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S Gallant

Publications and source records attributed to S Gallant.

At least 19 recordsLinked to original sources
PubMed1995

Sex differences in cytochromes oxidase and P-45011 beta in the rat adrenal cortex.

A comparative study of cytochrome c oxidase (COX) activity and expression as well as cytochrome P-45011 beta expression has been carried out on the adrenal cortex of male and female rats. COX has also been examined in rat liver. In addition, the effect of testosterone replacement in orchiectomized male rats on adrenal COX has also been investigated. Adult male rats had higher COX activity in adrenal (255%) and liver (144%) mitochondria compared to adult female rats. Male rat adrenals and liver also had increased levels of COX II, a mitochondria-encoded COX subunit, and of COX IV, a nucleus-encoded COX subunit, as measured by Western analysis. In contrast, cytochrome P-45011 beta levels were lower (48%) in adrenal mitochondria from male rats than those of female rats. There was no significant sex difference in the level COX II and COX IV mRNAs in adrenal or liver, whereas the cytochrome P-45011 beta mRNA was 4-fold higher in female adrenals than in males. In male rats, orchiectomy caused a 23% decrease and testosterone replacement a 66% increase in adrenal COX activity. There were no corresponding changes in the levels of mRNAs encoding for COX subunits, suggesting post-transcriptional effects of testosterone on COX. These results are consistent with a regulatory role of testosterone on the expression of components of the respiratory and steroidogenic electron transport chains.

Adrenal Cortex↗
PubMed1992

The inhibition of rat adrenal cytochrome P-45011 beta gene expression by androgens.

The synthetic androgen methylandrostenediol (MAD) and the naturally occurring one, testosterone, both bring about hypertensive cardiovascular disease when chronically administered to rats. The pathogenesis of this form of experimental hypertension is thought to result from inhibition of steroid 11 beta-hydroxylase activity. In contrast to the above androgens, 19-nortestosterone, androstenedione and dehydroepiandrosterone (DHEA) have been reported to be without effect in elevating blood pressure. To examine the mechanism(s) involved, we have in this study compared the effects of a number of androgens on adrenal cytochrome P- 45011 beta enzyme and mRNA steady state levels. These parameters were also correlated with the ability of adrenal mitochondria isolated from these groups to hydroxylate 11-deoxycorticosterone (DOC) to corticosterone and 18-hydroxy-11-deoxycorticosterone (18-hydroxy-DOC). Rats treated for seven days with 10 mg per day of dihydrotestosterone, testosterone, 19-nortestosterone or MAD showed a profound decrease in cytochrome P-45011 beta mRNA levels (to less than 20% of controls). This was accompanied by similar changes in both the level and activity of the enzyme. Androstenedione and DHEA were less potent in effecting these changes. In addition, for MAD and testosterone we tested the dose dependence of these changes and found that increasing doses (0.1 mg to 10 mg per day) of either androgen caused progressive decreases in the parameters measured. To assess selectivity we also determined the steady state level of cytochrome P-450scc mRNA in rats treated with the various androgens. In contrast to what was found with cytochrome P-45011 beta, the mRNA transcript for cytochrome P-450scc was equal to or above control levels. We conclude that, in general, the extent of inhibition of cytochrome P-45011 beta enzyme and mRNA level by a given androgen correlates with its reported facility in producing hypertension in rats. Increased secretion of DOC continues to be a likely mechanism for the development of this hypertension but with some androgens extra-adrenal effects may be involved.

Adrenal Glands↗
PubMed1991

Dose-dependent response to phenylpropanolamine: inhibition of orthostasis.

Phenylpropanolamine, a widely consumed over-the-counter drug, is known to elevate blood pressure, but the mechanism is unknown; it may be both a direct and indirect sympathomimetic. This study investigated the effects of 75-mg sustained-release phenylpropanolamine, 75-mg phenylpropanolamine plus 400-mg caffeine, and 150-mg phenylpropanolamine on blood pressure, plasma norepinephrine, and epinephrine levels in 16 normotensive subjects in a double-blind, placebo-controlled crossover design. Mean peak phenylpropanolamine levels of 317 +/- 26, 152 +/- 17, and 157 +/- 17 ng/mL for 150-mg phenylpropanolamine, 75-mg phenylpropanolamine, and 75-mg phenylpropanolamine plus 400-mg caffeine, respectively, were reached at about 3.6 hours after dosing. The maximal increases in supine diastolic blood pressures after all three phenylpropanolamine-containing drugs were almost three times that after placebo (P less than .05), but peak blood pressures occurred at about 2.3 hours earlier than peak phenylpropanolamine levels. Blood pressure increases correlated with phenylpropanolamine plasma levels (r = .49 for systolic blood pressure and r = .34 for diastolic blood pressure; P less than .0001 for both). Norepinephrine levels increased after the administration of 150-mg phenylpropanolamine and 75-mg phenylpropanolamine plus 400-mg caffeine; norepinephrine increases correlated with phenylpropanolamine levels (r = .34, P less than .0001). The expected increment in norepinephrine induced by standing was significantly decreased by phenylpropanolamine in a dose-dependent mode. The study supports the idea that phenylpropanolamine as both a direct (at alpha -1 and alpha-2 receptors) and an indirect sympathomimetic agent.

Blood Pressure↗
PubMed1991

The gene expression of cytochrome P-450(11) beta during adrenal regeneration in the rat: studies using in situ hybridization.

Low levels of mRNA for the key adrenal steroidogenic enzyme, cytochrome P-450(11) beta, have been reported in the early stages of adrenal regeneration. To determine whether the defect in cytochrome P-450(11) beta gene expression is located in the adrenal zona fasciculata or glomerulosa, in situ hybridization techniques have been employed. Sections from 1 week regenerating adrenals were probed with sense and anti-sense cytochrome P-450(11) beta RNA. The signal was intense in the zona fasciculata cells in control adrenals but very low in those of adrenal regenerates. These data establish that the low levels of mRNA transcripts of cytochrome P-450(11) beta are localized to the zona fasciculata cells responsible for 11-deoxycorticosterone secretion in regenerating adrenals.

Adrenal Glands↗
PubMed1991

Expression of adrenal cytochromes P-450 in testosterone-induced hypertension.

Chronic treatment of rats with the naturally occurring androgen, testosterone, leads to hypertension and cardiovascular disease. This effect is believed to be mediated through the adrenal gland and in particular by action on the steroid 11 beta-hydroxylase enzyme system. To study the possible mechanism of this effect, the enzyme system was examined at several time periods up to the time that hypertension develops. Rats were treated with testosterone (10 mg/day) for 3, 7, 21, and 42 days. Levels of cytochrome P-450(11) beta enzyme and messenger RNA (mRNA) were determined as well as 11 beta-hydroxylase enzyme activity. A significant decrease in enzyme activity was observed after 3 days of treatment. This correlates with a profound decrease in the level of cytochrome P-450(11) beta enzyme as determined by Western blot analysis. A large decrease in cytochrome P-450(11) beta mRNA was also observed after 3 days of treatment. All three parameters remained low throughout the treatment period. The decrease in 11 beta-hydroxylase enzyme activity appears to result from a lower enzyme level brought about by decreased concentrations of mRNA transcripts.

Adrenal Glands↗
PubMed1990

Adverse drug effects attributed to phenylpropanolamine: a review of 142 case reports.

Phenylpropanolamine (PPA) is contained in about 106 products, over half of which are available over-the-counter (OTC). Most are cough/cold remedies; nine are OTC diet aids. More than nine million Americans were using OTC diet aids in 1981, making PPA the fifth most used drug in the United States, responsible for over $200 million in revenues. The safety of PPA remains controversial. Although most controlled studies indicate minimal pressor effects with recommended doses, adverse drug reactions (ADRs) continue to be documented. Since 1965, 142 ADRs have been reported in 85 studies, 69% of these in North America. Many such cases may go unrecognized. About two thirds of all ADRs occurred in females and in patients under 30. Of ADRs attributed to legitimately sold PPA products, 85% occurred after consumption of OTC products versus only 15% after prescription drugs. The PPA product often contained combination ingredients, or PPA was consumed along with additional drugs. An overdose of PPA was taken in about a third of the cases. After ingestion of non-overdose amounts, 82% of the ADRs were severe. The most frequent side effects involved symptoms compatible with acute hypertension, with severe headache the most common complaint. Twenty-four intracranial hemorrhages, eight seizures, and eight deaths (most due to stroke) were associated with PPA ingestion. We have summarized these data in an effort to alert clinicians to the prevalence of usage of PPA products and the potential for adverse effects. In patients who present with elevated blood pressure or signs of acute hypertension, especially hypertensive encephalopathy of undetermined origin, we recommend inquiry about recent ingestion of PPA-containing diet aids and cough/cold products and suggest having such patients remain upright rather than supine.

Drug Combinations↗
PubMed1990

Phenylpropanolamine increases plasma caffeine levels.

The effects of the widely consumed drugs caffeine and phenylpropanolamine are mediated through activation of the central and sympathetic nervous systems. Severe, life-threatening, and occasionally fatal hypertensive reactions have been reported after their combined use. This study examined the possible pharmacokinetic interaction of phenylpropanolamine and caffeine. Sixteen normal subjects received combinations of caffeine, phenylpropanolamine, and placebo. In subjects receiving 400 mg caffeine plus 75 mg phenylpropanolamine, the mean (+/- SEM) peak plasma caffeine concentration of 8.0 +/- 2.2 micrograms/ml was significantly greater than after 400 mg caffeine alone (2.1 +/- 0.3 micrograms/ml; t[24] = 2.4; p less than 0.01). Physical side effects were more frequent after the phenylpropanolamine-caffeine combination than after either drug alone or after placebo. Greater increases in both systolic and diastolic blood pressures occurred after the combination than after either drug alone. Because caffeine levels can be increased greatly when certain other drugs are coconsumed, these data indicate that phenylpropanolamine may enhance absorption or inhibit elimination of caffeine and may explain increased side effects reported after their combined use.

Adult↗
PubMed1989

Evidence for a menstrual-linked artifact in determining rates of depression.

This is the first empirical report suggesting a menstrual-linked artifact in determining rates of depression. We investigated the effects of perceived menstrual cycle phase, and premenstrual and postmenstrual timing in the cycle, on scores for a self-report measure of depression that is widely used in epidemiological studies, the Center for Epidemiologic Studies Depression Scale (CES-D). The first study used a cross-sectional design and the second used a follow-up design with repeated measures across the menstrual cycle. Both studies assessed a community-based sample of regularly menstruating women. In the second study, testing was also done at 2-week intervals in men for comparison purposes. Both studies supported the hypothesis of a significant menstrual cycle-related effect on CES-D scores. The menstrual-linked effect is greater than the test-retest variability observed in men, such that women more often tend to meet the cut-off criteria for depression on the CES-D premenstrually, as compared with postmenstrually. Thus it is possible that cyclic variations in ratings on the CES-D may elevate epidemiological estimates of depression, as defined by RDC criteria, for menstruating women. Further longitudinal assessment in randomly selected samples will be needed in order to clarify whether a menstrual-linked effect is substantial and specific enough to require correction, or documentation of cycle phase, in epidemiological studies of depression.

Adult↗
PubMed1989

Cytochromes P-45011 beta, P-450scc and adrenodoxin gene expression during adrenocortical regeneration in the rat.

Circulating levels of 11-deoxycorticosterone are increased during the development of adrenal-regeneration hypertension. The present studies were undertaken to examine the mechanisms involved in this increase. Plasmids containing cDNA inserts coding for cytochrome P-45011 beta, cytochrome P-450scc and adrenodoxin were used to determine, by Northern blot analysis, mRNA levels at 1, 2 and 3 weeks of adrenal regeneration. There was a striking decrease in mRNA transcripts for all three enzymes during the first week of regeneration when compared with intact adrenal tissue. Over the next 2 weeks the mRNA levels increased to 64% for P-45011 beta, to 80% for P-450scc and to 82% for adrenodoxin. Actin mRNA levels were 70% of control levels in the first week but were back to control levels by the second week. The present findings suggest that decreased expression of steroid 11 beta-hydroxylase could contribute to the increased secretion of 11-deoxycorticosterone during the early stages of adrenal regeneration.

Actins↗
PubMed1988

Regulation by chronic drug administration of neuronal and cardiac calcium channel, beta-adrenoceptor and muscarinic receptor levels.

Chronic administration of atropine (40-100 mg/kg, 23 days) produced a 29-33% increase in muscarinic receptors, measured by [3H]quinuclidinyl benzilate binding, in rat brain. Diisopropyl phosphorofluoridate (0.9 mg/kg, 14 days) produced a 35% decrease in muscarinic receptors. Propranolol administration (800 micrograms/kg/hr, 10 days) increased beta-adrenoceptors, measured by [3H]dihydroalprenolol binding, by 69 and 50% in brain and heart respectively. Isoproterenol administration (800 micrograms/kg/hr, 10 days) produced a 50% reduction in cardiac beta-adrenoceptors but did not alter brain receptors. These drug treatments were without effect on binding of the Ca2+ channel ligands, [3H]nimodipine and [3H]nitrendipine, to brain or heart respectively. However, chronic administration of nifedipine for 20 days (36 and 360 micrograms/kg/hr) did produce down-regulation of both cardiac and neuronal Ca2+ channels and a similar down-regulation of beta-adrenoceptors. Co-regulation of Ca2+ channels and neurotransmitter receptors may occur but may not be an automatic consequence of either receptor or channel regulation.

Animals↗
PubMed1988

Effect of thyroid status on beta-adrenoceptors and calcium channels in rat cardiac and vascular tissue.

To determine the influence of thyroid hormone on beta-adrenoceptors and Ca2+ channels, rats were treated with thyroxine (75 micrograms/100 g sc daily for 5 days) or propylthiouracil (0.05% in drinking water for 30 days). beta-Adrenoceptor density in ventricular tissue, measured by [125I]iodocyanopindolol binding, was significantly increased and decreased respectively, following thyroxine or propylthiouracil treatment to 124.7 +/- 7.11 fmol/mg protein and 71.98 +/- 5.37 fmol/mg protein from euthyroid (control) levels of 93.7 +/- 4.58 fmol/mg protein. Ca2+ channel density, measured by [3H]nitrendipine binding, was altered in the opposite direction; it was significantly decreased and increased to 324 +/- 24 fmol/mg protein and 691 +/- 31 fmol/mg protein from 562 +/- 35 fmol/mg protein after thyroxine or propylthiouracil treatment, respectively. No changes in affinity of either ligand were observed. Responses of isolated papillary muscles from propylthiouracil-treated animals accorded with changes seen in the binding studies. The geometric mean EC50 of isoproterenol increased from 9.5 x 10(-9) mol/l to 5.5 x 10(-8) mol/l, and the EC50 for calcium decreased from 3.16 x 10(-3) mol/l to 1.36 x 10(-3) mol/l; moreover, the responsiveness to the Ca2+ channel activator Bay K 8644 was increased. The corresponding responses in thyroxine-treated animals could not be examined because of prominent arrhythmic activity. As with papillary muscles the sensitivity of left atria to isoproterenol was decreased after treatment with propylthiouracil, with geometric mean EC50 values increasing from 3.21 x 10(-9) mol/l to 89.4 x 10(-9) mol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

Premenstrual symptom changes and plasma beta-endorphin/beta-lipotropin throughout the menstrual cycle.

The beta-endorphin (BE) hypothesis of premenstrual symptomatology was assessed in 15 healthy, drug-free normally cycling women. Cycle-phase assignment was aided by measurement of basal body temperature and plasma progesterone. For the entire group, peripheral plasma BE concentrations by radioimmunoassay (with substantial beta-lipotropin (BL) cross-reactivity) were generally unvarying across the menstrual cycle. High and low symptom subgroups were defined by retrospective and prospective daily self-reports of premenstrual changes. For the cycle studied, moderate to extreme symptom severity was defined according to premenstrual increases in impaired concentration, water retention and negative affect. No between-groups difference was observed for any cycle-phase for absolute values of beta-endorphin (BE/BL). When difference scores were examined, there was a positive time-lag correlation between follicular-to-periovulatory changes in BE/BL and the subsequent luteal increase in impaired concentration over the periovulatory baseline (rs = 0.82); considering the number of comparisons, however, the correlation fails to reach significance. The salience of various types of stressors on mood was assessed; there was a trend for "task-demands" to account for a greater percentage of negative attributions premenstrually compared to post-menstrually, for the entire group. The relative inconsistency in plasma BE/BL from cycle to cycle may be related in part, to the lack of stability in certain cycle characteristics from month to month. Future studies of BE/BL across the menstrual cycle may benefit from a demanding task in a provocative stress-paradigm.

Adult↗
PubMed1987

Resistance to mineralocorticoid-induced hypertensive vascular disease.

To support our contention that the Wistar-Furth rat is resistant to mineralocorticoid hypertension, we assessed the effects of deoxycorticosterone (DOC) administration or renal artery stenosis on the development of hypertension in the Sprague-Dawley and Wistar-Furth rat strains. Weekly administration of mineralocorticoid in the form of DOC pivalate resulted in rapid, severe hypertensive cardiovascular disease in Sprague-Dawley rats. Within 5 weeks the mean conscious systolic blood pressures in steroid-treated and control rats were 186 +/- 4 and 118 +/- 5 mm Hg, respectively. In contrast, blood pressures of Wistar-Furth rats were only moderately elevated, even after 10 weeks of DOC pivalate administration (136 +/- 2 vs 116 +/- 2 mm Hg for controls). Furthermore, none of the steroid-treated Wistar-Furth animals exhibited cardiovascular lesions. In parallel studies, littermates of these rat strains were subjected to renal artery stenosis and blood pressures were determined weekly in conscious rats. Silver clip constriction of the left renal artery, in the presence of the contralateral kidney, resulted in a rapid, sustained elevation of blood pressure in both Sprague-Dawley and Wistar-Furth rat strains (177 +/- 4 and 176 +/- 5 mm Hg, respectively). Corticosteroid levels were also determined in DOC-treated Sprague-Dawley and Wistar-Furth rats. The regimen employed resulted in a 10-fold increase in DOC levels as compared with controls, and the levels achieved were comparable in both strains. Thus, the Wistar-Furth rat appears to be selectively resistant to mineralocorticoid hypertensive vascular disease and thus affords a model for studying mechanisms of steroid hypertension.

Animals↗
PubMed1981

The phosphorylation of adrenal proteins in response to adrenocorticotropic hormone.

The phosphorylation of rat adrenal protein components in response to adrenocorticotropin has been studied in adrenal quarters, isolated cells, and in vivo. In adrenal quarters, adrenocorticotropic hormone (ACTH)-stimulated phosphorylation or dephosphorylation of proteins was not affected by the presence of protein synthesis inhibitors despite a total inhibition of steroidogenesis. (The term dephosphorylation refers to an apparent decrease in the labeling of a particular protein with 32P at various times after the addition of ACTH. This may be due to enzymatic removal of phosphate or protein degradation or complexation of this protein with another cellular component.) Studies with isolated cell preparations identified several proteins that are phosphorylated or dephosphorylated in response to hormone. These changes in phosphorylation were also observed in adrenal quarters and correlated well with ACTH-stimulated steroidogenesis as determined by temporal analysis and dose-response studies of corticosterone production. In vivo injection of male hypophysectomized rats with [32P]phosphate and ACTH demonstrated changes in the labeling of six adrenal proteins. Many of the proteins phosphorylated in vivo were also demonstrated to be phosphorylated in both in vitro systems. Finally, the injection of a physiological dose of ACTH appeared to selectively activate the type I cAMP-dependent protein kinase within the microsomal fraction as determined by the binding of a photoaffinity-labeled reagent. These results suggest that alterations in phosphorylation of adrenal proteins in response to ACTH is proximal to or independent of the obligatory role of protein synthesis in acute steroidogenesis.

Adrenal Glands↗
PubMed1980

On the mechanism of action of adrenocorticotropic hormone. The role of ACTH-stimulated phosphorylation and dephosphorylation of adrenal proteins.

The regulatory role of phosphorylation of adrenal proteins as it relates to the mechanism of action of adrenocorticotropic hormone (ACTH) has been studied. ACTH, cyclic AMP, or cyclic GMP were added to rat adrenal quarters which had been preincubated with [32P]phosphate. 32P-labeled proteins in subcellular fractions were identified after separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. The addition of ACTH consistently resulted in the phosphorylation and dephosphorylation of specific adrenal proteins and produced characteristic phosphorylation patterns (autoradiographs) for each subcellular fraction which were very different from control. The changes in phosphorylation of proteins preceded corticosterone production. Also, the degree of phosphorylation of these specific proteins followed a dose-response relationship with ACTH which correlated well to the dose-response for corticosterone production. When cAMP was added to adrenal quarters, the resulting phosphorylation changes were identical to those induced by ACTH. When cGMP was added to adrenal quarters, the resulting phosphorylation patterns were very similar to those produced by control incubations. ACTH or cAMP stimulated corticosterone production 6-fold when compared to control or cGMP-treated tissue. These results suggest that tropic action of ACTH is mediated by cAMP by both phosphorylation and dephosphorylation of specific adrenal proteins.

Adrenal Glands↗