Zuranolone - synthetic neurosteroid in treatment of mental disorders: narrative review.

With each passing year, the number of people suffering from mental disorders grows at a disturbing speed. Neuroactive steroids are a new promising group of drugs with the potential for use in many diseases like postpartum depression, postnatal psychosis, major depression, insomnia, bipolar disorder, and Parkinson's tremor, due to their ability to modulate the activity of GABAA receptor. Neurosteroids are progesterone metabolites that are synthesized from cholesterol or steroid hormones in various brain regions. They regulate neuronal development, regeneration, and neurotransmission. They are implicated in mood disorders, anxiety disorders, schizophrenia, PTSD, and impulsive aggression. Neurosteroids have been studied for their potential to prevent or treat neurodegenerative diseases such as Alzheimer's disease and HIV-associated dementia. They can promote neurogenesis, neuronal survival, myelination, and memory function. They can also affect the growth and sensitivity of hormone-dependent brain tumors such as gliomas. Zuranolone, a newly registered neurosteroid drug has shown huge flexibility in both clinical and ambulatory treatment thanks to its pharmacokinetic traits, especially the possibility for oral administration, unlike its predecessor Brexanolone. Zuranolone is a synthetic positive allosteric modulator of the GABAA receptor that can be taken orally. The review aims to summarize the current knowledge on zuranolone as a novel neurosteroid drug for various mental disorders, especially for postpartum mental disorders for which this drug was meant originally. It covers studies indexed in the PubMed, Scopus, and Web of Science databases published since 2017. Keywords used in the search, as well as inclusion and exclusion criteria, are given in the aims and methodology section. The review explains the evidence for the role of neurosteroids, especially allopregnanolone, in the pathophysiology and treatment of postpartum depression. It discusses the mechanisms of neurosteroid action, the changes in neurosteroid levels during pregnancy and postpartum, and the clinical trials of brexanolone and zuranolone, two synthetic analogs of allopregnanolone, for postpartum depression. It provides an overview of the biosynthesis and metabolism of neurosteroids in the central and peripheral nervous system. Furthermore, it explains the different sources and pathways of neurosteroid production and the factors that influence their synthesis and regulation, such as stress, hormones, drugs, and genetic variations. The review also explores the potential relevance of neurosteroids for other psychiatric disorders, such as major depression, bipolar disorder, post-traumatic stress disorder (PTSD), schizophrenia, and premenstrual dysphoric disorder. Finally, it highlights the associations between neurosteroid levels and symptom severity and the effects of neurosteroid modulation on mood, cognition, and neuroplasticity.

Healthy Food Pyramid as Well as Physical and Mental Activity in the Prevention of Alzheimer's Disease.

The ageing of the population is resulting in neurodegenerative diseases, including Alzheimer's disease (AD), which are an increasing social, economic and medical problem. Diet and physical activity are now considered as important modifiable factors that help prevent or delay the development of AD and other dementia-related diseases. The pyramid of healthy nutrition and lifestyle is a way of presenting the principles, the implementation of which gives a chance for proper development and a long healthy life. The basis of the pyramid, in the first place, is physical activity. Our review of the literature in the PubMed database supports the hypothesis that complementary factors, such as proper diet, physical exercise and mental activity, have a positive impact on the prevention of neurodegenerative diseases. The nutritional recommendations for healthy adults primarily include the consumption of vegetables, fruits, cereals, legumes, vegetable oils and fishes. Therefore, the introduction of Mediterranean and Asian diets may reduce the risk of the neurodegenerative diseases associated with dementia, whereas dairy products and meat-the main sources of L-carnitine-should be consumed in moderate amounts. The aim of our work is to provide up-to-date knowledge about the appropriate dietary model and healthy lifestyle elements and their impact on good health and the long life of people.

Serum Amyloid Biomarkers, Tau Protein and YKL-40 Utility in Detection, Differential Diagnosing, and Monitoring of Dementia.

Introduction: The diagnosis and treatment of dementia is one of the greatest challenges in contemporary health care. The widespread use of dementia biomarkers would improve the quality of life of patients and reduce the economic costs of the disease. The aim of the study was to evaluate the usefulness of proteins related to the Alzheimer's disease pathogenesis-amyloid beta isoform (Aß) and total tau protein (t-tau), as well as the quite recently discovered marker YKL-40 in the most common types of dementia. Methods: 60 dementia (AD-Alzheimer's disease, VaD-vascular dementia, MxD-mixed dementia) and 20 cognitively normal subjects over 60 years old were examined. Subjects with dementia of etiology different than AD or VaD and with neoplastic or chronic inflammatory diseases were excluded. Concentrations of Aß40, Aß42, t-tau, and YKL-40 were measured in serum using ELISA kits on admission and after 4 weeks of inpatient treatment. ANOVA and Tukey's test or Dunn's test were used to perform comparison tests between groups. Correlations were measured using Pearson's coefficient. Biomarker diagnostic utility was assessed with ROC analysis. Results: YKL-40 differentiates between cognitively normal and mild dementia patients with 85% sensitivity and specificity and t-tau with 72% sensitivity and 70% specificity. YKL-40 and t-tau concentrations correlate with each other and with the severity of clinically observed cognitive decline. Conclusions: YKL-40 is a sensitive and specific biomarker of early dementia and, to a lesser extent, of dementia progression, however, many comorbidities may influence its levels. In such conditions, less specific but still reliable t-tau may serve as an alternative marker. Obtained results did not confirm the diagnostic utility of amyloid biomarkers.

Biomarkers of Post-COVID Depression.

The COVID-19 pandemic is spreading around the world and 187 million people have already been affected. One of its after-effects is post-COVID depression, which, according to the latest data, affects up to 40% of people who have had SARS-CoV-2 infection. A very important issue for the mental health of the general population is to look for the causes of this complication and its biomarkers. This will help in faster diagnosis and effective treatment of the affected patients. In our work, we focused on the search for major depressive disorder (MDD) biomarkers, which are also present in COVID-19 patients and may influence the development of post-COVID depression. For this purpose, we searched PubMed, Scopus and Google Scholar scientific literature databases using keywords such as 'COVID-19', 'SARS-CoV-2', 'depression', 'post-COVID', 'biomarkers' and others. Among the biomarkers found, the most important that were frequently described are increased levels of interleukin 6 (IL-6), soluble interleukin 6 receptor (sIL-6R), interleukin 1 ß (IL-1ß), tumor necrosis factor α (TNF-α), interferon gamma (IFN-γ), interleukin 10 (IL-10), interleukin 2 (IL-2), soluble interleukin 2 receptor (sIL-2R), C-reactive protein (CRP), Monocyte Chemoattractant Protein-1 (MCP-1), serum amyloid a (SAA1) and metabolites of the kynurenine pathway, as well as decreased brain derived neurotrophic factor (BDNF) and tryptophan (TRP). The biomarkers identified by us indicate the etiopathogenesis of post-COVID depression analogous to the leading inflammatory hypothesis of MDD.

Mental Disorders, Cognitive Impairment and the Risk of Suicide in Older Adults.

More than 600 million people are aged 60 years and over are living in the world. The World Health Organization estimates that this number will double by 2025 to 2 billion older people. Suicide among people over the age of 60 is one of the most acute problems. The factors strongly associated with suicide are mentioned: physical illnesses, such as cancer, neurologic disorder, pain, liver disease, genital disorders, or rheumatoid disorders. Moreover, neurologic conditions, especially stroke, may affect decision-making processes, cognitive capacity, and language deficit. In addition to dementia, the most common mental disorders are mood and anxiety disorders. A common symptom of these disorders in the elderly is cognitive impairment. This study aimed to present the relationship between cognitive impairment due to dementia, mood disorders and anxiety, and an increased risk of suicide among older people. Dementia is a disease where the risk of suicide is significant. Many studies demonstrated that older adults with dementia had an increased risk of suicide death than those without dementia. Similar conclusions apply to prodromal dementia Depression is also a disease with a high risk of suicide. Many researchers found that a higher level of depression was associated with suicide attempts and suicide ideation. Bipolar disorder is the second entity in mood disorders with an increased risk of suicide among the elderly. Apart from suicidal thoughts, bipolar disorder is characterized by high mortality. In the group of anxiety disorders, the most significant risk of suicide occurs when depression is present. In turn, suicide thoughts are more common in social phobia than in other anxiety disorders. Suicide among the elderly is a serious public health problem. There is a positive correlation between mental disorders such as dementia, depression, bipolar disorder, or anxiety and the prevalence of suicide in the elderly. Therefore, the elderly should be comprehensively provided with psychiatric and psychological support.

Peripheral Markers of Depression.

Major Depressive Disorder (MDD) is a leading cause of disability worldwide, creating a high medical and socioeconomic burden. There is a growing interest in the biological underpinnings of depression, which are reflected by altered levels of biological markers. Among others, enhanced inflammation has been reported in MDD, as reflected by increased concentrations of inflammatory markers-C-reactive protein, interleukin-6, tumor necrosis factor-α and soluble interleukin-2 receptor. Oxidative and nitrosative stress also plays a role in the pathophysiology of MDD. Notably, increased levels of lipid peroxidation markers are characteristic of MDD. Dysregulation of the stress axis, along with increased cortisol levels, have also been reported in MDD. Alterations in growth factors, with a significant decrease in brain-derived neurotrophic factor and an increase in fibroblast growth factor-2 and insulin-like growth factor-1 concentrations have also been found in MDD. Finally, kynurenine metabolites, increased glutamate and decreased total cholesterol also hold promise as reliable biomarkers for MDD. Research in the field of MDD biomarkers is hindered by insufficient understanding of MDD etiopathogenesis, substantial heterogeneity of the disorder, common co-morbidities and low specificity of biomarkers. The construction of biomarker panels and their evaluation with use of new technologies may have the potential to overcome the above mentioned obstacles.

Salivary Carbohydrate-Deficient Transferrin in Alcohol- and Nicotine-Dependent Males.

Serum carbohydrate-deficient transferrin (CDT), an 80 kDa glycoprotein, is one of the most commonly employed biomarkers to detect alcohol dependence. Some salivary glycoproteins such as α-amylase, clusterin, haptoglobin, light/heavy-chain immunoglobulin, and transferrin, which alter glycosylation in alcohol-dependent persons, have been suggested to be potential alcohol markers. However, their identification is based on indirect analysis of lectin glycosidic bonds and molecular weight. We investigated the CDT content in the saliva of alcohol- and nicotine-dependent men. The CDT concentration (ng/mL, ng/mg protein) was determined by an Enzyme-Linked Immunosorbent Assay (ELISA) commercial kit in 55 men: 20 healthy social drinkers (C), 10 chronic cigarette smokers (S), 10 alcohol-dependent non-smokers (A), and 15 alcohol-dependent smokers (AS). Surprisingly, there were no differences in the concentrations of CDT between the studied groups. Salivary pH was the lowest in the AS and the highest in the A group. Therefore, salivary CDT cannot be used as an alcohol dependence marker as measured by ELISA. We suggest that direct identification of glycoproteins is necessary to search for potential salivary alcohol biomarkers. Molecules smaller than 40 kDa, which easily translocate from blood to the saliva, might be preferred as salivary alcohol markers.

Diagnostic Value of Salivary Markers in Neuropsychiatric Disorders.

A growing interest in the usability of saliva has been observed recently. Using saliva as a diagnostic material is possible because it contains a varied range of composites, organic and inorganic like proteins, carbohydrates, and lipids, which are secreted into saliva. Moreover, this applies to drugs and their metabolites. Saliva collection is noninvasive, and self-collection is possible. There is a lack of risk of injuries related to injection with needle, and it is generally safe. Human saliva has been successfully used, for example, in the diagnosis of many systemic diseases like cancers, autoimmunological diseases, infectious diseases (HIV, hepatitis, and malaria), and endocrinological diseases, as well as diseases of the gastrointestinal tract. Also, it is used in toxicological diagnostics, drug monitoring, and forensic medicine. The usefulness of saliva as a biological marker has also been extended to psychiatry. The specificity of mental illness and patients limits or prevents cooperation and diagnosis. In many cases, the use of saliva as a marker seems to be the most sensible choice.

Long-term changes of salivary exoglycosidases and their applicability as chronic alcohol-drinking and dependence markers.

OBJECTIVES: Investigation of long-term dynamic changes of salivary activity/output of exoglycosidases, deglycosylation processes and their applicability as alcohol markers. METHODS: Exoglycosidase (α-fucosidase (FUC), ß-galactosidase (GAL), ß-glucuronidase (GLU), ß-hexosaminidase (HEX, HEX A and HEX B isoenzymes) and α-mannosidase (MAN)) activities were measured in the saliva of healthy social drinking controls (C), alcohol-dependent non-smokers (ANS) and alcohol-dependent smokers (AS) at the 1st, 15th, 30th and 50th day of abstinence after chronic alcohol drinking. RESULTS: The activity of exoglycosidases was 2-3-fold (MAN), 2-6 fold (FUC), 8-25-fold (HEX A) and 19-40-fold (GLU) higher in the ANS and AS groups than in controls, and had good/excellent sensitivity, specificity and accuracy. The higher outputs of exoglycosidases were in the AS and ANS groups than in controls at the 1st day (GLU, HEX A) and at the 50th day (GLU, FUC, MAN) of abstinence. We found numerous correlations between alcohol-drinking days with GLU and HEX A, alcohol amounts with HEX A and duration of alcohol dependence with FUC and MAN activity/output. CONCLUSIONS: Salivary exoglycosidases/deglycosylation processes were still very high up to 50 days after the end of alcohol consumption. We found markers of chronic alcohol consumption (HEX A), alcohol dependence (FUC and MAN) and chronic alcohol consumption and dependence (GLU).

Probiotic Lactobacillus Plantarum 299v decreases kynurenine concentration and improves cognitive functions in patients with major depression: A double-blind, randomized, placebo controlled study.

BACKGROUND: Interactions between the digestive system and the brain functions have become in recent years an important field of psychiatric research. These multidirectional interactions take place in the so called microbiota-gut-brain axis and emerging scientific data indicate to the significant role of microbiota in the modulation of the central nervous system (CNS) including affective and cognitive functions. OBJECTIVE: An assessment of psychobiotic and immunomodulatory effects of probiotic bacteria Lactobacillus Plantarum 299v (LP299v) by measuring affective, cognitive functions and biochemical parameters in patients with MDD undergoing treatment with selective serotonin reuptake inhibitors (SSRI). DESIGN: Seventy nine patients with MDD were randomized and allocated to a double-blind, placebo-controlled trial. Participants received either a SSRI with the probiotic LP299v (n = 40) for a period of 8 weeks or a SSRI with the placebo of the probiotic (n = 39) for the same period. The severity of psychiatric symptoms was assessed using Hamilton Depression Rating Scale (HAM-D 17), Symptom Checklist (SCL-90) and Perceived Stress Scale (PSS-10). Cognitive functions were assessed using the Attention and Perceptivity Test (APT), Stroop Test parts A and B, Ruff Figural Fluency Test (RFFT), Trail Making Test (TMT) Parts A and B and the California Verbal Learning Test (CVLT). Biochemical parameters such as tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxykynurenine (3HKYN), anthranilic acid (AA), 3-hydroxy anthranilic acid (3HAA), tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin 1-beta (IL-1b) and cortisol plasma concentrations were measured. RESULTS: Sixty participants finished the study and were analyzed: 30 participants in the LP299v group and 30 participants in the placebo group. There was an improvement in APT and in CVLT total recall of trials 1-5 in the LP299v group compared with the placebo between baseline and after 8 weeks of intervention. There was a significant decrease in KYN concentration in the LP299v group compared to the placebo group. We also observed significant increase in 3HKYN:KYN ratio in the LP299v group compared with the placebo group. Additionally, Repeated Measures ANOVA revealed a significant effect of interaction of Treatment x time for AA concentration. However, results of post hoc analysis did not reach statistical significance in neither probiotic nor placebo group. There were no significant changes of TNF-α, IL-6 and IL-1b and cortisol concentrations in neither probiotic nor placebo groups. CONCLUSIONS: Augmentation of SSRI treatment with probiotic bacteria Lactobacillus Plantarum 299v improved cognitive performance and decreased KYN concentration in MDD patients. Decreased KYN concentration could contribute to the improvement of cognitive functions in the LP299v group compared to the placebo group. To our knowledge results of this study are the first evidence of improvement of cognitive functions in MDD patients due to probiotic bacteria and this is the first evidence of decreased KYN concentration in MDD patients due to probiotic bacteria.

Exposure to Ti4Al4V Titanium Alloy Leads to Redox Abnormalities, Oxidative Stress, and Oxidative Damage in Patients Treated for Mandible Fractures.

Due to the high biotolerance, favourable mechanical properties, and osseointegration ability, titanium is the basic biomaterial used in maxillofacial surgery. The passive layer of titanium dioxide on the surface of the implant effectively provides anticorrosive properties, but it can be damaged, resulting in the release of titanium ions to the surrounding tissues. The aim of our work was to evaluate the influence of Ti6Al4V titanium alloy on redox balance and oxidative damage in the periosteum surrounding the titanium miniplates and screws as well as in plasma and erythrocytes of patients with mandibular fractures. The study included 31 previously implanted patients (aged 21-29) treated for mandibular fractures and 31 healthy controls. We have demonstrated increased activity/concentration of antioxidants both in the mandibular periosteum and plasma/erythrocytes of patients with titanium mandibular fixations. However, increased concentrations of the products of oxidative protein and lipid modifications were only observed in the periosteum of the study group patients. The correlation between the products of oxidative modification of the mandible and antioxidants in plasma/erythrocytes suggests a relationship between the increase of oxidative damage at the implantation site and central redox disorders in patients with titanium miniplates and screws.

Association of MIR137 With Symptom Severity and Cognitive Functioning in Belarusian Schizophrenia Patients.

MicroRNA-137 (miRNA-137; miR-137) is one of the important post-transcriptional regulators of the nervous system development, and its MIR137 gene rs1625579 polymorphism was reported to be a potential regulator for schizophrenia susceptibility. However, schizophrenia characteristics controlled by MIR137 rs1625579 polymorphism are still insufficiently understood. There were 3 groups included in the study: (a) subjects with diagnosis of schizophrenia (n = 150; 81-females, 69-males), (b) mentally healthy people (control group; n = 102; 66-females, 36-males) and (c) Belarusian indigenous male group (n = 295). Associations of rs1625579 with schizophrenia, symptom's severity and cognitive performance [by using Positive and Negative Syndrome Scale (PANSS) and Wisconsin Card Sorting Test (WCST), respectively] were studied, when compared to controls. Allele and genotype frequencies were investigated in Belarusian indigenous males. Rs1625579 displayed no association with schizophrenia in Belarusian population. Significant "symptom severity-genotype" interactions were revealed for schizophrenia patients. Patients with T/G genotype displayed lower severity of positive symptoms and general psychopathology compared to homozygous subjects. T/T genotype was associated with the highest symptom's severity. The negative symptom scores and the total PANSS-score were significantly higher in females carrying genotype T/T vs. T/G+G/G; no significant gene-phenotype associations were found in males. WCST parameters did not show any association with rs1625579 polymorphism. MIR137 rs1625579 polymorphism might be an important sex-dependent factor influencing severity of schizophrenia psychopathological manifestations. These findings also contribute to the knowledge on candidate gene effects on characteristics related to schizophrenia phenotype. As miR 137 is considered to be cancer therapeutic target, miR-137 may also explain the lower incidence of cancer in schizophrenia patients. Further studies with larger sample size are needed to confirm these novel findings.

Immune suppression of IgG response against dairy proteins in major depression.

BACKGROUND: Interactions between the digestive system, brain functions and immunoglobulin G (IgG) mediated immunity against food antigens became recently a topic of growing interest in psychiatry research. Psychological stress can activate hypothalamic-pituitary-adrenal axis (HPA) with subsequent hypercortisolemia. It can also influence intestinal permeability and dynamics of IgG response. Major depression can by accompanied either by activation of inflammatory response or by immune suppression (e.g. decreased antibody production) where hypercortisolemia is a significant immune modulator. The aim of our study was to assess IgG immune response against 44 food products in depressed patients and controls along with markers of psychological stress, inflammation, psychometric and dietary parameters. METHODS: Serum IgG concentrations against 44 food antigens, plasma cortisol, TNF-α, IL-6, IL-1b concentrations were measured and psychometric parameters were evaluated using Hamilton Depression Rating (HAM-D 17), Perceived Stress (PSS-10), and Symptom Checklist (SCL-90) scales in 34 depressed patients and 29 controls. Dietary parameters such as frequency of exposure to food antigens, appetite and weight change were assessed. RESULTS: There was a significantly lower IgG concentration against dairy in depressed patients compared to controls (post hoc p < 0.05) when there was a high exposure (consumption) to dairy. Our research revealed a significant interaction of IgG concentration against dairy proteins and exposure to dairy between groups (F (2.63) = 3.92, p = 0.025, η2 = 0.12). There was no significant difference in mean IgG concentration against food antigens between patients and controls. We found increased concentration of cortisol in depressed patients (t (1.61) = 2.37, p = 0.02) compared to controls. Patients with melancholic depression had significantly higher (M rank  = 21.27) concentration of cortisol (U = 41, p = 0.006), when compared with the non-melancholic group of patients (M rank  = 12.16). Cortisol concentration significantly positively correlated with HAM-D 17 (r = 0.442, p = 0.009) and with phobias in SCL-90 scale in patients' group (r = 0.531, p = 0.001). There was decreased concentration of TNF-α (t = 4.256, p < 0.001) in depressed patients compared to controls. IgG concentration of 38.63% food products positively correlated with TNF-α concentration in depressed patients compared to 9.09% of those in healthy controls. CONCLUSIONS: We observed an immune suppression of IgG response to dairy proteins in depressed patients. Hypercortisolemia with involvement of decreased concentration of TNF-α might play a significant role in suppression of IgG response in depressed patients.

Prevention of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDA) accounts for 95% of all pancreatic cancers. About 230,000 PDA cases are diagnosed worldwide each year. PDA has the lowest five-year survival rate as compared to others cancers. PDA in Poland is the fifth leading cause of death after lung, stomach, colon and breast cancer. In our paper we have analysed the newest epidemiological research, some of it controversial, to establish the best practical solution for pancreatic cancer prevention in the healthy population as well as treatment for patients already diagnosed with pancreatic cancer. We found that PDA occurs quite frequently but is usually diagnosed too late, at its advanced stage. Screening for PDA is not very well defined except in subgroups of high-risk individuals with genetic disorders or with chronic pancreatitis. We present convincing, probable, and suggestive risk factors associated with pancreatic cancer, many of which are modifiable and should be introduced and implemented in our society.

[Depression and inflammation in rheumatic diseases]. / Depresja i proces zapalny w chorobach reumatologicznych.

It is known that the prevalence of depression in rheumatologic patients is higher than in the general population. Socioeconomic factors are not a sufficient explanation of mood disorder in these patients. Symptoms reported by patients with chronic inflammatory diseases resemble changes defined as "sickness behavior". Mood disorders among somatic patients could be explained by disturbances of the immune system according to the monoaminergic theory of depression. Inflammatory factors such as IL-1 (interleukin-1), IL-2 (interleukin-2), IL-6 (interleukin-6), TNF-α (tumor necrosis factor α), and IFN-γ (interferon-γ) act within the CNS (central nervous system). They get through from peripheral tissues as well as being synthesized de novo by neurons. This cytokine activity correlates positively with depression intensity as well as with genetic polymorphism of the serotonin (5-HT) transporter. The theory of glucocorticoid resistance-mediated depression (limbic-hypothalamic-pituitary-adrenal [LHPA] axis) is also connected with gained proinflammatory cytokines activity. It might assume the form of a vicious circle. Depressed mood is probably linked with depression in immune-mediated diseases. An elevated level of proinflammatory cytokines is able to activate IDO (indoleamine 2,3-dioxygenase)--an enzyme catabolizing tryptophan (5-HT precursor). Those reactions probably play the main role at the biochemical level. IDO metabolites extensively disturb neurotransmission. 3-Hydroxykynurenine (3OH-KYN), quinolinic acid (Quin) and kynurenic acid (KYNA) are neurotoxic by releasing oxidative stress mediators. Moreover, they activate MAO (monoamine oxidase), which degrades neurotransmitters responsible for stable mood. Bidirectional communication between the neuroendocrine and immune systems is significant for depression treatment, as well as CNS protection against incremental neurodegeneration among seemingly diverse diseases.

Serum ß-glucuronidase as a potential colon cancer marker: a preliminary study.

AIM: Colorectal cancer is characterized by high morbidity and mortality in developed countries. The lack of low-cost, easy-to-use screening diagnostic methods is one of the causes of late diagnosis of colorectal cancer. Beta-glucuronidase (GLU) is a lysosomal exoglycosidase involved in degradation of glycosaminoglycans of the cell membranes and extracellular matrix of normal and cancerous colon tissues. The aim of our research was to evaluate the activity of GLU in the serum of colorectal cancer and estimate its potential value in the diagnosis of colorectal cancer. MATERIAL AND METHODS: Blood samples were collected from 21 patients with colorectal adenocarcinoma and 17 healthy subjects. GLU activity was determined by the colorimetric method of Marciniak et al. by measuring the amount of p-nitrophenol released from 4-nitrophenyl-beta-D-glucuronide, at λ = 405 nm. RESULTS: We found significantly greater activity of GLU (p<0.0001) in the serum of patients with colorectal cancer, as compared to the healthy subjects. The serum GLU activity significantly differentiates patients with colorectal cancer from healthy individuals. CONCLUSIONS: Serum GLU activity has diagnostic value and may be used in the diagnosis of colon adenocarcinoma.

Salivary alcohol dehydrogenase in non-smoking and smoking alcohol-dependent persons.

Increasing attention to the importance of saliva testing is not surprising because smoking and alcohol drinking act synergistically on oral tissues, and their metabolite levels, e.g., acetaldehyde, are much higher in saliva than in blood. The activity of salivary alcohol dehydrogenase (ADH) comes from oral microbiota, mucosa, and salivary glands. The purpose of this study was to investigate the involvement of ADH in the oral health pathology of smoking (AS) and non-smoking (ANS) alcohol-dependent males. The results indicated that the AS group had a more significant and longer duration (until the 30th day of alcohol abstinence) decrease in ADH activity and output than the ANS group (until the 15th day of alcohol abstinence) compared to controls (social drinkers; C). The decreased salivary flow (SF) in alcoholics was observed longer in the ANS group (until the 30th day of alcohol abstinence), whereas in the AS group SF normalized at the 15th day, probably due to the irritating effect of tobacco smoke on the oral mucosa. Because saliva was centrifuged to remove cells and debris (including microbial cells), the detected salivary ADH activity was derived from salivary glands and/or oral mucosa. A more profound and longer decrease in ADH activity/output in smoking than non-smoking alcoholics was likely due to the damaged salivary glands and/or oral mucosa, caused by the synergistic effect of alcohol drinking and smoking. The lower values of salivary ADH in smoking than non-smoking alcoholics might also be partly due to the reversed/inhibited ADH reaction by high levels of accumulated acetaldehyde.

Association between serum testosterone levels, body mass index (BMI) and insulin in male patients with schizophrenia treated with atypical antipsychotics--olanzapine or risperidone.

OBJECTIVE: A sufficient amount of testosterone (T) is essential for adequate sexual functioning but also for cognitive and psychological well-being. Most recent studies have demonstrated that higher BMI and other symptoms of metabolic syndrome are associated with alterations in sex steroid hormone concentrations. Although, neuroleptics are known to cause a significant and sustained weight excess, the relationships between body mass index and the level of testosterone in psychiatric patients have not been thoroughly studied. The main purpose of the present study was to examine the correlations between testosterone, estradiol BMI, and insulin in male patients diagnosed with schizophrenia and treated with olanzapine or risperidone. METHODS: The study included 78 males diagnosed with schizophrenia according to the DSM-IV diagnostic classification hospitalized in psychiatric inpatient units (42 on risperidone and 36 on olanzapine). The initial and final evaluation of testosterone (T), estradiol, prolactin (PRL) and insulin serum levels were performed at week 3 and 8 after the onset of the new treatment, respectively. RESULTS: At week 3, the mean serum prolactin was markedly higher, whereas testosterone level was lower in risperidone patients compared to those treated with olanzapine. T level was negatively affected by the studied medication (risperidone), increased prolactin and a higher BMI. At week 8, the mean serum prolactin level was markedly higher in risperidone patients. Higher values of BMI and serum insulin were the most prominent factors independently associated with decreased plasma testosterone levels at that measurement point. Individual changes of T level between week 3 and 8 were positively correlated with the corresponding changes in estradiol levels. CONCLUSIONS: T serum levels appear to be independently linked with BMI, insulin and prolactin in both investigated neuroleptics. Further research is needed to elucidate the relationship between reproductive hormones and metabolic parameters in patients with schizophrenia under neuroleptic treatment.

Salivary exoglycosidases as markers of alcohol dependence.

BACKGROUND: Some salivary markers of alcohol abuse/dependence have been proposed so far: aminotransferases, gamma-glutamyltransferase, ethanol, ethyl glucuronide, ethyl sulfate, sialic acid, ß-hexosaminidase A, oral peroxidase, methanol, diethylene/ethylene glycol, α-amylase, clusterin, haptoglobin, heavy/light chains of immunoglobulins and transferrin. AIM: To investigate the effect of chronic alcohol drinking and smoking on the activity (pKat/ml) and output (pKat/min) of salivary lysosomal exoglycosidases: α-fucosidase (FUC), α-mannosidase (MAN), ß-galactosidase (GAL), and ß-glucuronidase (GLU), and their applicability as markers of alcohol dependence. METHODS: The activity of FUC, MAN, GAL and GLU was measured colorimetrically in the saliva of healthy social drinkers, alcohol-dependent non-smokers and alcohol-dependent smokers. RESULTS: We observed an increased salivary activity of FUC, GAL, GLU and MAN, as well as an increased output of GAL and GLU, in comparison with controls. The highest increase in the activity/output was found in salivary GLU and MAN (GLU, even 7- to 18-fold), and the least in GAL. We found an excellent sensitivity and specificity and a high accuracy (measured by the area under the ROC curve) for salivary FUC, GLU and MAN activities. The salivary GLU activity positively correlated with the number of days of last alcohol intoxication. Salivary activity of FUC, GAL and MAN, but not GLU, positively correlated with the periodontal parameters such as gingival index and papilla bleeding index. CONCLUSIONS: Although we found an excellent sensitivity and specificity as well as a high accuracy for the salivary activity of FUC, GLU and MAN, the GLU activity seems to be mostly applicable as a marker of chronic alcohol drinking (alcohol dependence).