Basal Blood Levels Research Articles

Behavioral responses to ethanol in rats perinatally exposed to low lead levels.

Wistar rats were exposed to 220 ppm of lead (Pb) in the drinking water from conception to the end of the nursing period (postnatal day 25). Maternal blood Pb levels at this time were 25 microg/dl. Male offspring were tested at the age of 35 or 70 days. We studied the anxiolytic response to 0.5-2.0 g/kg ethanol in an elevated plus maze test and preference for increasing ethanol solutions (2%, 4%, and 6%, v/v) in a free-choice paradigm; we also determined basal blood levels of corticosterone. Results demonstrated that, at 35 days of age, experimental rats were hypersensitive to the anxiolytic effect of ethanol and showed greater voluntary intake of this drug. In addition, 35-day-old Pb-treated rats exhibited higher basal levels of corticosterone as compared with those of controls. These differences disappeared at 70 days. Our findings are discussed in terms of either Pb-induced alterations in the development of the CNS or higher levels of corticosterone in experimental animals. Possible Pb-ethanol effects interactions are also considered.

Selective serotonin reuptake inhibitors and neuroendocrine function

Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are effective drugs for the treatment of several neuropsychiatric disorders associated with reduced serotonergic function. Serotonergic neurons play an important role in the regulation of neuroendocrine function. This review will discuss the acute and chronic effects of SSRIs on neuroendocrine function. Acute administration of SSRIs increases the secretion of several hormones, but chronic treatment with SSRIs does not alter basal blood levels of hormones. However, adaptive changes are induced by long-term treatment with SSRIs in serotonergic, noradrenergic and peptidergic neural function. These adaptive changes, particularly in the function of specific post-synaptic receptor systems, can be examined from altered adrenocorticotrophic hormone (ACTH), cortisol, oxytocin, vasopressin, prolactin, growth hormone (GH) and renin responses to challenges with specific agonists. Neuroendocrine challenge tests both in experimental animals and in humans indicate that chronic SSRIs produce an increase in serotonergic terminal function, accompanied by desensitization of post-synaptic 5-HT 1A receptor-mediated ACTH, cortisol, GH and oxytocin responses, and by supersensitivity of post-synaptic 5-HT 2A (and/or 5-HT 2C) receptor-mediated secretion of hormones. Chronic exposure to SSRIs does not alter the neuroendocrine stress-response and produces inconsistent changes in α 2 adrenoceptor-mediated GH secretion. Overall, the effects of SSRIs on neuroendocrine function are dependent on adaptive changes in specific neurotransmitter systems that regulate the secretion of specific hormones.

Increase in Resting Levels of Superoxide Anion in the Whole Blood of Uremic Patients on Chronic Hemodialysis

Recently, we developed a new method to measure the resting level of superoxide anion in whole blood using an ultrasensitive chemiluminescence analyzer and lucigenin amplification. The advantage of this method is that the assay system can be performed in the absence of leukocyte isolation and stimulant administration. In this study, we applied this method to measure the blood resting levels of superoxide anion in 104 uremic patients on chronic hemodialysis (CHD) and 98 sex- and age-matched healthy controls to clarify the influence of HD on blood levels of superoxide anion. Simultaneously, the plasma levels of copper, zinc superoxide dismutase (Cu,Zn-SOD), glutathion peroxidase (GPX), myeloperoxidase (MPO) and lactoferrin (Lacto-F) were measured. The results showed that the basal blood levels of superoxide anion, Cu,Zn-SOD, and MPO in CHD patients were significantly greater than those of healthy controls. However, there was no difference in the basal plasma levels of Lacto-F and GPX between CHD patients and healthy controls. One session of HD further increased the blood levels of superoxide anion, MPO, Lacto-F and Cu,Zn-SOD but not GPX. These results suggest that the blood levels of superoxide anion are higher in CHD patients and further increase after one session of HD. This mechanism should be studied further.

Magnesium supplementation in patients with congestive heart failure.

To evaluate several potential clinical indicators of magnesium status (diet, blood, urine, 24-hour load retention) in patients with congestive heart failure before, during, and after oral magnesium supplementation.Twelve patients with New York Heart Association class II-III heart failure and 12 age and sex matched healthy control subjects were supplemented with 10.4 mmol oral magnesium lactate for 3 months. For the determination of magnesium status, samples of whole blood, serum, plasma, red blood cells, and urine (24-hour) were collected. Four-day dietary intake records were reviewed. A 4-hour IV magnesium load retention study was performed before and 3 months after magnesium supplementation. A non-supplemented control group was similarly studied.At baseline, magnesium intakes for all groups were below the RDA. No significant differences were seen in serum, plasma, ultrafiltrates of serum or plasma or red cell magnesium concentrations among groups over time. At baseline 5/27 subjects (19%) compared to 11/27 subjects (41%) after supplementation demonstrated normal magnesium retentions (< 25%). Magnesium excretions among groups were significantly different during supplementation. Percent magnesium retentions among groups were not different.Supplementation with 10.4 mmol oral magnesium daily for 3 months did not significantly alter blood levels or magnesium retention; however, patients demonstrated lower retention of magnesium after supplementation. Differences in magnesium retention was not related to basal magnesium intake, blood levels or excretion. Unfortunately, even an intensive effort at characterizing magnesium status did not identify a clinical indicator of utility for differentiating patients with congestive heart failure before, during, and after 3 months of magnesium supplementation.

Early increase in blood nitric oxide, detected by electron paramagnetic resonance as nitrosylhaemoglobin, in haemodialysis.

The objective of this study was to determine intradialytic blood levels of nitric oxide (NO), in patients undergoing chronic haemodialysis. This was done by detection of nitrosylhaemoglobin by a sensitive technique of spin trap electron paramagnetic resonance at 0, 5, 15, 60, 180 and 240 min of a 4-h standard bicarbonate dialysis, using the same dose (6000 U) of heparin and different dialysis membranes. The study group included 12 patients treated with cellulose-derived dialysis membranes (nine with cuprophan and three with cellulose triacetate) and 10 patients treated with synthetic membranes (five with polysulfone and five with polymethylmethacrylate). Control groups included 11 normal subjects and six patients with end-stage renal failure who were receiving intermittent peritoneal dialysis. Basal blood levels of nitrosylhaemoglobin in haemodialysis patients were significantly higher than normals, but similar to peritoneal dialysis patients. A significant increase (P < 0.01) in nitrosylhaemoglobin level was detected at 15 min of haemodialysis irrespective of the membrane used. A decrease to basal levels at 180 min was observed in all but two cuprophan-treated patients who, in contrast to the others, had a symptomatic hypotension at the end of the session and a further increase in blood nitric oxide. Patients undergoing peritoneal dialysis did not show any change in blood levels of nitrosylhaemoglobin during the first 180 min of the procedure. Thus, a constant increase in nitrosylhaemoglobin levels was observed early in haemodialysis, but not in peritoneal dialysis patients. Very preliminary evidence was obtained for a role of nitric oxide in the vascular instability at the end of haemodialysis in a few patients who had hypotensive episodes.

Subhypnotic Doses of Propofol Do Not Possess Antidopaminergic Properties

In order to investigate the possible interactions of propofol with the dopaminergic system, a prospective, randomized, double-blind, placebo-controlled study was performed on the profile of prolactin secretion, since prolactin blood levels are known to increase when dopaminergic receptors are blocked. Ten fasting female patients scheduled to receive cancer chemotherapy were allocated to receive either propofol at a rate of 1 mg [center dot] kg-1 [center dot] h-1 or Intralipid[R] 0.1 ml [center dot] kg-1 [center dot] h-1. The study included two consecutive chemotherapy cycles; each patient received in a random order propofol or Intralipid[R]. The infusions were started 4 h prior to induction of chemotherapy; prolactin blood levels were determined at time 0, 30, 60, 120, and 240 min (end of the study period). The basal prolactin blood levels were 14.2 +/- 4.3 vs 12.8 +/- 2.7 and 10.7 +/- 1.7 vs 14.0 +/- 3.6 ng/mL at the end of the study for propofol and Intralipid[R], respectively. These results suggest that the antiemetic properties of propofol are not mediated via interactions with the dopaminergic system. (Anesth Analg 1997;84:196-8)

Pulsatile release of oxytocin in newborn infants.

Recently, a pulsatile, basal oxytocin blood level has been described in human adults. To investigate if such a hormone profile exists already during the neonatal period, we collected blood samples continuously with 20-s fractions for 4 min in 1-day-old infants (n = 26). Plasma oxytocin concentrations were determined by a specific radioimmunoassay. The values were further analysed by the pulse detection program PULSAR. We found that 42% of the infants presented one peak in the oxytocin level during a 4-min period. The peak constituted a 111 +/- 66% (mean +/- SD) increment of the baseline value. It is suggested that the release of oxytocin during basal conditions occurs in a pulsatile way in newborn infants and that these hormone pulses reflect fluctuations in the activity of the hypothalamic neurosecretory cells.

Increased 17‐OH‐Progesterone levels following hCG stimulation in men with idiopathic oligozoospermia and raised FSH levels

Leydig cell function was investigated in 71 men with idiopathic oligospermia and compared to 14 fertile controls by assessing the steroidogenic response to GnRH and the repetitive administration of hCG (1500 IU x3). The oligospermic men were divided into two groups according to their basal serum FSH values (FSH < 8, n = 35; FSH > 8, n = 36), this level being defined by the mean + 3 SD of the levels in normal men (3.71 + 4.08 mIU/ml). Oversecretion of LH was supported by the findings of: (a) higher basal LH levels (p < 0.0001) in both oligospermic groups, although still within the normal range; (b) higher Dmax LH and area LH (p < 0.0001) levels in the FSH > 8 group; (c) a strong position correlation (p < 0.001) of the above parameters with the respective levels of FSH. No difference in basal testosterone levels was observed between the three groups, whereas basal levels of 17-OHP were significantly higher (p < 0.05) in the group with FSH > 8. The testosterone/LH ratio was significantly (p < 0.0001) lower in the FSH > 8 group, and was correlated inversely to the basal blood levels of FSH (p < 0.0001) and to the area LH (p < 0.04). After the hCG test, there was no difference in the testosterone and oestradiol response between the groups, whereas the secretion of 17-OHP and the ratio of 17-OHP/testosterone was significantly higher (p < 0.0001) in the group with FSH > 8 compared with the other two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin and sugar concentration changes in mammary secretion in sheep during the periparturient period

The radioimmunoassayable concentration of insulin in isolated whey fractions of mammary secretion of sheep (n = 28) was measured. The concentrations were high on the last 2 days of pregnancy (550 +/- 80 and 580 +/- 77 microU/ml, respectively), higher on the day of parturition (780 +/- 71 microU/ml) and lower on the next day (290 +/- 54 microU/ml). During the following 4 consecutive days the concentrations gradually decreased to an almost basal blood level (14 microU/ml). The high insulin concentration in the mammary secretion during the periparturient period might be the result of intensified transfer of insulin through the blood-mammary barrier and increasing needs for this hormone by developing mammocytes and probably for the newborn lambs (n = 42) adapting to extra-uterine life. Conversely to the consecutive decrease in insulin, progressively increasing concentrations of sugars in mammary secretions were observed (from 2.1 +/- 0.22% on the second day prior to parturition to 5.5 +/- 0.13% on the fifth day post partum.

Effects of prolonged sodium restriction on the morphology and function of rat adrenocortical autotransplants

Regenerated adrenocortical nodules were obtained by implanting fragments of the capsular tissue of excised adrenal glands into the musculus gracilis of rats (Belloni et al. 1990). Five months after the operation, operated rats showed a normal basal blood level of corticosterone, but a very low concentration of circulating aldosterone associated with a slightly increased plasma renin activity (PRA). Regenerated nodules were well encapsulated and some septa extended into the parenchyma from the connective-tissue capsule. The majority of parenchymal cells were similar to those of the zonae fasciculata and reticularis of the normal adrenal gland, while zona glomerulosa-like cells were exclusively located around septa (juxta-septal zone; JZ). In vitro studies demonstrated that nodules were functioning as far as glucocorticoid production was concerned, while mineralocorticoid yield was very low. Prolonged sodium restriction significantly increased PRA and plasma aldosterone concentration, and provoked a marked hypertrophy of JZ, which was due to increases in both the number and average volume of JZ cells. Accordingly, the in vitro basal production of aldosterone and other 18-hydroxylated steroids was notably enhanced. The plasma level of corticosterone, as well as zona fasciculata/reticularis-like cells and in vitro production of glucocorticoids by regenerated nodules were not affected. These findings, indicating that autotransplanted adrenocortical nodules respond to a prolonged sodium restriction similar to the normal adrenal glands, suggest that the relative deficit in mineralocorticoid production is not due to an intrinsic defect of the zona glomerulosa-like JZ, but is probably caused by the impairment of its adequate stimulation under basal conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Somatostatin release induced by gastrin-releasing peptide in man. Effect of proximal gastric vagotomy and cholinergic blockade

The influence of intragastric pH on the basal release of somatostatin has been studied in healthy controls and in duodenal ulcer patients. In addition the somatostatin response to gastrin-releasing peptide infusion has been evaluated both regarding the effect of intragastric pH and the influence of vagal innervation and muscarinic blockade. No difference was found in basal blood levels, when changing the intraluminal pH, although a slightly higher basal somatostatin concentration was noticed in patients with duodenal ulcer disease. Neither proximal gastric vagotomy nor cholinergic blockade had any effect on basal somatostatin concentrations. GRP infused in stepwise increasing doses from 20 pmol/kg/h to 400 pmol/kg/h induced a small but significant response. This effect of GRP was most evident, when the stomach was perfused with 0.1 M HCl. The small, somatostatin response to GRP infusion was not influenced by vagal denervation of the parietal cell area, neither by cholinergic blockade. Despite the previously observed effects of vagotomy and cholinergic blockade on gastrin release induced by GRP, a corresponding inverse effect on somatostatin is not apparent.

Reduced angiotensin II induced vascular reactivity in chronic renal failure

Eight patients with chronic renal failure before the stage of dialysis (Group 1), 11 patients on regular dialysis treatment (Group 2) and 14 healthy control subjects (Group 3) were studied before, during and after angiotensin II (AII)-infusion. Blood pressure (BP), heart rate (HR), plasma levels of AII, aldosterone (Aldo), arginine vasopressin (AVP), noradrenaline (NA) and adrenaline (A), and serum concentrations of parathyroid hormone (PTH), calcium and magnesium were determined. AII induced vascular reactivity was reduced both in Group 1 and 2 compared with Group 3. Basal AII was the same in the three groups, and only in dialysis patients was AII induced vascular reactivity negatively correlated to basal AII. Aldo and NA were higher in Group 2 than in Group 3, and AVP was higher in both groups of patients compared with controls. HR declined during AII induced elevation of BP in the control subjects but not in the patients. Neither PTH, serum calcium nor serum magnesium was correlated to BP or vascular reactivity. It can be concluded that AII induced vascular reactivity is reduced both in patients with renal failure before dialysis and in patients on regular dialysis treatment. Basal blood levels of Aldo and NA are increased in dialysis patients and AVP is increased in both groups of patients, but neither these abnormalities nor blood levels of PTH, calcium or magnesium seem to be the background upon which the abnormal vascular reactivity develops.

Severity of Coronary Artery Disease and Basal Fibrinolysis

Basal venous blood levels of several components of the fibrinolytic enzyme system (plasminogen activator, plasminogen, fibrin degradation products, alpha 2-antiplasmin, and alpha 2-macroglobulin) were measured in 100 white men with angiographically defined coronary artery disease. The tests of fibrinolysis were not related to the severity of coronary artery disease, as indicated either by the number of vessels involved or by a coronary score system. Fibrinogen levels, however, did show a modest association with the extent of coronary atheroma (r = 0.21, p less than 0.05). Triglyceride levels were associated with the inhibitors of fibrinolysis: positively with alpha 2-antiplasmin (r = 0.31, p less than 0.005) and negatively with alpha 2-macroglobulin (r = -0.25, p less than 0.05). The alpha 2-antiplasmin levels were significantly elevated in patients with hypertriglyceridaemia. Neither smoking nor beta-blockade had any effect on the tests of fibrinolysis. This study adds support to the association of plasma fibrinogen with ischaemic heart disease.

Effects of dopamine receptor stimulation on opiate-induced modifications of pituitary-gonadal function.

We evaluated the effects of the dopaminergic drug bromocriptine (Br) on prolactin (PRL), luteinizing hormone (LH) and testosterone (Te) levels in a homogeneous group of opiate addicts in a methadone maintenance program (20 mg twice daily). Basal blood levels of PRL, LH and Te were determined in 15 adult male drug addicts, before 30 and 60 days after Br administration (7.5 mg/day) was started. 15 healthy volunteers served as controls for the evaluation of basal values of the hormones. Before treatment PRL values were high, while LH and Te levels were lower than normal. 30 days later, PRL lowered significantly while LH and Te increased significantly. 60 days later, the blood hormone values were still significantly different from pretreatment values, and close to the normal range. This observation shows that Br, probably through an increase of dopaminergic tone, may counteract some effects of opiates on the hypothalamic-pituitary-gonadal axis.

Basal plasma somatostatin in biliary stone patients.

We have searched for elevated basal plasma somatostatin in patients with documented cholelithiasis (n = 37) and compared the data with healthy control subjects (n = 27). Using an acidic assay system for measuring somatostatin in unprocessed plasma, we could not find deviations from normal values in biliary stone patients. Also basal blood levels of other islet cell hormones (insulin, glucagon) and minerals (calcium, magnesium) are unchanged. Further studies are needed to find out whether an abnormal response of plasma somatostatin to appropriate stimuli can play a role in the etiology of biliary stones.

Norepinephrine clearance and pressor effect in normal and hypertensive man.

Whether and to what extent the sympathetic nervous system participates in the development of essential hypertension has remained largely unclear. The role of the adrenergic effector - cardiovascular response axis in the pathogenesis of essential hypertension was investigated by combined analysis of blood levels, total plasma clearance and cardiovascular pressor effects of norepinephrine (NE). Measurements of plasma NE and blood pressure were performed before, during and after an intravenous infusion of NE at stepwise increasing rates in approximately age and sex-matched groups of 28 normal subjects and 35 patients with essential hypertension. The threshold of the pressor effect of NE was lower in hypertensive than in normal subjects (20 +/- 10 vs. 42 +/- 26 ng/kg min; P < 0.001); but the slope of the dose - resonse curve and basal endogenous plasma NE were in the average similar. Total plasma NE clearance estimated under steady state conditions was similar in normal and hypertensive subjects (5.3 +/- 2.5 vs. 5.4 +/- 2.31/min). NE clearance corrleated inversely with basal plasma NE in normal subjects (r = 0.57; P < 0.005). The plasma half-life of NE was about 2 min. These findings demonstrate that basal blood levels and total plasma clearance of NE during NE infusion are usually normal in essential hypertension. A low threshold of the pressor effect of NE in the presence of normal adrenergic activity may contribute to the development and/or maintenance of essential hypertension.

Pituitary and ovarian responsiveness to a graded gonadotropin releasing factor stimulation test in women using a low-estrogen or a regular type of oral contraceptive

The hypothalamic-pituitary-ovarian axis was evaluated in 47 women who were using mechanical contraception (MC) (N = 20), standard oral contraceptives containing 50 micrograms (μg) or more of estrogen (SOC) (N = 17), and a low-estrogen oral contraceptive containing 35 μg of ethinyl estradiol (LEOC) (N = 10). In the last half of their cycles, measurements were made of basal blood levels of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH), prolactin, estradiol, progesterone, testosterone, and dihydrotestosterone. The SOC group had significantly lower concentrations of basal LH, FSH, estradiol, progesterone, and testosterone. The LEOC group showed only decrease in estradiol. In addition, the women were all evaluated with a sequentially administered intravenous gonadotropin-releasing factor (GNRF) test in which 10 samples of blood were drawn over 4.5 hours for analysis of FSH and LH, and in which GNRF was administered as a 0.5 μg, 5.0 μg, and 50.0 μg bolus. There was a significantly suppressed response for both gonadotropins in the SOC group. The women using the low-estrogen oral contraceptive had no suppression of the FSH response, and the LH response was suppressed only after the maximal GNRF stimulation (50.0 μg). The gonadotropin responses to all GNRF injections were significantly different between the SOC and LEOC subgroups. These data suggest that some of the physiologic effects of oral contraceptive steroids, such as pituitary gonadotropin suppression, are dose-related, and that, therefore, the low-estrogen type of oral contraceptives have potentially fewer adverse effects and, presumably, may produce amenorrhea less often.

Clinical study on functioning pituitary adenomas (prolactin secreting and growth hormone secreting adenomas) (author's transl)

1. Thirteen of 35 chromophobe adenoma cases revealed abnormally high blood levels of prolaction (1380-15000 ng/ml). In these cases high levels of prolactin was disclosed in the cerebrospinal fluid and the media in which the tumor specimens were incubated. Three of these 13 cases were verified to have had recurrence in 3 years after treatment, while the other 22 cases with relatively lower prolactin levels showed no recurrence. Quantitative determination on PEG, according to our own method, showed that tumor size of these abnormally high prolactin cases was larger than that of relatively lower prolactin cases. Abnormally high blood levels of prolactin were found to maintain more than 1000 ng/ml after surgery and irradiation. 2. Sixteen cases of growth hormone secreting adenoma was examined endocrinologically. From the examination of GH responsiveness to various stimuli, these 16 cases were supposed to be classified to 3 types, i.e. TRH-responsive type (8 cases), LH-RH-responsive type (4 cases) and non-responsive type (4 cases). In 5 cases of the TRH-responsive type, the basal blood levels of GH decreased significantly in one year after irradiation. 3. In three groups of pituitary adenomas, i.e. prolactin secreting adenoma (13 cases), GH secreting adenoma (16 cases) and non-functining adenoma (22 cases), the frequency of impaired ACTH and gonadotropin secretion was observed to be the highest in prolactin secreting adenomas and the lowest in GH secreting adenomas, however the frequency of impaired TSH secretion was the highest in GH secreting adenomas and the lowest in the prolactin secreting adenomas.

Effect of synthetic luteinizing hormone-releasing hormone (LH-RH) on the release of gonadotrophins in children and adolescents. VI. Relations to age, sex and puberty.

ABSTRACT Plasma gonadotrophins (LH and FSH) were radio-immunoassayed before and after injection of 0.1 mg/m2 of synthetic luteinizing hormone-releasing hormone (LH-RH) in infants 1 to 12 months old, prepubertal children aged more than 12 months, and pubertal subjects of both sexes. The pubertal changes of gonadotrophins include a highly significant increase of LH pituitary mobilizable reserve in both sexes, while the FSH reserve shows a significant decrease in females and no significant variation in males. From the first year of life up to childhood, the basal blood levels of FSH and LH decrease significantly in girls but do not vary in boys, while the FSH reserve decreases significantly in girls and increases significantly in boys, the LH reserve showing a non-significant decrease in both sexes. In the first year of life, girls show a very significantly higher FSH secretion and reserve than boys, while boys have a significantly higher LH reserve than girls. After the end of the first year up to the onset of puberty, the FSH reserve remains significantly higher in girls than in boys. The interpretation of these facts is discussed.

Basal prolactin blood levels in three strains of rat with differing incidence of 7,12-Dimethylbenz (a) anthracene induced mammary tumours

The incidence of mammary tumours induced tn three strains of rat is different. Plasma prolactin levels have been measured in these strains of rat during the dioestrous phase of the oesttous cycle. The strain showing the highest incidence of induced mammary tumours also showed the highest circulating prolactin levels.