adenomatous polyposis coli (APC) gene, additional factors may influence the age of onset and number of duodenal adenomas. This study compared the genotype distributions of duodenal detoxification enzyme isoforms in patients with FAP and controls. METHODS: The study included 85 patients with FAP and 218 healthy age- and sex-matched controls. Genotyping of all participants using polymerase chain reaction was performed to detect polymorphisms in isoforms of uridine 5'-diphosphate glucuronosyltransferases (UGTs) and glutathione S-transferases (GSTs): UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A10, UGT2B4, UGT2B7, UGT2B15, GSTA1, GSTP1, GSTM1 and GSTT1. RESULTS: The variant genotypes of UGT1A3 were less common in patients with FAP than in controls (odds ratio 0.39 (95 per cent confidence interval 0.22 to 0.67)). There were no associations between FAP and the other polymorphic genes. The polymorphisms investigated had no predictive value for the severity of duodenal adenomatosis in patients with FAP. CONCLUSION: Although the variant genotypes of UGT1A3 were less common in patients with FAP than in those without, this did not modulate the severity of duodenal adenomatosis.
Assuntos
Polipose Adenomatosa do Colo/enzimologia , Neoplasias Duodenais/enzimologia , Genes APC , Glucuronosiltransferase/genética , Glutationa Transferase/genética , Polimorfismo Genético/genética , Adulto , Feminino , Genótipo , Humanos , MasculinoRESUMO
To eliminate the risk of colorectal cancer in patients with familial adenomatous polyposis (FAP), reconstructive proctocolectomy is performed. Although most colonic mucosa is resected during the ileal pouch anal anastomosis, adenomas and carcinomas may develop in the pouch. This may be caused by altered cell kinetics due to intraluminal changes in the pouch. In 32 patients with FAP, biopsy specimens from the mucosa of the pouch and also of the afferent ileal loop were taken. Tissue sections were immunohistochemically processed with the monoclonal antibodies M30 and MIB-1 to assess apoptotic and proliferative indices, respectively. Cell proliferation was also assessed by a modified sign test. There were no significant differences in apoptotic rates between the mucosa of the pouch and the mucosa of the afferent ileal loop. However, cell proliferation was significantly higher in the mucosa of the pouch vs afferent ileal loop, both by using the quantitative (68.3% vs 61.6%, p = 0.001) and semiquantitative methods (p < 0.05). Our newly developed semiquantitative approach outperformed previously described methods. The higher cell proliferation in the pouch as compared to the afferent ileal loop may contribute to the increased risk for adenomas and carcinomas in the pouch of patients with FAP and emphasizes the need for regular endoscopic surveillance.
Assuntos
Polipose Adenomatosa do Colo/patologia , Divisão Celular , Bolsas Cólicas/patologia , Células Epiteliais/patologia , Adenoma/patologia , Polipose Adenomatosa do Colo/cirurgia , Adolescente , Adulto , Idoso , Anticorpos Monoclonais , Apoptose , Carcinoma/patologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/prevenção & controle , Feminino , Humanos , Íleo/patologia , Imuno-Histoquímica , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Proctocolectomia RestauradoraRESUMO
Current treatments of subfertile couples are usually empiric, as the true cause of subfertility often remains unknown. Therefore, we outline the role of nutritional and biochemical factors in reproduction and subfertility. A literature search was performed using MEDLINE, Science Direct and bibliographies of published work with both positive and negative results. The studies showed that folate has a role in spermatogenesis. In female reproduction, folate is also important for oocyte quality and maturation, implantation, placentation, fetal growth and organ development. Zinc has also been implicated in testicular development, sperm maturation and testosterone synthesis. In females, zinc plays a role in sexual development, ovulation and the menstrual cycle. Both folate and zinc have antioxidant properties that counteract reactive oxygen species (ROS). Thiols, such as glutathione, balance the levels of ROS produced by spermatozoa and influence DNA compaction and the stability and motility of spermatozoa. Oocyte maturation, ovulation, luteolysis and follicle atresia are also affected by ROS. After fertilization, glutathione is important for sperm nucleus decondensation and pronucleus formation. Folate, zinc, ROS and thiols affect apoptosis, which is important for sperm release, regulation of follicle atresia, degeneration of the corpus luteum and endometrial shedding. Therefore, the concentrations of these nutrients may have substantial effects on reproduction. In conclusion, nutritional and biochemical factors affect biological processes in male and female reproduction. Further research should identify pathways that may lead to improvements in care and treatment of subfertility.
Assuntos
Antioxidantes/metabolismo , Ácido Fólico/metabolismo , Infertilidade/etiologia , Infertilidade/prevenção & controle , Zinco/metabolismo , Antioxidantes/administração & dosagem , Apoptose , Feminino , Fertilidade , Ácido Fólico/administração & dosagem , Humanos , Masculino , Zinco/administração & dosagemRESUMO
BACKGROUND: The glutathione S-transferases (GST) can metabolise endogenous and exogenous toxins and carcinogens by catalysing the conjugation of diverse electrophiles with reduced glutathione (GSH). Variations of GST enzyme activity could influence the susceptibility of developing cancers in certain areas of the gastrointestinal tract. AIMS: The expression of the components of the glutathione system in the colon was investigated with respect to age, gender and localisation. METHODS: Biopsies of macroscopically normal mucosa from both proximal and distal colon were collected from 208 patients (106 females, 102 males; mean age 61 years), who underwent colonoscopy for various clinical reasons. GSH content, total GST enzyme activity and the levels of the GST isoenzymes glutathione S-transferase P1 (GSTP1) and glutathione S-transferase M1 (GSTM1) were determined. RESULTS: GST enzyme activity, GSH and GSTP1 levels decreased significantly from proximal to distal colon (GST activity: 264 vs. 244 nmol/min/mg protein, p < 0.001, GSH content: 32 vs. 30 nmol/mg protein, p = 0.022 and GSTP1 levels: 2.25 vs. 2.10 mug/mg protein, p < 0.001). In female patients there was a significant stepwise increase of GST-activities and GSTP1 levels from the age of under 50 years to over 70 years. Oral sex hormone substitution among female patients between 50 and 70 years suppressed GST-activities and GSTP1 content. CONCLUSIONS: The GSH-system in the colonic mucosa is expressed at a lower level in the distal colon (sigma) than in the colon transversum; whether this small difference translates into variations of incidence of colorectal cancer remains to be seen. Females express higher enzyme levels as they grow older, while in males no significant age effects were found. Elderly females might be better equipped with protective GSH-enzymes in the colon than males and this could contribute to the lower incidence of colorectal carcinomas in females.
Assuntos
Envelhecimento/metabolismo , Colo Transverso/enzimologia , Neoplasias do Colo/enzimologia , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Glutationa S-Transferase pi/biossíntese , Glutationa Transferase/biossíntese , Mucosa Intestinal/enzimologia , Proteínas de Neoplasias/biossíntese , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/patologia , Colo Transverso/patologia , Neoplasias do Colo/patologia , Feminino , Glutationa/metabolismo , Humanos , Incidência , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores SexuaisRESUMO
BACKGROUND: Adenomas can develop in the pouch after colectomy with ileal pouch-anal anastomosis (IPAA) in patients with familial adenomatous polyposis (FAP). Glutathione S-transferases (GSTs) have a protective role in carcinogenesis. GST activity is much higher in the ileum than in the colon. The present study examined the hypothesis that the protective capacity of GSTs may be lowered as a result of colonic metaplasia of the ileal pouch. METHODS: Levels of GSTs, glutathione and cysteine, and the degree of inflammation and colonic metaplasia were quantified in biopsies from the pouch and afferent loop of 26 patients with FAP. RESULTS: GST enzyme activity, and levels of GST alpha, glutathione and cysteine in the pouch were significantly lower than those in the afferent loop (308 versus 398 nmol per min per mg protein (P<0.001), 4604 versus 5286 ng per mg protein (P=0.010), 27.1 versus 34.8 nmol per mg protein (P=0.023) and 0 versus 4.8 nmol per mg protein (P=0.009) respectively). No correlation was found between inflammation or colonic metaplasia of the pouch and GST enzyme activity in the pouch. CONCLUSION: After IPAA, GST detoxification activity in the pouch is significantly lower than that in the afferent ileal loop, which may promote tumorigenesis.
Assuntos
Polipose Adenomatosa do Colo/enzimologia , Colo/enzimologia , Bolsas Cólicas , Glutationa Transferase/metabolismo , Proctocolectomia Restauradora/efeitos adversos , Polipose Adenomatosa do Colo/patologia , Polipose Adenomatosa do Colo/cirurgia , Adolescente , Adulto , Idoso , Biópsia por Agulha/métodos , Colectomia/métodos , Colo/patologia , Bolsas Cólicas/patologia , Cisteína/metabolismo , Feminino , Glutationa/metabolismo , Humanos , Masculino , Metaplasia/enzimologia , Metaplasia/patologia , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Colon carcinogenesis is a multifactorial process influenced by hereditary as well as environmental factors. The glutathione/glutathione S-transferase detoxification system in the colon is important for protection against carcinogens. We investigated the levels of glutathione/glutathione S-transferase in normal colon mucosa of patients with colorectal cancer and in patients at high risk for colorectal cancer compared with those in healthy controls. MATERIALS AND METHODS: Glutathione content was analyzed by high-performance liquid chromatography, and glutathione S-transferase enzyme activity by spectrophotometric determination with 1-chloro 2,4-dinitrobenzene. Normal colon tissue of patients with colon adenoma (n = 64), colorectal cancer (n = 37), familial adenomatous polyposis (FAP; n = 19), hereditary non-polyposis colorectal cancer families with (HNPCC+Ad; n = 34) or without (HNPCC-Ad; n = 33) adenoma was investigated. RESULTS: Glutathione levels were significantly lower in the normal colon mucosa of patients with cancer, FAP, HNPCC-Ad or HNPCC+Ad compared with adenoma patients or healthy controls. Glutathione S-transferase enzyme activity in the distal colon was significantly lower in patients with cancer or FAP compared with the adenoma patients or healthy controls, whereas values in carcinoma patients were significantly lower compared with both the HNPCC-Ad and HNPCC+Ad groups. CONCLUSIONS: An association of low colonic glutathione/glutathione S-transferase activity levels and high clinical risk for the development of colorectal cancer was observed. This low glutathione detoxification capacity might contribute to the colon cancer risk.
Assuntos
Colo/química , Neoplasias Colorretais/química , Glutationa/análise , Adenoma/química , Adenoma/enzimologia , Polipose Adenomatosa do Colo/química , Polipose Adenomatosa do Colo/enzimologia , Adulto , Colo/enzimologia , Neoplasias do Colo/química , Neoplasias do Colo/enzimologia , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais Hereditárias sem Polipose/química , Neoplasias Colorretais Hereditárias sem Polipose/enzimologia , Feminino , Glutationa Transferase/metabolismo , Humanos , Mucosa Intestinal/química , Mucosa Intestinal/enzimologia , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND: Thiols are scavengers of reactive oxygen species (ROS). We aim to investigate associations between thiols in various fluids in (sub)fertile couples and fertility outcome parameters. METHODS: In 156 couples undergoing assisted reproduction techniques (ART), we measured the concentrations of glutathione (GSH), cysteine (Cys), homocysteine (Hcy) and cysteinylglycine (CGS) and fertility outcome parameters in the ejaculate, purified spermatozoa and follicular fluid. RESULTS: All thiols were detectable in most ejaculates, spermatozoa and follicular fluids, of which Cys concentrations were highest. Thiol concentrations in the ejaculate were similar in fertile and subfertile men. However, Hcy in follicular fluid was higher in women with endometriosis compared with women in the idiopathic subfertile group (P=0.04). The GSH, Cys, Hcy and CGS concentrations in spermatozoa of subfertile men were significantly higher compared with men in the idiopathic subfertile group and fertile men (P<0.001). Most notably, Hcy concentrations in both the ejaculate and follicular fluid were negatively associated with embryo quality on culture day 3 in the IVF/ICSI procedure. CONCLUSIONS: Spermatozoa of subfertile men contain significantly higher thiol concentrations as compared with those of fertile men. The detrimental effect on embryo quality of a high Hcy concentration in the ejaculate and in follicular fluid is intriguing and may suggest that Hcy is inversely associated with fertility outcome.
Assuntos
Líquido Folicular/química , Glutationa/análise , Homocisteína/análise , Infertilidade/fisiopatologia , Sêmen/química , Espermatozoides/química , Adulto , Cisteína/análise , Dipeptídeos/análise , Ejaculação , Endometriose/fisiopatologia , Feminino , Humanos , Infertilidade Masculina/fisiopatologia , Masculino , Espécies Reativas de Oxigênio/efeitos adversosRESUMO
BACKGROUND: Small intestinal malignancies in humans are rare; however, patients with coeliac disease have a relatively high risk for such tumours. Intestinal UDP-glucuronosyltransferases are phase II drug metabolism enzymes also involved in the detoxification of ingested toxins and carcinogens. As many toxins and carcinogens are ingested via food, the human gastrointestinal tract not only has an important role in the uptake of essential nutrients, but also acts as a first barrier against such harmful constituents of the food. Therefore, the gastrointestinal mucosa contains high levels of detoxification enzymes such as cytochromes-P450, glutathione S-transferases and UDP-glucuronosyltransferases. AIM: To compare the UDP-glucuronosyltransferase detoxification capacity in small intestinal mucosa of patients with coeliac disease vs. that in normal controls. METHODS: We assessed UDP-glucuronosyltransferase enzyme activities towards 4-methylumbelliferone in small intestinal biopsies of patients with coeliac disease (n = 22) and age- and sex-matched controls (n = 27). RESULTS: Small intestinal UDP-glucuronosyltransferase enzyme activity in controls was significantly higher than in patients with coeliac disease: 0.55 +/- 0.27 vs. 0.35 +/- 0.16 nmol/min mg protein, respectively (mean +/- s.d., P = 0.005). DISCUSSION: The low small intestinal UDP-glucuronosyltransferase detoxification activity in patients with coeliac disease may result in a deficient detoxification of potential carcinogens, and thus could explain in part the relatively high small intestinal cancer risk in these patients.
Assuntos
Doença Celíaca/metabolismo , Glucuronosiltransferase/metabolismo , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Carcinógenos/metabolismo , Feminino , Glucuronosiltransferase/deficiência , Humanos , Himecromona/análogos & derivados , Himecromona/metabolismo , Masculino , Pessoa de Meia-Idade , Toxinas Biológicas/metabolismoRESUMO
Early placental development is characterised by rapid cell differentiation and migration, matrix remodelling and angiogenesis. The enzyme NAD(P)H oxidase is a major source of superoxide anions implicated in signalling pathways regulating these processes in other systems. It is also thought to be involved in oxygen sensing and regulation of the expression of antioxidant genes. We therefore investigated NAD(P)H oxidase activity in placental tissues in early pregnancy and at term, and correlated this with antioxidant capacity. We collected placental tissues from women undergoing termination of pregnancy (n=19; gestational age 11(+6)+/-1(+0) weeks), and those with elective caesarean section at term after uncomplicated pregnancy (n=15; gestational age 38(+6)+/-0(+4) weeks). Tissues were assayed for superoxide production, using lucigenin chemiluminescence, and three independent markers of antioxidant capacity. In human placentas from normal deliveries at term substantial basal NAD(P)H activity was present. Activity was almost threefold higher in early pregnancy (P<0.0001). This was paralleled by higher total antioxidant capacity (P<0.0001), tissue glutathione concentrations (P<0.01) and gluthathione S-transferase enzyme activity (P<0.05) when compared to corresponding term placental values. NAD(P)H oxidase mediated superoxide generation could be an important modulator of the antioxidant defence response in early pregnancy.
Assuntos
Antioxidantes/metabolismo , NADPH Oxidases/metabolismo , Placenta/enzimologia , Primeiro Trimestre da Gravidez/metabolismo , Superóxidos/metabolismo , Feminino , Glutationa/análise , Glutationa Transferase/metabolismo , Humanos , Placenta/química , GravidezRESUMO
OBJECTIVE: To investigate an association between a family history of cardiovascular disease and severe preeclampsia and/or HELLP syndrome (Haemolysis, Elevated Liver enzymes, Low Platelets). METHODS: One hundred twenty-eight women with a history of severe preeclampsia and/or HELLP syndrome and 123 women with previous uncomplicated pregnancies only were included in the study. All participants completed questionnaires about diagnoses of cardiovascular diseases, hypertension, and hypercholesterolemia among their first-degree relatives, which were subsequently confirmed by the relatives' general practitioners. The main outcome measures were the prevalence of cardiovascular diseases, hypertension, and hypercholesterolemia among first-degree relatives of both groups. Statistical analysis was done using chi(2)-analysis. RESULTS: The prevalence of familial cardiovascular disease among women with a history of severe preeclampsia and/or HELLP syndrome (23%) compared to controls (19%) was not significantly different (OR 1.3, 95%CI 0.7-2.5). However, women with a history of severe preeclampsia and/or HELLP syndrome more often had one or more first-degree relatives with hypertension and/or hypercholesterolemia before the age of 60 years compared to controls (54% vs. 32%, respectively; OR 2.6, 95%CI 1.5-4.3). The prevalence of hypertension and hypercholesterolemia among first-degree relatives, irrespective of age, also was significantly higher among women with a history of severe preeclampsia and/or HELLP syndrome as compared to controls (60% vs. 42%, respectively; OR 2.0, 95%CI 1.2-3.4). CONCLUSION: Severe preeclampsia is associated with a positive family history of hypertension and/or hypercholesterolemia.
Assuntos
Síndrome HELLP/genética , Hipercolesterolemia/genética , Hipertensão/genética , Pré-Eclâmpsia/genética , Complicações na Gravidez/genética , Adulto , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Seguimentos , Humanos , Gravidez , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Glutathione S-transferases (GSTs) are present in large amounts in the human kidney, where they demonstrate a specific distribution. The assessment of urinary excretion of GST alpha (proximal tubules) and pi (distal and collecting tubules) could be helpful in determining if, and to what degree renal tubular damage is present in preeclampsia and whether this damage is in the proximal or distal region. METHODS: Urine samples were collected from 22 women with severe preeclampsia and/or HELLP syndrome (PE), from 30 non-pregnant women with a history of severe preeclampsia (HPE), from 18 women with uncomplicated pregnancies (PC) and from 30 non-pregnant women with a history of uncomplicated pregnancies (HPC). GSTA1-1 and GSTP1-1 were assayed by ELISA and were expressed as nanograms per 10 mmol creatinine (Cr). RESULTS: Median urinary GSTP1-1 concentrations were significantly (p<0.001) higher in women with preeclampsia [62.2 (4.3-291.2) ng/10 mmol Cr] compared to non-pregnant women with a history of preeclampsia [22.3 (0-142.6) ng/10 mmol Cr]). In addition, in normotensive pregnant women, urinary GSTP1-1 concentrations were significantly (p<0.01) higher [82.6 (8.3-206.7) ng/10 mmol Cr]) compared to non-pregnant controls [5.1 (0-66.7) ng/10 mmol Cr]. No difference in GSTP1-1 concentrations was found between women with preeclampsia and normotensive pregnant women. GSTA1-1 concentrations were not significantly different between the four groups of women investigated. There were no correlations between the degree of proteinuria and urinary GSTP1-1 or GSTA1-1 concentrations. CONCLUSION: GSTP1-1 metabolism in the distal tubule changes during normotensive as well as preeclamptic pregnancy. Whether this is due to tubular cell damage, disturbed resorption or an increase in cellular levels cannot be determined as yet.
Assuntos
Pressão Sanguínea/fisiologia , Glutationa S-Transferase pi/urina , Pré-Eclâmpsia/urina , Adulto , Biomarcadores/urina , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Glutationa Transferase/urina , Humanos , Túbulos Renais/metabolismo , Pessoa de Meia-Idade , Pré-Eclâmpsia/fisiopatologia , Gravidez , Proteinúria/etiologia , Proteinúria/urina , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
Interest in mechanisms of colon cancer prevention by food compounds is strong and research in this area is often performed with cultured colon cancer cells. In order to assess utility for screening of potential cancer-preventive (food) compounds, expression profiles of 14 human cell lines derived from colonic tissue were measured using cDNA microarrays with 4000 genes and compared with expression profiles in biopsies of human colon tumours and normal tissue. Differences and similarities in the gene expression profiles of the cell lines were analysed by clustering and principal component analysis (PCA). Cytoskeleton genes and immune response genes are two functional classes of genes that contributed to the differences between the cell lines. A subset of 72 colon cancer-specific genes was identified by comparing expression profiles in human colon biopsies of tumour tissue and normal tissue. A separation of the cell lines based on the tumour stage of the original adenocarcinoma was observed after PCA of expression data of the subset of colon cancer-specific genes in the cell lines. The results of this study may be useful in the ongoing research into mechanisms of cancer prevention by dietary components.
Assuntos
Adenocarcinoma/genética , Adenocarcinoma/patologia , Biomarcadores Tumorais/análise , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Perfilação da Expressão Gênica , Genes Neoplásicos , Adenocarcinoma/química , Adenocarcinoma/prevenção & controle , Adulto , Biópsia , Linhagem Celular Tumoral , Neoplasias do Colo/química , Neoplasias do Colo/prevenção & controle , Feminino , Mucosa Gástrica/patologia , Regulação Neoplásica da Expressão Gênica , Testes Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Proteínas de Neoplasias/análise , Análise de Sequência com Séries de Oligonucleotídeos , RNA Neoplásico/análiseRESUMO
New knowledge of placental development and function suggests that several common complications of pregnancy could share a similar origin. It is suggested that impaired placental development in early pregnancy may lead to placental oxidative stress and subsequently to the maternal syndromes such as recurrent early pregnancy loss and pre-eclampsia. Oxidative stress has been most extensively investigated in pre-eclampsia, resulting in hundreds of publications and many reviews. In general the literature points to the presence of placental and maternal oxidative stress. However, conformity amongst the relevant data is not absolute, most probably the result of the diversity of biomarkers investigated and the methods employed to assess oxidative stress, which generally depend on the assessment of end products of oxidative stress. Recently, new techniques have been developed that use different approaches based on the "real-time" measurement of oxidative stress by the redox status of thiols or the assessment of superoxide generation, whereas the role of Phase I/Phase II biotransformation pathways in oxidative stress was recognised. This review focuses on this biotransformation system, the thiol redox status and the involvement of these systems in oxidative stress associated with reproduction and pregnancy disorders, with the emphasis being laid on the syndrome of pre-eclampsia.
Assuntos
Estresse Oxidativo/fisiologia , Pré-Eclâmpsia/fisiopatologia , Complicações na Gravidez/fisiopatologia , Compostos de Sulfidrila/uso terapêutico , Adulto , Feminino , Glutationa/metabolismo , Humanos , Infertilidade/fisiopatologia , Pré-Eclâmpsia/metabolismo , Gravidez , Complicações na Gravidez/metabolismo , Superóxidos/metabolismoRESUMO
Colorectal cancer (CRC) is one of the most common malignancies in the Western world showing an increasing incidence, and has been associated with genetic and lifestyle factors. Individual susceptibility to CRC may be due partly to variations in detoxification capacity in the gastrointestinal tract. Genetic polymorphisms in detoxification enzymes may result in variations in detoxification activities, which subsequently might influence the levels of toxic/carcinogenic compounds, and this may influence the risk for CRC. To determine whether genetic polymorphisms in detoxification enzymes predispose to the development of CRC, 371 patients with sporadic CRC and 415 healthy controls were genotyped for polymorphisms in the important detoxification enzymes UDP-glucuronosyltransferase UGT1A1, UGT1A6, UGT1A7 and UGT1A8, and glutathione S-transferase GSTA1, GSTM1, GSTP1 and GSTT1. Patients and controls were all of Caucasian origin. DNA was isolated from either blood or tissue and tested by polymerase chain reaction followed by restriction fragment length polymorphism analyses. Logistic regression analyses showed significant age- and gender-adjusted risks for CRC associated with variant genotypes of UGT1A6 [OR 1.5, 95% (confidence interval) CI 1.03-2.3] and UGT1A7 (OR 2.4, 95% CI 1.3-4.6), whereas no associations were found between CRC and the other polymorphic genes as mentioned above. In conclusion, the data suggest that the presence of variant UGT1A6 and UGT1A7 genotypes with expected reduced enzyme activities, might enhance susceptibility to CRC.
Assuntos
Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/genética , Glucuronosiltransferase/genética , Glutationa Transferase/genética , Polimorfismo Genético/genética , Adulto , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Fatores de Risco , População BrancaRESUMO
Elevated plasma VEGF concentrations in preeclampsia are associated with local placental ischemia and endothelial dysfunction. We investigated the urinary VEGF excretion in women with severe preeclampsia (n=37) and its relation with proteinuria compared to that in healthy pregnant (n=32) and non-pregnant women (n=30). In women with severe preeclampsia VEGF levels were 54.0 (19.9-192.4) ng/mmol creatinine, significantly (p<0.0001) higher than levels in pregnant controls (28.2 (6.7-63.0) ng/mmol creatinine) and non-pregnant controls (29.5 (10.1-59.1) ng/mmol creatinine). Proteinuria was not significantly correlated with urinary VEGF levels. In conclusion, high urinary VEGF concentrations in severe preeclampsia might reflect increased renal production of VEGF rather than elevated VEGF levels in the systemic circulation.