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The thiourea group modulates the fluorescence emission decay of fluorescein-labeled molecules.

We have investigated the spectral properties and emission characteristics of fluorescein-5-thiocarbamoyl-N,N'-caproate (FITC-ACA) to examine the origin of the complex emission decay often observed in fluorescein-labeled molecules. The covalent attachment of fluorescein to epsilon-amino-n-caproic acid does not perturb the prototropic transitions of the chromophore or the general fluorescence characteristics of the various prototropic forms. However, both the monoanion and dianion forms of FITC-ACA are quenched relative to free fluorescein and exhibit a complex emission decay that is described by two discrete lifetimes. The thiourea group that links the chromophore to the caproic acid is shown to modulate the emission properties of the FITC-ACA. We show that the emission decay can also be analyzed using the asymmetric distribution model of Alcala et al. In this analysis, the tauL and tauu parameters that represent the lower and upper lifetime limits of the distribution reflect the quenched (0 ns) and unquenched lifetimes, respectively. The beta parameter that describes the distribution of lifetimes between the two limiting states can be related to the quenching efficiency of the thiourea group and to the structure and dynamics of the FITC-ACA molecule.

Fluorescein↗

Structure-function relationships affecting the insecticidal and miticidal activity of sugar esters.

Synthetic sugar esters are a relatively new class of insecticidal compounds that are produced by reacting sugars with fatty acids. The objective of this research was to determine how systematic alterations in sugar or fatty acid components of sugar ester compounds influenced their insecticidal properties. Sucrose octanoate, sorbitol octanoate, sorbitol decanoate, sorbitol caproate, xylitol octanoate, xylitol decanoate and xylitol dodecanoate were synthesized and evaluated against a range of arthropod pests. Dosage-mortality studies were conducted on pear psylla (Cacopsylla pyricola Foerster) on pear, tobacco aphid (Myzus nicotianae) Blackman and tobacco hornworm (Manduca sexta [Johannson]) on tobacco, and twospotted spider mite (Tetranychus urticae Koch) on apple in laboratory bioassays. These sugar esters were compared with insecticidal soap (M-Pede, Dow AgroSciences L.L.C., San Diego, CA), to determine how toxicologically similar these materials were against the arthropod pests. Substitutions in either the sugar or fatty acid component led to significant changes in the physical properties and insecticidal activity of these compounds. The sugar esters varied in their solubility in water and in emulsion stability, yet, droplet spread upon pear leaves occurred at low concentrations of 80-160 ppm and was strongly correlated with psylla mortalities (R2 = 0.73). Sequentially altering the sugar or fatty acid components from lower to higher numbers of carbon chains, or whether the sugar was a monosaccharide or disaccharide did not follow a predictable relationship to insecticidal activity. Intuitively, changing the hydrophile from sorbitol (C6) to xylitol (C5) would require a decrease in lipophile chain length to maintain hydrophilic-lipophilic balance (HLB) relationships, yet an increase in lipophile chain length was unexpectedly needed for increasing insecticidal activity. Thus, the HLB of these materials did not correlate with pear psylla mortalities. Initial insect bioassays and dosage-mortality data found significant differences among sugar ester compounds' toxicity to the range of arthropod species. Sucrose octanoate high in monoester content had the highest activity against the range of arthropod pests at low concentrations of 1200-2400 ppm. No single chemical structure for the xylitol or sorbitol esters were optimally effective against the range of arthropods we tested and sorbitol octanoate and xylitol decanoate had the highest insecticidal activity of this group. All of the sugar ester materials produced high T. urticae mortalities on apple at very low concentrations of 400 ppm. Overall, most of the sugar esters that were examined had superior insecticidal activity compared with insecticidal soap. Sugar ester chemistry offers a unique opportunity to design an insecticide or miticide specific to certain arthropod pests which would be valuable in crop integrated pest management (IPM) programs. Sucrose esters are currently used as additives in the food industry which makes them especially attractive as safe and effective insecticides.

Animals↗

Discrepancy between the potency of various trypsin inhibitors to inhibit trypsin activity and the potency to release biologically active cholecystokinin-pancreozymin.

Injection of various trypsin inhibitors into the lumen of the isolated perfused rat duodenum increased the amount of biologically active cholecystokinin-pancreozymin (CCK-BA) in the vascular perfusate. The potency to induce CCK-BA release of the various trypsin inhibitors differed. Injection of ethyl p-(6-guanidinohexanoyloxy) benzoate methanesulfonate (FOY-007; 100 mumol), p-ethoxy-carbamoyl-thio-6-guanidino caproate phosphate (FOY-129; 110 mumol), 4-(4-guanidino-benzoyloxy) phenylacetic acid (FOY-251; 128 mumol), N,N-dimethyl-carbamoylmethyl-4-(4-guanidinobenzoyloxy) phenylacetate methanesulfonate (FOY-305; 80 mumol), and p-aminobenzamidine dihydrochloride (p-ABA, Sigma; 300 mumol) caused release of CCK-BA amounting to 1,042, 247, 252, 682, and 302 pM, respectively. The potency to induce CCK-BA release was not correlated with the potency to inhibit trypsin activity. The present results do not support the hypothesis that a negative feed-back regulation of pancreatic enzyme secretion is exerted by intraluminal trypsin in the rat.

Animals↗

Ruminal VFA production with steers fed whole or ground corn grain.

Ruminal production and interchange rates of volatile fatty acids (VFA) were measured for steers fed corn grain in the whole or ground form. Liquid turnover rate was 29% greater (P less than .10) with steers fed the corn in the whole form. On a molar basis (mol/100 mol), ruminal concentrations of propionate were lower while those of butyrate, 3-methyl butyrate, valerate and caproate were greater with whole than with ground corn diets. Acid production differences followed similar trends with de novo production of butyrate being seven times greater and irreversible butyrate loss three times greater with whole than with ground corn diets. Conversion of acetate to butyrate was about 70% greater with whole than with ground corn diets. This conversion far exceeded other VFA exchange rates. Outflow of VFA to the omasum was calculated to equal 20, 25 and 12% of the irreversible loss of acetate, propionate and butyrate, respectively. Ruminal output of energy as VFA from the rumen equaled 60 and 43% of consumed energy with the whole and ground grain diets, respectively. Production rates of VFA were poorly correlated with ruminal concentrations except for butyrate. Less than 10% of the labeled carbon from acetate and butyrate was detected in plasma glucose, but the transfer coefficient from propionate uncorrected for crossover of label was 59%. Gluconeogenesis from propionate alone exceeded literature estimates for basal glucose requirements of nonlactating ruminants.

Acetates↗

Influence of chain length on the in vitro hydrolysis of model ester prodrugs by ocular esterases.

In designing ester prodrugs to improve corneal drug bioavailability, it is important to consider the influence of chain length on both corneal permeation and hydrolysis of the prodrug. However, the second factor has received relatively little attention. The purpose of this study was to evaluate whether the ocular hydrolysis of a homologous series of alpha- and beta-naphthyl esters was influenced by chain length. Solutions of each ester were incubated with selected ocular tissues and fluids of adult albino rabbits. For the alpha-series peak hydrolytic rate was reached at the caproate (C6) ester, coinciding with minimization in the value of the Michaelis-Menten constant (Km) and maximization in the value of maximum velocity (Vmax). For the beta-series peak hydrolytic rate was reached at the valerate (C5) ester. In contrast to the alpha-series this was primarily due to a large increase in value for Km. These findings indicate that the rate of ocular esterase-mediated hydrolysis varies within a homologous series of esters, and that this chain length dependency is influenced by the chemical nature of the parent compound.

Animals↗

Adaptation of lactating cows to rations containing urea.

Effects of a progressive change in 6 wk from a urea-free concentrate to one providing .34 (medium) or .66 g (high) urea/kg body weight on jugular blood composition and animal performance were studied with 27 cows. Consumption of dry matter was not affected even at the high rate of urea intake. Milk production was maximum when after 6 wk daily intake of urea reached .34 g/kg body weight, but higher rates of urea intake decreased milk yield and milk fat content. Butyrate through caproate were lower in milk lipids of urea-fed cows than for controls. While medium urea increased stearate, the high rate elevated linoleate. Ammonia and urea in serum were increased by transition to the high urea intake. Nonessential amino acids of serum were increased during adaptation to the medium rate of urea consumption but decreased with the high rate. Transitions to medium or high urea intakes did not affect the essential amino acids of serum. Adaptation of 6 wk was preferable to 3 wk to reach a daily intake of urea of .34 g/kg body weight in cows producing up to 18 kg of milk per day.

Animals↗

Copper intestinal absorption in the rat: effect of free fatty acids and triglycerides.

The absorption of some minerals has been shown to be affected by the presence of unhydrolyzed dietary triglycerides and free fatty acids generated from their partial hydrolysis. Since copper (Cu) can form poorly soluble soaps with long-chain fatty acids, we examined whether the uptake of Cu from the intestinal lumen is altered by the presence of fatty acids and triglycerides using an in vivo jejunal perfusion procedure. Long-chain fatty acids palmitate and stearate at 1.0 mM reduced Cu absorption rates compared with infusates without either fatty acid or triglycerides (means +/- SEM, controls: 104.4 +/- 8.8 pmole/min x cm vs palmitate: 12.5 +/- 17.6, P < 0.01; stearate:37.2 +/- 25.6, P < 0.05). Medium chain free fatty acids had no effect on Cu absorption (caprylate: 90.6 +/- 14.9, not significant; caproate: 69.5 +/- 14.2, not significant). Similarly, neither an emulsion of medium chain nor long-chain triglycerides at a total 1.0 or 2.5 mM concentration altered Cu absorption. The inhibitory effect of palmitate and stearate on Cu absorption was accompanied by a reduction in lumen-to-mucosa water influx (controls: 5.33 +/- 0.26 microl/min x cm vs palmitate: 3.20 +/- 0.70, P < 0.01; stearate: 3.36 +/- 0.52, P < 0.01). The data are consistent with a potential impairment of Cu intestinal absorption by long-chain free fatty acids which may accumulate in the jejunum following excessive fat intake and/or lipid malabsorption.

Animals↗

Production of volatile compounds in cheese by Pseudomonas fragi strains of dairy origin.

Volatile compounds produced in cheese by five Pseudomonas fragi strains isolated from 1-day-old raw milk cheeses were investigated. Each strain was representative of a different biochemical group of isolates of identical phenotypic characteristics, according to identification with API 20 NE strips. The five strains were ascribed to the species P. fragi after 16S rRNA sequencing because of their high degree of coincidence with P. fragi ATCC 4973. In each of two experiments, carried out on different days, five cheeses were made at laboratory scale from pasteurized milk separately inoculated with approximately 10(5) CFU/ml of each P. fragi strain. After 12 days at 10 degrees C, mean counts of P. fragi strains were close to 10(10) CFU/g in the outer part of cheeses and close to 10(8) CFU/g in the inner part. A total of 131 volatile compounds, 49 of which were further characterized, were identified in cheeses by gas chromatography-mass spectrometry after extraction with a purge and trap apparatus. Abundances of compounds were generally higher in the outer part of cheeses. Production of volatile compounds was clearly strain dependent. Only two strains produced ethyl esters, and three produced nonethyl esters. Ethyl acetate, ethyl butyrate, ethyl caproate, methyl acetate, isopropyl acetate, and propyl tiglate were the major esters, and ethanol, 2-propanol, and 3-methyl butanol were the major alcohols. Undecene was the major hydrocarbon, dimethyl sulfide and methyl thiocyanate the major sulfur compounds, and 2-pentanone the major ketone. Two aromatic compounds, styrene and o-dichlorobenzene, were present in all cheeses.

Aldehydes↗

Short-chain fatty acids and thyroid hormone interact in regulating enterocyte gene transcription.

BACKGROUND: Enterocyte differentiation is known to be regulated by a variety of extracellular compounds, among which are triiodothyronine (T3) and the short-chain fatty acids (SCFAs). Because several SCFAs are known to induce histone hyperacetylation, and T3 action has been recently linked to chromatin structure, we sought to investigate the interplay between SCFAs and T3 in regard to the enterocyte differentiation marker, intestinal alkaline phosphatase (IAP). METHODS: Caco-2 cells were transiently transfected with a reporter construct containing 2.4 kb of the human IAP gene 5' flanking region (IAP2.4CAT). Cotransfections were carried out with and without thyroid hormone receptor-1 (TR beta-1) or histone deacetylase-1 (HDAC-1) expression plasmids. Cells were treated with 5 mmol/L SCFAs (propionic, butyric, valeric, or caproic acids as propionate, butyrate, valerate, or caproate, respectively), with and without 10 nmol/L T3. Reporter gene activity was measured and the level of histone acetylation assessed by means of acid-urea-triton (AUT) gel assays. RESULTS: TR beta-1 cotransfection caused a marked decrease in IAP reporter gene activity, which is consistent with the well-known phenomenon of ligand independent repression (LIR), whereas T3 treatment reversed the LIR and caused further reporter gene activation. Treatment with SCFAs similarly resulted in a complete blockage of LIR, and, in fact, turned the TR beta-1 into a transcriptional activator, even in the absence of T3. Concomitant treatment with T3 and butyric acid produced an additive effect on IAP transactivation. In contrast, cotransfection with HDAC-1 attenuated the effects of SCFAs on IAP gene activation. AUT gel studies demonstrated histone hyperacetylation in response to SCFA treatment. CONCLUSION: One or more DNA cis-elements in the human IAP gene mediate ligand independent repression by the TR beta-1, an effect that can be entirely reversed by those SCFAs that induce histone hyperacetylation. In addition T3 and SCFAs can act in concert to induce IAP gene transcription, demonstrating an important link between triiodothyronine and histone hyperacetylation in regard to enterocyte-specific gene expression.

Alkaline Phosphatase↗

[Desulfacinum subterraneum sp.nov.--a new thermophilic sulfate-reducing bacterium isolated from a high temperature oil field ].

A new thermophilic sulfate-reducing bacterium isolated from the high-temperature White Tiger oil field (Vietnam) is described. Cells of the bacterium are oval (0.4-0.6 by 0.6-1.8 microns), nonmotile, non-spore-forming, and gram-negative. Growth occurs at 45 to 65 degrees C (with an optimum at 60 degrees C) at NaCl concentrations of 0 to 50 g/l. In the course of sulfate reduction, the organism can utilize lactate, pyruvate, malate, fumarate, ethanol, salts of fatty acids (formate, acetate, propionate, butyrate, caproate, palmitate), yeast extract, alanine, serine, cysteine, and H2 + CO2 (autotrophically). In addition to sulfate, the bacterium can use sulfite, thiosulfate, and elemental sulfur as electron acceptors. In the absence of electron acceptors, the bacterium can ferment pyruvate and yeast extract (a yet unrecognized capacity of sulfate reducers) with the formation of acetate and H2. The G + C content of DNA is 60.8 mol %. The level of DNA-DNA hybridization of the isolate (strain 101T) and Desulfacinum infernum (strain B alpha G1T) is as low as 34%. Analysis of the nucleotide sequence of 16S rDNA places strain 101T in the phylogenetic cluster of the Desulfacinum species within the sulfate reducer subdivision of the delta subclass of Proteobacteria. All these results allowed the bacterium studied to be described as a new species, Desulfacinum subterraneum sp. nov., with strain 101 as the type strain.

Electron Transport↗

Hydrogen production from wastewater by acidogenic granular sludge.

Sludge was granulated in a hydrogen-producing acidogenic reactor when operated at 26 degrees C, pH 5.5 treating a sucrose-rich wastewater. The influence of hydraulic retention time (HRT) and sucrose concentration on hydrogen production by the acidogenic granular sludge was investigated at a constant loading rate of 25 g-sucrose/(l x day). Results show that the gas composition was not greatly influenced by HRT or sucrose concentration. The hydrogen accounted for 57% to 68% of the biogas at HRT ranging 4.6-28.6 h and sucrose concentration ranging 4,800-29,800 mg/l. However, the hydrogen yield was more dependent on HRT and sucrose concentration. It ranged from 0.19 to 0.27 l/g-sucrose with the maximum yield occurring at HRT 13.7 h and sucrose concentration 14,300 mg/l in the wastewater. The acidified effluent was composed of volatile fatty acids and alcohols. The predominant products were butyrate (59-68%) and acetate (10-25%), plus smaller amounts of i-butyrate, valerate, i-valerate, caproate, methanol, ethanol, propanol, and butanol. The sludge yield averaged 0.2 g-VSS/g-sucrose. The carbon balance was 98-107% throughout the study.

Bacteria, Anaerobic↗

Polyunsaturated fatty acids and risk of preterm delivery.

Preterm delivery (PD) is characterized both by increased neonatal morbidity and mortality and by important late pathologic sequelae. From a clinical stand-point, PD may results from a medical condition where the continuation of pregnancy could bring about a marked risk for the foetus and/or for the mother, or from an adverse event where the pregnancy is going to end spontaneously before 37 weeks of gestation. In the past few years some epidemiological studies have shown that diet may interfere with complex multifactorial processes contributing to the preterm triggering of labour. The attention has been focused on polyunsaturated fatty acids (PUFA) such as alpha-linoleic acid, precursor of Omega-3 series, and linoleic acid, precursor Omega-6 series. Their importance in modulating Prostaglandin concentrations at different levels is already known. Moreover, it has been reported that in clinical situation, such as PD, the endogenous levels of PUFA are unbalanced, with a Omega-6 predominance. Experimental, observational and clinical studies suggest that dietary intake of Omega-3 fatty acids is capable of significantly prolonging the duration of gestation in the range of 4-7 days; such prolongation would possibly occur through the inhibition of prostaglandins E2 and F2 alpha. In Western population dietary intake of Omega-3 appears to be marginal, and recommended assumption could be reached only by a ten-fold increase in blue fish ingestion. The recommended intake of EPA + DHA should be 1.4 g/daily with a 1:2.5 EPA:DHA. It is therefore possible to conclude that in light of controlled clinical studies and of the actual categories of risk for preterm delivery, the dietary supplementation of Omega-3, in addition to other pharmacological measures (17alpha-hydroxyprogesterone caproate), could be implemented for the secondary and/or tertiary prophylaxis of preterm delivery.

Adult↗

Secondary structure of a herpes simplex virus glycoprotein D antigenic domain.

The peptide 6-amino caproyl-Pro-Ser-Leu-Lys-Met-Ala-Asp-Pro-Asn-Arg-Phe-Arg-Gly-Lys-Asp-Leu- Pro-6- amino caproate has been synthesized and its secondary structure has been investigated by 1H n.m.r. at 400 MHz. Resonances were assigned from 2D NOESY and COSY spectra, and the secondary structure was determined using NOEs, three-bond coupling constants, and exchange rates of amide protons. The peptide has two tight turns centered on the Pro-Asn and Arg-Gly pairs. The relationship between the secondary structure found here and the antigenic nature of the peptide is discussed.

Amino Acid Sequence↗

[Progestogen therapy in the treatment of endometrial cancer--clinical results and mechanism of steroid action].

The use of medroxyprogesterone acetate (MPA) in therapy of patients with endometrial cancer has been recently examined by the Japan Gynecological Cancer Treatment Group. The response rate of oral MPA was 23.6% (13/55 evaluables) and the average period up to the onset of response was 15.2 weeks (4-28 wks). The response rate was higher in well-differentiated tumors than in poorly differentiated ones. Although it is well known that steroid hormone action is mediated by steroid hormone receptor, the presence of progesterone receptor in cancer tissue seems to be not absolutely necessary for the responsibility to MPA, a potent progestational compound. The reason was studied, in vitro, in our laboratory by using the technique of human tumor clonogenic assay. In this system, MPA showed a marked suppressive effect on the colony formation of endometrial cancer cells. Similar effects were also observed with progesterone, 17 alpha-hydroxyprogesterone caproate and megestrol acetate. Norethindrone and norgestrel, which are both potent progestational compounds, showed almost no anticancer activity on Ishikawa cell in this in vitro system. It became clear that progestational activity was not always associated with anticancer activity, and norethindrone had no influence on the inhibitory effect of MPA, although norethindrone has a strong affinity for progesterone receptor. Similarly, RU 486, which is known as a potent antiprogestogen agent and has a high affinity to progesterone receptor, did not influence the effect of MPA. These results clearly indicated that the anticancer activity of MPA was not mediated by high affinity low capacity progesterone receptor, and a pharmacological effect must be considered for understanding the effect of MPA on endometrial cancer.

Estrenes↗

Synergistic effects of butyrate on platelet responses to arachidonate, A23187, PGE1, and forskolin.

With eukaryotic cells, butyrate is known to induce a series of morphological and biochemical changes that mimic cellular differentiation. With platelets, we have found that butyrate (10 mmol/L) caused an approximately threefold increase in sensitivity to calcium ionophore A23187 and arachidonate. Maximum aggregation was observed at agonist concentrations of 3 mumol/L and 170 mumol/L, respectively, as compared with required concentrations of 10 mumol/L and 400 mumol/L in the absence of butyrate. Similar effects were seen with isobutyric acid, and about one-half the effect was shown with valerate and caproate, but lower homologues showed no synergistic effect. No ultrastructural changes were observed in platelets incubated with butyrate, and the aggregation effects were reversible and returned to normal on removal of butyrate. Membrane fluidity was unchanged by butyrate as measured by changes in the fluorescence depolarization of diphenylhexatriene. Butyrate caused a 60% to 70% increase in the uptake of 3H-arachidonate. Butyrate also potentiated the inhibition of platelet function by prostaglandin E1 and forskolin and uptake of 3H-forskolin was increased approximately 20%. In contrast, platelet response to other agonists (ADP, epinephrine, collagen, thrombin, and platelet-activating factor) was essentially unaffected by butyrate. These results suggest that butyrate may increase the uptake of certain hydophobic agonists and antagonists by platelets. Similar mechanisms for uptake of endogenous effectors may explain the response of eukaryotic cells to butyrate in culture.

Alprostadil↗

Role of mitochondrial transamination in branched chain amino acid metabolism.

Oxidative decarboxylation and transamination of 1-14C-branched chain amino and alpha-keto acids were examined in mitochondria isolated from rat heart. Transamination was inhibited by aminooxyacetate, but not by L-cycloserine. At equimolar concentrations of alpha-ketoiso[1-14C]valerate (KIV) and isoleucine, transamination was increased by disrupting the mitochondria with detergent which suggests transport may be one factor affecting the rate of transamination. Next, the subcellular distribution of the aminotransferase(s) was determined. Branched chain aminotransferase activity was measured using two concentrations of isoleucine as amino donor and [1-14C]KIV as amino acceptor. The data show that branched chain aminotransferase activity is located exclusively in the mitochondria in rat heart. Metabolism of extramitochondrial branched chain alpha-keto acids was examined using 20 microM [1-14C]KIV and alpha-ketoiso[1-14C]caproate (KIC). There was rapid uptake and oxidation of labeled branched chain alpha-keto acid, and, regardless of the experimental condition, greater than 90% of the labeled keto acid substrate was metabolized during the 20-min incubation. When a branched chain amino acid (200 microM) or glutamate (5 mM) was present, 30-40% of the labeled keto acid was transaminated while the remainder was oxidized. Provision of an alternate amino acceptor in the form of alpha-keto-glutarate (0.5 mM) decreased transamination of the labeled KIV or KIC and increased oxidation. Metabolism of intramitochondrially generated branched chain alpha-keto acids was studied using [1-14C]leucine and [1-14C]valine. Essentially all of the labeled branched chain alpha-keto acid produced by transamination of [1-14C]leucine or [1-14C]valine with a low concentration of unlabeled branched chain alpha-keto acid (20 microM) was oxidized. Further addition of alpha-ketoglutarate resulted in a significant increase in the rate of labeled leucine or valine transamination, but again most of the labeled keto acid product was oxidized. Thus, catabolism of branched chain amino acids will be favored by a high concentration of mitochondrial alpha-ketoglutarate and low intramitochondrial glutamate.

Amino Acids, Branched-Chain↗

[Clinical trial of fluocortin butylester in a double-blind contralateral comparison versus fluocortolone and hydrocortisone acetate (author's transl)].

Butyl 6alpha-fluoro-11beta-hydroxy-3,20-dioxo-16alpha-methyl-1,4-pregnadien-21-oate (fluocortin butylester, Vaspit) is a recently developed corticosteroid, its distinguishing properties being that it is non-embryotoxic and has practially no systemic effects. In the course of 6 multicentre studies fluocortin butylester was tested in the forms of cream, ointment and fatty ointment in a comparison with corresponding formulations containing fluocortolone (Ultralan) caproate or pivalate, or hydrocortisone acetate. The total study population comprised 1705 patients with various dermal disorders. The results of these double-blind contralateral studies permit the conclusion that the efficacy of the Vaspit preparations ranges between those of fluocortolone and hydrocortisone acetate. Considering the risks involved with local corticosteroid therapy in children the development of a local corticosteroid with the properties of fluocortin butylester must be acknowledged as an advance.

Administration, Topical↗

Serum progesterone and estradiol in pregnant women selected for progestagen treatment.

Patients with two or more previous spontaneous second trimester abortions and vaginal cytology indicating a poor progestational response in current pregnancies were selected for treatment with Provera (medroxyprogesterone acetate) and/or Delalutin (17 alpha-hydroxyprogesterone caproate). Serum was examined serially for progesterone (P) and estradiol (E) by radioimmunoassay. Serum from 174 untreated patients with no known complications ranging from 6--40 weeks gestation provided normal distribution data. Of 14 progestagen-treated patients, four aborted during the second trimester. These all had chronically low (greater than 50% of observations were less than 1 standard deviation of the normal population) or falling P/E ratios. The rest delivered normal full-term infants although five of the 10 had chronically low P, seven had chronically low P/E ratios, and in one other P/E was falling. Chronically high E contributed to the low P/E ratio in three cases. Thus, these selected cases with poor obstetrical histories demonstrated steroid patterns outside the +/- 1 standard deviation range, although the steroid levels were still within the normal range. Serum progesterone and estradiol analysis may eventually be useful in identifying patients who will best respond to progestagen treatment.

Abortion, Habitual↗