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[Action of 17-hydroxyprogesterone caproate on the glandular hyperplasia of human endometrium].

The effect of 17-oxyprogesterone capronate on the proliferative activity and metabolic processes in the endometrium of patients with glandular hyperplasia of the endometrium was studied. It was shown that the proliferative activity was inhibited while the secretory processes in the glandular epithelium were activated. This effect was achieved only after a long-term (6-9 months) administration of the hormone.

Adult↗

[Effect of hydroxyprogesterone caproate on immunological skin tests and on the T-lymphocytes in cancer of the corpus uteri].

Under study was the effect of oxyprogesterone-capronate (500 mg daily, total dosage of 10 g) on delayed cutaneous hypersensitivity reaction (DCHR) to tuberculin and candidine as well as the level of T-lymphocytes and cortisol in the peripheral blood in 34 patients with primary cancer of the corpus uteri. Prior to the treatment there was a considerable negative correlation between metabolic and immunological indices. Under OPC exposure DCHR enhanced in 62% of observations. In 7 of 12 patients the level of T-lymphocytes was increased and blood cortiol level decreased in 6 of 11 patients. 58 per cent of the observations showed a parallelism between the effect of OPC on the skin tests and the tumor histostructure, and in 8 of 12 patients on the level of T-lymphocytes and the tumor histostructure.

Aged↗

Progesterone for prevention of recurrent preterm birth: impact of gestational age at previous delivery.

OBJECTIVE: Preterm birth occurs in 1 of 8 pregnancies and may result in significant morbidity and mortality. 17-alpha hydroxyprogesterone caproate (17-OHP caproate) has been found to be efficacious in reducing the risk of subsequent preterm delivery in women who have had a previous spontaneous preterm birth (sPTB). This analysis was undertaken to evaluate if 17-OHP caproate therapy works preferentially depending on the gestational age at previous spontaneous delivery. We hypothesized that treatment with 17-OHP caproate is more effective in prolonging pregnancy depending on the gestational age of the earliest previous preterm birth (20-27.9, 28-33.9 vs 34-36.9 weeks). STUDY DESIGN: This was a secondary analysis of 459 women with a previous sPTB enrolled in a randomized controlled trial evaluating 17-OHP caproate versus placebo. Effectiveness of 17-OHP caproate for pregnancy prolongation was evaluated based on gestational age at earliest previous delivery according to clinically relevant groupings (20-27.9, 28-33.9, and 34-36.9 weeks). Statistical analysis included the chi-square, Fisher exact, and Kruskal-Wallis tests, logistic regression, and survival analysis using proportional hazards. RESULTS: Gestational age at earliest previous delivery was similar between women treated with 17-OHP caproate or placebo (P = .1). Women with earliest delivery at 20 to 27.9 weeks and at 28 to 33.9 weeks delivered at significantly more advanced gestational age if treated with 17-OHP caproate than with placebo (median 37.3 vs 35.4 weeks, P = .046 and 38.0 vs 36.7 weeks, P = .004, respectively) and were less likely to deliver <37 weeks (42% vs 63%, P = .026 and 34% vs 56%, P = .005, respectively). Those with earliest delivery at 34 to 36.9 weeks were not significantly different between 17-OHP caproate or control. CONCLUSION: 17-OHP caproate therapy given to prevent recurrent PTB is associated with a prolongation of pregnancy overall, and especially for women with a previous spontaneous PTB at <34 weeks.

17-alpha-Hydroxyprogesterone↗

The use of progestational agents for preterm birth: lessons from a mouse model.

OBJECTIVE: On the basis of the recent Maternal Fetal Medicine Unit Networks clinical trial, the American College of Obstetricians and Gynecologists supports the administration of 17-alpha hydroxyprogesterone caproate to high-risk patients. Because inflammation/infection is believed to be a contributing factor in many cases of preterm birth, it is imperative to understand the effect of 17-alpha hydroxyprogesterone caproate treatment in this clinical situation. STUDY DESIGN: Using a mouse model of localized intrauterine inflammation, we investigated the ability of progestational agents to prevent preterm birth. On gestational day 15 (E15), dams were assigned randomly to treatment with 17-alpha hydroxyprogesterone caproate, medroxyprogesterone acetate, or vehicle before intrauterine infusion of lipopolysaccharide. All dams were monitored for morbidity and preterm birth. Three separate sets of experiments were performed to assess different outcomes at 6, 24, and 96 hours. At 6 and 24 hours, C-reactive protein, interleukin-6, and interleukin-10 levels were measured in maternal serum by enzyme-linked immunosorbent assay. RESULTS: Pretreatment with 17-alpha hydroxyprogesterone caproate or medroxyprogesterone acetate before intrauterine lipopolysaccharide treatment significantly decreased the preterm birth rate, compared with lipopolysaccharide treatment alone. Medroxyprogesterone acetate treatment was more effective than 17-alpha hydroxyprogesterone caproate treatment in the prevention of preterm birth and resulted in live pups at term. Treatment with 17-alpha hydroxyprogesterone caproate was associated with significant maternal morbidity. CONCLUSION: In the setting of intrauterine inflammation, progestational agents decrease the preterm birth rate but can result in maternal morbidity. 17-Alpha hydroxyprogesterone caproate should not be used in patients who are suspected of having subclinical infection and/or acute preterm labor. The mechanisms by which progestational agents inhibit preterm birth warrants further investigations so that the use of this drug to appropriate populations could be pursued without undue fetal or maternal harm.

17 alpha-Hydroxyprogesterone Caproate↗

Fatty acid toxicity and methyl ketone production in Aspergillus niger.

Vegetative hyphae of Aspergillus niger rapidly converted caproic acid into 2-pentanone. More caproic acid was required for maximal ketone production at alkaline as compared to acidic pH values. Further increases in caproate concentrations at each pH value tested (4.5, 5.5, 6.5, 7.5, and 8.5) resulted in inhibition of ketone production and O(2) uptake. At alkaline pH values (8.5 and 7.5), oxygen uptake above the endogenous level and the production of 2-pentanone were parallel. This relationship did not hold at acidic pH values. At these pH values, ketone production continued (pH 6.5) or attained a maximum (pH 5.5 and 4.5) at caproate concentrations at which oxygen uptake was inhibited below endogenous levels. These data indicate that endogenous oxygen uptake was not inhibited by caproate at alkaline pH values at concentrations which did inhibit caproate oxidation and 2-pentanone production. Conversely, at acidic pH values, endogenous oxygen uptake was vigorously inhibited by caproate at concentrations at which exogenous fatty acid oxidation and 2-pentanone production were less affected. Simon-Beevers plots of these data showed that the undissociated acid was the permeant form of caproic acid. The fatty anion appeared to be the active or inhibitory form of caproate within the cell. Vegetative hyphae of A. niger were poorly buffered. Once the hyphae were washed and resuspended in phosphate buffer, they were well buffered towards inhibitory concentrations of caproic acid. These findings suggest that the primary mechanism(s) by which caproate inhibits oxygen uptake and ketone formation does not involve a change in the intracellular pH.

Aspergillus↗

Formation of biocompatible reversed micellar systems using phospholipids.

Formation of reversed micellar systems using biocompatible components was revealed by a significant increase of water content in the organic phase. Soybean lecithin (SL), which is a mixture of different phospholipids, and phosphatidylcholine (PC) purified from soybean were used as the amphiphilic molecule. Fatty acid and fatty acid ethyl esters were used as the organic solvent. Reversed micelles were formed in the following combinations of (amphiphilic molecule)/(organic solvent): SL/ethyl caproate, SL/ethyl oleate, SL/ethyl linoleate, PC/ethyl caproate, and PC/oleic acid. Characterization of the micelles using small angle X-ray scattering analysis was presented. Reversed micelles formed in SL/ethyl caproate, SL/ethyl oleate, and PC/ethyl caproate systems were spherical. Their radius of gyration was about 40Å when the water concentration in the organic phase was maximal. Maximal water concentrations in SL/ethyl caproate and PC/ethyl caproate reversed micellar systems decreased with increasing salt concentration in the aqueous phase. Micelle sizes also decreased with increased salt concentration. The extraction of protein cytochrome c using the reversed micellar system was demonstrated. Application of these reversed micellar systems will expand to pharmaceutical and food industries.

Journal Article↗

Production of caproic acid by cocultures of ruminal cellulolytic bacteria and Clostridium kluyveri grown on cellulose and ethanol.

Ruminal cellulolytic bacteria (Fibrobacter succinogenes S85 or Ruminococcus flavefaciens FD-1) were combined with the non-ruminal bacterium Clostridium kluyveri and grown together on cellulose and ethanol. Succinate and acetate produced by the cellulolytic organisms were converted to butyrate and caproate only when the culture medium was supplemented with ethanol. Ethanol (244 mM) and butyrate (30 mM at pH 6.8) did not inhibit cellulose digestion or product formation by S85 or FD-1; however caproate (30 mM at pH 6.8) was moderately inhibitory to FD-1. Succinate consumption and caproate production were sensitive to culture pH, with more caproic acid being produced when the culture was controlled at a pH near neutrality. In a representative experiment under conditions of controlled pH (at 6.8) 6.0 g cellulose l-1 and 4.4 g ethanol l-1 were converted to 2.6 g butyrate l-1 and 4.6 g caproate l-1. The results suggest that bacteria that efficiently produce low levels of ethanol and acetate or succinate from cellulose should be useful in cocultures for the production of caproic acid, a potentially useful industrial chemical and bio-fuel precursor.

Animals↗

Progestational agents to prevent preterm birth: a meta-analysis of randomized controlled trials.

OBJECTIVE: To perform an updated systematic review with meta-analysis to further elucidate the efficacy of progestational agents for the prevention of preterm births in patients at elevated risk. DATA SOURCES: Computerized databases, references in published studies, and textbook chapters in all languages were used to identify randomized controlled trials (RCTs) evaluating the use of progestational agents for the prevention of preterm births in women at elevated risk. METHODS OF STUDY SELECTION: We identified RCTs that compared progestational agents with placebo for patients at risk for preterm birth and evaluated at least one of the following: delivery before 37 weeks of gestation, birth weight less than 2,500 g, threatened preterm labor, respiratory distress syndrome, and perinatal mortality. The primary outcomes assessed were preterm delivery and perinatal mortality. TABULATION, INTEGRATION, AND RESULTS: Ten studies met inclusion criteria for this review. For each study with binary outcomes, an odds ratio (OR) with 95% confidence intervals (CIs) was calculated for selected outcomes. Homogeneity was tested across the studies. Compared with women allocated to receive placebo, those who received progestational agents had lower rates of preterm delivery (26.2% versus 35.9%; OR 0.45, 95% CI 0.25-0.80). Similar results were noted when comparing patients who were specifically treated with 17alpha-hydroxyprogesterone caproate (29.3% versus 40.9%; OR 0.45, 95% CI 0.22-0.93). Additionally, subjects allocated to receive 17alpha-hydroxyprogesterone caproate had lower rates of birth weights less than 2,500 g (OR 0.50, 95% CI 0.36-0.71). No differences in rates of hospital admissions for threatened preterm labor or perinatal mortality were noted for subjects receiving progestational agents in general or for those receiving only 17alpha-hydroxyprogesterone caproate specifically. CONCLUSION: The use of progestational agents and 17alpha-hydroxyprogesterone caproate reduced the incidence of preterm birth and low birth weight newborns.

17 alpha-Hydroxyprogesterone Caproate↗

Does progesterone treatment influence risk factors for recurrent preterm delivery?

OBJECTIVE: To examine how demographic and pregnancy characteristics can affect the risk of recurrent preterm delivery and the how the effectiveness of progesterone treatment for prevention alters these relationships. METHODS: This was a secondary analysis of a randomized trial of 17alpha-hydroxyprogesterone caproate to prevent recurrent preterm delivery in women at risk. Associations of risk factors for preterm delivery (less than 37 completed weeks of gestation) were examined separately for the women in the 17alpha-hydroxyprogesterone caproate (n = 310) and placebo (n = 153) groups. RESULTS: Univariate analysis found that the number of previous preterm deliveries and whether the penultimate delivery was preterm were significant risk factors for preterm delivery in both the placebo and progesterone groups. High body mass index was protective of preterm birth in the placebo group. Multivariate analysis found progesterone treatment to cancel the risk of more than 1 previous preterm delivery, but not the risk associated with the penultimate pregnancy delivered preterm. Obesity was associated with lower risk for preterm delivery in the placebo group but not in the women treated with progesterone. CONCLUSION: The use of 17alpha-hydroxyprogesterone caproate in women with a previous preterm delivery reduces the overall risk of preterm delivery and changes the epidemiology of risk factors for recurrent preterm delivery. In particular, these data suggest that 17alpha-hydroxyprogesterone caproate reduces the risk of a history of more than 1 preterm delivery. LEVEL OF EVIDENCE: I.

17 alpha-Hydroxyprogesterone Caproate↗

13C NMR studies of butyric fermentation in Clostridium kluyveri.

The fermentation of 13C-labeled ethanol and acetate into butyrate and caproate by Clostridium kluyveri has been studied by using 13C NMR. The pathway involves the conversion of both ethanol and acetate into acetyl coenzymes A, two of which condense to form CoA-linked precursors of butyrate. If butyryl-CoA is involved in the condensation, caproate is the ultimate product. ATP is produced from acetyl-CoA via the reactions catalyzed by phosphotransacetylase and acetate kinase with acetate, a required carbon source, as a co-product. In spectra of whole cells incubated with the labeled carbon sources, label from ethanol appears rapidly in acetate, which then reaches a lower, steady-state concentration due to its re-entry into the pathway. The rapid initial production of acetate indicates equally rapid production of ATP. Label from acetate appears in ethanol only if ethanol is already present, indicating that this process is one of isotopic equilibration rather than net synthesis of ethanol from acetate. The ratio of butyrate to caproate produced depends strongly on the initial ratio of ethanol to acetate in the medium. The relative rates of utilization of ethanol and acetate vary as the fermentation proceeds. 13C-13C coupling in the butyrate and caproate produced from [1-13C]ethanol and [2-13C]acetate can be used to determine if the acetyl-CoA molecules arising from ethanol and acetate enter the same pool or if they remain separated. The data are consistent with random mixing of the acetyl-CoA produced from the two carbon sources.

Acetates↗