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K E Karlmar

Publications and source records attributed to K E Karlmar.

12 recordsLinked to original sources
PubMed2002

A new hydrostatic anti-G suit vs. a pneumatic anti-G system: preliminary comparison.

HYPOTHESIS: A newly developed hydrostatic anti-G suit is now commercially available. The suit is said to offer a high level of protection against +Gz acceleration. However, past experience shows that it is difficult to produce a hydrostatic suit with effective high-G protection. Careful testing is, therefore, needed to verify its efficacy. METHODS: The G-protective properties of the hydrostatic anti-G suit (Libelle; L) were compared with those of a pneumatic anti-G ensemble (AGE-39) used in the Swedish JAS 39 Cripen aircraft. Three pilots were studied during vertical (+Gz) acceleration in a centrifuge using the following: 1) the L-suit with varied straining maneuvers; 2) the AGE-39 in combination with full anti-G straining maneuvers (AGSM) throughout each high-G exposure (full maneuver; FM); and 3) the AGE-39 in combination with AGSM during the initial part of each high-G exposure (reduced maneuver; RM). G-intensity tolerance was established during exposures to rapid onset rate (ROR) profiles with G-plateau levels ranging from +6.0 to +9.0 Gz. G-endurance was studied during simulated aerial combat maneuvers (SACM) consisting of 10 cycles of 5.5 to 7.5 G. RESULTS: All three pilots tolerated 9.0 G with the pneumatic system both in the RM and FM conditions; their tolerances averaged 6.3 G (range 6.0 to 7.0 G) for the L suit. Thus, during the ROR exposures only the 6.0 G profile was completed by all subjects in all three conditions. At this G-load both muscle straining (as indicated by electromyographic activity in thigh and abdomen) and heart rate were higher in the L than in the RM condition. Mean arterial pressure at eye level was higher in the FM than in the L and RM conditions. Only one subject was able to complete the SACM profile in the L condition. In the RM condition all subjects completed the SACM profile and in the FM condition two subjects completed the SACM. CONCLUSIONS: Whether the AGE-39 was used in combination with maximal AGSM throughout the duration of each high-G exposure or with AGSM only during the initial part of the high-G exposure, G-intensity tolerance was 9.0 G. While wearing the L-suit, G-tolerance was 6.3 G. Thus, under the conditions tested, the G-protection afforded by the L-suit is not adequate for use in a 9-G aircraft.

Acceleration↗
PubMed1982

In vitro conversion of cholesterol into aldosterone and cortisol in different zones of the bovine adrenal cortex.

The individual steps in the formation of aldosterone and cortisol from cholesterol were assayed in different subcellular preparations from the inner and outer zones of bovine adrenal cortex. In zona glomerulosa the 11 beta-, 18- and 21-hydroxylase activities were relatively high, whereas the 17 alpha-hydroxylase activity was relatively low. Cholesterol side-chain cleavage and 3 beta-hydroxysteroid-delta 5-oxidoreductase activity were similar in zona glomerulosa and zona fasciculata-reticularis. The differences were however only quantitative. In no case one specific fraction was totally devoid of enzyme activity. The total content of mitochondrial cytochrome P-450 was relatively high in zona fasciculata-reticularis whereas the content of microsomal cytochrome P-450 was similar in the two fractions. In view of the relatively small differences observed, it seems likely that other factors than distribution of the above enzymes are of major importance for the specific production of gluco- and mineralocorticoids in the two layers.

3-Hydroxysteroid Dehydrogenases↗
PubMed1979

Adrenal hydroxylations in genetically obese and hypertensive rats.

The separate steps in the formation of aldosterone from cholesterol were studied in a strain of spontaneously hypertensive rats in which phenotypic obesity is inherited as a recessive trait (Koletsky rats). The obese and hypertensive state had little or no effect on side-chain cleavage of cholesterol, formation of progesterone from pregnenolone or 21-hydroxylation. Mitochondrial 18-hydroxylation of endogenous and exogenous corticosterone, however, as well as 18- and 11 beta-hydroxylation of deoxycorticosterone, were increased in obese hypertensive rats, both when compared with non-obese hypertensive siblings and when compared with healthy Sprague-Dawley rats. 18-Hydroxylation of corticosterone was increased more than 18-hydroxylation of deoxycorticosterone. In non-obese hypertensive rats, the adrenal content of mitochondrial cytochrome P-450 was lower than that in obese hypertensive rats but higher than that in rats of the conventional Sprague-Dawley strain. The results are discussed with respect to possible heterogeneity of adrenal cytochrome P-450 and to possible explanations for the changes observed.

Adrenal Glands↗
PubMed1979

Assay and properties of 18-hydroxylation of endogenous and exogenous corticosterone in rat adrenals. Evidence for heterogeneity of 18-hydroxylase activity.

A mass fragmentographic technique for assay of 18-hydroxylation of labeled (exogenous) and unlabeled (endogenous) corticosterone in adrenal mitochondria and in reconstituted cytochrome P-450 systems has been developed. An extract of an incubation of [14-14C]corticosterone is subjected both to thin-layer radiochromatography and to mass fragmentography (as O-methyloxime-trimethylsilyl ether derivative). In the latter procedure the ions at m/e 605 and 607 (specific for the derivatives of unlabeled and labeled 18-hydroxycorticosterone, respectively), at m/e 591 and 593 (specific for the derivatives of unlabeled labeled aldosterone, respectively) and at m/e 548 and 550 (specific for the derivatives of unlabeled and labeled corticosterone, respectively) were followed through the gas-liquid chromatography. From the ratio between the peaks obtained in the mass fragmentography and from the percentage conversion of [4-14C]corticosterone obtained in the thin-layer radiochromatography, the amount of endogenous and exogenous 18-hydroxycorticosterone and aldosterone could be calculated. The effects of time, enzyme, and substrate concentration of 18-hydroxylation were studied and optimal conditions for assay were determined. Under most conditions, the ratio between labeled and unlabeled 18-hydroxylated products was about constant, indicating that labeled and unlabeled corticosterone were not in equilibrium. It was ascertained that the 18-hydroxycorticosterone and aldosterone formed in the incubations were derived from corticosterone. [4-14C]18-Hydroxydeoxycorticosterone was not converted into aldosterone or 18-hydroxycorticosterone. In vitro studies with different 18-hydroxylase inhibitors (spironolactone, canrenone, and canrenoate-K) and studies with rats pretreated with KCl in drinking fluid suggest that 18-hydroxylation of corticosterone is catalyzed by an enzyme system different from that catalyzing 18-hydroxylation of deoxycorticosterone.

Adrenal Glands↗
PubMed1978

Effects of ascorbic acid deficiency on adrenal mitochondrial hydroxylations in guinea pigs.

The effect of ascorbic acid deficiency on adrenal hydroxylation of cholesterol and deoxycorticosterone in guinea pigs was studied by using mitochondria and isolated cytochrome P-450 fractions. The effects obtained were compared with the effects of long-term treatment with ACTH. Advanced scurvy as well as treatment with ACTH resulted in an increase in the weight of the adrenals, the total amount of cytochrome P-450, the cholesterol side-chain cleavage activity, the cortisol level in plasma, and the excretion of unconjugated cortisol in urine. Total 11beta- and 18-hydroxylation of deoxycorticosterone were not stimulated or were stimulated only to a small extent. It is suggested that the major effects observed in advanced scurvy are due to ACTH, the level of which was significantly increased, most probably as a consequence of the stress. In animals kept on a scorbutogenic diet for 2-4 weeks or, with a small dose of ascorbate added, for several weeks, changes were observed that could not be fully explained as effects of ACTH on normal adrenals. Although the plasma levels of ACTH and cortisol were increased only to a small extent and excretion of unconjugated cortisol in urine was unaffected, there was a significant increase in the total capacity of adrenal mitochondria to hydroxylate exogenous cholesterol. It is concluded that the level of ascorbate in the adrenals might be of some importance for the capacity to convert cholesterol into pregnenolone. The normal feed-back regulation is, however, intact in moderate ascorbate deficiency and the plasma level of cortisol is kept within normal limits.

Adrenal Glands↗
PubMed1977

Common characteristics of the cytochrome P-450 system involved in 18- and 11 beta-hydroxylation of deoxycorticosterone in rat adrenals.

18- and 11beta-Hydroxylation of deoxycorticosterone and side chain cleavage of cholesterol were studied in mitochondria and submitochondrial reconstituted systems prepared from rat and bovine adrenals. A mass fragmentographic technique was used that allows determination of hydroxylation of both exogenous and endogenous cholesterol. The following results were obtained. (1) Treatment of rats with excess potassium chloride in drinking fluid increased mitochondrial cytochrome P-450 as well as 18- and 11beta-hydroxylase activity in the adrenals. Cholesterol side chain cleavage was not affected. In the presence of excess adrenodoxin and adrenodoxin reductase, cytochrome P-450 isolated from potassium chloride-treated rats had higher 18- and 11beta-hydroxylase activity per nmol than cytochrome P-450 isolated from control rats. The stimulatory effects on 18- and 11beta-hydroxylation were of similar magnitude. (2) Long-term treatment with ACTH increased cholesterol side chain cleavage in the adrenals but had no effect on 18- and 11beta-hydroxylase activity. The amount of cytochrome P-450 in the adrenals was not affected by the treatment. It was shown with isolated mitochondrial cytochrome P-450 in the presence of excess adrenodoxin and adrenodoxin reductase that the effect of ACTH was due to increase of side chain cleavage activity per nmol cytochrome P-450. Side chain cleavage of exogenous cholesterol was affected more than that of endogenous cholesterol. (3) Gel chromatography of soluble cytochrome P-450 prepared from rat and bovine adrenal mitochondria yielded chromatographic fractions having either a high 18- and 11beta-hydroxylase activity and a low cholesterol side chain cleavage activity or the reverse. The ratio between 18- and 11beta-hydroxylase activity was approximately constant, provided the origin of cytochrome P-450 was the same. (4) Addition of progesterone to incubations of deoxycorticosterone with soluble or insoluble rat adrenal cytochrome P-450 competitively inhibited 18- and 11beta-hydroxylation of deoxycorticosterone to the same degree. Addition of deoxycorticosterone competitively inhibited 11beta-hydroxylation of progesterone with the same system. Progesterone was not 18-hydroxylated by the system. From the results obtained, it is concluded that 18- and 11beta-hydroxylation have similar properties and that the binding site for deoxycorticosterone is similar or identical in the two hydroxylations. The possibility that the same specific type of cytochrome P-450 is responsible for both 18- and 11beta-hydroxylation of deoxycorticosterone is discussed.

Adrenal Glands↗
PubMed1975

18-Hydroxylation of deoxycorticosterone by reconstituted systems from rat and bovine adrenals.

18-Hydroxylation of deoxycorticosterone was studies with rat or bovine adrenal mitochondria or with reconstituted systems obtained from these fractions. The reconstituted systems consisted of a partially purified preparation of cytochrome P-450 from rat adrenals and a partially purified NADPH-cytochrome P450 reductase preparation from bovine adrenals. In some experimenta a soluble cytochrome P-450 fraction from bovine adrenals was used. Adrenodoxine and adrenodoxine reductase were shown to be the active components of the NADPH-cytochrome P-450 reductase preparation. Optimal assay conditions were determined for 18-hydroxylation by the crude mitochondrial fraction as well as by the reconstituted systems. In the presence of excess NADPH-cytochrome P-450 reductase fraction, the rate of 18-hydroxylation was linear with time and with the amount of cytochrome P-450. In incubations with intact rat adrenal mitochondria to which Ca2+ and an excess NADPH had been added, NADPH-cytochrome P-450 reductase increased the rate of 18-hydroxylation about 100%, indicating that NADPH-cytochrome P-45o reductase was to some extent rate-limiting. The rate of 18-hydroxylation of deoxycorticosterone by the reconstituted system as well as by intact mitochondrial fraction was much higher than the rat of 18-hydroxylation of corticosterone and progesterone. When the cytochrome P-450 preparation from rat adrenals in the reconstituted system was substituted for cytochrome P-450 from bovine adrenals, the rate of 18-hydroxylation decreased considerably. Under all experimental conditions, the 18-hydroxylation of deoxycorticosterone occurred with a concomitant and efficient 11beta-hydroxylation. Provided the source of cytochrome P-450 was the same, the ratio between 11beta- and 18hydroxylation was constant under all conditions and was not significantly different in the presence of metopirone, carbon monoxide, cytochrome c or different steroids. It is suggested that identical or at least very similar types of cytochrome P-450 are involved in 11beta- and 18-hydroxylation of deoxycorticosterone.

Adrenal Glands↗