Is Balneotherapy Protective Against Oxidative Stress? A Pilot Study.

BACKGROUND/AIM: This study aimed to research the effects of Harkány healing water on oxidative stress. The study was performed in a randomized, placebo-controlled, double-blind setup. PATIENTS AND METHODS: Twenty patients with psoriasis who underwent a 3-week-long inward balneotherapy-based rehabilitation were enrolled. Psoriasis Area and Severity Index (PASI) score and Malondialdehyde (MDA) - a marker of oxidative stress - were determined, on admission and before discharge. Patients were treated with dithranol. RESULTS: The mean PASI score - determined on admission and before discharge - decreased significantly after the 3-week-long rehabilitation 8.17 vs. 3.51 (p<0.001). The baseline MDA value of patients with psoriasis was significantly higher compared to controls (3.0±3.5 vs. 8.4±7.4) (p=0.018). MDA levels of patients receiving placebo water increased significantly compared to MDA levels of patients receiving healing water (p=0.049). CONCLUSION: The effectiveness of dithranol resides in the formation of reactive oxygen species. No increased oxidative stress was found in the patients treated with healing water, thus healing water seems to be protective against oxidative stress. However, further research is needed to confirm these preliminary results.

A New and Validated, Randomised, Controlled Placebo Water Development Trial for Medicinal Water-based Research.

BACKGROUND/AIM: To develop and validate an easy-to-use and cheap method capable of producing placebo from tap water for medicinal water efficacy trials. PATIENTS AND METHODS: Patients were divided into two groups, medicinal water and tap water group. A single 20-minute-long treatment was performed in bathtubs. Patients were asked four times during the bath to tell if they were treated with medicinal water, tap water, or could not decide. Patients were scored, one point was given for each correct answer. RESULTS: A total of 174 patients were enrolled. No significant differences were found either between the average scores or the answers of the two groups. Being familiar with the Harkány medicinal water did not influence the rate of correct answers either. There was no statistically significant difference in the number of changes of opinions between the two groups. CONCLUSION: The used method is appropriate for producing a validated placebo from tap water.

Dominant Antibiotic Consumption Patterns Might Be Associated With the Prevalence of Multiple Sclerosis in European Countries.

BACKGROUND/AIM: With a prevalence of 50-300 per 100,000 people, about 2.3 million people are estimated to live with multiple sclerosis (MS) globally. The role of antibiotics in the development, or prevention of MS is controversial. We aimed to elucidate the association between antibiotic consumption and MS. PATIENTS AND METHODS: Pearson statistical comparisons were performed between the annual average antibiotic consumption patterns expressed in Defined Daily Dose/1,000 inhabitants/Day of the antibiotic consumption for the years of 1997-2018 in 30 European countries, with the respective prevalence of MS estimated for 2016. RESULTS: A positive correlation (promoting effect) has been observed between narrow spectrum penicillin (r=0.636) and tetracycline (r=0.412) consumption with MS prevalence. CONCLUSION: Countries, with high consumption of narrow spectrum penicillin and tetracycline, experience a higher prevalence of MS than other countries.

Antibiotic Consumption Patterns in European Countries May Be Associated with the Incidence of Major Carcinomas.

The possible role of the altered intestinal microbiome in the development of malignancies has been raised recently in several publications. Among external factors, antibiotics are considered to be the most important agent capable of producing dysbiosis in the gut flora, either temporally or permanently. The human microbiome has several beneficial effects in terms of maintaining appropriate human health, but its alteration has been implicated in the development of many illnesses. Our basic aim was to explore a possible relationship between the consumption of different antibiotic classes and the incidence of the most common cancer types (male, female) in European countries. A database of the average, yearly antibiotic consumption (1997-2018) has been developed and the consumption figures were compared to the eight, most frequent cancer incidence calculated for 2018 in 30 European countries. Pearson correlation has indicated different degrees of positive (supportive) and negative (inhibitor) significant associations between antibiotic consumption figures and cancer prevalence. It has been observed that certain antibiotic classes with positive correlation probably augment the incidence of certain cancer types, while others, with negative correlation, may show some inhibitory effect. The relatively higher or lower consumption pattern of different classes of antibiotics could be related to certain cancer prevalence figures in different European countries. Our results indicated that countries with relatively high consumption of narrow-spectrum penicillin (J01CE, J01CF) and tetracycline (J01A), like certain Scandinavian countries, showed a higher incidence of female colorectal cancer, female lung cancer, melanoma, breast, prostate and uterus corpus cancer. Countries with relatively higher consumption of broad-spectrum penicillin (J01CA, J01CR) and some broad-spectrum antibiotics (J01D, J01F, J01M), like Greece, Hungary, Slovakia, France, etc. showed a higher incidence rate of male lung cancer and male bladder cancer. The higher incidence rate of different cancer types showed association with the higher consumption of antibiotics with "augmenting" properties and with less consumption of antibiotics with "inhibitory" properties.

[Olanzapine pamoate injection -- experience and case reports from Hungarian clinical practice]. / Olanzapin pamoát injekció -- tapasztalatok és esettanulmányok a hazai klinikai gyakorlatból.

When treating schizophrenia and other psychotic disorders, clinicians often encounter the problems of non-adherence, which is almost the most common drawback of achieving remission and a better quality of life. The uncertain oral drug taking habits may lead to relapses and rehospitalizations. Using second generation long acting injectables we have more possibilities to avoid these problems. This review attempts to present and describe the pharmacological background of the modern long acting injectables including patient cases where olanzapine pamoate long acting injectable provided remission and better quality of life for the patients.

[The dopamin D3 receptor--the gray eminence of pharmacotherapy?]. / A dopamin D3 receptor - a farmakoterápia szürke eminenciása?

The dopamine system plays a crucial role in the pathophysiology of many neuropsychiatric disorders. Altough there is sufficient information and knowledge about several dopamine receptor subtypes and their functions, until the last decade the role of the D3 receptor was almost unclear. Recent research data proved that the D3 receptor might have a significant role in fine tuning the modulation of dopaminergic neurotransmission. Cariprazine is a novel agent developed in Hungary, its activity on the dopamine D3 receptor might open up new dimensions in the pharmacotherapy of schizophrenia and affective disorders.

[Application of lamotrigine in bipolar disorder--3T MR spectroscopy follow up (part 1)]. / Lamotrigin alkalmazása bipoláris zavarban - 3T MR spektroszkópiás utánkövetéssel (1. rész).

MR spectroscopy (MRS) is a widely used and useful additional tool in the diagnostic process of several neuropsychiatric disorders. Despite several MRS studies in bipolar spectrum research, establishing a clean image about special metabolite alterations in the disorder still needs further investigation. The first part of this case study presents a bipolar II patient and her first 3T MR spectroscopy in drug-naive conditions, comparing to a healthy subject. Having finished the first MRS investigation, we applied lamotrigine medication. The ongoing second part of the study will show the data of the second MRS scan, after 5 month of lamotrigine therapy.

[Lights off? Neurobiological and pharmacological aspects of the melatonergic-serotonergic synergism]. / Lights off? A melatonerg és szerotonerg szinergizmus neurobiológiai és farmakológiai aspektusai.

SSRI antiepressants have been widely used for treating depressive symptoms for more than two decades. Despite their frequent usage, meta-analyses proved that only 20-25% of the patients had achieved long term remission. The introduction and spreading of dual-acting agents increased remission rate, but many of the patients with depressive symptoms still suffer from the disorder due to partial pharmacotherapeutic efficacy. Chronobiological disturbances might play an important role both in the pathophysiology and in the ongoing symptoms of depression. Pathological alterations in the melatonergic system may act as the first, obscure signs of the onset of depression. Agomelatine, a new antidepressive agent may offer new possibilities in the pharmacotherapy of depression, due to its synergistic melatonergic-serotonergic activity.

[Neurobiological and pharmacologic aspects of atypical antipsychotic drugs]. / Az atípusos antipszichotikus hatásmechanizmus neurobiológiai és farmakológiai aspektusai.

Atypical (second generation) antipsychotic drugs have radically changed and revolutionized the pharmacological treatment of schizophrenia and related disorders. The currently approved atypical antipsychotic drugs, which are available, are characterized by relatively weak affinities for D2-type dopamine receptors and relatively high affinities for 5-HT2A serotonin receptors, when compared with typical (conventional) antipsychotic drugs. The strong interaction with 5-HT2A receptors, with a relative sparing of D2-type dopamine receptors, is likely responsible for the optimal effects of atypical antipsychotic drugs on affective and cognitive symptoms in comparison with conventional antipsychotic drugs. In addition to these actions, several atypical antipsychotic drugs are characterized by a "fast dissociation" rate from D2-dopamine receptors. Mediating special signal transduction pathways, their activity on neuronal survival and plasticity might also contribute to their clinical advantage over typical neuroleptic drugs. By modulating chemical neurotransmission and the intracellular signal transduction systems, antipsychotic drugs may influence a variety of functions regulating neuronal resilience and viability and may have their potential for neuroprotection.

[Domino principle--monoamines in bottom-view]. / A dominó elv--monoaminok alulnézetbol.

One of the first neurobiological theories of major depression was the monoamine deficiency hypothesis. The classic monoamine theory of depression suggested that a deficit in monoamine neurotransmitters in the synaptic cleft was the main and primary cause of depression. Recent and newer versions and modifications of the primary classic theory also mainly included this postulate, while other theories of depression preferred departing from the monoamine-based model altogether. Unfortunately, the clear neurobiology of major depression remains an elusive issue, despite intense research. It is clearly held that most, if not all, antidepressant pharmacotherapies treatments produce their therapeutic antidepressant effects, at least in part, by modulating monoamine systems (noradrenergic, serotonergic, and dopaminergic) by a selective or a multi-acting way; however, much less is known about the neurobiological pathology of these monoamine systems in depression. Much of the past 10-15 years of research in the biology of mood disorders has led to considerable evidence in depression implicating multiple system pathology, including abnormalities of monoamine as well as other neurotransmitter systems. These approaches and findings have led researchers to propose broader theories regarding the neurobiology of depression, just like a spreading disorder of specific neuronal networks in the brain. A model for the pathophysiology of depression ill be discussed in the next pages, after describing the main components of depression pathogenesis. Suggestion is that the primary defect emerges in the cross-regulation and vulnerability of special monoaminergic and non-monoaminergic neural networks, which leads to a decrease in the tonic release of neurotransmitters in their projection areas, altering postsynaptic sensitivity, and following, overexaggerated responses to acute increases in the presynaptic firing rate and transmitter release. It is proposed that the primary defect should be involved, in the noradrenergic innervation spreading from the locus coeruleus (LC). Dysregulation of the LC projection activities may lead in turn to malfunction of serotonergic and dopaminergic neurotransmission. Failure of the LC function could explain the basic impairments in the processing of novel information, intensive processing of irrational beliefs, and anxiety. Consecutive deficits in the serotonergic neurotransmission may contribute to the mood changes and reduction in the mesotelencephalic dopaminergic activity to loss of motivation, and anhedonia. Malfunction and dysregulation of CRF and other neuropeptides such as neuropeptide Y, galanin and substance P may reinforce the LC dysfunction and thus further weaken the adaptive ability to stressful stimuli. The new SNRI antidepressants seem to be more superior and effective in the treatment of major depression and in the prophylaxis of recurrent depressive episodes because of their coexistent noradrenergic activity.

[Mood stabilizers--past, present and future]. / Hangulatstabilizátorok--múlt, jelen és jövo.

Bipolar disorders are common, chronic, recurrent, and episodic mood disturbances, associated with variable dysfunctions in sleep, appetite, libido, activity, and cognition. These disorders are typically so severe that they impair occupational functioning. Until the discovery of lithium in the treatment of bipolar disorders, only electroconvulsive therapy was the available treatment of mania. After discovering the therapeutic effect of lithium in bipolar illness, the clinical outcome of the disorder has changed dramatically. Lithium has become the mainstay of the the treatment for bipolar disorders, however, the management of the illness has historically focused on the treatment of mania. Although the lifetime prevalence of bipolar disorder was originally estimated to be about 1%, the recent decade has brought more evidence, that the several clinical manifestations of the bipolar spectrum affects almost 5-6% of the general population. Lithium was absolutely helpful in euphoric mania, but with other types of disorder, especially bipolar depression and rapid cycling form, this efficacy significantly decreases. The newer mood stabilizers, carbamazepine and valproate have brought more possibilities to cover a broader zone of the bipolar spectrum. Although the new agents have offered a bit more protection against bipolar depression when used for prophylaxis, anyway, lithium, carbamazepine and valproate all are relatively ineffective against acute bipolar depression and rapid cycling. The third generation mood stabilizer lamotrigine has a broader and more effective efficacy in bipolar disorder, extending the therapeutic ranger especially in bipolar depression and in the difficult to treat rapid cycling subtype. This review provides a wide overview about the four most important mood stabilizers, lithium, carbamazepine, valproate and lamotrigine at the level of their synaptic and intracellular activities.

[Quetiapin in bipolar disorders]. / Quetiapin alkalmazása bipoláris zavarban.

Atypical antipsychotics are now widely used in the acute and long-term treatment in bipolar disorder. The role of atypical antipsychotics as acute agents, add-on medications; or as primary mood stabilizers in different phases of bipolar disorder is an important current research tendency. However, in bipolar disorder the mostly used indication of quetiapine is the management of acute manic phases, clinical data and the actual research results suggest that it may have both antidepressant and long-term antimanic effects. Quetiapine enhances the transmission of the central serotonergic networks, by its high antagonistic affinity for 5-HT(2A) and partial agonistic activity for the 5-HT(1A) receptors. The 5HT(1A) partial agonism causes an increase in the dopaminergic neurotransmission of the prefrontal cortex, and also, the affinity for the alpha 2-adrenoceptor brings a relative increase in extracellular noradrenergic release an tone in the prefrontal cortex. Latest research shows that quetiapine's main, active, human plasma metabolite, N-desalkyl quetiapine (norquetiapine), has a high inhibition affinity for the noradrenergic transporter. These data suggest that comparing to other atypical antipsychotics, norquetiapine may have a relatively strong antidepressant potential. Modifying the dopaminergic transmission by quetiapine's D2 receptor blocking activity results indirect mediating the cAMP-PKA and the arrestin-Akt-GSK-3 intracellular signal transduction pathways, which process may explain its long-term antimanic and mood stabilizing capability. Quetiapine's activity on nerve growth factors, histamine H1 receptor, proinflammatory networks may take an important additional part in its efficacy in bipolar depression. Its very fast dissociation from the D2 receptor is an important pharmakokinetic parameter for managing the optimal quetiapine dose in the daily clinical practice. This review tries to organize the actual information on quetiapine's multiplex activity in bipolar disorder.