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Biomedical subjects

P Eneroth

Publications and source records attributed to P Eneroth.

At least 109 records · Page 6Linked to original sources

Evaluation of seven different tumour markers for the establishment of tumour marker panels in gynecologic malignancies.

Seven tumour markers, i.e. squamous cell carcinoma antigen (SCC), cancer antigen 125 (CA 125), tissue polypeptide antigen (TPA), neopterin, C-reactive protein (CRP), carcinoembryonic antigen (CEA) and deoxythymidine kinase (TK) were analysed in sera from 104 women with benign and 61 women with malignant gynecologic diseases, in order to create tumour marker panels for various gynecologic malignancies, for monitoring and prediction of disease development. The incidence of elevated tumour marker levels, in cervical carcinoma was 78% when SCC, CA 125 and CEA were used. In ovarian carcinoma one of the markers CA 125, TPA and CEA was elevated in 91% and for endometrial carcinoma the best combination of markers was SCC, CA 125 and CEA (57%). No individual marker was superior to the above combinations. However, in patients with a fatal outcome of their malignant gynecologic disease (mean survival time from serum sampling was 16 months), the incidence of death was highest among those who had TPA elevated (91%) followed by neopterin (86%) and CRP (76%). Although intercurrent diseases affected tumour marker levels the markers picked up a majority of patients with a poor prognosis. This demonstrates the importance of interpreting tumour marker results against a background of detailed clinical information.

Adult↗

Longterm neuroendocrine and metabolic effects of physical training in intermittent claudication.

Twenty-five elderly patients with peripheral vascular disease and intermittent claudication were prospectively followed during a six-month session of physical training. Neuroendocrine and metabolic patterns as well as effects on walking performance were assessed during the training period. At the initial evaluation there was an inverse association between walking distance and serum cortisol and blood glucose levels. The walking distance increased during the training period. A positive effect on glucose homeostatis was seen with decreased basal fructosamine levels after training. During physical exercise a decrease in insulin and an increase in growth hormone was seen. Changes in growth hormone were, in contrast to insulin, more related to the pain level perceived than to the work load imposed. Apart from the marked effects on physical performance the results of the study suggest an improvement of hormonal and metabolic balance after physical training. This regularly applied exercise program improved the health status of rather old people.

Aged↗

Effects of chronic toluene exposure on central monoamine and peptide receptors and their interactions in the adult male rat.

The effects of chronic toluene exposure (CTE) (80 ppm, 6 h/day, 5 days/week, 3 months) were studied on neuropeptide and 5-hydroxytryptamine receptors, on protein phosphorylation levels and on catecholamine levels in various brain regions in the 15-month-old male rat. Behavioral parameters and serum levels of hypophyseal hormones and corticosterone were also analyzed. CTE selectively reduced [3H]neurotensin [( 3H]NT) binding in the basal layers of the orbital cortex. Instead, CTE increased the binding of [3H]etorphine in the nucleus accumbens and of [125I]vasoactive intestinal polypeptide [( 125I]VIP) in the area postrema and hypoglossal nucleus. Acute treatment with the irreversible monoamine receptor antagonist N-ethoxycarboxyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) increased the binding of [3H]NT in the orbital cortex in toluene exposed rats as compared with the reduced [3H]NT binding obtained in air exposed rats treated with EEDQ. Furthermore, the EEDQ induced increase in [125I]VIP binding in the area postrema and the hypoglossal nucleus was replaced by a reduced binding of [125I]VIP in EEDQ-treated CTE rats. CTE produced an overall increase in calcium-induced back phosphorylation and an overall decrease in cyclic adenosine monophosphate-induced back phosphorylation in the frontoparietal cortex. Noradrenaline stores tended to be reduced within various hypothalamic subnuclei and the serum prolactin levels were increased following CTE. However, no marked effects of CTE were seen on the behavioral parameters. In conclusion, the regional selectivity of CTE in disturbing [3H]NT and [125I]VIP binding may be due to the demonstrated vulnerability of monoamine-neuropeptide interactions to toluene.

Animals↗

Studies on the interaction between human serum protein fractions and 18O-labeled oxosteroids.

The nature of the interaction between progesterone or testosterone and human albumin as well as the interaction between progesterone and partially purified human transcortin has been studied. Modification of lysine residues of albumin with maleic anhydride resulted in a decreased binding of the steroid as judged from equilibrium dialysis experiments. This suggested that lysine residues in albumin interact with the oxosteroids. In order to check this hypothesis, steroids labeled with 18O in their oxo function (testosterone and progesterone) were synthesized for use as probes of the interactions. However, no loss of label was noted when testosterone or progesterone specifically 18O-labeled in their oxo functions were incubated with albumin. This suggested that no covalent interaction between the steroidal oxo group and albumin took place. This was in contrast to the results obtained with 3,20-18O-labeled progesterone and partially purified transcortin, where a complete loss of 18O label in the protein-bound steroid was found. The nonbound steroid showed an almost complete retention of label. These results indicate a participation of steroid oxo groups in the binding of progesterone to transcortin. Of the possible mechanisms discussed, imine bonds between the steroid and transcortin seem most likely although other types of interactions cannot be ruled out.

Blood Proteins↗

Effects of acute intermittent exposure to cigarette smoke on hypothalamic and preoptic catecholamine nerve terminal systems and on neuroendocrine function in the diestrous rat.

Diestrous female rats were exposed to the smoke from one to four cigarettes. Exposure to unfiltered cigarette smoke produced dose- and time-dependent reductions of catecholamine levels and dose- and time-dependent increase in catecholamine utilization in the various hypothalamic and preoptic dopamine and noradrenaline nerve terminal systems. These effects were counteracted by pretreatment with the ganglion blocking agent mecamylamine (1 mg/kg). Exposure to cigarette smoke was also found to produce a dose- and time-dependent inhibition of serum prolactin, LH and FSH levels which was counteracted by pretreatment with mecamylamine. Exposure to the smoke from one cigarette (but not from four cigarettes) increased serum TSH levels. In combination with tyrosine hydroxylase inhibition the exposure to cigarette smoke produced a dose- and time-dependent inhibition of plasma ACTH levels, an action which was counteracted by pretreatment with mecamylamine. The results demonstrated a sex difference (cf. Anderson et al. 1985c), in the nicotine-induced changes of TSH and ACTH secretion despite a general increase in hypothalamic and preoptic dopamine and noradrenaline utilization in both the male and the diestrous female rat. The differences in the neuroendocrine actions of acute intermittent exposure to cigarette smoke in the diestrous rat and the normal male rat are discussed.

Animals↗

Effects of chronic imipramine treatment on glucocorticoid receptor immunoreactivity in various regions of the rat brain. Evidence for selective increases of glucocorticoid receptor immunoreactivity in the locus coeruleus and in 5-hydroxytryptamine nerve cell groups of the rostral ventromedial medulla.

Glucocorticoid receptor (GR) immunoreactivity (IR) was analyzed semi-automatically in the forebrain and in the lower brain stem of male rats treated for two weeks with imipramine (10 mumol/kg). Serum corticosterone and aldosterone levels were determined by means of radioimmunoassay procedures. The microdensitometric analysis demonstrated a selective increase in the GR IR in the nerve cell nuclei of the locus coeruleus (A6), of the ventral part of the reticular gigantocellular nucleus (B3L) and of the nucleus raphae magnus (B 3 M), whereas a small reduction of GR IR was found in the nucleus raphe obscurus (B2). In the morphometric analysis significant increases in the mean profile area of nuclear GR IR, which may be secondary to the increase in GR IR, were observed in the B 3 M. The serum corticosterone and aldosterone levels were not found to be significantly altered. The selective changes of GR IR may reflect the presence of an altered number of GR in these nerve cell groups and/or an altered translocation of GR to the nuclei. It is of substantial interest that these changes were observed in the presence of unchanged serum levels of corticosterone and aldosterone. It seems possible that adaptive changes in monoamine synapses induced by the chronic imipramine treatment may be responsible for the changes in GR IR found in the noradrenaline (NA) and 5-hydroxytryptamine (5-HT) cell bodies, respectively. The present results open up the possibility that chronic imipramine treatment may help to maintain the glucocorticoid receptor function in the locus coeruleus and in the 5-HT cell groups of the rostral ventromedial medulla of depressed patients.

Aldosterone↗

Effect of prostaglandins on human sperm function in vitro and seminal adenosine triphosphate content.

The aim of the present study was to evaluate the effect of addition of physiologic amounts of different prostaglandins normally present in semen, on sperm motility, on sperm penetration capacity in cervical mucus in vitro, and on the adenosine triphosphate (ATP) concentration in semen. Semen samples were obtained from volunteers who were attending the fertility outpatient clinic. Sperm motility was measured on a video recorder with a built-in timer, sperm penetration by the Kremer test, and ATP by bioluminescence assay. The addition of 19-hydroxy prostaglandin (PG) E to ejaculates positively stimulated sperm motility and sperm penetration capacity. The opposite effect was observed with 19-hydroxy PGF. PGE1, PGE2, and PGF2 alpha had no effect on either parameter, while PGF1 alpha reduced the sperm motility. The addition of 19-hydroxy PGE to ejaculates increased and the addition of 19-hydroxy PGF reduced semen concentrations of ATP. However, only the last-mentioned effect was statistically significant (P less than 0.05). It is suggested that, in particular, 19-hydroxy PGE and 19-hydroxy PGF are important regulators of sperm motility and that the effect may be mediated via effects on the ATP content in the spermatozoa.

Adenosine Triphosphate↗

The effects of oral administration of prostaglandin E2 on the human ejaculate.

A single 1 mg dose of prostaglandin (PG) E2 was given orally to 19 men. Ejaculates were obtained 90 minutes and 24 and 48 hours thereafter. Before treatment, each man delivered another three semen samples with the same time intervals as during the study period. PGE2 was also administered to seven men during naproxen treatment and ejaculates were sampled as above. PGE2 did not influence the 90 minutes' posttreatment ejaculates, but after 24 hours there was a significant (P less than 0.05) decrease in sperm counts as compared to the control samples. The change in sperm count was suggested to be due to an effect of PG on the contractile elements in the deferent duct. Sperm motility, viability, and morphology as well as semen volume and adenosine triphosphate (ATP) content remained unchanged. The total semen PGE content was increased 24 hours after treatment from 169 micrograms/ejaculate to 213 micrograms/ejaculate (P = 0.02). In the combined PGE2/naproxen treatment the PGE levels were significantly (P less than 0.05) elevated in the ejaculate 48 hours after treatment. The increase may indicate an increased de novo synthesis of prostaglandins. Based on the results from the analysis of the composition of the 19-hydroxy PGF-isomers with and without naproxen treatment, it is speculated that oral PGE2 influences the cyclo-oxygenase activity.

Administration, Oral↗

Plasma and pituitary gonadotropins and prolactin after hysterectomy and treatment with uterine extracts in female rats. A kinetic study.

The kinetic of changes in plasma concentrations and pituitary contents of FSH, LH, prolactin after hysterectomy and treatment with steroid-free uterine extracts were studied in adult, non-pregnant female rats. The post-castration rise of plasma and pituitary FSH and plasma LH was inhibited but the plasma prolactin was elevated by hysterectomy. Steroid-free uterine extracts from previously castrated animals increased the plasma FSH, LH and prolactin concentrations in hysterectomized females 48 hours after administration. Uterine extracts from intact and oestradiol-substituted-castrated animals decreased the pituitary prolactin content 48 h after single i.p. injection. Pituitary FSH and LH contents were not affected by single dose of uterine extracts at any time which were examined. It is concluded that the uterus may play some role in the synthesis and release of pituitary gonadotropins and prolactin.

Animals↗

Aspects on reference values for tumor markers in human prostatic carcinoma.

The efficiency of the tumor markers prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), neopterin, and osteocalcin was tested with regard to their ability to predict cancer death within 2 years plus survival beyond 2 years in a series of patients with newly diagnosed prostate cancer. For all markers, an elevated level suggested a tumor with a worse prognosis. Moreover, the extent to which the level was increased carried additional information. The prognostic efficiency was routinely improved by selecting cutoff levels higher than the standards suggested by the radioimmunoassay (RIA) kit manufacturers. Seventy-four percent of the patients with elevated levels of neopterin were still alive after 2 years when 8 nmol/L was selected as the upper normal value compared to only 43% at 12 nmol/L. At a cut-off value of 3 micrograms/L for osteocalcin, 79% of the patients with elevated levels were still alive after 2 years compared with only 20% when 7 micrograms/L was selected. Such adjustments to higher cutoff levels could be made without increasing the number of "false-negatives." The efficiency of PAP to predict short-term prognosis was poor at the standard cutoff level of 1.9 microgram/L. Not until 20 micrograms/L was selected did the efficiency exceed 80%. PSA was highly sensitive but little specific at any of the cutoff levels tested with regard to ability to indicate prognosis.

1-Carboxyglutamic Acid↗

Effects of acute haloperidol treatment on regional catecholamine levels and utilization in rats exposed to toluene.

The aim of the present investigation was to evaluate whether the responses of central catecholamine (CA) neurons to CA receptor blockade by haloperidol are altered upon toluene exposure. Male rats were exposed to air or toluene (80 ppm) for 5 and 4 days, 6 h day-1. CA levels and utilization were determined in discrete regions of the forebrain and hypothalamus as well as in the substantia nigra (SN) and anteromedial frontal cortex (AMFC). Serum levels of corticosterone, thyroid stimulating hormone, luteinizing hormone and prolactin were determined by radioimmunoassay procedures. Toluene exposure led to increased dopamine (DA) utilization in the AMFC and increased CA utilization in the paraventricular hypothalamic nuclei. In air-exposed rats haloperidol (1 mg kg-1, i.p., 2 h before killing) increased DA utilization in the marginal part of the nucleus caudatus putamen (CAUD). In toluene-exposed rats, haloperidol induced significant depletions of DA stores in the SN and in the medial and central parts of the CAUD. In the posterior nucleus accumbens (ACC) DA utilization was significantly increased. Combined haloperidol and toluene treatment selectively decreased DA levels in the ACC and SN, and significantly increased DA utilization in the CAUD, as compared with the air-exposed control group. Furthermore, after combined treatment, there was a specific increase in noradrenaline (NA) utilization in the SN and in CA utilization in the medial palisade zone of the median eminence. Serum prolactin levels were substantially raised in both the air and toluene groups after the haloperidol treatment. In conclusion, acute haloperidol treatment preferentially reduces DA levels and increases DA and NA utilization in the SN and in discrete tel- and diencephalic areas in rats exposed to toluene.

Animals↗

Secretory IgA against herpes simplex virus in cervical secretions.

A recently developed method to recover proteins from cervical secretions was combined with methods to detect minute concentrations of herpes simplex virus (HSV) type specific antibodies to measure the concentrations of locally produced antibodies in women with genital infections. Forty nine women attending a sexually transmitted disease (STD) clinic were included. Cervical secretions were obtained by suction into a plastic catheter. Soluble proteins were recovered from the secretions by elution with hyperosmolar sodium chloride. A rabbit antibody to human secretory component, which was conjugated to horseradish peroxidase, was used to measure secretory IgA (S-IgA) that was HSV type specific. For comparison, HSV type specific IgG was measured in serum samples from the patients. Of the 49 women, 16 yielded detectable HSV type 2 (HSV 2) S-IgA in secretions. Twelve of them also reacted to the HSV type common antigen, but only five had HSV 2 IgG detectable in their serum. S-IgA against HSV was found in significantly more women with a clinical diagnosis of acute cervicitis than in others. This could be explained by a general increase in local antibody production and immunity triggered by previous contacts with HSV. It is concluded that local mucosal immunity to HSV 2 can be detected in women who do not have a specific humoral antibody response to the virus. For seroepidemiological studies of infection with HSV 2 this local immunity may be considered to be a factor that gives an underestimation of the true incidence of HSV 2 infection.

Acute Disease↗

Involvement of D1 dopamine receptors in the nicotine-induced neuro-endocrine effects and depletion of diencephalic catecholamine stores in the male rat.

Male rats were treated acutely with nicotine (4 x 2 mg/kg, 30-min time intervals, total treatment time 2 h) or exposed to cigarette smoke from 4 x 1 cigarette (30-min time intervals, total treatment time 2 h). Some rats were pretreated with the D1 dopamine (DA) receptor antagonist SCH 23390 (0.1-3.0 mg/kg, i.p.), or with the D2 DA receptor antagonists remoxipride and raclopride (1 mg/kg, i.p.), or with the 5-hydroxytryptamine 2 (5-HT2) receptor antagonist ketanserin (0.3 mg/kg, i.p.) 5 min before nicotine treatment or the acute intermittent exposure to cigarette smoke. Some rats were treated with the D1 DA receptor agonist SK&F 38393 (1-10 mg/kg, i.p.) 15 min, 30 min or 2 h before decapitation. Hypothalamic and pre-optic catecholamine (CA) levels were measured by quantitative histofluorimetry in discrete DA and noradrenaline (NA) nerve terminal systems. Serum thyroid-stimulating hormone (TSH), prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), vasopressin, corticosterone and testosterone levels were determined by radioimmunoassay procedures. Nicotine treatment and to a minor degree also acute intermittent exposure to cigarette smoke produced a reduction in serum prolactin, LH and TSH but not in serum FSH, vasopressin and testosterone levels. Nicotine treatment also increased serum corticosterone levels. Pretreatment with the D1 DA receptor antagonist SCH 23390 (1-3 mg/kg) counteracted the lowering of serum LH, but not of prolactin and TSH levels induced by nicotine or exposure to cigarette smoke. SCH 23390 alone (1-3 mg/kg) increased serum TSH levels. Remoxipride, raclopride or ketanserin did not counteract any of the neuro-endocrine actions induced by nicotine treatment. However, ketanserin alone lowered serum prolactin levels. SK&F 38393 increased serum TSH, prolactin and LH levels. It was found that nicotine treatment and exposure to cigarette smoke with few exceptions produced a depletion of CA stores in NA and DA nerve terminals of the hypothalamus, pre-optic area and median eminence which was counteracted by SCH 23390 (1 mg/kg) but not by remoxipride, raclopride (1 mg/kg) or ketanserin (0.3 mg/kg). The results indicate that D1 but not D2 DA or 5-HT2 receptors may modulate the NA and DA release in the median eminence, the hypothalamus and the pre-optic area induced by nicotinic cholinoceptor activation. Furthermore, D1 DA receptors in the median eminence may at least in part mediate the inhibitory effects of nicotine on LH but not on TSH and prolactin secretion, although there appears to exist a D1 DA receptor in the median eminence which inhibits TSH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Outcome of pregnancy in relation to maternal serum alpha-fetoprotein levels in the second trimester. An evaluation of a screening program and a longitudinal follow-up.

120 women with elevated alpha-fetoprotein (AFP) in pregnancy week 16-17 were subsequently supervised every 4th week until a few days postpartum. A group of 102 women with normal (n = 78) or low (n = 24) serum AFP concentrations in pregnancy week 16-17 were studied in the same way. In the last week before parturition the AFP serum level declined and the decrease was more pronounced with increasing gestational duration up to pregnancy week 41. The AFP level relationship between the women was stable on average throughout the pregnancies. Smoking was found to be related to elevated maternal serum AFP levels in pregnancy week 16-17. Among mothers younger than 25 years, 72% of those with high or very high AFP serum levels in pregnancy week 16-17 were smokers. Among women with elevated or much elevated maternal serum AFP levels in pregnancy week 16-17, male fetuses predominated. But only those carrying female fetuses gave premature birth to small-for-date children. Further analysis of the data revealed that if such a woman was a multipara, there was a 54% risk of a small-for-date premature female baby. Other data indicate that this risk may be increased by smoking and maternal age. It is recommended that this category of mothers with elevated AFP in pregnancy week 16-17 is continuously supervised during pregnancy.

Adult↗

Oestradiol synergizes with 5 alpha-dihydrotestosterone or 3 alpha- but not 3 beta-androstanediol in inducing sexual behaviour in castrated rats.

Castrated male rats were treated with constant-release implants filled with testosterone, oestradiol-17 beta, 17 beta-hydroxy-5 alpha-androstan-3-one (5 alpha-dihydrotestosterone; DHT), 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-Adiol) or 5 alpha-androstane-3 beta,17 beta-diol (3 beta-Adiol). Only testosterone activated the sexual behaviour of the rats. If combined with oestradiol, DHT or 3 alpha-Adiol induced the behaviour, but 3 beta-Adiol failed to have this effect. Oestradiol inhibited the in-vitro formation of [14C]Adiols from [14C]DHT by combined preoptic and hypothalamic tissue, but only when given in high doses. No effect on the formation of [14C]Adiols from [14C]DHT was found in rats treated in vivo with DHT or with the combination of DHT and oestradiol which effectively stimulated sexual behaviour. These results do not support the suggestion that oestradiol may synergize with androgens to induce sexual behaviour in castrated rats by inhibiting androgen metabolism.

Androstane-3,17-diol↗

Changes in job strain in relation to changes in physiological state. A longitudinal study.

A sample of 73 men and women aged 22-63 years and working in six different occupations (air traffic controllers, waiters, physicians, symphony orchestra musicians, baggage handlers, and airplane mechanics) participated in a longitudinal study four times during a year. The spontaneous variations in job strain (determined as the self-reported ratio between psychological demands and decision latitude) were substantial. The average difference between the occasion with the highest level of strain and the occasion with the lowest level was 25% of the total mean. Systolic blood pressure during workhours, as well as self-reported sleep disturbance, increased when demands increased in relation to decision latitude. Among men with a depressive tendency (according to a diary) morning plasma prolactin levels increased markedly with increasing job strain. Among subjects with a positive family history of hypertension the increase in systolic blood pressure at work was particularly pronounced, and among the men in this group a lower than expected level of morning cortisol was found measured during the period with the highest level of strain.

Adult↗