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PubMed1984

Hormone load tests in the first half of pregnancy--a diagnostic and therapeutic approach.

In view of still unsolved problems concerning disturbances in early pregnancy, the efficacy of various substances with regard to endocrine systems in the first trimester of pregnancy has been investigated. Seventy-five women, who had been referred to our hospital for an authorized termination of pregnancy during weeks 7-9 of gestation, and 6 women between weeks 10 and 16 of gestation volunteered to take part in the study. After single administration of the test substances, blood was drawn from an indwelling catheter with one group of patients at hourly intervals over an 8-hour period, while with all other patients this was done at 3-hourly intervals over a 24-hour period. In all samples beta-HCG, progesterone (P), estradiol-17 beta (E2), and 17 alpha-hydroxyprogesterone (17-OHP) were determined. The following substances were studied in detail: HCG, allylestrenol, 17-hydroxyprogesterone caproate, tamoxifene, R 5020, betamethasone, and dehydroepiandrosterone sulfate (DHAS). Two hundred and seventy-one women with imminent abortion were either treated with allylestrenol (n = 130) or simple clinotherapy and no medication (n = 141). One hundred and two women had a miscarriage, while 168 carried to term. The serum concentrations of beta-HCG, P, E2 and estriol (E3) were determined serially. Twelve women with a history of repeated miscarriages were treated with vaginal progesterone suppositories. Five of them experienced another miscarriage. The serum concentrations of beta-HCG and P were determined serially. It could be shown that diagnostics in early pregnancy have been complemented by assessment of the E2-increase after DHAS loading. Maternal serum concentrations were not affected by administration of HCG and various progestational agents including allylestrenol. Only in the case of parenteral or vaginal application of progesterone could increased serum concentrations of this hormone be demonstrated. Progesterone substitution in early pregnancy may, therefore, be chosen under special conditions as possible therapeutic procedure.

17 alpha-Hydroxyprogesterone Caproate↗
PubMed1981

[Autoradiographic study of hormonal regulation of proliferating golden hamster uterus cells during postnatal ontogeny].

Study of the effects of octestrol, 17-hydroxyprogesterone caproate and tamoxifen on uterine cell proliferation in golden hamsters aged one to twenty days has shown the existence in the uterine epithelium of two cell populations with varying sensitivity to sex hormones. The cells of uterine glands being formed by day 12 of postnatal ontogenesis were found to be insensitive to the proliferation-inhibiting effect of progesterone and little sensitive to the proliferation-stimulating action of the estrogen. The epithelial cells lining the uterine cavity show a high sensitivity to sex hormones. The absence of changes in proliferative activity of the epithelial cells exposed to tamoxifen allows a suggestion that ontogenetic changes in the proliferative activity of the uterine cells do not depend on the presence of endogenous hormones.

17 alpha-Hydroxyprogesterone Caproate↗
PubMed1982

Signal function of metabolism of neutral amino acids and 2-keto acids for initiation of insulin secretion.

2-Ketocaproate and 2-ketoisocaproate were equally potent insulin secretagogues. The insulin secretory potency of L-leucine was less than half of that of the keto acids and L-norleucine did not induce any insulin release by isolated islets and by the perfused pancreas from ob/ob mice. Rates of decarboxylation of 2-keto-[1-14C]isocaproate and of 2-keto-[1-14C]caproate were equally high. The finding is consistent with the view that enhanced production of reducing equivalents is necessary for initiation of insulin release. The rates of decarboxylation and transamination of L-[1-14C]leucine by isolated pancreatic islets were several times higher than the rates observed with L-[1-14C]norleucine. Thus, the high activity of the pancreatic islet branched-chain amino acid aminotransferase may be important for the recognition of L-leucine as an insulin secretagogue by pancreatic B-cells.

Animals↗
PubMed1981

[Use of gestagens to control in vitro growth of endometrial carcinoma (author's transl)].

The impact of three gestagens, hydroxyprogesterone caproate, norethisterone acetate, and D-norgestrel, on in vitro cell cultures was tested in 40 test tubes and ten cover glasses. All tested cultures were of endometrial carcinomas. Cytomorphological changes were recordable from more than half of all cultures and interpreted as sensitivity to gestagens of the carcinoma concerned. No differences were safely established regarding effectiveness of different gestagens and different concentrations. In vitro gestagen action was clearly demonstrated by determination of nuclear overlap indexes of the cover glass cultures. No answer has yet been found as to whether reduction in nuclear overlap index, following addition of gestagens, had been caused by cellular modification. - Sensitivity of endometrial carcinoma to gestagens in vitro depended clearly on the degree of morphological differentiation.

17 alpha-Hydroxyprogesterone Caproate↗
PubMed1994

[Influence of anti-androgen therapy for prostatic hypertrophy on lipid metabolism].

Antiandrogen therapy has an important role in the treatment of patients with benign prostatic hypertrophy who lack indication for surgery. Herein, the effects on lipid metabolism of administration of antiandrogen agents for benign prostatic hypertrophy are reported. Eighty patients with benign prostatic hypertrophy were each treated with the antiandrogen agents, chlormadinone acetate, allylestrenol, gestonolone caproate and oxendolone for 12 months. The levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), alpha-lipoprotein, apoprotein, and maronediardehyde (MDA) were measured every 4 weeks after initiation of antiandrogen treatment. In the chlormadinone acetate group, the TG level was significantly decreased between 3 and 6 months after treatment (p < 0.05). In the oxendolone group, the alpha-lipoprotein level was also elevated between 3 and 6 months and between 6 to 12 months after treatment (p < 0.05). The MDA level was also significantly elevated 6 and 12 months after treatment. However, the levels of the other lipids were within the normal range. In conclusion, the changes in the levels of plasma lipoprotein, apoprotein and MDA resulting from antiandrogen therapy were unlikely to be a cause of ischemic coronary disease.

Aged↗
PubMed1993

Morphological aspects of the hormone-induced pathomorphosis of endometrial carcinoma.

The paper presents the results of treatment of 488 patients with primary endometrial carcinoma. All patients received adjuvant hormonotherapy (oxyprogesterone caproate, and some patients previously oestrogens) in combination with surgery and postoperative irradiation. The study of tumor morphology on ultrastructural level and by histochemical methods provided additionally useful findings. Depending on the degree of changes in the tumor structure after hormone therapy it appeared possible to distinguish the following varieties of results: 1) Complete regression of tumor. 2) An increase in structural and functional differentiation as compared with the initial level differentiation of tumor. 3) Absence or doubtful effect. In the paper the working classification of malignant adrenogenic tumors of the uterus is presented.

17 alpha-Hydroxyprogesterone Caproate↗
PubMed1996

Exploration for drug therapy in endometrial carcinoma.

OBJECTIVE: To explore the therapeutic effect of three drugs, i.e., hydroxyprogesterone caproate (HPC), Tamoxifen (TMX) and Aminoglutethimide (AG), in the treatment of endometrial carcinoma. METHODS: The patients were collected by double-blind method and classified into 6 groups (3 groups used single drug and 3 groups used combined drugs) at random. The patient was given assigned drug therapy for 10 days according to her group after being admitted to the hospital. Operations were performed 7-10 days after drug therapy. Plasma FSH, LH, E2 and P were measured by standard radioimmunoassay of WHO. ER and PR in cancer tissues were examined by enzyme linked histochemistry. Cancer tissues obtained before and after drug therapy were examined pathologically. RESULTS: The values of FSH, LH and E2 decreased and that of P increased after single drug therapy in the group treated with HPC; and the values of FSH, LH, E2 and P all decreased in the groups treated with TMX and AG respectively (P < 0.05). The values of FSH, LH and E2 decreased to different extent in the groups treated with combined drugs. The changes of FSH and E2 are remarkable (P < 0.05). The value of P increased a little with no statistical difference (P > 0.05). PR and ER usually increased after treatment with TMX, but decreased with HPC or AG, or combined drugs. The pathological changes indicate that the tumors responded to all of the three drugs. The response to TMX was most significant, following which was HPC. CONCLUSIONS: HPC and TMX are two drugs proved to be useful in endometrial carcinoma. AG also can be used to treat endometrial carcinoma. It adds a new drug to the drug therapy for endometrial carcinoma.

17 alpha-Hydroxyprogesterone Caproate↗
PubMed1998

Alcohol inhibition and specificity studies of lipase B from candida antarctica in organic solvents

Alcohol inhibition of the lipase B from Candida antarctica has been studied through two different approaches: using the same inhibitor (1-butanol) in different organic solvents and using different inhibitors (differing in chain length) in the same solvent. The competitive inhibition constant values obtained in each case correlate with the calculated activity coefficients of the substrate, suggesting that desolvation of the alcohol is the major force changed. Data dispersion observed using the second approach has been interpreted to come from contributions of enzyme-inhibitor interactions to the binding energy. On the other hand, deacylation has been found to be much less influenced by the solvent variation than the acylation step, despite of the fact that solvation of the substrate involved in this step (the alcohol) is expected to change more than for the ester. Concerning the specificity behavior of the enzyme, a bimodal pattern was observed for the deacylation rate dependence on the alcohol chain length, with the highest values for hexanol (C6) and decanol (C10). With regard to the ester specificity, ethyl caproate (C6) is the preferred one. These results have been confronted with those reported for the lipase from Candida rugosa. Copyright 1998 John Wiley & Sons, Inc.

Journal Article↗
PubMed2000

Stimulation of adipose differentiation related protein (ADRP) expression in adipocyte precursors by long-chain fatty acids.

Adipose differentiation related protein (ADRP) is a 50-kDa protein expressed in adipocytes and transcriptionally activated when adipocyte precursors differentiate into mature adipocytes. Recent experiments have demonstrated that ADRP is a fatty acid binding protein that specifically facilitates the uptake of long-chain fatty acids. The present investigation provides evidence that ADRP mRNA and protein expression in preadipocytes is stimulated by fatty acids in a time- and dose-dependent fashion. ADRP mRNA expression was maximally stimulated at fatty acid concentrations of or above 10(-5) M. Stimulation of ADRP expression was observed with the nonmetabolizable fatty acid 2-bromopalmitate and with natural fatty acids. Stimulation of ADRP mRNA expression by fatty acids peaked between 5 and 8 hr and decreased by 24 hr. Stimulation of ADRP expression by fatty acids was completely inhibited by treatment with actinomycin D, suggesting that fatty acid stimulates ADRP gene expression at the transcriptional level. Comparison of the effect of several fatty acids with varying carbon chain lengths indicated that long-chain fatty acids were active in stimulating ADRP, whereas short-chain fatty acids such as caproate and 2-bromooctanoate had no effect. The degree of saturation of fatty acids did not influence their ability to stimulate ADRP expression. These studies provide new information on the regulation of ADRP and identify a new target regulated by fatty acids during adipose differentiation.

Adipocytes↗
PubMed1999

1H-NMR analysis of microbial-derived organic acids in primary root carious lesions and saliva.

In addition to lowered pH values, the molecular profile and concentrations of microbial-derived organic acids in carious dentin are important demineralization parameters involved in the induction, development and progression of dental caries. High-resolution proton ((1)H) NMR spectroscopy was employed to examine the organic acid status of primary root carious lesions. (1)H-NMR analysis of post-neutralized perchloric acid extracts of active carious lesions revealed that at an operating frequency of 600 MHz, the (1)H-NMR-detectable organic acid composition of carious dentin samples (mean molecular percentage content +/- standard error; the mean molecular percentage content is defined here as the mean of the concentration of each (1)H-NMR-visible organic acid/anion expressed as a percentage of total (1)H-NMR-detectable organic acid/anion level in each sample) was acetate 51 +/- 2%, formate 37 +/- 2%, lactate 5 +/- 1%, propionate 3 +/- 0.8%, pyruvate 2.4 +/- 0.3%, n-butyrate 1.2 +/- 0.2%; succinate 0.1 +/- 0.1%; iso-butyrate, n- and iso-valerate, and n- and iso-caproate (total) <0.2%. Further components detectable included alanine, glycine, choline, phosphorylcholine, trimethylamine oxide, methanol, glycolate and assorted saccharides. In view of their high dissociation constants (K(a)), our results demonstrate that formic and pyruvic acids (K(a) = 1.77 x 10(-4) and 3.20 x 10(-3) mol/dm(3), respectively) contribute substantially to the decreased pH values associated with active caries lesions (cf. lactate K(a) = 1.40 x 10(-4) mol/dm(3)), and hence the pathogenesis of primary root caries.

Aged↗
PubMed2004

Developmental toxicity evaluation of trimethylolpropane caprylate caprate in Sprague-Dawley rats.

The developmental toxicity potential of trimethylolpropane caprylate caproate (TMPCC, CAS no. 11138-60-6) was evaluated in rats. Sprague-Dawley rats were administered TMPCC in a corn oil suspension dermally at dose levels of 0, 200, 600, or 2,000 mg/kg/day on gestation days (GD) 6-15 (sperm positive day=GD 0). Caesarean sections were performed on GD 20 and fetuses were evaluated for viability, growth, and external, visceral, and skeletal abnormalities. Each group consisted of 25 females, with at least 22 per group being pregnant. The two highest dose levels caused some local irritation at the site of application, but no decreases in maternal weight gain. There were no differences from control in any of the developmental parameters measured, including embryo/fetal viability, fetal weight, malformations, or variations. TMPCC did not cause any developmental toxicity in the Sprague-Dawley rat at dermal dosages up to 2,000 mg/kg/day.

Abnormalities, Drug-Induced↗
PubMed2007

Production of bio-hydrogen by mesophilic anaerobic fermentation in an acid-phase sequencing batch reactor.

The pH and hydraulic retention time (HRT) of an anaerobic sequencing batch reactor (ASBR) were varied to optimize the conversion of carbohydrate-rich synthetic wastewater into bio-hydrogen. A full factorial design using evolutionary operation (EVOP) was used to determine the effect of the factors and to find the optimum condition of each factor required for high hydrogen production rate. Experimental results from 20 runs indicate that a maximum hydrogen production rate of 4,460-5,540 mL/L/day under the volumetric organic loading rate (VOLR) of 75 g-COD/L/day obtained at an observed design point of HRT = 8 h and pH = 5.7. The hydrogen production rate was strongly dependent on the HRT, and the effect was statistically significant (P < 0.05). However, no significant effect (P > 0.05) was found for the pH on the hydrogen production rate. When the ASBR conditions were set for a maximum hydrogen production rate, the hydrogen production yield and specific hydrogen production rate were 60-74 mL/g-COD and 330-360 mL/g-VSS/day, respectively. The hydrogen composition was 43-51%, and no methanogenesis was observed. Acetate, propionate, butyrate, valerate, caproate, and ethanol were major liquid intermediate metabolites during runs of this ASBR. The dominant fermentative types were butyrate-acetate or ethanol-acetate, representing the typical anaerobic pathway of Clostridium species. This hydrogen-producing ASBR had a higher hydrogen production rate, compared with that produced using continuous-flow stirred tank reactors (CSTRs). This study suggests that the hydrogen-producing ASBR is a promising bio-system for prolonged and stable hydrogen production.

Anaerobiosis↗
PubMed1993

Studies for a genotoxic potential of some endogenous and exogenous sex steroids. I. Communication: examination for the induction of gene mutations using the Ames Salmonella/microsome test and the HGPRT test in V79 cells.

The mutagenicity results and data of nine progestins (cyproterone acetate, dehydrospirorenone, gestodene, gestonorone caproate, levonorgestrel, norethisterone, norethisterone acetate, norethisterone enanthate, norethynodrel), one hypothetical metabolite (6,7-epoxy-cyproterone acetate), four estrogens (estradiol, ethinylestradiol, cyclodiol, cyclotriol), and four other sex steroids (atamestane, lilopristone, onapristone, propylmesterolone) are reported. All 17 sex steroids were investigated using the Ames salmonella/microsome direct plate incorporation protocol, and seven were additionally tested using the preincubation modification. Seven sex steroids were also studied in the HG-PRT test with V79 cells for the induction of gene mutations in mammalian cells. The metabolite was examined in the Ames salmonella/microsome assay using the standard protocol and the preincubation modification. In all assays the test compounds were investigated up to concentration levels where cytotoxicity and/or visible precipitation occurred or at least the solubility limit of the test compound was reached. For all assays, evaluation of the data indicates that neither any of the sex steroids nor the hypothetical metabolite was able to induce gene mutations whether in the absence or the presence of an extrinsic metabolizing system (S9 mix).

Animals↗
PubMed1984

Cervicovaginal abnormalities in BALB/c mice treated neonatally with sex hormones.

Newborn female BALB/cCrgl mice received hormone treatments (daily for 5 days): 10(-1) micrograms diethylstilbestrol (DES), 2 X 10(-1) micrograms DES, 2 micrograms DES, 100 micrograms progesterone (P), 137 micrograms 17 alpha-hydroxyprogesterone caproate, 10(-1) micrograms DES + 100 micrograms P, 2 micrograms DES + 100 micrograms P, 5 micrograms testosterone (T), 20 micrograms T, 20 micrograms 5 alpha-dihydrotestosterone (DHT), or sesame oil and were examined at 25 days, 35 days, or from 10 to 30 days of age. Three major cervicovaginal abnormalities were noted: adenosis (heterotopic columnar epithelium) in the fornices; altered common cervical canal (aberrantly simplified cervical lumen), and twin fornix (lateral branching of either or both fornices). Only DES, administered alone or in conjunction with P, resulted in adenosis and altered common cervical canal. At 25 days, all mice given 2 X 10(-1) micrograms DES showed adenosis. At 35 days, 75% of mice given 10(-1) micrograms or 2 micrograms DES showed adenosis. Adenosis incidence following 10(-1) micrograms DES was decreased by concomitant P. Altered common cervical canal was present in more than 90% of mice treated with DES alone at both 25 and 35 days; concomitant P lowered the incidence in mice receiving 10(-1) micrograms DES. Neonatal exposure to endogenous prolactin from a pituitary transplant did not modify the response. Twin fornix was not evident 10 days after neonatal androgen treatment. The frequency increased significantly by day 15 of treatment, reaching 100% by day 20; incidence then declined to 86% and 63% on days 25 and 30 after treatment, respectively. Thus, neonatal sex hormone administration results in various cervicovaginal changes, some transient, decreasing with age in young mice.

Abnormalities, Drug-Induced↗
PubMed1986

Frequent occurrence of polyovular follicles in ovaries of mice exposed neonatally to diethylstilbestrol.

The occurrence of polyovular follicles (PF) was examined at 10-34 days of age in the ovaries of BALB/cCrgl female mice given five daily injections of 0.1 microgram diethylstilbestrol (DES), 2 micrograms DES, 100 micrograms progesterone (P), 137 micrograms 17 alpha-hydroxyprogesterone caproate (HPC), 20 micrograms testosterone (T), 20 micrograms 5 alpha-dihydrotestosterone (5 alpha-DHT), or oil vehicle alone starting on the day of birth, and of C57BL/Tw females given five neonatal injections of 1 microgram DES, 20 micrograms 17 beta-estradiol (E2), 50 micrograms 5 alpha-DHT, 50 micrograms 5 beta-DHT, or the vehicle alone. Ovaries of 30-day-old C57BL mice given five daily injections of 1 microgram DES starting at 3-25 days of age were also examined. PF incidence (% of PF per ovary) and PF frequency (% of mice with PF) were significantly greater in BALB/c mice receiving injections of DES, P, HPC, and T than in the controls. In DES-treated mice at 34 days, PF incidence (2-13 oocytes/follicle) was 120-340 times higher than in the controls. BALB/c mice treated with T, P, and HPC showed PF incidence (two to four oocytes/follicle) three- to six-fold higher than in the controls. In 30-day-old C57BL mice treated with T, E2, and DES, PF incidence also increased by two- to 50-fold. 5 alpha-DHT and 5 beta-DHT failed to increase PF incidence. PF incidence was significantly increased only when neonatal DES treatment was begun on days 0 to 3, but was reduced when started at days 10-25.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1997

Comparison of the effect of different short chain fatty acids on the growth and differentiation of human colonic carcinoma cell lines in vitro.

The aim of this study was to compare the effects of acetate, propionate, butyrate, iso-butyrate, valerate, iso-valerate and caproate on cell growth and on the activities of alkaline phosphatase (AP) and dipeptidyl aminopeptidase IV (DPP IV) by three human colonic adenocarcinoma cell lines. In addition to butyrate, propionate and valerate inhibited cell proliferation of the three cell lines. The other SCFAs did not influence cell proliferation. AP and DPP IV activities were strongly stimulated by butyrate on two of the three cell lines. On HT-29, AP was strongly stimulated, however DPPIV expression remained undetectable. Propionate and valerate exhibited a weaker stimulation, the other SCFAs being ineffective. The effect of SCFAs on cell proliferation and differentiation clearly depends on the number of carbons and on the configuration of the basic structure of the molecule.

Alkaline Phosphatase↗
PubMed1998

Treatment with progesterone analogues decreases macrophage Fcgamma receptors expression.

Macrophage Fcgamma receptors (FcgammaRs) are critical for host defense against infection and have an important role in immune cytopenias. Modulation of macrophage FcgammaRs expression is a potential therapeutic approach to immune disorders. Glucocorticoids and synthetic progesterone analogues decrease macrophage FcgammaRs expression. We assessed the effect of treatment with commonly employed progestins on the expression of macrophage FcgammaRs using an experimental model in the guinea pig. Eight clinically available progesterones, medroxyprogesterone acetate (P3), megestrol acetate (P4), medrogestone (P5), alylestrenol (P6), linestrenol (P7), didrogesterone (P8), norethisterone (P9), and gestonorone caproate (P10) and two endogenous progesterones, progesterone (P1) and 17 alpha-hydroxyprogesterone (P2), were studied. Following in vivo treatment of guinea pigs, we determined the clearance of IgG-sensitized erythrocytes in vivo, the binding of IgG-sensitized erythrocytes by isolated splenic macrophages, and splenic macrophage Fcgamma receptor cell surface expression. All progesterones impaired the clearance of IgG-sensitized erythrocytes by decreasing splenic macrophage Fcgamma receptor expression. P5, P6, P7, and P8 were less effective. Flow cytometry and fluorescence microscopy with monoclonal antibodies demonstrated that progesterones decreased the cell surface expression of FcgammaR2 more than that of FcgammaR1,2. Clinically employed progestins impair the clearance of IgG-coated cells by decreasing splenic macrophage FcgammaRs expression. Thus, progesterones are candidate drugs for the treatment of immune disorders.

Animals↗
PubMed2000

Reactivity and Coaggregation of p-Nitrophenyl Esters with Polymer Micelles at Solid Surfaces.

The polymer micelle, poly[(N-(n-dodecyl)-4-vinylpyridiniumco-N-ethyl-4-vinylpyridinium) bromide], PDE, containing 30% dodecyl groups has been found to promote the adhesion of lipophiles to various surfaces including quartz, polystyrene, and poly(methyl methacrylate) cuvette surfaces from aqueous solutions. The adsorption of PDE/ester coaggregates to the surfaces was studied by hydrolysis of p-nitrophenyl esters in aqueous PDE(30) solutions. The extent of reaction of p-nitrophenyl myristate, an ester with a linear acyl carbon chain length of 14, can be viewed as a probe to study the adhesion of the PDE/ester coaggregates to the cuvette surfaces. The difference between initial concentration of ester and concentration of hydrolysis product, p-nitrophenoxide ion, gives the concentration of unreacted ester in the aggregates or film adhering to the solid surface. Up to 40% of p-nitrophenyl myristate was found unreacted on the surface of quartz cuvettes after apparent completion of the reaction. No adhesion of the related caproate ester with a linear acyl carbon chain length of 6 was detected. Copyright 2000 Academic Press.

Journal Article↗