Napoleon Waszkiewicz

Effect of risperidone and olanzapine on reproductive hormones, psychopathology and sexual functioning in male patients with schizophrenia.

OBJECTIVE To study the effect of drugs on the hypothalamo-pituitary-gonadal (HPG) axis we compared the endocrine actions of two neuroleptics with different receptor affinity profiles-risperidone and olanzapine in male schizophrenic patients. METHODS We investigated the levels of prolactin, estradiol, testosterone, LH, FSH and testicular peptide hormone-inhibin B, and we assessed psychopathology (PANSS), sexual function (ASEX) and treatment adherence (DAI-10) in 89 male schizophrenic inpatients treated with olanzapine or risperidone administered orally. The initial and final evaluations were carried out at weeks 3 and 8 after the onset of treatment, respectively. RESULTS At initial evaluation the mean serum prolactin and inhibin B levels were markedly higher, whereas testosterone level was lower in patients treated with risperidone, than in those treated with olanzapine. In 5 out of 50 subjects from risperidone group (10%) and in 1 from olanzapine group (2.6%) testosterone levels were below the lower limit (<241ng/ml), which reflected Leydigs cell impairment. In one patient receiving risperidone and in three receiving olanzapine, inhibin B level was below 80pg/ml, indicating Sertolis cell dysfunction. At the final evaluation the mean serum prolactin level was markedly higher in patients taking risperidone, whereas their FSH levels were lower than in patients receiving olanzapine. In all investigated groups, except for the risperidone-hyperprolactinemic group inhibin B levels were negatively correlated with serum FSH. The mean LH, FSH, testosterone and estradiol levels were within the normal reference range at initial and final evaluation. The non-adherence to medications and ASEX scores were significantly higher in risperidone groups. Sexual dysfunction and medication non-adherence was not related to prolactin or gonadal hormone levels. CONCLUSIONS Risperidone elicited higher PRL elevation than olanzapine. Treatment with this medication can be associated with disturbances in reproductive hormones (testosterone) and gonadotropins (FSH). The cause of olanzapine-elicited reduction of inhibin B level and the lack of negative correlation between FSH and inhibin B in patients with risperidone-induced hyperprolactinemia require further investigation. Patients receiving risperidone showed higher level of sexual dysfunction and treatment non-adherence than those treated with olanzapine.

Proton magnetic resonance spectroscopy study of brain metabolite changes after antipsychotic treatment.

INTRODUCTION Proton magnetic resonance spectroscopy (¹H MRS) enables the observation of brain function in vivo. The aim of our study was to evaluate the effects of antipsychotic medication on metabolite levels in the brain of schizophrenic patients based on a ¹H MRS examination. METHODS We examined 42 patients previously diagnosed with chronic schizophrenia twice: firstly, after the neuroleptic wash-out (baseline) and secondly, under stable medication (follow-up, after treatment). The study had a naturalistic design and several different neuroleptic medications were used during the treatment phase. The clinical evaluation, MRI and MRS procedures were performed. The group of 26 healthy controls were also examined to compare MRS results. RESULTS We found a significantly lower NAA/Cr (N-acetylaspartate/creatine) ratio in the frontal lobe and thalamus in patients (after the wash-out) as compared to controls. After treatment a significant decrease of the Glx/Cr ratio in the temporal lobe and a trend for an increase of the NAA/Cr ratio in the thalamus were observed. CONCLUSION Our results confirm that antipsychotic medication modifies brain metabolism measured by means of ¹H MRS. The pattern of the changes suggests a neuroprotective action of antipsychotic medication in schizophrenia.

Alcohol abuse and glycoconjugate metabolism

The relationship between alcohol consumption and glycoconjugate metabolism is complex and multidimensional. This review summarizes the advances in basic and clinical research on the molecular and cellular events involved in the metabolic effects of alcohol on glycoconjugates (glycoproteins, glycolipids, and proteoglycans). We summarize the action of ethanol, acetaldehyde, reactive oxygen species (ROS), nonoxidative metabolite of alcohol — fatty acid ethyl esters (FAEEs), and the ethanol-water competition mechanism, on glycoconjugate biosynthesis, modification, transport and secretion, as well as on elimination and catabolism processes. As the majority of changes in the cellular metabolism of glycoconjugates are generally ascribed to alterations in synthesis, transport, glycosylation and secretion, the degradation and elimination processes, of which the former occurs also in extracellular matrix, seem to be underappreciated. The pathomechanisms are additionally complicated by the fact that the effect of alcohol intoxication on the glycoconjugate metabolism depends not only on the duration of ethanol exposure, but also demonstrates dose- and regional-sensitivity. Further research is needed to bridge the gap in transdisciplinary research and enhance our understanding of alcohol- and glycoconjugate-related diseases.

The Effect of the Binge Drinking Session on the Activity of Salivary, Serum and Urinary β-Hexosaminidase: Preliminary Data

Our report is the first to show that an acute ingestion (6 h) of a relatively large, yet tolerable dose of alcohol (120-160 g), significantly increases activity of total serum beta-hexosaminidase (total beta-HEX), beta-HEX A and beta-HEX B isoenzymes, as well as salivary total beta-HEX and urinary beta-HEX A, in eight infrequent binge drinkers. An increase in the activity of serum and urinary total HEX is mainly due to its secretory isoenzyme beta-HEX A.

Glycoconjugates in the detection of alcohol abuse

Up to 30% of all hospital admissions and health-care costs may be attributable to alcohol abuse. Ethanol, its oxidative metabolites, acetaldehyde and ROS (reactive oxygen species), non-oxidative metabolites of alcohol [e.g. FAEEs (fatty acid ethyl esters)] and the ethanol-water competition mechanism are all involved in the deregulation of glycoconjugate (glycoprotein, glycolipid and proteoglycan) metabolic processes including biosynthesis, modification, transport, secretion, elimination and catabolism. An increasing number of new alcohol biomarkers that are the result of alcohol-induced glycoconjugate metabolic errors have appeared in the literature. Glycoconjugate-related alcohol markers are involved in, or are a product of, altered glycoconjugate metabolism, e.g. CDT (carbohydrate-deficient transferrin), SA (sialic acid), plasma SIJ (SA index of apolipoprotein J), CETP (cholesteryl ester transfer protein), β-HEX (β-hexosaminidase), dolichol, EtG (ethyl glucuronide) etc. Laboratory tests based on changes in glycoconjugate metabolism are useful in settings where the co-operativeness of the patient is impaired (e.g. driving while intoxicated) or when a history of alcohol use is not available (e.g. after trauma). In clinical practice, glycoconjugate markers of alcohol use/abuse let us distinguish alcoholic from non-alcoholic tissue damage, having important implications for the treatment and management of diseases.

The Effect of Acute Ethanol Intoxication on Salivary Proteins of Innate and Adaptive Immunity

BACKGROUND Human salivary proteins: peroxidase, lysozyme, lactoferrin, and IgA, participate in the protection of oral tissues, as well as upper digestive and respiratory tracts, against a number of microbial pathogens. In the current study, we investigated the effect of acute consumption of a large dose of ethanol on representative human salivary proteins of the innate and adaptive immune systems. METHODS Eight healthy male volunteers drank an average of 2.0 g (1.4 to 2.5 g/kg) body weight of ethanol, in the form of vodka, in the 6-hour period. Samples of resting whole saliva were collected 12 hours before, then 36 and 108 hours after, the alcohol consumption. The levels of total protein, immunoglobulin A, lysozyme and lactoferrin as well as peroxidase activity were determined in saliva. RESULTS At 36 hours after alcohol consumption, salivary protein and lysozyme concentrations as well as peroxidase activity were significantly decreased (p = 0.002, p = 0.043, and p = 0.003, respectively), in comparison to the values obtained at 12 hours before drinking. Between 36 and 108 hours after alcohol consumption, the salivary protein and lysozyme concentrations, as well as peroxidase activity showed a tendency to increase, although at 108 hours after the drinking session, the concentration of protein and peroxidase activity were still significantly lower than before drinking. There was no significant change in the level of lactoferrin, after the drinking session. The salivary concentration of IgA tended to increase at 36 hours after alcohol consumption, and at 108 hours it was significantly higher (p = 0.028), when compared to IgA concentration in the saliva collected before drinking (from 8% to 26% and 32% of total protein content, respectively). CONCLUSION Our report is the first to show that acute ingestion of relatively large, yet tolerable dose of alcohol, significantly disturbs salivary antimicrobial defense system. Reduced lysozyme level and decreased peroxidase activity may contribute to increased susceptibility to infections, when acute alcohol intake coincides with exposure to pathogens.

Salivary antioxidants in patients with systemic sclerosis

BACKGROUND In spite of relatively large amount of evidence that oxidative stress is implicated in the pathogenesis of systemic sclerosis, there is no study analyzing antioxidants profile of the saliva of these patients. The aim of this study was to compare salivary antioxidants in subjects with systemic sclerosis and the healthy controls. METHODS The unstimulated and stimulated salivary flow and the specific activity of peroxidase, superoxide dismutase 1, the total amount of uric acid, and total antioxidant status were determined in two subgroups of systemic sclerosis women and healthy controls. RESULTS A significant increase in the specific activity of peroxidase, a significant decrease in the total amount of uric acid and total antioxidants status in unstimulated saliva as well as a significant increase in all antioxidants examined in stimulated saliva of group with normal salivary flow rate as compared to the healthy controls were observed. Our results showed a significant decrease in the specific activity of peroxidase in unstimulated and a significant decrease in all antioxidants examined in stimulated saliva of the group with hyposalivation as compared to the group with normal salivary flow rate. CONCLUSIONS Our results prove that impairment of the salivary glands in the course of systemic sclerosis may be attributed to free radicals, and it is correlated with disease duration.

Proton Magnetic Resonance Spectroscopy Changes After Antipsychotic Treatment

Proton magnetic resonance spectroscopy ((1)H MRS) enables the observation of brain function in vivo. Several brain metabolites can be measured by the means of (1)H MRS: N-acetylaspartate (NAA), choline containing compounds (Cho), myo-inositol (mI) and glutamate (Glu), glutamine (Gln) and GABA (together as Glx complex or separately). (1)H MRS measures have been found to be abnormal in psychotic disorders such as schizophrenia. Here we specifically review the influence exerted by antipsychotic drugs on brain metabolism, as detected by (1)H MRS. We systematically reviewed the available literature and uncovered 27 studies, 16 before-after treatment and 11 cross-sectional. Most of them addressed the effects of antipsychotics in schizophrenia and mainly focusing on NAA alterations. Follow up studies indicated antipsychotic drugs may act by increasing NAA levels in selected brain areas (the frontal lobe and thalamus), especially during the short-time observation. This phenomenon seems to vanish after longer observation. Other studies indicated that glutamate measures are decreasing along with the duration of the disease, suggesting both a neurodegenerative process present in schizophrenic brain as well as an influence of antipsychotics. The above results were reviewed according to the most recent theories in the field accounting for the impact of antipsychotics (1)HMRS measures.

Exoglycosidase markers of diseases.

Exoglycosidases are hydrolases involved in lysosomal degradation of oligosaccharide chains of glycoconjugates (glycoproteins, glycolipids and proteoglycans). In tissues and body fluids, a higher exoglycosidase specific activity is found in N-acetyl-β-hexosaminidase, than β-glucuronidase, α-L-fucosidase, β-galactosidase, α-mannosidase and α-glucosidase. Determination of exoglycosidases (especially N-acetyl-β-hexosaminidase and β-glucuronidase) in body fluids could be an inexpensive, easy to perform and sensitive test for pathological evaluation, as well as in screening and monitoring many diseases, including alcohol abuse, risk of arteriosclerosis, bacterial infections (e.g. Lyme borreliosis), chronic inflammatory processes, such as rheumatoid arthritis and juvenile idiopathic arthritis, asthma, autoimmune hepatitis and primary biliary cirrhosis, as well as cancers.

Rheumatoid arthritis patients with xerostomia have reduced production of key salivary constituents

OBJECTIVE The aim of this study was to assess the relationship between complaints of xerostomia in patients with rheumatoid arthritis (RA) with the total output of the salivary proteins of innate and adaptive immunity. STUDY DESIGN The salivary output and specific activity of peroxidase and specific contents of lysozyme, lactoferrin, and secretory immunoglobulin A (sIgA) were determined in xerostomic RA patients, nonxerostomic RA patients, and healthy control subjects. RESULTS Compared with nonxerostomic RA and healthy control groups, xerostomic RA patients had significantly decreased output of saliva and protein, decreased peroxidase activity, and a significantly lower specific content of peroxidase and sIgA. Compared with the RA control group, xerostomic RA patients had significantly lower specific content of all salivary proteins examined. CONCLUSIONS The results indicate that xerostomia in patients with RA may be a harbinger of diminished saliva production regarding quantity and quality, and may be indicative of impairment of the salivary immune system of the oral cavity in xerostomic RA patients.