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Environmental Science & Technology May 2021Diverse organic compounds, many derived from consumer products, are found in sewage sludge worldwide. Understanding which of these poses the most significant...
Diverse organic compounds, many derived from consumer products, are found in sewage sludge worldwide. Understanding which of these poses the most significant environmental threat following land application can be investigated through a variety of predictive and cell-based toxicological techniques. Nontargeted analysis using high-resolution mass spectrometry with predictive estrogenic activity modeling was performed on sewage sludge samples from 12 wastewater treatment plants in California. Diisobutyl phthalate and dextrorphan were predicted to exhibit estrogenic activity and identified in >75% of sludge samples, signifying their universal presence and persistence. Additionally, the application of an estrogen-responsive cell bioassay revealed reductions in agonistic activity during mesophilic and thermophilic treatment but significant increases in antagonism during thermophilic treatment, which warrants further research. Ten nontarget features were identified (metoprolol, fenofibric acid, erythrohydrobupropion, oleic acid, mestranol, 4'-chlorobiphenyl-2,3-diol, medrysone, scillarenin, sudan I, and ,-didesmethyltramadol) in treatment set samples and are considered to have influenced the estrogenic activity observed. The combination of predictive and estrogenicity with nontargeted analysis has led to confirmation of 12 estrogen-active contaminants in California sewage sludge and has highlighted the importance of evaluating both agonistic and antagonistic responses when evaluating the bioactivity of complex samples.
Topics: Estrogens; Estrone; Sewage; Water Pollutants, Chemical; Water Purification
PubMed: 33909413
DOI: 10.1021/acs.est.0c07846 -
Fertility and Sterility Jul 1977Forty 3-hour oral glucose tolerance tests (OGTTs) were performed in 10 assumedly healthy female volunteers 19 to 30 years old, each serving four times as her own... (Comparative Study)
Comparative Study
Forty 3-hour oral glucose tolerance tests (OGTTs) were performed in 10 assumedly healthy female volunteers 19 to 30 years old, each serving four times as her own control. Each subject was taking a sequential type oral contraceptive containing either 50 microgram of ethinylestradiol or 80 microgram of mestranol alternatingly in four consecutive treatment cycles. The OGTTs were performed on the 6th day of each cycle, during pure estrogen medication. Blood glucose and serum insulin values did not differ significantly under either estrogen as tested by the t-test for paired observations. Our results do not support the findings of others that mestranol has a more pronounced or even exclusively adverse effect on glucose tolerance as compared with ethinylestradiol.
Topics: Adult; Blood Glucose; Carbohydrate Metabolism; Contraceptives, Oral; Contraceptives, Oral, Sequential; Ethinyl Estradiol; Female; Glucose Tolerance Test; Humans; Insulin; Mestranol; Pregnancy
PubMed: 872954
DOI: 10.1016/s0015-0282(16)42675-0 -
The Journal of Clinical Endocrinology... Nov 2022It is essential to improve the current predictive ability for type 2 diabetes (T2D) risk.
CONTEXT
It is essential to improve the current predictive ability for type 2 diabetes (T2D) risk.
OBJECTIVE
We aimed to identify novel metabolic markers for future T2D in Chinese individuals of Han ethnicity and to determine whether the combined effect of metabolic and genetic markers improves the accuracy of prediction models containing clinical factors.
METHODS
A nested case-control study containing 220 incident T2D patients and 220 age- and sex- matched controls from normoglycemic Chinese individuals of Han ethnicity was conducted within the Wuxi Non-Communicable Disease cohort with a 12-year follow-up. Metabolic profiling detection was performed by high-performance liquid chromatography‒mass spectrometry (HPLC-MS) by an untargeted strategy and 20 single nucleotide polymorphisms (SNPs) associated with T2D were genotyped using the Iplex Sequenom MassARRAY platform. Machine learning methods were used to identify metabolites associated with future T2D risk.
RESULTS
We found that abnormal levels of 5 metabolites were associated with increased risk of future T2D: riboflavin, cnidioside A, 2-methoxy-5-(1H-1, 2, 4-triazol-5-yl)- 4-(trifluoromethyl) pyridine, 7-methylxanthine, and mestranol. The genetic risk score (GRS) based on 20 SNPs was significantly associated with T2D risk (OR = 1.35; 95% CI, 1.08-1.70 per SD). The area under the receiver operating characteristic curve (AUC) was greater for the model containing metabolites, GRS, and clinical traits than for the model containing clinical traits only (0.960 vs 0.798, P = 7.91 × 10-16).
CONCLUSION
In individuals with normal fasting glucose levels, abnormal levels of 5 metabolites were associated with future T2D. The combination of newly discovered metabolic markers and genetic markers could improve the prediction of incident T2D.
Topics: Humans; Diabetes Mellitus, Type 2; Case-Control Studies; Genetic Markers; Asian People; China
PubMed: 35977051
DOI: 10.1210/clinem/dgac487 -
Genomics Sep 2020Gliomas account for 75% of the primary malignant brain tumors and a majority of lower-grade gliomas (LGG) inevitably develop into glioblastoma. The dysregulation of...
Gliomas account for 75% of the primary malignant brain tumors and a majority of lower-grade gliomas (LGG) inevitably develop into glioblastoma. The dysregulation of lncRNAs play a crucial role in LGG. In the present study, we first screened out six differentially expressed lncRNAs (AC021739.2, AL031722.1, AL354740.1, FGD5-AS1, LINC00844, and NEAT1) based on TCGA and GTEx RNA-seq databases. LncRNA prognostic signature was then established by Kaplan-Meier and multivariate Cox proportional hazards regression, with its predictive value validated by time-dependent receiver operating characteristic (ROC) curves. After lncRNA-miRNA-mRNA regulatory networks were established by Cytoscape 3.7.2, Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed, with results enriched in various malignancy-related functions and pathways. Finally, six putative drugs (irinotecan, camptothecin, mitoxantrone, azacitidine, mestranol, and enilconazole) were predicted by Connectivity Map. In conclusion, we identified a 6-lncRNA prognostic signature with its ceRNA networks, and six candidate drugs against LGG.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Brain Neoplasms; Female; Glioma; Humans; Male; MicroRNAs; Middle Aged; Prognosis; RNA, Long Noncoding; RNA, Messenger; Risk; Young Adult
PubMed: 32447005
DOI: 10.1016/j.ygeno.2020.05.016 -
Journal of Clinical Pathology Mar 1979
Topics: Abnormalities, Drug-Induced; Adrenal Glands; Contraceptives, Oral, Combined; Ethynodiol Diacetate; Female; Humans; Male; Mestranol; Pregnancy
PubMed: 429599
DOI: 10.1136/jcp.32.3.305 -
Environmental Health Perspectives Apr 1983Published reports have described an increased incidence of adenomas and of hepatocellular carcinomas in livers of women with a history of long-term oral contraceptive...
Published reports have described an increased incidence of adenomas and of hepatocellular carcinomas in livers of women with a history of long-term oral contraceptive use. Evidence derived from human and experimental animals suggests that oral contraceptive steroids may be liver tumor promoters. Experiments were designed to determine the initiating and/or promoting potential of two oral contraceptive steroids, namely mestranol and norethynodrel. The results show that: mestranol and norethynodrel can promote DEN-initiated hepatocarcinogenesis, as indicated by increased numbers of gamma-glutamyl transpeptidase-positive, putative preneoplastic lesions and by the appearance of carcinomas. Various synthetic estrogens fail to cause detectable levels of DNA damage in hepatocytes. Mestranol has weak, if any, initiating potential. Neither mestranol nor norethynodrel exhibits antiglucocorticoid activity. Mestranol and norethynodrel inhibit metabolic cooperation in V-79 Chinese hamster cells. Taken together, these results and those reported by others demonstrate that oral contraceptive steroids are relatively strong promoters of hepatocarcinogenesis and have little if any genotoxic effect.
Topics: Animals; Carcinogens; Cell Communication; Cocarcinogenesis; Contraceptives, Oral; Contraceptives, Oral, Hormonal; Female; Liver; Liver Neoplasms; Liver Neoplasms, Experimental; Rats; Tyrosine Transaminase
PubMed: 6135605
DOI: 10.1289/ehp.8350109 -
Fertility and Sterility 1966
Topics: Contraceptives, Oral; Female; Humans; Mestranol; Norethindrone
PubMed: 5901012
DOI: 10.1016/s0015-0282(16)35826-5 -
Journal of Lipid Research Jun 1986In an investigation of alterations in cholesterol metabolism during contraceptive steroid use, we studied plasma clearance of chylomicron remnants. Six healthy women...
In an investigation of alterations in cholesterol metabolism during contraceptive steroid use, we studied plasma clearance of chylomicron remnants. Six healthy women were studied on and off contraceptive steroid therapy. Remnant clearance was measured from the disappearance of retinyl palmitate administered intravenously in plasma endogenously labeled with retinyl palmitate. We also measured cholesterol in HDL and its subfractions and postheparin lipoprotein lipase and hepatic triglyceride lipase activities. Plasma decay of retinyl palmitate was biexponential. The rapid component, reflecting chylomicron remnant removal, accounted for about 90% of the total clearance in all studies. During contraceptive steroid intake, both rapid and slow decay constants and the calculated plasma clearance rates were significantly increased (mean values: rapid decay constant, control 0.048 versus treated 0.101 min-1, P less than 0.05; slow decay constant, 0.004 versus 0.014 min-1, P less than 0.01; plasma clearance 74 versus 115 ml/min, P less than 0.025) indicating enhanced hepatic uptake of chylomicron remnants and probably an increased hepatic uptake of higher density lipoproteins (d greater than 1.006 g/ml). Total postheparin lipolytic activity and lipoprotein lipase activity were depressed in all six women (P less than 0.05) and hepatic triglyceride lipase activity was increased in four of five subjects. Contraceptive steroids also caused a decrease in the HDL2/HDL3 cholesterol ratio (P less than 0.05), implying impaired peripheral lipoprotein triglyceride hydrolysis and/or increased HDL2 clearance by hepatic triglyceride lipase. In conclusion, during intake of contraceptive steroids, the plasma clearance of chylomicron remnants and higher density lipoproteins was increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adult; Biological Transport, Active; Cholesterol; Cholesterol, HDL; Chylomicrons; Contraceptives, Oral; Diterpenes; Female; Humans; Lipids; Liver; Metabolic Clearance Rate; Retinyl Esters; Vitamin A
PubMed: 3746133
DOI: No ID Found -
The Medical Journal of Malaysia Mar 1976
Topics: Amenorrhea; Animals; Contraceptives, Oral; Dogs; Female; Haplorhini; Humans; Infertility; Male; Progesterone; Rabbits
PubMed: 822261
DOI: No ID Found -
Fertility and Sterility Jun 1985Clinical and laboratory evaluations of nine hirsute women were performed for determination the efficacy of combination drug therapy. Each patient had previously failed...
Clinical and laboratory evaluations of nine hirsute women were performed for determination the efficacy of combination drug therapy. Each patient had previously failed to respond to single drug therapy with oral contraceptives (OC), dexamethasone (DEX), or spironolactone (S) and received S (100 to 150 mg) and either an OC (mestranol, 0.05 to 0.08 mg, and norethindrone, 1 mg) or DEX (0.5 mg) daily. Total testosterone, dehydroepiandrosterone sulfate, free testosterone, and sex-hormone-binding globulin were measured before therapy and 4 to 6 weeks after initiation of therapy and were compared with the responses to OC (n = 7), DEX (n = 8), and S (n = 6). A satisfactory clinical response in the rate of hair growth was defined as at least a doubling of the time interval between adjunctive therapies (electrolysis, shaving, or bleaching) and patient satisfaction with treatment. The responses of the androgenic parameters were not statistically different between combination and single drug therapy. Although all patients noted a subjective improvement in hair growth, eight of nine fulfilled the criteria for a clinical response (P less than 0.001). Transient diuresis was the only side effect noted. The study suggests that combination drug therapy is an efficacious and well-tolerated approach to the management of unresponsive hirsutism.
Topics: Contraceptives, Oral; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Dexamethasone; Drug Therapy, Combination; Female; Hirsutism; Humans; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin; Spironolactone; Testosterone
PubMed: 3158552
DOI: No ID Found