Search PubMed⌕ Search

Biomedical subjects

M Maes

Publications and source records attributed to M Maes.

At least 91 records · Page 5Linked to original sources
PubMed1999

Influence of psychological stress on immune-inflammatory variables in normal humans. Part II. Altered serum concentrations of natural anti-inflammatory agents and soluble membrane antigens of monocytes and T lymphocytes.

The effects of academic examination stress on serum concentrations of interleukin (IL)-1 receptor (R) antagonist (A), soluble(s) IL-2R, sIL-6R, soluble glycoprotein 130 (sgp130), Clara cell protein (CC16), sCD8 and sCD14 were evaluated in 38 university students. The relationships among changes in the above immune-inflammatory variables, levels of serum cortisol, and scores on the Perceived Stress Scale (PSS) or the State-Trait Anxiety Inventory (STAI) were examined. Academic examination stress was associated with significant increases in PSS and STAI scores, and in serum sgp130 and sCD8 values. Academic examination stress was associated with significantly decreased serum sCD14 concentrations in students with high, but not low, stress perception. There were stress-induced differences in serum IL-1RA, sIL-6R and CC16 concentrations between students with high vs. low stress-induced anxiety. The stress-induced increase in serum sCD8 was significantly more pronounced in male students, whereas the increase in serum sgp130 was more pronounced in female students taking contraceptive drugs. These results suggest that: (1) psychological stress induces immune-inflammatory changes pointing toward complex regulatory responses in IL-6 signalling, a decreased anti-inflammatory capacity of the serum, and interactions with T cell and monocytic activation; and that (2) sex hormones may modify stress-induced immune-inflammatory responses.

Adaptation, Psychological↗
PubMed1999

Lowered omega3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients.

Depression is associated with a lowered degree of esterification of serum cholesterol, an increased C20:4omega6/C20:5omega3 ratio and decreases in omega3 fractions in fatty acids (FAs) or in the red blood cell membrane. The aims of the present study were to examine: (i) serum phospholipid and cholesteryl ester compositions of individual saturated fatty acids (SFAs), monounsaturated FAs (MUFAs) and polyunsaturated FAs (PUFAs) in major depressed patients vs. healthy volunteers; (ii) the relationships between the above FAs and lowered serum zinc (Zn), a marker of the inflammatory response in depression; and (iii) the effects of subchronic treatment with antidepressants on FAs in depression. The composition of the FAs was determined by means of thin layer chromatography in conjunction with gas chromatography. Lipid concentrations were assayed by enzymatic colorimetric methods. The oxidative potential index (OPI) of FAs was computed in 34 major depressed inpatients and 14 normal volunteers. Major depression was associated with: increased MUFA and C22:5omega3 proportions and increased C20:4omega6/C20:5omega3 and C22:5omega6/C22:6omega3 ratios; lower C22:4omega6, C20:5omega3 and C22:5omega3 fractions in phospholipids; lower C18:3omega3, C20:5omega3 and total (sigma)omega3 FAs, and higher C20:4omega6/C20:5omega3 and sigmaomega6/sigmaomega3 ratios in cholesteryl esters; lower serum concentrations of phospholipids and cholesteryl esters; and a decreased OPI. In depression, there were significant and positive correlations between serum Zn and C20:5omega3 and C22:6omega3 fractions in phospholipids; and significant inverse correlations between serum Zn and the sigmaomega6/sigmaomega3, C20:4omega6/C20:5omega3, and C22:5omega6/C22:6omega3 ratios in phospholipids. There was no significant effect of antidepressive treatment on any of the FAs. The results show that, in major depression, there is a deficiency of omega3 PUFAs and a compensatory increase in MUFAs and C22:5omega6 in phospholipids. The results suggest that: (i) there is an abnormal metabolism of omega3 PUFAs in depression; (ii) the FA alterations in depression are related to the inflammatory response in that illness; and (iii) the disorders may persist despite successful antidepressant treatment.

Adult↗
PubMed1999

Decreased platelet alpha-2 adrenoceptor density in major depression: effects of tricyclic antidepressants and fluoxetine.

BACKGROUND: It has been suggested that major depression is accompanied by a subsensitivity of central alpha 2-adrenoceptors (alpha 2-ARs) and, consequently, by an impaired negative feedback on the presynaptic catecholaminergic neuron, which, in turn, may induce a disinhibition of noradrenergic output and norepinephrine release in response to any activation. METHODS: The maximum number of platelet binding sites (Bmax) and their affinity for [3H]-rauwolscine, a selective alpha 2-AR antagonist, were measured in unmedicated and medicated major depressed patients and in normal volunteers. Specific binding was defined as that inhibited by idazoxan, another alpha 2-AR antagonist. RESULTS: Unmedicated major depressed patients had significantly decreased platelet [3H]-rauwolscine binding Bmax values compared to normal volunteers. [3H]-rauwolscine binding Kd values did not differ significantly between unmedicated major depressed patients and normal controls. [3H]-rauwolscine binding Kd values were significantly higher in depressed patients treated with tricyclic antidepressants than in unmedicated patients. Subchronic treatment with fluoxetine did not significantly alter either [3H]-rauwolscine binding Bmax or Kd values. [3H]-rauwolscine binding Bmax values were significantly greater in men than in women. CONCLUSIONS: The results suggest that i) major depression is accompanied by decreased platelet alpha 2-AR density; and that ii) subchronic treatment with tricyclic antidepressants, but not fluoxetine, results in a decreased affinity of rauwolscine for platelet alpha 2-ARs.

Adult↗
PubMed1999

Alterations in immune functions during normal aging and Alzheimer's disease.

It is thought that aging induces immune changes, which are related to the pathophysiology of Alzheimer's disease (DAT). In this study, the total number of leukocytes, white blood cell differentiation, mitogen-induced lymphocytic proliferation, neutrophil phagocytosis and superoxide release, and prostaglandin E2 (PGE2) production by mitogen-stimulated whole blood cultures were comparatively investigated between healthy adults (range 22-45 years) and healthy elderly volunteers (range 70-91 years), and between DAT patients (range 56-94 years) and age-matched control subjects. Healthy elderly volunteers showed significantly lower phytohemagglutinin (PHA)-induced lymphocyte proliferation and percentage and absolute number of basophils than young volunteers. In normal volunteers, there were significant and negative correlations between age and the number of basophils. Patients with DAT showed a trend toward significantly higher PHA-induced lymphocyte proliferation and significantly decreased percentage and absolute number of large unstained cells than healthy volunteers. In DAT patients, the total number of leukocytes and the percentage and number of neutrophils were positively correlated with age. All other immune-inflammatory variables were not significantly altered either by the aging process or DAT. The present study suggests that aging and DAT may differently affect some immune variables.

Adult↗
PubMed1999

In vitro immunoregulatory effects of lithium in healthy volunteers.

RATIONALE: There is now some evidence that major depression is associated with activation of the inflammatory response system (IRS). Lithium is effective in the treatment and prophylaxis of major depression and shows significant immunoregulatory functions. OBJECTIVE: The aims of the present study were to examine the in vitro effects of lithium on the unstimulated and lipolysaccharide (LPS) + phytohemagglutinin (PHA)-induced production of proinflammatory cytokines, such as interleukin-6 (IL-6), IL-8, tumor necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma), and negative immunoregulatory cytokines or proteins, such as IL-10 and the IL-1 receptor antagonist (IL-1RA). METHODS: The in vitro effects of lithium carbonate at low (10(-4) M and 10(-5) M) and therapeutic (10(-3) M) concentrations on the above cytokines and the IL-1RA were examined in nine healthy volunteers on whole blood supernatant cultured for 72 h. RESULTS: Lithium (10(-3) M) in the presence of LPS+PHA significantly increased the stimulated production of IFNgamma, IL-8, TNFalpha, IL-1RA and IL-10. Lithium (10(-3) M) significantly increased the unstimulated production of IL-8 and IL-10. CONCLUSIONS: The results suggest that lithium has significant immunoregulatory effects by increasing the production of both proinflammatory cytokines (IFNgamma, TNFalpha and IL-8) and negative immunoregulatory cytokines or proteins (IL-10 and the IL-1RA).

Adjuvants, Immunologic↗
PubMed1999

Higher serum prolyl endopeptidase activity in patients with post-traumatic stress disorder.

BACKGROUND: It is reported that psychiatric disorders, such as depression and schizophrenia, are associated with changes in serum activity of prolyl endopeptidase (EC 3.4.21.26), a cytosolic endopeptidase, which cleaves peptide bonds on the carboxylside of proline in proteins of relatively small molecular mass. AIMS AND METHODS: The aims of the present study were to examine serum PEP activity in patients with post-traumatic stress disorder (PTSD) versus healthy volunteers. PEP activity has been determined by a fluorimetric assay. RESULTS: Serum PEP activity was significantly higher in patients with PTSD than in normal volunteers. Serum PEP activity was significantly higher in patients with PTSD and concurrent major depression than in patients with PTSD without major depression. In PTSD patients, there were no significant correlations between serum PEP activity and severity of PTSD symptoms. CONCLUSIONS: The results show that PTSD and, in particular, PTSD with concurrent major depression is associated with increased activity of PEP. RELEVANCE: these results may be of importance for the (i) neuroendocrine pathophysiology of PTSD since PEP degrades neuropeptides, such as arginine vasopressin (AVP) and thyrotropin releasing hormone (TRH); and (ii) etiology of PTSD, since PEP degrades behaviorally active neuropeptides, such as AVP, TRH, oxytocin, neurotensin and substance P, which play a key role in positive reinforcement, social interactions, emotions and stress responsivity.

Adult↗
PubMed1999

Seasonal and circadian rhythms in suicide in Cagliari, Italy.

BACKGROUND: In previous studies of the seasonality of suicide, peaks have often been found in the number of suicides in the spring and early summer in both northern and southern hemispheres. The purpose of the present study was to investigate the distribution of suicide as to month, seasons, day of the week, and time of the day. METHOD: Data on suicides in Cagliari (Italy) in the period 1990-1994 were analyzed by means of spectral analysis, cosinor and multiple regression analysis. RESULTS: Two seasonal rhythms, i.e. an annual and a semiannual rhythm, accounted for 25% of the variation in the total number of suicides. The peak number of suicides occurred in February with a second less significant peak in June and July. Lows were found in November and December. There were no significant differences in number of suicides in relation to days of the week. Three rhythms, i.e. 24 hours (circadian), 8 hours and 1 hour, explained 63.9% of the variance in the number of suicides by time of the day. Peak numbers in number of suicides were found between 08:31 and 12:30h, while the number of suicides was also significantly higher between 12:31h and 20:30h than between 20.31h and 8.30h. Age and gender did not significantly affect the seasonal and circadian rhythms in suicide. CONCLUSIONS: The results show that there is a significantly seasonal variation and a highly significant variation by time of the day in suicide in Cagliari, Italy.

Adult↗
PubMed1999

Lower serum zinc in major depression in relation to changes in serum acute phase proteins.

There is now some evidence that major depression is accompanied by activation of the inflammatory response system (IRS). Other signs of IRS activation, which have been reported in major depression are lowered serum zinc (Zn) and serum albumin (Alb) concentrations. In serum, Zn is closely bound to Alb. The aims of the present study were to replicate previous findings that major depression is accompanied by lowered serum Zn and Alb and to examine whether the decrease in serum Zn may be explained by that in serum Alb. The above variables were determined in 48 major depressed patients and in 15 age-sex-matched healthy volunteers. Serum Zn and Alb were significantly lower in major depressed patients than in normal volunteers. In healthy volunteers and major depressed patients, there were significant and positive correlations between serum Zn and Alb. We found that 53.8% of the variance in serum Zn could be explained by the combined effects of serum Alb and diagnostic classification. The results suggest that lower serum Zn in depression is in part explained by lowered serum Alb and by another depression-related mechanism. It is suggested that lower serum Zn in depression may be secondary to sequestration of metallothionein in the liver, which may be related to increased production of interleukin-6.

Acute-Phase Proteins↗
PubMed1999

The immune-inflammatory pathophysiology of fibromyalgia: increased serum soluble gp130, the common signal transducer protein of various neurotrophic cytokines.

Fibromyalgia is a chronic, painful musculoskeletal disorder characterized by widespread pain, pressure hyperalgesia, morning stiffness and by an increased incidence of depressive symptoms. The etiology, however, has remained elusive. The aim of the present study was to examine the inflammatory response system (IRS) in fibromyalgia. Serum interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), sgp130, sIL-1R antagonist (IL-1RA) and sCD8 were determined in 33 healthy volunteers and in 21 fibromyalgia patients, classified according to the American College of Rheumatology criteria. Severity of illness was measured with several pain scales, dolorimetry and the Hamilton Depression Rating Scale (HDRS). Serum sgp130 was significantly higher and serum sCD8 significantly lower in fibromyalgia patients than in healthy volunteers. Serum sIL-6R and sIL-1RA were significantly higher in fibromyalgia patients with an increased HDRS score (> or = 16) than in normal volunteers and fibromyalgia patients with a HDRS score < 16. In fibromyalgia patients, an important part of the variance in sCD8 (50.3%) and IL-1RA (19.3%) could be explained by the HDRS score; 74.3% of the variance in sIL-6R was explained by the combined effects of pain symptoms and the HDRS score; and 25.9% of the variance in serum sgp130 was explained by stiffness. The results support the contention that pain and stiffness in fibromyalgia may be accompanied by a suppression of some aspects of the IRS and that the presence of clinically significant depressive symptoms in fibromyalgia is associated with some signs of IRS activation.

Antigens, CD↗
PubMed1999

Lower activity of serum peptidases in abstinent alcohol-dependent patients.

This study examines i) the activity of serum prolyl endopeptidase (PEP) and dipeptidlyl peptidase IV (DPP IV) in detoxified alcohol-dependent patients without liver disease versus normal controls, and ii) the relationships between serum DPP IV and PEP activity and the production of cytokines or cytokine receptors, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), interferon-y (IFN-y), IL-1 receptor antagonist (IL-1RA), and IL-10, and granulocyte-macrophage colony stimulatory factor (GM-CSF). Alcohol-dependent patients had significantly lower serum PEP and DPP IV activity than normal controls. We found that 58.3% and 50.0% of the alcohol-dependent patients, respectively, had PEP and DPP IV activities, which were lower than the mean control values minus 2 SD. There were significant inverse correlations between lowered serum DPP IV and PEP activity and the increased production of IL-6, INF-gamma, IL-IRA, IL-10, and GM-CSF. These results show that lower serum DPP IV and PEP activity may be related to the pathophysiology of alcohol dependence.

Adult↗
PubMed1999

Serotonergic and noradrenergic markers of post-traumatic stress disorder with and without major depression.

Some studies have suggested that disorders in the peripheral and central metabolism of serotonin (5-HT) and noradrenaline (NE) may play roles in the pathophysiology of post-traumatic stress disorder (PTSD). This study examines (1) the availability of plasma total tryptophan, the precursor of 5-HT, and tyrosine, the precursor of NE; and (2) the platelet 5-HT transporter and alpha 2-adrenoceptor (alpha 2-AR) binding sites in patients with PTSD and healthy volunteers. High-performance liquid chromatography (HPLC) was employed to measure plasma tryptophan and tyrosine as well as amino acids known to compete with the same cerebral transport system; that is, valine, leucine, phenylalanine, and isoleucine. The maximum number of binding sites (Bmax) and their affinity (Kd) for binding to [3H]-paroxetine and [3H]-rauwolscine, a selective alpha 2-AR antagonist, were determined. [3H]-paroxetine and [3H]-rauwolscine binding Kd values were significantly higher in patients with PTSD than in healthy volunteers. [3H]-rauwolscine binding Kd values were significantly higher in patients with PTSD and concurrent major depression (MD) than in PTSD patients without MD and healthy volunteers. Plasma tyrosine concentrations and the ratio of tyrosine/valine + leucine + isoleucine + phenylalanine + tryptophan were significantly higher in PTSD patients with MD than in those without MD and healthy volunteers. The results show that PTSD is accompanied by lower affinity of paroxetine binding sites and that PTSD with concurrent MD is accompanied by lower affinity of alpha 2-ARs and increased plasma tyrosine availability to the brain. The results suggest that (1) serotonergic mechanisms, such as defects in the 5-HT transporter system, may play a role in the pathophysiology of PTSD; and (2) that catecholaminergic mechanisms, such as increased precursor availability and lowered affinity of alpha 2-ARs, may play a role in the pathophysiology of PTSD with concurrent MD.

Adrenergic alpha-Antagonists↗
PubMed1999

Negative immunoregulatory effects of antidepressants: inhibition of interferon-gamma and stimulation of interleukin-10 secretion.

There is now some evidence that major depression is accompanied by activation of the inflammatory response system. There is also some evidence that antidepressants may suppress the release of cytokines, such as interleukin-1 beta (IL-1 beta) and IL-6 by activated monocytes and IL-2 and interferon-gamma (IFN gamma) by activated T cells. This study was carried out to examine the effects of clomipramine, sertraline, and trazodone on the stimulated production of IFN gamma, a pro-inflammatory cytokine, and IL-10, a negative immunoregulatory cytokine. Whole blood of nine healthy volunteers was stimulated with PHA, 5 micrograms/mL and LPS, 25 micrograms/mL for 72 hr with and without incubation with clomipramine, 10(-6) and 10(-9) M, sertraline, 10(-6) and 10(-8) M, and trazodone, 10(-6) and 10(-8) M. All three antidepressants significantly reduced IFN gamma secretion, whereas clomipramine and sertraline significantly increased IL-10 secretion in culture supernatant. All three antidepressants significantly reduced the IFN gamma/IL-10 ratio. The results suggest that antidepressants, at concentrations in the therapeutical range, have negative immunoregulatory effects through inhibition of IFN gamma and stimulation of IL-10 release.

Adult↗
PubMed1999

HPA axis and cytokines dysregulation in schizophrenia: potential implications for the antipsychotic treatment.

The authors discuss literature evidence on the possible dysfunctioning of HPA axis and the inflammatory response system (IRS) in schizophrenia in relation to a more comprehensive bio-pathogenetic hypothesis of the disorder and to the development of specific clinical patterns or 'core' schizophrenic symptoms, like those included in the so called negative/depressive dimension. The dysfunctions of HPA axis and IRS could be linked to some neurodevelopmental damage in relevant brain areas like hippocampus and it could involve mainly the glutamatergic pathways (e.g. NMDA receptors). Moreover, these changes could have some predictive value for response to typical antipsychotics (specifically for negative symptoms and drug resistance) in schizophrenia. Finally, the differential activity of typical versus atypical antipsychotic compounds on the basic HPA axis and IRS dysregulations in schizophrenia could account, at least partly, for the better clinical stabilization achieved in patients treated with the latter drugs compared to those receiving conventional neuroleptics.

Animals↗
PubMed1999

The fetomaternal dependency of cord blood interleukin-6.

Interleukin-6 (IL-6) plays a major role in hematopoiesis, immune functioning, and the acute phase response. In umbilical cord blood, this cytokine was thought to be a marker of neonatal defense to stress and infection, however, neonatal IL-6 production is immature. We speculated that a maternal influence exists on neonatal IL-6, at least during uncomplicated deliveries. Of the 81 healthy parturients included in this study, 51 delivered vaginally, 20 with and 31 without epidural analgesia, and 30 underwent elective cesarean section, 20 with epidural and 10 with general anesthesia. Maternal blood was sampled on hospital admission and just after delivery. Neonatal blood was collected from the umbilical cord. A significant positive correlation was found between neonatal cord blood interleukin-6 levels and maternal serum IL-6 levels on admission (r = 0.57, p <0.001) and just after delivery (r = 0.79, p <0.001). This was not influenced by the type of delivery or anesthesia. Neonatal IL-6 levels were weakly negatively correlated with the duration of gestation and with the Apgar score 1 min after birth. A feto-maternal dependency of neonatal IL-6 on maternal serum IL-6 levels implies a priming or modulatory role of the maternal immune system on that of the neonate.

Analgesia, Obstetrical↗
PubMed1999

Pindolol and mianserin augment the antidepressant activity of fluoxetine in hospitalized major depressed patients, including those with treatment resistance.

The aims of this study were to examine whether pindolol, a serotonin (5-hydroxytryptamine [5-HT])-1A receptor antagonist, and mianserin, a 5-HT2A/C and alpha2-adrenoceptor (alpha2-AR) antagonist, may augment the clinical efficacy of fluoxetine, a selective serotonin reuptake inhibitor, and shorten the latency of onset of antidepressive activity in the treatment of major and treatment-resistant depression (TRD). Ten days after admission to the hospital, 31 major depressed patients were randomly assigned using a double-blind, controlled design to receive fluoxetine 20 mg daily, fluoxetine 20 mg daily plus pindolol 7.5 mg daily, or fluoxetine 20 mg plus mianserin 30 mg daily for 5 weeks. The 17-item Hamilton Rating Scale for Depression (HAM-D) score was the primary outcome measure. Analysis of efficacy was conducted according to the intent-to-treat analysis principle considering the change from baseline to endpoint. It was found that fluoxetine plus pindolol and fluoxetine plus mianserin were significantly more effective than fluoxetine alone. Using an outcome measure of 50% reduction in the HAM-D, a 60% response rate was found in patients treated with either fluoxetine plus pindolol or fluoxetine plus mianserin compared with a 9% response rate in patients treated with fluoxetine alone. The HAM-D score 1 week after starting fluoxetine plus mianserin decreased more than 4 points and was significantly greater than that obtained by fluoxetine alone. The results suggest that pindolol and mianserin augment the efficacy of fluoxetine in the treatment of TRD and that mianserin, but not pindolol, may significantly shorten the latency of onset of antidepressive action when combined with fluoxetine.

Adult↗
PubMed1999

The effects of psychological stress on leukocyte subset distribution in humans: evidence of immune activation.

The aim of the present study was to examine the effects of academic examination stress on leukocyte subset distribution in university students. Thirty-eight university students had repeated blood collections for white blood cell differentiation and flow cytometric assay of lymphocytic subsets a few weeks before and after (i.e. two baseline conditions) as well as the day before a difficult academic examination (i.e. stress condition). Flow cytometry was used to determine the number of peripheral blood mononuclear cells (PBMC). In students, who were reactors to psychological stress (criterion based on changes in the Perceived Stress Scale, PSS), but not in stress non-reactors, a significant increase in the number of neutrophils, monocytes, CD8(+), CD2(+)CD26(+), and CD2(+)HLA-DR+ T cells and CD19(+) B cells, and significant reductions in the CD4(+)/CD8(+) T cell ratio were observed in the stress condition. There were significant and positive relationships between the stress-induced changes in perceived stress (PSS scale) and number of leukocytes, neutrophils, CD2(+), CD2(+)CD26(+) and CD2(+)HLADR+ T cells, and CD19(+) B cells. There were significant and negative relationships between the stress-induced changes in the CD4(+)/CD8(+) ratio and the stress-induced changes in the PSS scale. Female students taking oral contraceptives showed significantly higher stress-induced responses in number of leukocytes, neutrophils and CD19(+) B cells than male and female students without use of oral contraceptives. The results suggest that academic examination stress induces changes in the distribution of PBMC, which indicate immune activation and which are probably orchestrated by a stress-induced production of cytokines.

Adult↗
PubMed1999

Lower serum zinc in relation to serum albumin and proinflammatory cytokines in detoxified alcohol-dependent patients without apparent liver disease.

Recently, it was reported that there may be an activation of the inflammatory response system in detoxified alcohol-dependent patients without apparent liver disease (AWLD). The aims of the present study were to examine serum zinc (Zn) concentrations, total serum protein (TSP) and patterns obtained in the electrophoretically separated protein fractions in relation to serum interleukin-6 (IL-6) and IL-8 concentrations in detoxified AWLD patients. Zn, TSP, SP electrophoresis, and serum IL-6 and IL-8 concentrations were determined in detoxified AWLD patients and age-matched healthy volunteers. Serum Zn, TSP and the serum concentrations of albumin (Alb) and the beta fraction were significantly lower in detoxified AWLD patients than in healthy volunteers. The percentage of the alpha2 fraction was significantly higher in detoxified AWLD patients. Lower serum Zn in detoxified AWLD patients was attributable to lowered serum Alb. Lower serum Alb was significantly and negatively correlated to increased serum IL-8. The percentage of the alpha1 and alpha2 fractions were significantly and positively related to serum IL-6 and IL-8. The results show that there is an in vivo activation of the inflammatory response system in detoxified AWLD patients and that lower serum Zn may be causally related to lower serum Alb.

Adult↗