Beata Konarzewska

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

OBJECTIVEnTo 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.nnnMETHODSnWe 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.nnnRESULTSnAt 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.nnnCONCLUSIONSnRisperidone 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.

INTRODUCTIONnProton 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.nnnMETHODSnWe 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.nnnRESULTSnWe 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.nnnCONCLUSIONnOur 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.

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.

Proton magnetic resonance spectroscopy measures related to short-term symptomatic outcome in chronic schizophrenia.

INTRODUCTIONnProton magnetic resonance spectroscopy (¹H MRS) enables the evaluation of in vivo brain function. The purpose of the study was to compare ¹H MRS measurements in schizophrenic patients, who were clinical responders after short-term antipsychotic treatment, with non-responders and healthy controls.nnnMETHODSnWe investigated a group of 47 patients diagnosed with schizophrenia. Patients were examined twice--once after a period of at least 7 days without neuroleptics and the second time at least 4 weeks after therapy with stable doses of medication. The follow-up was available in 42 patients. Baseline MRS measurements of clinical responders were compared with non-responders and the group of healthy controls (N=26). We assessed the following metabolite ratios: NAA (N-acetylaspartate), Glx (complex of GABA, glutamine and glutamate), Cho (choline) and mI (myo-inositol) to creatinine (Cr) in the left frontal and temporal lobes and the thalamus.nnnRESULTSnResponders showed a significantly lower baseline frontal Glx/Cr level than non-responders. Both groups had a significantly lower NAA/Cr ratio in the frontal lobe than the controls, but only non-responders had a significantly lower NAA/Cr ratio in the thalamus.nnnCONCLUSIONSnOur results confirm the relationship between the glutamatergic system and pathophysiology of schizophrenia and suggest a significant value of ¹H MRS examination in the assessment of the future treatment effect.

Decrease in salivary lactoferrin output in chronically intoxicated alcohol-dependent patients

Salivary lactoferrin is a glycoprotein involved in the elimination of pathogens and the prevention of massive overgrowth of microorganisms that affect oral and general health. A high concentration of lactoferrin in saliva is often considered to be a marker of damage to the salivary glands, gingivitis, or leakage through inflamed or damaged oral mucosa, infiltrated particularly by neutrophils. We conducted a study to determine the effect of chronic alcohol intoxication on salivary lactoferrin concentration and output. The study included 30 volunteers consisting of ten non-smoking male patients after chronic alcohol intoxication (group A), and 20 control nonsmoking male social drinkers (group C) with no history of alcohol abuse. Resting whole saliva was collected 24 to 48 hours after a chronic alcohol intoxication period. Lactoferrin was assessed by enzyme-linked immunosorbent assay. For all participants, the DMFT index (decayed, missing, or filled teeth), gingival index (GI) and papilla bleeding index (PBI) were assessed. The differences between groups were evaluated using the Mann-Whitney U test. We noticed significantly decreased salivary flow (SF) in alcohol dependent patients after chronic alcohol intoxication (A), compared to the control group (C). Although there was no significant difference in salivary lactoferrin concentration between the alcohol dependent group A and the control group C, we found significantly decreased lactoferrin output in group A compared to group C. We found a significant correlation between the amount of daily alcohol use and a decrease in lactoferrin output. There was a significant increase in GI and a tendency of PBI to increase in group A compared to group C. We demonstrated that chronic alcohol intoxication decreases SF and lactoferrin output. The decreased lactoferrin output in persons chronically intoxicated by alcohol may be the result of lactoferrin exhaustion during drinking (due to its alcohol-related lower biosynthesis or higher catabolism) or to decreased function of neutrophils affected by the ethanol. The poorer periodontal state in alcohol dependent persons compared to controls may be a result of lower salivary flow and decreased protection of the oral cavity by lactoferrin.

The effect of chronic alcohol intoxication and smoking on the activity of oral peroxidase

Peroxidase is the most important antioxidant enzyme in saliva. Through peroxidation of thiocyanate in the presence of H2O2, peroxidase catalyses the formation of bacteriocidic compounds such as hypothiocyanate. The purpose of this study was to evaluate the effect of chronic alcohol intoxication and smoking on the activity of oral peroxidase (OPO). A total of 37 volunteers participated in the study. This cohort consisted of 17 male alcohol-dependent smoking patients after chronic alcohol intoxication (AS group, alcohol + smoking) (mean age: 42 years; range: 26–55) (100–700 g/day of alcohol; 10–20 cigarettes/day) and 20 control male social drinkers (CNS group, control non-smokers) with no history of alcohol abuse or smoking (mean age: 42 years; range: 30–53). Salivary peroxidase activity was measured by the colorimetric method. The differences between groups were evaluated using the Mann–Whitney U test. There was significantly higher activity of OPO (p = 0.00001) and significantly lower salivary flow (SF) (p = 0.007) in alcohol-dependent smokers after chronic alcohol intoxication compared to the control group. OPO activity significantly correlated with the number of days of alcohol intoxication, but not with smoking. Gingival index (GI) was significantly higher in smoking alcohol-dependent persons than in the control group, and correlated with OPO activity. The sensitivity of the OPO test was 70% in smoking alcoholics, while specificity was 95%. The increased activity of OPO suggests chronic oxidative stress is more likely due to ethanol action than to smoking. Smoking alcohol-dependent persons have a worse periodontal status than controls. OPO activity as a marker of chronic alcohol abuse may help in the diagnosis of alcoholism.

Binge drinking–induced liver injury

We read with interest the excellent article by Ioannou and colleagues demonstrating that diet may be an important determinant of liver disease, after adjusting for potential confounders including daily consumption of protein, carbohydrates, alcohol, fat, tea, and coffee; as well as sex, body mass index, etc.1 Alcohol consumption variable was categorized as none, 0 to 1, 1 to 2, and 2 drinks/day. In characterizing excessive alcohol consumers as those who consume 2 drinks/day, we may consider persons who drink alcohol chronically (alcoholics) or persons who occasionally drink higher amounts of alcohol (binge drinkers). Only 5% and 15% of persons suffering from cirrhosis or liver cancer, respectively, drank excessively.1 However, it would be prudent to divide them into occasional (binge) and chronic drinkers in further studies. The drastic increase in alcohol-induced liver injury and mortality rates is alarming.2 The binge drinking phenomenon that is now spreading throughout young populations worldwide is at least in part responsible for this drastic increase in liver injury.2 Binge drinking is characterized by the consumption of alcohol leading to intoxication (drinking to get drunk), often measured as having more than four (women) or five (men) number of drinks on one occasion.3 On more than 30% of occasions when men go out to drink, they consume binge amounts of alcohol.2 In the literature, alcohol binging has been described to increase the risk for numerous acute adverse health and social events including injuries, violence, suicide, acute myocardial infarction, etc.4 but liver consequences were often ignored. Most of experimental data concerning the impact of binge drinking on pathogenesis of the liver injury may not be completely extrapolated to humans, because most of the studies are based on animal models that do not completely mimic liver injury in humans (except a few studies describing oxidative stress involvement in pathogenesis of human liver lesions).2,5 During the drinking session, binge drinkers often think they remain within the recommended safe weekly limits of alcohol consumption ( 168 g of alcohol or fewer than 21 units).6 Furthermore, routine laboratory tests are not sensitive enough to detect harmful effects of single-occasion drinking on the liver, because pronounced changes are only measurable after very high and prolonged ethanol consumption.4 -Hexosaminidase, a very sensitive marker of harmful drinking to the liver, has been shown to increase in serum and urine after a single binge drinking session.3 Various mechanisms are responsible for alcohol-induced -hexosaminidase elevation: increase in lysosomal membrane permeability and leakage of the enzyme from lysosomes and subsequently from affected hepatocytes to the blood, delayed removal of -hexosaminidase by injured liver, and enhanced synthesis of the enzyme by activated reticuloendothelial cells.6 The impact of chronic alcohol consumption on liver tissue injury is well known and widely described by researchers. Less attention has been paid to binging-induced hepatoxicity, even though binge drinking is much more common than chronic alcoholism.4 The deleterious effect of binge drinking on the liver is an alarming public health issue that requires better prevention. Therefore, further studies focusing on binging-induced human liver injury seem to be warranted.

Underappreciated role of binge drinking in the risk of lung cancer

In their article, Tariola and colleagues1 reported that binge drinking was not associated with an increased risk of lung cancer among non-smokers, but among smokers it was. However, the number of lung cancer cases among non-smokers was relatively small and they concluded that larger studies are needed to clarify this controversial association. Generally, evidences of association between alcohol consumption and lung cancer seem to be insufficient; however, seven prospective studies suggested that the strongest effect of alcohol on …

The Salivary β-HEX A% Index as an Excellent Marker of Periodontitis in Smoking Alcohol-Dependent Persons

Background. Severe periodontitis leading to tooth loss is found in 5–15% of most populations worldwide. Aim. The applicability of salivary β-hexosaminidase (β-HEX A%, percentage of β-HEX A isoenzyme to total β-HEX) and β-HEX B% (β-HEX B/β-HEX) indexes was investigated as a possible marker of periodontitis. Methods. Thirty three alcohol-dependent smokers (AS) and 32 healthy controls (C) were enrolled in the study. The activity of β-HEX was measured spectrophotometrically. Results. β-HEX A% was significantly higher and β-HEX B% was lower in AS than in C group. We found a significant correlation between β-HEX A% and gingival index (GI) and an inverse correlation between β-HEX A% and salivary flow (SF), in all groups. Salivary β-HEX A% index in smoking alcoholics at 0.23 had excellent sensitivity (96%) and specificity (91%); the AUC for β-HEX A% was high (0.937). There were no correlations between amount/duration-time of alcohol drinking/smoking and β-HEX A% or β-HEX B%. We found significant correlations between the time period of denture wearing and GI, papilla bleeding index (PBI), and decayed missing filled teeth index (DMFT) and between GI and the amount of smoked cigarettes per day. Conclusion. Bad periodontal state was most likely due to the nicotine dependence. Salivary β-HEX A% is a promising excellent marker for the diagnosis of periodontitis.