Circulating opioid peptides in chronic renal failure: acute effect of dialysis treatment

In 14 patients affected by chronic renal failure (7 males and 7 females) it has been evaluated the secretion of beta LPH, beta EP, ACTH and Cortisol in basal conditions and immediately after a dialytic treatment. For beta LPH and beta EP measurements on each thawed plasma a silic acid extraction and a successive peptides separation by a Sephadex G-75 column chromatography preceeded the two specific RIAs. Basal beta LPH plasma levels resulted significantly higher than in normal controls, while that of beta EP, ACTH and Cortisol were in the normal range. The dialytic treatment was able to increase ACTH and Cortisol plasma levels, without to modified beta LPH and beta EP plasma levels.     

Neonatal adaptive phenomenon: secretion of beta-lipotropin, and beta-endorphin in the first week of life

beta Lipotrophin and beta Endorphin plasma levels have been measured in 35 newborns subdivided in 5 groups of 12, 24, 48, 72 and 168 hours of life, 10 umbilical mixed blood samples were also evaluated. After plasma extraction (3 ml) and G-75 Sephadex column chromatography, the peptides were measured by two specific RIAs. beta LPH and beta EP levels were high in umbilical cord plasma (241.0 +/- 43.3 and 70.0 +/- 8.5 pg/ml respectively). A progressive decrement was then observed until the 72th hour of life (28.1 +/- 13.2 and 8.7 +/- 4.8 pg/ml respectively) but the elevated levels found at 24th hour demonstrate an active synthesis and release from fetal and neonatal pituitary. After a slight and transient decreased activity during the first week of life, the statistically significant increase of both beta LPH and beta EP observed at seven day indicate that at this moment pituitary function is restored.     

Diurnal rhythms of proopiomelanocortin-derived N-terminal peptide, beta-lipotropin, beta-endorphin and adrenocorticotropin in normal subjects and in patients with Addison's disease and Cushing's disease

In order to clarify the diurnal pattern of secretion of plasma immunoreactive (IR) proopiomelanocortin (POMC)-derived peptides, IR-N-terminal peptide (Nt), IR-beta-endorphin (Ep), IR-beta-lipotropin (LPH), and IR-ACTH (ACTH) in normal subjects and in patients with Addison's disease and Cushing's disease, we measured these 4 peptides in the same plasma obtained at 0900 h and then every three hours until 0600 h at the next day. All four peptides showed diurnal rhythms with the peaks at 0600 h, and the nadirs of ACTH, LPH, Ep and Nt were at 0000 h, 0000 h, 1800 h and 0300, respectively in normal subjects. In patients with Addison's disease, these four peptides also showed diurnal rhythms with the peaks at 0600 h for ACTH and Ep and at 0900 h for LPH and Nt, and the nadirs at 2100 h for ACTH and Ep and at 0000 h for LPH and Nt. The molar ratios of Ep/ACTH, LPH/ACTH and Nt/ACTH in plasma also presented diurnal variations in normal subjects and in patients with Addison's disease. On the other hand, in patients with Cushing's disease, ACTH, LPH and Nt showed no rhythmicity or change in molar ratios of Ep/ACTH, LPH/ACTH or Nt/ACTH. Only Ep showed diurnal variation. The molar ratios of Ep/ACTH, LPH/ACTH and Nt/ACTH in patients with Cushing's disease were significantly higher than those in normal subjects and in patients with Addison's disease at 0000 h.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human plasma immunoreactive beta-lipotropin: correlation with basal and stimulated plasma ACTH concentrations.

A sensitive radioimmunoassay for human β-lipotropin (LPH) has been developed utilizing an N-terminal antibody which exhibits no cross-reactivity with β_h-MSH and appears to be species specific, with less than 10% crossreactivity with rat, ovine or bovine LPH. 0800-0900 mean plasma LPH concentrations were 47.9±5.7 pg/ml (5 normal subects), 100.5±13.2 pg/ml (Cushing's Disease (CD) n=6), 769.3±390.4 pg/ml (Nelson's Syndrome (NS) n=5). Mean plasma ACTH/plasma LPH ratios were: 1.96±0.13 (normal subjects), 1.69±0.11 (CD) and 1.16±0.07 (NS) Plasma ACTH and LPH rose in parallel in response to insulin-induced hypoglycemia in 4 normal subjects. There was a 375% increase in plasma ACTH concentration, a 474% increase in plasma LPH concentration. Plasma ACTH/LPH ratios in specimens obtained following attainment of peak concentrations were significantly lower than those in either control or peak specimens.     

Effects of corticotropin-releasing factor (CRF) on aldosterone and 18-hydroxycorticosterone in essential hypertension and primary aldosteronism

The effects of ovine corticotropin releasing factor (o-CRF) on plasma aldosterone, 18-OH-corticosterone (18-OHB), plasma adrenocorticotropin (ACTH) and cortisol were determined in eight patients with primary aldosteronism, six with aldosterone-producing adenoma (APA) and two with idiopathic hyperaldosteronism (IHA). The results were compared with those in six normal subjects and eleven patients with essential hypertension (EHT, 5 with low renin and 6 with normal renin). In patients with APA, the peak plasma aldosterone and 18-OHB responses to 100 micrograms iv of o-CRF (226% and 113% increase from baseline, respectively) were greater than those in EHT and normal subjects. The net integrated aldosterone and 18-OHB responses (840 +/- 156, and 419 +/- 121 ng/dl.hr, respectively) were also significantly greater (p less than 0.01) in APA than those in normals and EHT. In two patients with IHA, both the peak and net integrated aldosterone response were smaller than those in APA, in spite of nearly identical plasma ACTH and cortisol responses. These results suggest that augmented responses of mineralocorticoids to o-CRF may be characteristic of aldosteronism due to APA, mediated by CRF-induced ACTH, and possibly other proopiomelanocortin (POMC)-derived peptides.     

Reduced ACTH, while normal beta-endorphin CSF levels in early epileptic encephalopathies

Since ACTH and the opioids display opposite effects on experimentally-induced seizures, cerebrospinal fluid (CSF) levels of ACTH and beta-endorphin (beta-EP) were measured in 6 children (4-8 months) affected by infantile spasms with hypsarhythmia, an idiopathic early onset encephalopathy, and in 8 age-matched controls. beta-EP levels in the patients (76.3 +/- 14.7 fmol/ml, M +/- SD) did not differ from those in controls (109.8 +/- 42.7) while babies with epileptic encephalopathy showed reduced ACTH levels in the CSF (3.8 +/- 1.5) as compared to controls (9.0 +/- 3.7, p less than 0.01). This resulted in an increased beta-EP/ACTH ratio. Another patient previously treated with ACTH showed a normal CSF level of ACTH (9.0) with a normal beta-EP/ACTH ratio while in clinical and EEG remission. These results are consistent with the hypothesis that some infantile seizures unrelated to brain injuries could originate from an ACTH deficiency at central level and/or an imbalance of neuropeptidergic pathways.     

Effects of ACTH on plasma levels of adrenal steroids in essential hypertension.

Plasma concentrations of progesterone (P), deoxycorticosterone (DOC), 17-hydroxyprogesterone (17-OH P), corticosterone (B), deoxycortisol (S), cortisol (F) and aldosterone (A) in 8 control subjects (mean age: 40.5 years) and 10 patients with essential hypertension (EH) (mean age: 48.5 years) were determined before, 4 and 8 hours after an infusion of ACTH at a rate of 25 units per 8 hours. Secretion rates (SR) of 18-hydroxy-11-deoxycorticosterone (18-OH DOC) were measured 24 hours before and again on the day of ACTH infusion. All subjects were studied on the fourth day of a diet containing 135 mEq of sodium and 90 mEq of potassium. There was no statistically significant difference between 8 control subjects and 10 patients with EH in the 7 plasma steroid levels and the SR of 18-OH DOC before ACTH infusion. The mean plasma P response to ACTH was slightly lower in controls than in patients with EH, while that of 17-OH P (in male subjects) was slightly higher. The mean plasma B response was significantly lower after 4 hours of ACTH infusion (p less than 0.01), while that of DOC was significantly higher after 8 hours of ACTH infusion (p less than 0.05) in patients with EH. The mean plasma S rose significantly more in patients with EH (p less than 0.025) at 4 and 8 hours after ACTH infusion. The mean plasma F response to ACTH infusion was slightly lower in patients with EH than in controls. The mean response of 18-OH DOC SR to ACTH infusion was slightly higher in patients with EH than in controls. The mean plasma A response was significantly higher in patients with EH than in controls 4 (p less than 0.05) and 8 hour (p less than 0.001) after an ACTH infusion. These results could be explained in part by abnormalities in the 17- and 11-hydroxylase systems, and that the abnormality in 11-hydroxylation was more pronounced than that in the 17-position. Furthermore, we suspect that the sensitivity of adrenal aldosterone to ACTH might be increased or another accelerated pathway to aldosterone biosynthesis might exist in patients with EH.     

Age-related increase of kynurenic acid in human cerebrospinal fluid - IgG and beta2-microglobulin changes

Kynurenic acid (KYNA) is an endogenous metabolite in the kynurenine pathway of tryptophan degradation and is an antagonist at the glycine site of the N-methyl-D-aspartate as well as at the alpha 7 nicotinic cholinergic receptors. In the brain tissue KYNA is synthesised from L-kynurenine by kynurenine aminotransferases (KAT) I and II. A host of immune mediators influence tryptophan degradation. In the present study, the levels of KYNA in cerebrospinal fluid (CSF) and serum in a group of human subjects aged between 25 and 74 years were determined by using a high performance liquid chromatography method. In CSF and serum KAT I and II activities were investigated by radioenzymatic assay, and the levels of beta(2)-microglobulin, a marker for cellular immune activation, were determined by ELISA. The correlations between neurochemical and biological parameters were evaluated. Two subject groups with significantly different ages, i.e. <50 years and >50 years, p < 0.001, showed statistically significantly different CSF KYNA levels, i.e. 2.84 +/- 0.16 fmol/microl vs. 4.09 +/- 0.14 fmol/microl, p < 0.001, respectively; but this difference was not seen in serum samples. Interestingly, KYNA is synthesised in CSF principally by KAT I and not KAT II, however no relationship was found between enzyme activity and ageing. A positive relationship between CSF KYNA levels and age of subjects indicates a 95% probability of elevated CSF KYNA with ageing (R = 0.6639, p = 0.0001). KYNA levels significantly correlated with IgG and beta(2)-microglobulin levels (R = 0.5244, p = 0.0049; R = 0.4253, p = 0.043, respectively). No correlation was found between other biological parameters in CSF or serum. In summary, a positive relationship between the CSF KYNA level and ageing was found, and the data would suggest age-dependent increase of kynurenine metabolism in the CNS. An enhancement of CSF IgG and beta(2)-microglobulin levels would suggest an activation of the immune system during ageing. Increased KYNA metabolism may be involved in the hypofunction of the glutamatergic and/or nicotinic cholinergic neurotransmission in the ageing CNS.     

Exercise capacity, energy metabolism, and beta-adrenoceptor blockade. Comparison between a beta 1-selective and a non-selective beta blocker

The effects of beta 1 and beta 1/2 blockade on exercise capacity were studied in 9 healthy normotensive subjects. Progressive maximal bicycle ergometer tests, followed by an endurance test at 80% of maximal work load, were performed during randomized, double-blind 3 day treatment periods with placebo, atenolol (beta 1) and oxprenolol (beta 1/2). The reduction of maximal work capacity (ca. 10%) was similar with atenolol and oxprenolol, despite a more pronounced maximal heart rate reduction with atenolol (from 175 +/- 2 to 132 +/- 3 beats.min-1) than with oxprenolol (to 138 +/- 2 beats.min-1). Exercise time during the endurance test was reduced from 36 +/- 4 min with placebo to 27 +/- 3 min with atenolol (p less than 0.05) and 24 +/- 3 min with oxprenolol (p less than 0.01) (atenolol vs. oxprenolol: p less than 0.05). During the endurance test, plasma glycerol and non-esterified fatty acid concentrations were reduced with both atenolol and oxprenolol. The glycerol reduction was more pronounced with oxprenolol than with atenolol, plasma NEFA concentrations being similar. Plasma glucose and lactate concentrations were reduced by oxprenolol but not with atenolol. These data show that submaximal exercise capacity at work loads representing similar relative exercise intensities is reduced during non-selective and beta 1-selective beta blockade. This reduction may be related to the effects of beta 1 blockade on energy metabolism, with possibly an additional effect of beta 2 blockade.     

Effects of ovine corticotropin-releasing hormone and FK 33-824 (met-enkephalin analogue) on the secretions of proopiomelanocortin-derived N-terminal peptide, beta-lipotropin, beta-endorphin and adrenocorticotropin in patients with Addison's disease

The responses of plasma immunoreactive (IR) proopiomelanocortin (POMC)-derived N-terminal peptide (Nt), IR-beta-endorphin (Ep), IR-beta-lipotropin (LPH) and IR-ACTH levels to ovine corticotropin-releasing hormone (CRF) and FK 33-824 (Met-Enkephalin analogue) were studied in nine patients with Addison's disease. The basal plasma levels (mean +/- SE) of IR-Nt, IR-Ep, IR-LPH and IR-ACTH were significantly higher in patients with Addison's disease (4459 +/- 975 pg/ml, 132 +/- 25 pg/ml, 4425 +/- 1030 pg/ml, 553 +/- 89 pg/ml, respectively) than in the normal controls (202 +/- 38 pg/ml, 7 +/- 2 pg/ml, 101 +/- 18 pfi/ml, 53 +/- 16 pg/ml, respectively). Ovine CRF produced rapid and concomitant increases in plasma levels of IR-Nt, IR-Ep, IR-LPH and IR-ACTH. Ep and ACTH levels reached a peak at 30 min. On the other hand, Nt and LPH levels reached a peak at 60 min and these levels gradually decreased up to 120 min. The molar concentrations of these IR-peptides in plasma were changed in close parallel fashion to one another. FK 33-824 produced a pronounced and concomitant fall in IR-Nt, IR-EP, IR-LPH, and IR-ACTH levels. These results support the theory that Nt, Ep, LPH and ACTH are produced simultaneously from POMC as a common precursor in the pituitary gland and are secreted concomitantly under various conditions such as stimulation by CRF and inhibition by FK 33-824 in patients with Addison's disease.     

Effects of synthetic ovine corticotropin-releasing factor (CRF) on plasma ACTH and cortisol in 31 normal human males

Responses of plasma ACTH and cortisol to corticotropin-releasing factor (CRF) were evaluated in 31 normal human males. 1.0 micrograms/ks of sterilized synthetic ovine CRF was administered to the subjects, aged 19 to 53 yr and weighing 50 to 78 kg, at between 9:30 a.m. and 10:30 a.m. as an intravenous bolus injection after an overnight fast. Blood specimens were drawn before and 15, 30, 60, 90 and 120 min after injection for later determination of plasma ACTH and cortisol concentrations by radioimmunoassays. Plasma ACTH and cortisol levels for all subjects rose significantly (p less than 0.001) from the basal level (mean +/- SEM, 26.8 +/- 4.5 pg/ml and 12.6 +/- 0.9 micrograms/dl) to peak levels (58.4 +/- 5.5 pg/ml and 22.9 +/- 1.0 micrograms/dl) at 30 min and at 60 min, respectively. Although the plasma concentrations of ACTH and cortisol thereafter declined gradually, the levels at 120 min (43.4 +/- 5.2 pg/ml and 18.9 +/- 0.9 micrograms/ml, respectively) were still significantly higher than the basal levels (p less than 0.001). Significant inverse correlations were observed between the basal levels of each hormone and the ratio of the peak level to the basal level (p less than 0.01), and the increases in plasma ACTH and cortisol concentrations were either not significant or much smaller for the individuals in whom the basal levels were higher than 65 pg/ml and 17.0 micrograms/dl, respectively. No serious subjective symptom was observed during the experimental period in any of the subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Amyloid beta peptide ratio 42/40 but not A beta 42 correlates with phospho-Tau in patients with low- and high-CSF A beta 40 load

Neurochemical dementia diagnostics (NDD) can significantly improve the clinically based categorization of patients with early dementia disorders, and the cerebrospinal fluid (CSF) concentrations of amyloid beta peptides ending at the amino acid position of 42 (A beta x-42 and A beta 1-42) are widely accepted biomarkers of Alzheimer's disease (AD). However, in subjects with constitutively high- or low-CSF concentrations of total A beta peptides (tA beta), the NDD interpretation might lead to erroneous conclusions as these biomarkers seem to correlate better with the total A beta load than with the pathological status of a given patient in such cases. In this multicenter study, we found significantly increased CSF concentrations of phosphorylated Tau (pTau181) and total Tau in the group of subjects with high CSF A beta x-40 concentrations and decreased A beta x-42/x-40 concentration ratio compared with the group of subjects with low CSF A beta x-40 and normal A beta ratio (p<0.001 in both cases). Furthermore, we observed significantly decreased A beta ratio (p<0.01) in the group of subjects with APOE epsilon 4 allele compared with the group of subjects without this allele. Surprisingly, patients with low-A beta x-40 and the decreased A beta ratio characterized with decreased pTau181 (p<0.05), and unaltered total Tau compared with the subjects with high A beta x-40 and the A beta ratio in the normal range. We conclude that the amyloid beta concentration ratio should replace the 'raw' concentrations of corresponding A beta peptides to improve reliability of the neurochemical dementia diagnosis.     

Plasma immunoreactive corticotrophin and lipotrophin in Cushing's syndrome and Addison's disease.

Plasma immunoreactive corticotrophin (ACTH) and lipotrophin (LPH) were measured in patients with raised circulating concentrations from a pituitary or an ectopic source. They were measured again in seven patients after they had received hydrocortisone. Plasma ACTH concentrations were higher than LPH concentrations in patients with a pituitary source of their hormones, whereas this relation was reversed when the source was ectopic. After hydrocortisone administration the half life of immunoreactive ACTH was 40 minutes and that of LPH 95 minutes, resulting in a reversal of the normal relation of ACTH to LPH. The use of two antisera with different specificities for measuring LPH has further shown that pituitary LPH differs from ectopic LPH. Relatively less gamma-LPH than beta-LPH was produced from ectopic sources, the relation being reversed in patients with a pituitary source for their raised concentrations. Measuring plasma LPH as well as ACTH might therefore help in deciding whether a patient with Cushing''s syndrome has a pituitary or ectopic source of ACTH, which sometimes presents a difficult clinical problem.     

Radioimmunoassay of 5-androstene-3 beta,17 beta-diol in plasma and in breast cyst fluid

A simple and reliable radioimmunoassay for the determination of 5-androstene-3 beta, 17 beta-diol in peripheral plasma and in breast cyst fluid, after a chromatography on Celite microcolumn has been described and evaluated. The antiserum used was raised in rabbits injected with dehydroepiandrosterone-15 alpha-(O-carboxymethyl)-bovine serum albumin. In men below 40 years of age the levels ranged from 0.85 to 2.80 ng/ml (mean +/- SEM: 1.52 +/- 0.11; n = 24) and from 0.50 to 2.20 ng/ml (mean +/- SEM: 0.93 +/- 0.09; n = 20) in men aged between 41 and 62 years. The mean level was significantly different (P less than 0.001) between the 2 groups. A significant correlation (r = -0.56; P less than 0.01) was demonstrated between age and all male levels. In females the mean plasma level was in the follicular phase: 0.81 +/- 0.07 ng/ml (range: 0.40-1.50; n = 17; age: 19-41 years) and in the luteal phase: 0.83 +/- 0.05 ng/ml (range: 0.40-1.30; n = 29; age: 18-43 years). No cyclical change and no correlation with age could be evidenced. A significant difference (P less than 0.001) was shown between females and the young male group. In breast cyst fluid the levels ranged from 0.05 to 13.70 ng/ml (mean +/- SEM: 2.36 +/- 0.86; n = 20) whereas the sulfate concentrations ranged from 75 to 7500 ng/ml (mean +/- SEM: 1891 +/- 565; n = 15), thus demonstrating very wide inter-individual variations.     

Reduced cerebrospinal fluid levels of immunoreactive pro-opiomelanocortin related peptides (including beta-endorphin) in anorexia nervosa

The discovery that the endogenous opioid peptides contribute to the modulation of appetitive behavior and neuroendocrine function has raised questions as to whether disturbances of opioids contributes to the pathophysiology of eating disorders. To assess central nervous system (CNS) beta-endorphin in patients with anorexia nervosa we measured cerebrospinal fluid (CSF) beta-endorphin concentrations before, and at intervals after weight correction. In addition, we measured three sister peptides (beta-lipotropin, adrenocorticotropic hormone (ACTH), and the N-terminal fragment) derived from the same precursor molecule, pro-opiomelanocortin (POMC) to determine whether possible disturbances might extend to sister peptides. Underweight anorectics (58 +/- 5% of average body weight (ABW), n = 10) had significantly lower CSF concentrations of all 4 peptides compared to healthy controls (102 +/- 10% ABW, n = 11). CSF concentrations of all 4 POMC-related peptides were found to be significantly increased when the same anorectics were restudied 4 to 6 weeks after weight gain (83 +/- 4% ABW). After weight gain, levels of CSF beta-endorphin, beta-lipotropin, and ACTH were similar to controls, whereas levels of CSF N-POMC remained significantly less than controls. Another group of women, previously underweight with anorexia nervosa, but weight-restored (93 +/- 11% ABW, n = 12) for greater than 1 year had CSF concentrations of all 4 POMC-related peptides that were similar to controls. We conclude that underweight anorectics have state-associated disturbances of CNS beta-endorphin as well as other POMC-related peptides. These abnormalities are part of the neurobiological syndrome of anorexia nervosa and may contribute to the characteristic alterations in behavior and neuroendocrine function.     

Proteomic analysis of human ventricular cerebrospinal fluid from neurologically normal, elderly subjects using two-dimensional LC-MS/MS

A two-dimensional liquid chromatography separation scheme coupled to tandem mass spectrometry (2-D LC-MS/MS) was utilized to profile the proteome of human CSF. Ventricular CSF samples acquired post-mortem from 10 cognitively normal elderly subjects (mean +/- SEM Braak stage = 1.7 +/- 0.2) were analyzed to determine their protein composition. Raw CSF samples were subjected to an immunobased processing method to remove highly abundant albumin and immunoglobulin (Ig), allowing better detection of lower-abundance proteins. Samples were subjected to trypsin proteolysis followed by C18 solid-phase extraction. Tryptic CSF peptides were separated using a 2-D LC column, in which both strong cation exchange (SCX) and C18 phases were packed into a single capillary. MS/MS spectra of CSF peptides were searched against a human sub-database of the NBCI nonredundant database using the SEQUEST algorithm. Search results were further filtered using DTAselect, and individual samples were compared to one another using Contrast. Using this method, we were able to unambiguously identify 249 CSF proteins from 10 subjects. Of these proteins, 38% were unique to individual subjects, whereas only 6% were common to all 10 subjects. These results suggest considerable subject-to-subject variability in the CSF proteome.     

Localization of immunoreactive beta-endorphin and adrenocorticotropic hormone and pro-opiomelanocortin mRNA to rat testicular interstitial tissue macrophages.

Pro-opiomelanocortin (POMC) gene expression and POMC peptides have been demonstrated in the Leydig cells of the testis, although selective removal of the Leydig cells with the cytotoxic drug ethane dimethane sulfonate did not significantly reduce levels of testicular POMC mRNA or peptides in adult rats. Since macrophages in the rat spleen synthesize POMC peptides, we investigated whether isolated macrophages from the adult rat testis may be an additional source of POMC-derived peptides. Testicular macrophages were isolated by collagenase treatment of adult rat testes and adherence to siliconized glass coverslips; the biological, cytochemical and immunological characteristics of the attached cells were compared with those of Leydig cells purified by Percoll gradient centrifugation. Macrophages in the cell preparations were identified by positive esterase cytochemical staining, latex bead ingestion, and immunocytochemical staining with ED2 (a macrophage-specific monoclonal antibody), and an absence of 3 beta-hydroxysteroid dehydrogenase cytochemical staining. Leydig cells in the purified preparations were positive for 3 beta-hydroxysteroid dehydrogenase and esterase staining but negative with ED2, and were not phagocytic. Based on these criteria, the purities of the macrophage and Leydig cell preparations employed in this study were estimated to be 87 +/- 4% and 91 +/- 3%, respectively. Cytoplasmic beta-endorphin (beta EP) immunoreactivity (ir) was present in 62 +/- 9% of cells in the purified Leydig cell preparations--confirming these cells as a source of POMC-derived peptides. In addition, ir-beta EP and ir-ACTH were localized to the cytoplasm of a similar proportion of cells (beta EP, 62.5 +/- 5%; ACTH, 64 +/- 5%) in macrophage preparations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Central ACTH deficit in degenerative and vascular dementia

Cerebrospinal fluid (CSF) concentrations of ACTH, beta-lipotropin (beta-LPH) and beta-endorphin (beta-EP) were measured in 15 patients affected by dementia, who underwent also a brain computerized tomography (CT), and in 13 age-matched healthy volunteers. ACTH CSF levels of patients (4.0 +/- 2.4 fmol/ml, M +/- SD) were significantly lower than in controls (9.8 +/- 5.0, P less than 0.01) the lowest values being found in Alzheimer type of dementia (ATD: 3.1 +/- 2.5) and in patients with radiological evidence of cortical atrophy (2.5 +/- 1.2), independently of the probable origin of dementia. Although beta-LPH and beta-EP levels of patients fell within normal range, they were lower in ATD than in dementia sustained on a vascular origin. There was no variation of either peptides concentration in relation to CT findings. These data indicate the ACTH impairment as typical of dementia, supporting in humans the positive role of this peptide on learning and mnesic functions. Moreover, the maintained CSF levels of both beta-LPH and beta-EP in the dementia sustained on a vascular origin, while lower values were found in ATD, could represent a differentiation between vascular and degenerative diseases of the Central Nervous System (CNS).     

Beta endorphin levels in CSF during methadone maintenance

Recent studies have shown that plasma beta endorphin levels of patients on methadone maintenance are comparable to controls. Furthermore, CSF levels of related peptides in methadone patients also do not differ from controls, although CSF levels of beta endorphin have not been specifically measured. In the current study we compared both CSF and plasma levels of beta endorphin in 11 patients on methadone maintenance for at least 10 months to levels in 13 controls getting spinal anesthesia for surgery. The CSF beta endorphin levels of the methadone maintained patients were significantly higher than the controls (52.3 vs 21.7 pg/ml), while plasma levels of beta endorphin (29.6 vs 31.1 pg/ml) and cortisol (13.8 vs 12.6 micro g/dl) [corrected] did not differ. Covarying for age differences between the samples, slightly increased the magnitude of this difference in CSF beta endorphin levels. Plasma levels of beta endorphin did not correlate with CSF levels, but did correlate with plasma levels of cortisol (r = 0.51, P less than 0.02). These findings supported previous studies of plasma beta endorphin levels. However, the dissociation of beta endorphin levels in plasma and CSF within this patient population was a new finding.     

The value of urine osmolality as an index of stress in the ovine fetus

In ovine fetuses, during 100-130 days of gestation, urine osmolalities less than 175 mosmol/kg water were associated with plasma immunoreactive adrenocorticotrophin (ACTH) concentrations below 40 pg/ml in 40/41 samples. In 18/29 fetuses with urine osmolalities greater than 175 mosmol/kg water plasma ACTH was significantly elevated. In 38 samples of fetal blood there was a significant correlation between plasma ADH and ACTH concentrations. By least squares regression the equation to the line was [ACTH] = 5.06 + 3.70 [ADH] (r = 0.62, P less than 0.001). In 50 samples from fetuses of gestational ages 100-140 days, with urine osmolalities of 302 +/- 86 mosmol/kg (mean +/- SD) the blood pH, pO2 and pCO2 values were not significantly different from those in 50 samples from fetuses with urine osmolalities of 125 +/- 22 mosmol/kg. It is proposed that the measurement of fetal urine osmolality provides a good index of fetal stress. A fetus with a urine osmolality less than 175 mosmol/kg is almost invariably in the optimum, unstressed condition.