Search

The hypolipidemic action of 1,1-bis [4'-(l "-carboxy-1 "-methyIpropoxy)-phenyl] cyclohexane (S-8527) was studied in rats, mice and rabbits under various experimental conditions to compare the effects with those of clofibrate. Oral ingestion of S-8527 to normal rats for 7 days lowered serum triglycerides and cholesterol by about 27% at 1 mg/kg and 20% at 3 mg/kg, respectively. The hypolipidemic effect of S-8527 was considered to be twenty to thirty times more potent than that of clofibrate but a hepatomegaltc effect of S-8527 was not observed at its effective dose ranging from 1 to 30 mg/kg. S-8527 at 3 mg/kg decreased liver triglyceride concentration by about 20% but the decrease of triglyceride concentration was not observed in clofibrate treated groups. Liver cholesterol concentration was not decreased with any of the doses of S-8527 while clofibrate decreased liver cholesterol concentration by about 20% at 300 mg/kg. However, there were no differences in total content of cholesterol in liver between S-8527 and clofibrate treated groups. With Triton injected rats, a single oral dose of 100 mg/kg of S-8527 depressed the increase of serum triglycerides by about 50% while clofibrate did not. In glycerol-fed rats, S-8527 decreased serum and liver triglycerides more effectively than clofibrate, and in normal mice and cholesterol-fed mice, S-8527 was found to be more active than clofibrate, however the hepatomegalic effect of S-8527 was less than that of clofibrate. Hypolipidemic effects in rabbits were not observed with either S-8527 or clofibrate.

The addition of dopamine (1–100μM) to homogenates of rat striatum incubated with ATP evoked a 120% increase in the rate of cyclic 3′5′ adenosine monophosphate (cyclic AMP) production. The effects of added dopamine were mimicked by the addition of the compound S 584 [1-3,4-(dihydroxybenzyl)-4-(2-pyrimidinyl) piperazine] (1–100 μM), a catechol metabolite of the dopaminergic stimulant drug piribedil (ET 495). The latter substance was itself inactive in this system at these concentrations. The stimulation of cyclic AMP production by dopamine and by S 584 was potently inhibited by the dopamine antagonist dru chlorpromazine and spiroperidol (1–10 μM). It is possible that the dopaminergic effects elicited by piribedil may be mediated through the active metabolite S 584.

SummaryThe response of chick and mouse fibroblasts to adrenal and non-adrenal steroids was studied in a perfusion apparatus. Cholic acid, estradiol, and pregnenolone induced no changes in fibroblasts. DOCA, DOCG, and Compound S caused a great increase in the size of the cells. The nucleus and heterochromatic material within the nucleus were greatly increased in size. There was an increase in the number of mitochondria and a tendency to lay down large numbers of fibers.

When Zn and Mg were contained together in die-casting aluminum alloys by the content equivalent to ADC 12, the effects of the both metals on the mechanical properties and corrosion resistance at room temperature and the effects on the change of mechanical properties after tempering (T5 treatment) were investigated.The following results were obtained.(1) The effects on the mechanical properties at room temperature were the same in die-cast specimens and mold cast specimens. Zn and Mg contents had little effects on tensile strength, but yield strength (0.2%), elongation, hardness, and impact value were affected by Mg content more remarkably as compared with Zn. Yield strength (0.2%) and hardness were higher for higher Mg content (0.30%), while elongation and impact were higher for lower Mg content (0.08%). On the other hand, yield strength (0.2%) was almost constant for the increase of Zn content, but hardness slightly increased with the increase of Zn. Furthermore, elongation and impact value had also the same tendency as above.(2) The suitable tempering (T5 treatment) conditions of the specimens (having chemical components used in these experiments) would be at 150°C and for 8hr in the air atmosphere. The effects on mechanical properties were more sensitive after T5 treatment was performed. Especially, yield strength (0.2%) and hardness of higher Mg content specimens were substantially increased. The effects of T5 treatment on tensile strength were not observed for any contents of Mg. Elongation and impact value had the same tendencies in almost uniform decreasing with the increase of tempering time for any contents of Mg. However, they were always higher for lower Mg content (0.08%) than higher one (0.30%).(3) In salt water (3% NaCl) immersion test, the specimens, which had been cast by permanent molds, showed weight loss directly proportional to immersion time. Mg content had almost no effects, but Zn content had slight effects on corrosion resistance. On the other hand, in die-cast specimens, which had undergone salt spray (5±1wt.%) test at 35°C, yield strength (0.2%) even after 2 months period test was not different from that value at room temperature. However, the effects of spraying time appeared on tensile strength, elongation, and impact value. The above effects were more remarkable in Zn content as compared with Mg in all specimens.(4) In specimens of higher Mg content (0.30%), the presence of S compound (Al2CuMg) was microscopically observed. It was supposed that the above compound had the very effects on mechanical properties and other properties after ageing and T5 treatment.

The Δ 4 -hydrogenases of male rat-liver supernatant fractions convert unsubstitued testosterone derivatives to the 4,5-dihydro-3-keto compounds which are then reduced further to 3-hydroxysteroids by saturated 3-keto reductases which are also present in these fractions. Introduction of a halogen substituent at the C-2α, C-4, C-6α or C-6β position not only increases the reduction rate but promotes an abnormal enzymic pathway, Δ 4 -3-ol formation. This reduction, which proceeds in the presence of TPNH or DPNH is believed to be mediated by the saturated 3-keto reductases and is rationalized on the basis of electronic destabilization of the α,β-unsaturated ketone moiety by electronegative substituents with stabilization of the proposed transition state for reduction. In contrast, methyl substitution retards reduction which is explained on electronic and in some cases steric grounds.

1. When sufficiently concentrated sickle cell hemoglobin containing solutions are exposed to a constant stream of CO2 gas, the hemolysates gel. This gelling phenomenon is indicative of the presence of S hemoglobin and cannot be obtained with any other type of human hemoglobin in the absence of S pigment. The lowest S hemoglobin concentration (Gm. per cent) of a hemolysate at which the gelling phenomenon can still be elicited is designated as its lowest gelling point. 2. A simple apparatus was developed to analyze the gelling phenomenon under standardized conditions. It could be shown that the lowest gelling points of hemolysates prepared from erythrocytes of the sickle cell trait (containing A + S hemoglobins), of the "C variant" (containing C + S hemoglobins), and from sickle cell anemia cells (containing S + F hemoglobins) differ distinctly. Further experiments suggest that the presence of A hemoglobin decreases the minimal amount of S pigment required for gel formation, and that type C hemoglobin reduces this amount even further. F hemoglobin seems to exert no significant influence on the gelling phenomenon. Serum albumin is also capable of decreasing the amount of S hemoglobin required for gelation. 3. A sickled erythrocyte is visualized as an S hemoglobin tactoid or gel, specifically influenced by the companion pigment which interacts with the S compound. Thus, in the sickle cell trait, a positive sickling test is not only caused by the presence of S hemoglobin, but also by its interaction with A hemoglobin. Only in the sickle cell anemia cells does sickling seem to depend solely upon the interaction of the S hemoglobin molecules. 4. The readily demonstrable differences of the lowest gelling points of hemolysates prepared from the various types of sickling red cells form the basis of the diagnostic gelling test which distinguishes sharply between sickle cell anemia and sickle cell trait erythrocytes. By this procedure atypical cases of sickle cell disease, for example, those whose erythrocytes contain C hemoglobin, may also be detected.

High concentrations of S were found in narrow bands at sites of calcification 1 in rachitic as well as normal calf tissues, measured by microscopic elemental X-ray analysis. These bands correlated with staining by Sudan black and Astrablau. Infra-red microspectrophotometric analysis of tangential sections from the periosteal line of new bone from calf mandible revealed absorption bands consistent with the presence of organic sulfates. Extractability of S compounds by hyaluronidase after pyridine treatment from points in calcifying matrix was significantly less than from adjacent points in a growing but non-calcifying matrix, based on Sudan black staining as a marker of calcification. The possible distinctive nature of these abundant S compound is discussed in the light of negative evidence for sulfated lipids and strong bases. The data illustrate that differences in the total content and extractability of S compounds can be measured in properly identified sites of calcification with areas 20 μ in diameter and 10 μ tissue thickness.

17β-(2-alkylamino-(or 2-arylamino- or 2-N, N-alkylarylamino-)-4-thiazolyl) androst-4-en-3-one derivatives were prepared from Reichstein's compound S 21-iodide, cortisone 21-iodide and desoxycorticosterone 21-iodide or corresponding 21-mesylate with N-alkylthiourea, N-arylthiourea or N, N-alkylarylthiourea respectively. Some of these compounds were found to have a digitalis-like properties (cardiac glucoside properties) as a result of pharmacological test.

Application of Gibberella soubinetii to various steroid showed the formation of 15α-hydroxylated compound from progesterone and deoxycorticosterone, and 6β-hydroxylated compound from Reichstein's compound S and 17α-hydroxyprogesterone. Corticosterone afforded, by this reaction, 15α-hydroxycorticosterone derivative with one tertiary hydroxyl, whose structure has not been determined. Fusarium lycopersici also showed the same reaction as Gibberella soubinetii.

The isolation of a new adrenocortical metabolite from the urine of two women suffering from Cushing's syndrome due to adrenal carcinoma has been described. The substance has been characterized as 3α, 17α, 21-trihydroxypregnane-20-one (tetrahydro Compound S; THS). Since it was isolated after β-glucuronidase hydrolysis of the urines, this metabolite was apparently excreted in the form of its glucuronoside conjugate. The possible relationship between the occurence of THS in the urine of these patients with Cushing's syndrome and the excessive edema they exhibited has been noted. In addition THS has been isolated in 5% yield from the urine of a bilaterally adrenalectomized patient to whom Reichstein's Compound S was administered orally.

Twenty elderly subjects with an average age of 73.0 years (range 66–82) underwent standardized surgery (laparotomies). Thirteen younger subjects with an average age of 45.4 years (range 23–58) served as controls. Changes in plasma cortisol, plasma compound S and eosinophil cell count were checked throughout the first 24 hours after surgery. A maximum increase in the plasma cortisol concentration exceeding the spontaneous initial value by 150 and 110 per cent respectively was observed, in the young and elderly subjects. An insignificant rise only was seen in the plasma compound S concentration. The eosinophil cell count fell to less than 50 n/μl. The variations in the three parameters, observed in the geriatric group, indicate a less marked response to surgical stress although no evidence was found for the existence of any significant age difference. Between the fourth and eighth postoperative day, an intravenous metyrapone test was carried out in 13 elderly and 10 young subjects. The changes in the concentration of plasma cortisol and plasma compound S and in the eosinophil cell count were recorded. When exposed to an apparently identical stimulation of the feedback system during the postoperative phase, the elderly patients showed a much greater response than that seen in the younger patients. The possibility that the pituitary-adrenal system in the elderly develops a higher sensitivity following repeated exposures to stress, is discussed. Exhaustion of the pituitary-adrenal system during the postoperative phase was not demonstrated in the elderly.

The effect of 1,1-bis[4′-(1′-carboxy-1′-methylpropoxy)-phenyl]cyclohexane (S-8527) on cholesterol metabolism and serum and liver lipids in rats has been studied. In some experiments S-8527 was compared to ethyl α- p -chlorophenoxyisobutyrate (Atromid-S, Clofibrate). When fed to rats for 3 weeks at a level of 0.03% of the diet, S-8527 did not affect weight gain but caused hepatomegaly. The extent of hepatomegaly (11% above control) was not as great as that seen with Atromid-S (42%). Serum cholesterol and triglyceride levels were significantly reduced, but liver lipid levels were not influenced. Cholesterol synthesis by liver slices from rats fed 0.3% of the drug for 3 weeks was reduced significantly ( P 14 C]acetate and P 14 C]cholesterol to 14 CO 2 by rat liver mitochondrial preparations was unaffected. One day after [4- 14 C]cholesterol was administered to rats fed S-8527 for 2 weeks significantly less [ 14 C]cholesterol was recoverable from the sera of treated rats ( P

A rapid analytical method has been developed to follow the biological oxidation of 17-α-oxy-11-desoxy-corticosterone (Reichstein compound S) to hydrocortisone. Paper chromatography is too slow to follow the progress of a preparative microbiological steroid transformation. However, 17-α-oxy-11-desoxy-corticosterone can be separated in a sufficiently pure state for photometric assay by a simple extraction from fermentation broths containing several steroids. This extraction, coupled with the formation of a sulphuric acid chromogen, permits estimation of the steroid in fermentation liquors. The steady decrease of the 17-α-oxy-11-desoxy-compound thus estimated proved to be a true indication of the progress of the oxidation process, allowing it to be stopped at the most favourable time.

11α-Hydroxy derivatives of progesterone, 17α-hydroxyprogesterone, deoxycorticosterone, and Reichstein's compound S were obtained solely by the use of Gloeosporium kaki and Glomerella lagenarium. These fungi did not affect corticosterone.

Metyrapone (SU-4885) induced a spontaneous appetite for 0.15 M NaCl solution when administered i.p. to rats at a dose of 11.0 mg/kg body weight. Induction of the salt appetite is attributed to an accumulation of desoxycorticosterone resulting from inhibition of the 11β hydroxylation enzymes in the biosynthetic pathway of the adrenal cortex. Although accumulation of Δ 4 -androstene-3, 17-dione would also be expected to occur after inhibition of the 11β hydroxylation enzymes by metyrapone, administration of this steroid at graded doses (35, 70, 150 and 300 μg/kg body weight) failed to elicit a salt appetite in rats. The results support the hypothesis that changes in concentration of mineralocorticoid hormone in the blood affect appetite for NaCl solution. Another steroid intermediate, 17α hydroxydesoxycorticosterone (Reichstein's Compound S) had no significant effect on spontaneous NaCl appetite under the conditions of these experiments.

A detailed analysis of 12 samples of human adrenal vein blood, collected from patients with mammary carcinoma, is reported. Cortisol has been isolated from every sample and identified. The isolation and identification of corticosterone in 6 instances, Compound S in 5 instances, and llj8-hydroxy-A4- androstene-3,17-dione in 10 instances is also reported. The isolation of 17ahydroxyprogesterone from 5 samples and dehydroepiandrosterone from 1 sample and their identification is reported for the first time.

When the -S-S- compound ELLMAN'S reagent was combined either with the respiratory inhibitor antimycin or the uncoupling agent 2, 4-dinitrophenol an ATP-energized mitochondrial volume change was induced. Thus ELLMAN'S reagent behaved as an electrophilic thiol reagent analogous to showdomycin and N-ethylmaleimide. These results encouraged the search for possible reactions between the pivotal mitochondrial thiol group and biologically important substances which contain the -S-S- grouping even though older reports in the literature of the induction of mitochondrial swelling by biologically important -S-S- compounds were recently discounted.

A method utilizing the steroid-binding properties of corticosteroid-binding globulin (CBG, transcortin) was described in 1963 for the routine determination of corticoids in 1 ml of plasma (J Clin Endocr 23: 293, 1963) and later modified to reduce the time required (J Clin Endocr 24: 919, 1964). A 100-fold increase in sensitivity has now been achieved by using tritiated steroids in place of 14C-labeled steroids, by utilizing the CBG's of species other than man, and by using adsorption in place of dialysis or gel filtration. The use of several insoluble adsorbing agents (Fuller's earth, Florisil, coated charcoal) to separate protein-bound and unbound steroids was investigated and their effects on specificity were studied. The use of these techniques in plasma, urine and cerebrospinal fluid was vindicated. With these methods, cortisol can be measured routinely in 0.01 ml of plasma or 0.1 ml of cerebrospinal fluid, and progesterone in 0.3 ml of plasma. Compound S (11-desoxycortisol), corticosterone, ...

Cultured cells of Stachylidium bicolor was applied to Reichstein's compound S, deoxycorticosterone, 14α, 21-dihydroxypregn-4-ene-3, 20-dione, and corticosterone. The compound S produced hydrocortisone, deoxycorticosterone produced 11β-and 14α-hydroxylated compounds, and 14α, 21-dihydroxypregn-4-ene-3, 20-dione gave the 11β-hydroxy compound. Oxidation product was not obtained from corticosterone.

SU-4885 inhibits 11β-hydroxylation of steroids by the human adrenal cortexand leads to a decrease in cortisol secretion, a “compensatory” rise in ACTH secretion, and the secretion of large quantities of 11-desoxycorticosteroids such as compound S. Compound S and its metabolites are readily measurable in biologic fluids as 17-hydroxycorticoids. In normal subjects, therefore, SU-4885 induces a rise in total blood and urinary 17-hydroxycorticoids. Since this response to SU-4885 is dependent upon a rise in ACTH secretion it affords, in patients who do not have frank adrenal insufficiency, a sensitive means of testing the reserve capacity of the pituitary gland to secrete ACTH. Of 9 patients with chromophobe adenomas tested in this manner, 6 were found to have “limited pituitary reserve.” This was true also of 2 out of 5 patients with acromegaly, 3 out of 6 patients with cachexia, and 1 patient with post-traumaticdiabetes insipidus. Of 7 patients with active Cushing's disease due to adrenal hyperplasi...

This study was made on the changes of the Vickers hardness, the electric resistance, the differential dilatation and the thermal analysis in the artificial age-hardening of, , the 24S type super duralumin SD1 (Cu 4%, Mg 1.6%) and SD2 (Cu 3%, Mg 2.5%). The results can be summarized as follows:- The abnormal changes, observed at the dilatation curve and the thermal change in the ageing at a room temperature, are attributed to the migration of dissolved atoms prior to the precipitation. The abnormal phenomena, which were produced at about 250°C in the course of slow heating, have been assured to be resulted from the precipitation of compound S (or S and CuAl2). The precipitation of compound S and CuAl2 could not be separated to observe in this experiment.

Eine monomolekulare Schicht eines Farbstoffs S befindet sich im Abstand von z.B. 50 A von einer monomolekularen Schicht eines Farbstoffs A. Werden die Molekule von S durch Licht angeregt, so findet ein strahlungsloser ubergang von Anregungsenergie von S nach A statt, und eine sensibilisierte Fluoreszenz von A wird beobachtet. Befindet sich im Abstand von z.B. 50 A von der A-Schicht eine monomolekulare Schicht eines weiteren Farbstoffs A′, so findet nach der optischen Anregung von S ein strahlungsloser Energie-ubergang nach A und von da aus weiter nach A′ statt, und man beobachtet die Fluoreszenz von A′. Die Stoffe S, A, A′ sind so beschaffen, das das Absorptionsmaximum von A etwa an derselben Stelle wie das Fluoreszenzmaximum von S und ebenso das Absorptionsmaximum von A′ etwa an derselben Stelle wie das Fluoreszenzmaximum von A liegt. A monomolecular layer of a dyestuff S is situated at a distance of, say, 50 A from a monomolecular layer of a dyestuff A. If the molecules of S are excited by light, excitation energy is transferred from S to A without any radiation and sensitized fluorescence of A can be observed. If at a distance of, say, 50 A from the A layer there is a monomolecular layer of another dyestuff A′ then after compound S has been optically excited an energy transfer, without radiation, to A occurs, and from there further to A′; and the fluorescence of A′ can be observed. The compounds S, A and A′ are constituted in such a way that the absorption maximum of A is at about the same point as the fluorescence maximum of S, and similarly the absorption maximum of A′ is at about the same point as the fluorescence maximum of A.

5β-Pregnane-3α, 17α, 20α, 21-tetrol (l) and 5β-pregnane-3α, 17α 20β, 21-tetrol (II) have been isolated and identified from the urine of a girl with congenital adrenal hyperplasia. The total 5β-pregnane-3α, 17α, 20(α+β),21-tetrol consisted of 60% of I and 40% of II. The final identity of the compounds was established by gas chromatography — mass spectrometry. The mass spectra of the two trimethylsilyl isomers were closely related to each other in contrast to the spectra of five other pairs of C 21 -C-20(α and β)-hydroxy steroid-trimethylsilyl-ethers. The mass spectra of free I and II also exhibited many common features, but were less similar to each other than their trimethylsilyl derivatives.

The results of a preliminary study on the biosynthesis of adrenocortical hormones by the human adrenal gland in vitro are presented. The substrates investigated were 3β-hydroxy-Δ5-pregnene-20-one, progesterone, 17α-hydroxyprogesterone, compound S (17α21-dihydroxy-Δ4-pregnene-3,20-dione) and deoxycorticosterone. The results have led to the proposal of the following tentative scheme of adrenocortical biosynthesis by the human adrenal

(1931). Lagrange's Compound Pendulum. The American Mathematical Monthly: Vol. 38, No. 1, pp. 1-8.

The “hyalinosis syndrome” is the name applied, by Selye (1946, 1950), to the cardiovascular-renal changes which occur in salt-treated, unilaterally nephrectomized rats administered such steroids as desoxycorticosterone acetate (DCA) or Reichstein’s Compound S (desoxocortisone) for prolonged periods. The characteristic changes of this syndrome are hypertension, renal and cardiac hypertrophy, nephrosclerosis, glomerular hyalinization, “rheumatic-like” cardiac nodules and frequently periarteritis nodosa. Up to the present time such changes have been observed only after treatment with steroids known to possess appreciable mineralocorticoid activity. This fact, plus the observation that certain stresses, as well as the administration of lyophilized anterior pituitary powder (LAP) or alkaline pituitary extract (APE) also produced the hyalinosis syndrome, led Selye to postulate (1946, 1950) that similar pathological conditions in the human might be pathogenetically related to hyperfunction of the anterior pituit...

Studies of ACTH release from rat pituitary tissue incubates were performed in an effort to determine if glucocorticoids act directly on the pituitary to influence ACTH secretion. The spontaneous release of ACTH from pituitary halves or quarters incubated in Krebs-Ringer bicarbonate was not altered by the addition of 5 μg/ml of dexamethasone-21-PO4. Synthetic lysine or arginine vasopressin (10–100 mU/ml) induced release of ACTH into the incubation media. The addition of dexamethasone-21-PO4 to the incubation media in concentrations of 0.05 μg/ml or greater inhibited vasopressin-induced ACTH release. Another glucocorticoid, methylprednisolone, also inhibited vasopressin-induced ACTH release. Compound S and desoxycorticosterone, which are not glucocorticoids, in concentrations of 100 μg/ml, and thyroxine in a concentration of 2 μg/ml did not affect vasopressin-induced ACTH release. These studies are consistent with the concept that glucocorticoids act directly at the pituitary to inhibit activation of ACTH s...

Cortisol added in vitro in concentrations of 0.025 μg/ml and higher, significantly inhibited the metabolism of [14C6]glucose to CO2, fatty acid, and protein during the prolonged incubation of adipose tissue from 96-h fasted normal rats. The steepest portion of the dose response curve was well within the expected range of physiological concentrations of free cortisol in plasma. Deoxycorticosterone and Reichstein compound S were less effective, while triamcinolone and prednisolone exceeded cortisol in potency. Tetrahydrocortisol was without any effect.

HE linear order of four genes in chromosome I of the tomato has T been well established, principally from data obtained by LINDSTROM (1932) and MCARTHUR (1934). LESLEY (1931) has shown one of the genes in this linkage group to be related to resistance to the curly top virus disease, and LINDSTROM (1932) has demonstrated a decided relationship between fruit size and the genes in this pair of chromosomes. YEAGER (1937) has data that demonstrate the presence of a fifth gene in the group and considers this to be a major gene for fruit shape and size. The four genes that have been located by linkage tests and their arrangement are as follows : d dwarf plant recessive to D, standard plant p pubescence on the fruit recessive to P, smooth fruit o pear shape fruit recessive to 0, round fruit s compound inflorescence recessive to S, simple inflorescence

The effect of 1,1-bis[4′-(1′-carboxy-1′-methylpropoxy)-phenyl]cyclohexane (S-8527) on serum and liver lipids was studied in rats and compared with clofibrate. When rats were given a daily oral dose of 10 mg/kg or 30 mg/kg of S-8527 for 14 days, marked reduction of serum cholesterol and triglycerides was observed and the decreases were more pronounced than those in rats treated with 100 mg/kg or 300 mg/kg of clofibrate. There was no significant increase in liver weight, while clofibrate caused significant hepatomegaly. A similar hypolipidemic effect was observed when S-8527 was given mixed in the diet at concentrations of 0.01% or 0.03% and a more marked effect was noted in rats fed on a semisynthetic diet that contained sucrose as the only carbohydrate source. S-8527 lowered the hepatic triglyceride level but slightly raised the cholesterol level.

Transformation of REICHSTEIN'S compound S or progesterone by various microorganisms such as fungi, bacteria and streptomycetes of about 700 strains has been studied (Table 1). The actions of several strains upon various corticoid steroids were investigated and the transformed steroids were isolated and their structures determined. From these results it was revealed that almost all of the microorganisms tested have a certain kind of substrate specificity in their actions as shown in Table 2.

In many automated numerical algorithms, the calculations are stopped when the difference between two successive approximations is less than a preassigned tolerance. The dependability of this procedure for Simpson’s compound rule has been investigated. Classes of functions have been determined for which the above criterion is (a) always valid, and (b) asymptotically valid. A new exit rule is proposed which appears to be less conservative than the standard technique.

The effect of DHEA in vivo on the biosynthesis of the adrenal steroids, with special consideration of the 11β-hydroxylation, has been studied in dogs. The biosynthesis of cortisol, corticosterone and aldosterone from deoxycorticosterone and compound S of Reichstein by the dog adrenal gland has been investigated after perfusion with a solution of 5 % glucose saturated with DHEA. The results indicate a decreasedconversion of deoxycorticosterone and compound S of Reichstein (11-deoxycortisol) to corticosterone and cortisol, respectively, as shown by plasma levels, following perfusion with DHEA. Total production of aldosterone by the adrenal tissue was also decreased following perfusion with DHEA, as is evident from the incubation studies. (Endocrinology 84: 98, 1969)

A CONSIDERABLE volume of investigation in man as well as in animals has indicated that the adrenal cortex might be involved in hypertensive disease, either in a causal or supportive r61e (Soffer, 1948; Perera, 1950). Some impetus to these studies has been given by the exploration of the hypertensive properties of desoxycorticosterone acetate (DCA) (Selye, Hall and Rowley, 1943; Friedman, Polley and Friedman, 1948). In view of these findings, it seemed of importance to us to determine whether any compounds, either by reason of their structural or physiological properties, might oppose the known cardiovascular-renal effects of DCA. To this end we have set up a simple screening test and have thus far explored the action of progesterone, testosterone, estradiol, 21-acetoxy pregnenolone, “12-keto DCA,” Compound S (11-desoxy-17-hydroxycorticosterone acetate), Compound A (11-dehydrocorticosterone), cortisone, hyaluronidase, Lipo-Adrenal Cortex (Upjohn) and pitressin. Of these, only Lipo-Adrenal Cortex, in large ...

Fungal cells from Curvularia lunata were entrapped in a crosslinked polyacrylamide gel. The gel-cells obtained as granules were applied in the microbial transformation of Reichstein compound S leading to cortisol through an 11-β-hydroxylation step. Some kinetic studies of this conversion using gel-cells were carried out. In addition, it was shown that gel-cell granules which had lost part of their 11-β-hydroxylase activity on storage could be reactivated yielding preparations with increased activity. From Corynebacterium simplex a steroid dehydrogenase catalyzing the Δ1- dehydrogenation of cortisol leading to prednisolone was isolated and partially purified. The preparation was entrapped in a crosslinked polyacrylamide gel and the gel-enzyme granules obtained used in steroid dehydrogenation processes.