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Biomedical subjects

P Eneroth

Publications and source records attributed to P Eneroth.

At least 163 records · Page 9Linked to original sources

Nutritional status and endocrine response to hemorrhage.

Hyperglycemia-inducing hyperosmolality has recently been proven beneficial in the maintenance of blood volume and extracellular fluid volume during early hemorrhagic hypotension. Fed animals benefitted from better plasma refill compared with starved ones when subjected to equal blood loss. Using lightly sedated fed and 24-30 h starved rats, hormones with relevance to glucose homeostasis were studied during 90 min of hemorrhagic hypotension of 70 mmHg (1 mmHg = 133.32 Pa). Marked differences in the overall hormonal developments were found between the two groups. In fed rats, insulin and glucagon responses were initially attenuated, while somatostatin increased to an early peak level at 30 min, returning to basal at 90 min. In starved rats, somatostatin increased gradually during the 90 min. Adrenaline release was massive in both groups. Corticosterone showed no increase from basal levels in the fed group during hemorrhage, while starved rats increased their basal level fourfold already at 30 min. These data are presented as evidence that changing nutritional status alters hormonal response to hypovolemic stress.

Animals↗

Quantitation of human cervical mucin during consecutive days and hourly during one day at midcycle.

Cervical mucin was quantitated in individual samples collected daily during midcycle in 14 normally menstruating women. Quantitation was performed with a recently developed lectin-mediated light scattering (nephelometry) method after separation of soluble proteins from the mucin. Furthermore, mucin was quantitated in individual samples in another group of 12 women from whom cervical secretion samples had been collected hourly from 8.00 to 12.00 a.m. There were significant differences between cycle days (p less than 0.05; two-way analysis of variance) for total amounts of mucin secreted and for mucin concentrations. But during repeated sample collection, only the total amounts of mucin secreted and not the concentrations were affected. From trend analysis data it could be concluded that both mucin contents and water contents increased at midcycle.

Adult↗

Serum levels of neopterin as related to the prognosis of human prostatic carcinoma.

In 93 patients suffering from prostatic cancer, serum levels of neopterin, a pteridine reflecting activation of the immune defence system, were measured at the time of diagnosis and 6 and 12 months after treatment with orchidectomy or estrogens. Neopterin levels were initially greater than 10 nM/l in 27% of the patients and in this group tumor recurrences occurred in 28% as compared to 7% in the group with neopterin less than 10 nM/l. No apparent correlation between tumor stage and grade and neopterin levels could be demonstrated. Neopterin levels decreased significantly after onset of treatment (p less than 0.001), which implicates a hormone dependence. But still patients with initially elevated serum neopterin levels, and thus an assumed activated immune defence system at the time of diagnosis, had lower survival rates than those without elevated neopterin levels (p less than 0.001). It is concluded that elevated levels of neopterin in serum is a sign of poor prognosis in human prostatic cancer.

Aged↗

Activation of sexual behaviour in castrated rats: the role of oestradiol.

Sexual behaviour was induced in castrated male rats with oestradiol-17 beta- or testosterone-filled constant-release implants. Testosterone-induced sexual behaviour was unaffected by treatment with the 5 alpha-reductase inhibitor 17 beta-N,N-diethylcarbamoyl-4-aza-5 alpha-androstan-3-one (4-MA; 16.7 mg/day) but treatment with the aromatization inhibitor 1,4,6-androstatriene-3,17-dione (ATD; 10 mg/day) prevented testosterone from inducing the behaviour. Sexual behaviour could be activated in castrated rats treated with testosterone plus ATD by treatment with 4-MA or with implants filled with a low dose of oestradiol. Lordosis behaviour induced in ovariectomized rats with testosterone-filled implants and progesterone was blocked by ATD treatment and could not be activated with 4-MA but oestradiol implants restored the display of lordosis in the testosterone plus ATD-treated females. 4-MA inhibited the in-vitro formation of [14C]5 alpha-dihydrotestosterone from [14C]testosterone by combined preoptic and hypothalamic tissue at all doses tested and a high dose of oestradiol exerted a similar effect. The results suggest that androgen aromatization is required for testosterone-activated female sexual behaviour but not for testosterone-activated male sexual behaviour. It is suggested that oestradiol normally acts to control the sexual behaviour of male rats by modifying neural androgen metabolism.

Androgens↗

Non-steroid hormones and tissue polypeptide antigen (TPA) in emetic and non-emetic pregnancy.

In order to investigate further the endocrine and metabolic features of the common condition emesis gravidarum, serum concentrations of some non-steroid hormones and tissue polypeptide antigen (TPA) were determined in 102 healthy pregnant women. 62 complained of nausea and vomiting in early pregnancy. Significantly higher and lower levels of human chorionic gonadotropin were noted in early and late pregnancy, respectively, in women with emesis gravidarum. A significant rise in serum prolactin and TPA was found throughout pregnancy in all subjects, no differences between emetic and non-emetic pregnancies being registered. Serum concentrations of growth hormone (hGH) showed a significant decline as pregnancy advanced. Emetic women demonstrated higher hGH levels in late pregnancy than did asymptomatic subjects. Free T4 concentrations remained stable when comparing early with late pregnancy, no dissimilarities being found between women with and without nausea and vomiting in pregnancy. These data do not support the hypothesis of major metabolic disturbances as an etiologic factor for nausea and vomiting in pregnancy. However, as overt differences between emetic and non-emetic pregnancy were found, hormonal factors may be involved in the pathogenesis of this condition.

Adult↗

Effects of infusion of the beta-adrenoceptor agonist terbutaline on serum magnesium in pregnant women.

Seventeen third trimester pregnant women received a 30-min intravenous infusion of terbutaline 20 micrograms/min. The drug caused a prompt (30 min) drop in serum potassium (p less than 0.001) and a decrease after 120 min in serum magnesium concentrations (p less than 0.002). No significant changes in calcium or sodium levels were observed. The altered serum magnesium concentrations were significantly (p less than 0.05) correlated to increases in plasma free fatty acid levels but not to elevated plasma glucose concentrations. Whatever the mechanism for the lowering of serum magnesium may be, the potential danger of administering a beta-adrenoceptor agonist to pregnant women with low serum potassium and magnesium levels is underlined.

Adult↗

Effects of TRH and a rat TSH preparation on discrete hypothalamic and forebrain catecholamine nerve terminal networks in the hypophysectomized male rat.

A rat pituitary TSH preparation in doses of 10 and 100 micrograms/kg produced rapid and marked increases in dopamine (DA) levels and alpha-methyltyrosine-induced decline consistent with increased DA synthesis and release in the medial and lateral palisade zones (MPZ, LPZ) of the median eminence, and reduced noradrenaline (NA) turnover in the paraventricular hypothalamic nucleus (PA) of the hypophysectomized male rat. The TSH serum levels measured in these rats 2 h after the injection were within the physiological range after the injection of 10 micrograms/kg. TRH given intravenously in a dose of 100 micrograms/kg produced rapid and marked increases of DA release in the MPZ and LPZ of the median eminence and reduction of NA turnover in the PA of the hypophysectomized male rat. The TRH injection did not alter the serum levels of prolactin, TSH, T3 and T4. The results indicate that TRH-TSH-DA interactions take place in the local circuits in the median eminence thus supporting the view that a short and an ultrashort feedback action of rTSH and TRH respectively may exist in the median eminence. The rapid action of the rat TSH preparation as well as of TRH further supports this concept. The rat TSH preparation and TRH produced marked reductions in NA turnover in the PA. These results support the possibility that rat TSH and TRH may, via an action on the hypothalamus, influence the facilitatory noradrenergic mechanism operating at the soma-dendritic level of the TRH immunoreactive neurons projecting to the median eminence. Thus, the existence of a neuronal feedback loop from the medio-basal hypothalamus into the paraventricular hypothalamic nucleus is postulated.

Animals↗

The effect of a prostaglandin synthetase inhibitor on the hormonal profile and the endometrium in women.

A prostaglandin synthetase inhibitor, naproxen, was given continuously throughout the menstrual cycle at a dose of 250 mg twice daily to 10 healthy fertile women (group 1) and at a dose of 1000 mg per day to eight women in the secretory phase (group 2). Blood samples were withdrawn three times a week during a control cycle and during the treatment cycle. Luteinizing hormone, follicle-stimulating hormone, prolactin, estradiol, and progesterone were analyzed. Endometrial biopsies were taken in the secretory phase of the control cycle and in the treatment cycle of group 1 and on the first day of menstruation of group 2. Naproxen treatment did not suppress ovulation in any cycle and did not affect the corpus luteum function either in group 1 or in group 2. In only one of the endometrial samples taken in the secretory phase (group 1) was the density of the lysosomes increased in the treatment cycle compared to the control cycle. The specimen taken during the early menstrual period (group 2) showed an increase in glandular epithelium and height following naproxen treatment. Furthermore, a significant increase in the number of plasmolemmal vesicles per square micrometer was observed in the capillary endothelial cells after the administration of 1000 mg of naproxen per day. This suggests that the transcellular exchange of water-soluble molecules in the endothelial cells was more active after the administration of a prostaglandin synthetase inhibitor than in the control group. In spite of the significant morphologic changes observed in the naproxen-treated material the onset of menstrual bleeding could not be prevented. The mechanism of the onset of menstruation needs to be further investigated.

Cyclooxygenase Inhibitors↗

Tissue polypeptide antigen (TPA) as a prognostic aid in human prostatic carcinoma.

Serum levels of tissue polypeptide antigen (TPA) and prostatic acid phosphatase (PAP) in serum, the presence or absence of skeletal metastases, tumor grade, patient age, and erythrocyte sedimentation rate (ESR) were determined in 50 patients with prostatic adenocarcinoma before onset of any therapy. Crude survival rates were estimated for a 5-year period after the time of diagnosis. The prognostic value was estimated by means of the log rank test and multivariate life table analysis. The TPA, PAP, tumor stage, and ESR all appeared to be useful as prognostic markers. Tumor grade and patient age were not significantly related to crude survival. The TPA proved to be the most reliable prognostic marker in single test estimates as well as in a multivariate life table analysis (p less than 0.01).

Acid Phosphatase↗

6-Oxygenation of 3-oxo-4-ene-steroids in high yields after 3-imine-formation.

3-Imine formation between primary amines and 3-oxo-4-ene-steroids, followed by hydrolysis of the imines (either spontaneously during work up or induced by acetic acid) has been shown to cause 6-oxygenation of the steroids tested (17 beta-hydroxy-4-androsten-3-one, 4-androstene-3,17-dione, 4-pregnene-3,20-dione and 4-cholesten-3-one). The main products are the 6 beta-hydroxy- and the 6-oxo-derivatives of the respective steroid. These derivatives were identified by chromatographic mobilities and by gas chromatography-mass spectrometry. The formation of 6 beta-hydroperoxy-derivatives is suggested and these derivatives were tentatively identified. The highest yields of 6-oxygenated products (30-50%) were found when cadaverine and spermine were reacted with the steroids. The addition of reduced glutathione during hydrolysis of the steroid 3-imines of cadaverine, hexylamine and ethanolamine as well as addition of ascorbic acid during the hydrolysis of the steroid 3-imines of cadaverine substantially reduced the 6-oxygenation. Steroid 3-imine formation and hydrolysis which yields 6-oxygenated derivatives has also been shown to occur during work up (evaporation) of organic solvent extracts of rat liver microsomes (105,000 g sediments) to which 17 beta-hydroxy-4-androsten-3-one, 4-androstene-3,17-dione, 4-pregnene-3,20-dione or 4-cholesten-3-one respectively had been added. It is concluded that there is a risk that these organic reactions are mistaken for enzymatic conversions during in vitro investigations of 3-oxo-4-ene-steroids.

Animals↗

Neonatal exposure to toluene: effects on the development of liver microsomal cytochrome P-450 and serum hormone levels in the rat.

Lactating Sprague-Dawley rats and their pups were exposed on postnatal days 1-7, 6 h/day, to 80, 500 and 1000 ppm toluene, respectively, by inhalation. Exposure to 80 ppm toluene decreased the liver microsomal AHH activity and the rate of 7 alpha- and 6 beta-hydroxylation of androstenedione in 8-day-old-pups. On the other hand, neonatal exposure to 500 or 1000 ppm toluene resulted in a significant increase in AHH and 7-ethoxyresorufin O-deethylase activities and in the formation of 16-oxygenated metabolites of androstenedione in 8-day-old animals. Exposure to toluene increased the cytochrome P-450 content at all 3 dose levels in male but not in female pups. Twenty-one days after neonatal exposure no such effects were seen in young animals of either sex. In 56-day-old male rats, however, neonatal exposure to 80 ppm toluene resulted in a decreased rate of 6 beta-hydroxylation of androstenedione and a reduced AHH activity. No such effects were seen in female rats of the same age. Neonatal exposure to toluene affected the body and liver weights in 8-day-old pups of both sexes but had no effect on these parameters in 21-day-old animals of either sex. Exposure to 80 ppm toluene during the neonatal period gave a significantly increased body weight of 56-day-old male but not of female rats of the same age although this treatment increased liver weight in both sexes at this age. Serum testosterone levels were decreased in 21-day-old male rats following neonatal exposure to 80 or 500 ppm toluene and in 56-day-old male rats exposed neonatally to 1000 ppm toluene. In conclusion, exposure to toluene during the first week of life caused significant changes in various liver microsomal cytochrome P-450 dependent enzyme activities in 8-day-old pups, whereas the long-term effects on liver metabolism of the adult animal were small.

Androstenedione↗

The effect of naproxen on the concentration of prostaglandins in human seminal fluid.

Whole ejaculates were examined for their content of prostaglandins (PGs) during medication with 250 mg naproxen three times daily for 2 weeks. Six volunteers delivered semen samples before, periodically during, and after the period of medication. During treatment with naproxen, the concentration of PGE, PGF, 19-hydroxy-PGE, and 19-hydroxy-PGF significantly decreased. One week after cessation of medication the PG concentration had returned almost to that found before treatment. The four 19-hydroxy-PGF compounds could be determined separately and the relation between them estimated. The proportion of 8 alpha-19-hydroxy-PGF2 alpha increased, whereas that of 8 beta-19-hydroxy-PGF1 alpha decreased significantly during the medication period. No significant influence of the treatment on sperm density or motility could be observed. It is concluded that treatment with naproxen, a potent inhibitor of PG synthesis, significantly reduces the concentration of all PGs present in human seminal fluid. The implication of the effect on human fertility is discussed.

Alprostadil↗

Leukotriene C4 as a mediator of luteinizing hormone release from rat anterior pituitary cells.

This study demonstrates that leukotriene C4, at concentrations in the picomolar range, released luteinizing hormone (LH) but not growth hormone (GH) from dispersed rat anterior pituitary cells. Leukotriene B4, another lipoxygenase pathway product of arachidonic acid, had no effect on LH or GH release. The stimulatory effect of leukotriene C4 could be seen after 0.5 but not after 3 hr of incubation. This was in contrast to the dose-dependent LH-releasing hormone (LHRH)-induced LH release that was not measurable after 0.5 hr but was fully established after incubation for 3 hr. Furthermore, the LH-releasing ability of leukotriene C4 was blocked in the presence of high doses of LHRH. The immunohistochemical analysis revealed leukotriene C4-immunoreactive fibers at all levels of the median eminence, mainly in the lateral parts. These fibers exhibited a marked overlap distribution with LHRH-immunoreactive fibers and elution-restaining experiments revealed identity of at least a large proportion of the leukotriene C4- and LHRH-immunoreactive fibers. Furthermore, cell bodies in the preoptic area contained both leukotriene C4- and LHRH-like immunoreactivities, suggesting localization of these two compounds in the same neurons.

Animals↗

Regression analysis of catecholamine utilization in discrete hypothalamic and forebrain regions of the male rat: effects of thyroidectomy.

The effects of thyroidectomy (4 weeks) on dopamine (DA) and noradrenaline (NA) turnover rates were determined by means of regression analysis. The disappearance of catecholamine (CA) fluorescence (using quantitative histofluorimetry) after tyrosine hydroxylase inhibition (alpha-methyl-DL-p-tyrosine methyl ester) has been investigated in discrete hypothalamic and forebrain DA and NA nerve terminal systems of the male rat. A time-dependent monophasic CA fluorescence disappearance was observed in all CA nerve terminal systems of the sham-operated and thyroidectomized rats. In the thyroidectomized rat, DA turnover in the anterior nucleus accumbens and in the medial and lateral palisade zones of the median eminence (ME) was reduced while DA turnover in the posterior nucleus accumbens was increased as compared to control rats. Furthermore, NA turnover was increased in the paraventricular hypothalamic nucleus (PA) and reduced in the dorsomedial hypothalamic nucleus (DM) and in the 'border zone' (lateral hypothalamus). Radioimmunoassay of hormones in serum demonstrated marked increases in TSH levels and reduced concentrations of GH, prolactin, corticosterone, triiodothyronine and thyroxine. The reduced DA turnover in the external layer of the ME and the increased NA turnover in the PA may indicate an inhibitory dopaminergic mechanism in the ME and a facilitatory noradrenergic mechanism in the PA in the regulation of TSH secretion. These mechanisms seem to interact with thyroid hormones. The reduced NA turnover demonstrated in the DM and in the border zone may be related to the lowering of growth hormone levels and pulsatility caused by thyroidectomy. Finally, the DA nerve terminal systems in the anterior and posterior parts of the nucleus accumbens are differently regulated by changes in the brain-pituitary-thyroid axis.

Animals↗

Effects of acute intermittent exposure to cigarette smoke on catecholamine levels and turnover in various types of hypothalamic DA and NA nerve terminal systems as well as on the secretion of adenohypophyseal hormones and corticosterone.

Male rats were exposed to cigarette smoke (Walton Horizontal Smoking Machine) from one to four cigarettes (Kentucky reference IR-1 type). Catecholamines in the diencephalon were measured by quantitative histofluorimetry in discrete dopamine (DA) and noradrenaline (NA) nerve terminal systems. Blood TSH, prolactin, LH, FSH, ACTH, vasopressin and corticosterone levels were determined by radioimmunoassay procedures. Exposure to unfiltered, but not to filtered (Cambridge glass fibre filters) cigarette smoke resulted in dose-dependent reductions of NA levels in the various hypothalamic NA nerve terminal systems. Evidence was obtained that exposure to unfiltered but not to filtered cigarette smoke resulted in dose-dependent increases of amine turnover (alpha MT-induced CA disappearance experiments) in the various DA and NA nerve terminal systems in the hypothalamus. The lowering of TSH, LH and prolactin secretion induced by unfiltered smoke were probably induced by nicotine and were independent of tyrosine hydroxylase inhibition. Furthermore, unfiltered cigarette smoke produced a dose-related increase in corticosterone secretion. The inhibitory effects of TSH, LH and prolactin secretion were probably in part related to the ability of unfiltered smoke via its nicotine component to activate the lateral and medial tubero-infundibular DA neurons. The increases in corticosterone secretion may at least in part be related to a smoke induced increase in the facilitatory influence of paraventricular NA nerve terminals on CRF activity.

Adrenocorticotropic Hormone↗

Acute continuous exposure to cigarette smoke produces discrete changes in cholecystokinin and substance P levels in the hypothalamus and preoptic area of the male rat.

By means of a Walton Horizontal Smoking Machine, male rats were exposed to the smoke from I-4 cigarettes burned in a continuous fashion. Cholecystokinin (CCK) and substance P levels (determined by means of radio-immunoassay) were measured in discrete hypothalamic and preoptic regions. Acute continuous exposure to cigarette smoke induced increases in CCK levels in the paraventricular hypothalamic region as well as decreases in CCK levels in the median eminence. Furthermore, this treatment resulted in decreased CCK and substance P levels in the medial preoptic region. The results have been interpreted to indicate that CCK and substance P containing neuronal systems can be regulated by cholinergic nicotine-like receptors.

Animals↗