Cecal volvulus - a rare cause of acute abdomen with ileus.

In this article, we present case reports of two patients admitted to the University Hospital in Pilsen for acute abdomen due to a disorder of the passage through the gastrointestinal tract (GIT). Both were indicated for surgery. The patients were diagnosed intraoperatively with rarely occurring cecal volvulus (CV). The findings required an ileocecal resection; nevertheless, both patients fully recovered despite the need the resection.

Potential impact on mental health in patients with treatment-resistant schizophrenia - clozapine augmentation with long-acting parenteral antipsychotics: a case series.

INTRODUCTION: The rate of pharmacoresistance among in patients diagnosed with schizophrenia is around 30%. Clozapineis the drug of choice for these patients; however, an adequate response to treatment doesn't always occur. One of the possible augmentation approaches, specifically for non-adherent patients, is the administration of long-acting parenteral antipsychotics. Our goal was to evaluate previous experiences of administering a combination of the atypical antipsychotic clozapine and long-acting injectable antipsychotics to pharmacoresistant patients at the Department of Psychiatry the Czech Republic and to assess the safety and effectiveness of such administration. METHODS: A retrospective evaluation of patient case studies was conducted for those who were hospitalized in the Ward for the therapy of Psychotic disorders between 2016 and 2020 and had a medication history of combining clozapine and depot antipsychotics. RESULTS: Over half of the patients had no illness relapses during the observed period. The clinical manifestation of adverse effects from combination therapy appears low in our patient sample, primarily involving mild and pharmacologically manageable side effects (tachycardia). Only one of the cases recorded neutropenia, which led to discontinuation of clozapine; the patient was maintained on long-acting injectable antipsychotics medication. CONCLUSION: From our findings, it can be inferred that augmenting clozapine with depot antipsychotics is a potential therapeutic intervention that pharmacoresistant patients could benefit from. However, it is essential to emphasize that this therapeutic approach should only be administered after carefully considering the patient's existing treatment. It should be strictly individualized based on the treating physician's or clinical pharmacist's sufficient professional experience.

Exploring the Association between Schizophrenia and Cardiovascular Diseases: Insights into the Role of Sigma 1 Receptor.

Contemporary society is characterized by rapid changes. Various epidemiological, political and economic crises represent a burden to mental health of nowadays population, which may at least partially explain the increasing incidence of mental disorders, including schizophrenia. Schizophrenia is associated with premature mortality by at least 13-15 years. The leading cause of premature mortality in schizophrenia patients is high incidence of cardiovascular diseases. The specific-cause mortality risk for cardiovascular diseases in schizophrenia patients is more than twice higher as compared to the general population. Several factors are discussed as the factor of cardiovascular diseases development. Intensive efforts to identify possible link between schizophrenia and cardiovascular diseases are made. It seems that sigma 1 receptor may represent such link. By modulation of the activity of several neurotransmitter systems, including dopamine, glutamate, and GABA, sigma 1 receptor might play a role in pathophysiology of schizophrenia. Moreover, significant roles of sigma 1 receptor in cardiovascular system have been repeatedly reported. The detailed role of sigma 1 receptor in both schizophrenia and cardiovascular disorders development however remains unclear. The article presents an overview of current knowledge about the association between schizophrenia and cardiovascular diseases and proposes possible explanations with special emphasis on the role of the sigma 1 receptor.

Changes in gene expression in pressure ulcers debrided by different approaches - a pilot study.

Pressure ulcers (PUs), also known as pressure injuries, are chronic wounds that represent potential lifelong complications. Pressure ulcers of a deep category (III and IV) are often indicated for surgical treatment - debridement and surgical reconstruction. Sharp surgical debridement is widely used in the debridement of PUs; however, the Versajet® hydrosurgery system is becoming an increasingly popular tool for tangential excision in surgery due to its numerous advantages. This work focused on the expression of selected genes, especially those associated with oxidative stress, in PUs debrided by two approaches - sharp surgical debridement and debridement using Versajet® hydrosurgery system. Expression of following genes was evaluated: NFE2L2, ACTA2, NFKB1, VEGFA, MKI67, HMOX1, HMOX2, HIF1A, and SOD2. ACTB and PSMB were used as housekeeping genes. So far, five patients have been enrolled in the study. Preliminary results suggest no significant difference in gene expression with different pressure ulcer treatment approaches except NFE2L2, despite the macroscopic differences. However, the results revealed correlations between the expression of some genes, namely HIF1A and SOD2, VEGFA and SOD2 and VEGFA and HIF1A. These results may indicate a connection between hypoxia, oxidative stress, pressure ulcer healing processes and angiogenesis.

Anesthetized guinea pig as a model for drug testing.

Based on the World Health Organization statistics, cardiovascular diseases represent the major cause of death worldwide. Although a wide range of treatment approaches and pharmaceuticals is available, the therapy is often not effective enough and therefore health risks for the patient persist. Thus, it is still essential to test new drug candidates for the treatment of various pathophysiological conditions related to cardiovascular system. In vivo models represent indispensable part of preclinical testing of such substances. Anesthetized guinea pig as a whole-body model allows to evaluate complex reactions of cardiovascular system to tested substance. Moreover, action potential of guinea pig cardiomyocyte is quite comparable to that of human. Hence, the results from this model are then quite well translatable to clinical medicine. Aim of this paper was to summarize the methodology of this model, including its advantages and/or limitations and risks, based on the effects of two substances with adrenergic activity on the ECG parameters. The model of anesthetized guinea pig proved to be valuable and suitable for testing of drugs with cardiovascular effects.

Mineral water Vincentka and its influence on mucosal ulcers.

Gastropathy is one of the most common diseases of the human gastrointestinal tract. Apart from its consequences in the stomach, it is also manifested in other parts of the digestive tract, particularly in the duodenum. The aim of this pilot study was to verify on animal model the empirically observed alleviation of gastropathy symptoms in patients who underwent a drinking treatment of Vincentka natural mineral water during their spa treatment. Sixteen male Wistar rats were included in the study. The animals were randomly divided into two groups: experimental group (E; n=8) and control group (C; n=8). The experimental protocol consisted of three phases: (1) handling phase (7 days); (2) mineral water (E)/tap water (C) administration (7 days); (3) acute gastritis induction (1 day). Twenty-four hours after the induction of acute gastritis, the animals were sacrificed. The collected tissues (stomach and duodenum) and blood were examined by standard histological microscopy, and by immunohistochemical and biochemical methods. Histopathological analysis revealed significantly reduced damage to the gastric mucosa in the experimental group. Significantly different values of blood plasma antioxidant capacity, oxidative stress parameters and blood plasma biochemical parameters were also found. Based on these results, we conclude that the mineral water Vincentka has a positive impact on development and symptoms of acute gastric ulcers.

Hematological findings in non-treated and gamma-irradiated mice deficient for MIC-1/GDF15.

Several members of the TGF-beta family are known to effectively regulate the fate of hematopoietic progenitor cells in a complex and context-dependent manner. Growth differentiation factor-15 (GDF15) is a divergent member of the TGF-beta family. This stress-induced cytokine has been proposed to possess immunomodulatory functions and its high expression is often associated with progression of a variety of pathological conditions. GDF15 is also induced by chemotherapy and irradiation. Very few fundamental studies have been published regarding the effect of GDF15 in hematopoiesis. In this study, we analyzed the hematological status of untreated and gamma-irradiated mice deficient for GDF15 as a result of genetic knock-out (KO), in order to clarify the regulatory role of GDF15 in hematopoiesis. Significant differences between GDF15 KO mice and their pertinent WT controls were found in the parameters of blood monocyte numbers, blood platelet size, and distribution width, as well as in the values of bone marrow granulocyte/macrophage progenitor cells. Different tendencies of some hematological parameters in the GDF15 KO mice in normal conditions and those under exposure of the mice to ionizing radiation were registered. These findings are discussed in the context of the GDF15 gene function and its lack under conditions of radiation-induced damage.

Cardiac sigma receptors - an update.

More than four decades passed since sigma receptors were first mentioned. Since then, existence of at least two receptor subtypes and their tissue distributions have been proposed. Nowadays, it is clear, that sigma receptors are unique ubiquitous proteins with pluripotent function, which can interact with so many different classes of proteins. As the endoplasmic resident proteins, they work as molecular chaperones - accompany various proteins during their folding, ensure trafficking of the maturated proteins between cellular organelles and regulate their functions. In the heart, sigma receptor type 1 is more dominant. Cardiac sigma 1 receptors regulate response to endoplasmic reticulum stress, modulates calcium signaling in cardiomyocyte and can affect function of voltage-gated ion channels. They contributed in pathophysiology of cardiac hypertrophy, heart failure and many other cardiovascular disorders. Therefore, sigma receptors are potential novel targets for specific treatment of cardiovascular diseases.

Automated database-guided expert-supervised orientation for immunophenotypic diagnosis and classification of acute leukemia.

Precise classification of acute leukemia (AL) is crucial for adequate treatment. EuroFlow has previously designed an AL orientation tube (ALOT) to guide towards the relevant classification panel (T-cell acute lymphoblastic leukemia (T-ALL), B-cell precursor (BCP)-ALL and/or acute myeloid leukemia (AML)) and final diagnosis. Now we built a reference database with 656 typical AL samples (145 T-ALL, 377 BCP-ALL, 134 AML), processed and analyzed via standardized protocols. Using principal component analysis (PCA)-based plots and automated classification algorithms for direct comparison of single-cells from individual patients against the database, another 783 cases were subsequently evaluated. Depending on the database-guided results, patients were categorized as: (i) typical T, B or Myeloid without or; (ii) with a transitional component to another lineage; (iii) atypical; or (iv) mixed-lineage. Using this automated algorithm, in 781/783 cases (99.7%) the right panel was selected, and data comparable to the final WHO-diagnosis was already provided in >93% of cases (85% T-ALL, 97% BCP-ALL, 95% AML and 87% mixed-phenotype AL patients), even without data on the full-characterization panels. Our results show that database-guided analysis facilitates standardized interpretation of ALOT results and allows accurate selection of the relevant classification panels, hence providing a solid basis for designing future WHO AL classifications.

Disruption of dopamine D1/D2 receptor complex is involved in the function of haloperidol in cardiac H9c2 cells.

AIMS: Haloperidol is an antipsychotic agent and acts as dopamine D2 receptor (D2R) antagonist, as a prototypical ligand of sigma1 receptors (Sig1R) and it increases expression of type 1 IP3 receptors (IP3R1). However, precise mechanism of haloperidol action on cardiomyocytes through dopaminergic signaling was not described yet. This study investigated a role of dopamine receptors in haloperidol-induced increase in IP3R1 and Sig1R, and compared physiological effect of melperone and haloperidol on basic heart parameters in rats. MATERIALS AND METHODS: We used differentiated NG-108 cells and H9c2 cells. Gene expression, Western blot and immunofluorescence were used to evaluate haloperidol-induced differences; proximity ligation assay (PLA) and immunoprecipitation to determine interactions of D1/D2 receptors. To evaluate cardiac parameters, Wistar albino male rats were used. KEY FINDINGS: We have shown that antagonism of D2R with either haloperidol or melperone results in upregulation of both, IP3R1 and Sig1R, which is associated with increased D2R, but reduced D1R expression. Immunofluorescence, immunoprecipitation and PLA support formation of heteromeric D1/D2 complexes in H9c2 cells. Treatment with haloperidol (but not melperone) caused decrease in systolic and diastolic blood pressure and significant increase in heart rate. SIGNIFICANCE: Because D1R/D2R complexes can engage Gq-like signaling in other experimental systems, these results are consistent with the possibility that disruption of D1R/D2R complex in H9c2 cells might cause a decrease in IP3R1 activity, which in turn may account for the increase expression of IP3R and Sig1R. D2R is probably not responsible for changes in cardiac parameters, since melperone did not have any effect.

Tolerance of isolated rabbit hearts to short ischemic periods is affected by increased LV mass fraction.

Hypertrophied hearts are known for increased risk of arrhythmias and are linked with reduced ischemic tolerance. However, still little is known about state characterized only by increased left ventricle (LV) mass fraction. Seventeen isolated rabbit hearts with various LV mass were divided into two groups according to LV weight/heart weight ratio (LVW/HW ratio), namely group H and L (with higher and lower LVW/HW ratio, respectively) and underwent three short cycles of global ischemia and reperfusion. The differences in electrogram (heart rate, QRS(max), mean number, onset and dominant form of ventricular premature beats) and in biochemical markers of myocardial injury (creatine kinase, lactate dehydrogenase - LDH) and lipid peroxidation (4-hydroxy-2-nonenal - 4-HNE) were studied. As compared to group L, hearts in group H exhibited lower tolerance to ischemia expressed as higher incidence and severity of arrhythmias in the first ischemic period as well as increase of LDH and 4-HNE after the first reperfusion. In the third cycle of ischemia-reperfusion, the preconditioning effect was observed in both electrophysiological parameters and LDH release in group H. Our results showed consistent trends when comparing changes in electrograms and biochemical markers. Moreover, 4-HNE seems to be good potential parameter of moderate membrane alteration following ischemia-reperfusion injury.

Non-invasive assessment of vascular system function and damage induced by anthracycline treatment in the pediatric cancer survivors.

Anthracyclines represent one of the important classes of anti-cancer drugs; however, their major disadvantage is their profound cardiovascular toxicity. This study aimed to evaluate influence of anthracyclines on cardiovascular stiffness parameters estimated from pulse wave (PW). PW was measured in 59 cancer survivors treated with anthracyclines in childhood and in 248 healthy age-matched controls. Both patients and controls were divided into three age groups (13 - 15, 16 - 18 and 19 - 24 years). Central PW augmentation index (C-AI75) and augmentation pressure (C-AP75), both normalized to heart rate 75 bpm, were calculated as parameters of arterial wall stiffness. Central Buckberg sub-endocardial viability ratio (SEVR) was calculated as a parameter of diastolic function. Patients and controls were compared in each age group. C-AI75 and C-AP75 were significantly increased in patients in age groups 16 - 18 and 19 - 24 years. SEVR was decreased in patients in the oldest age group. Our results suggest that although toxic influence of anthracyclines to arterial wall and heart are developing during childhood and puberty, they can be detected rather in the adulthood. These changes are yet subclinical; however, their presence indicates potentially increased cardiovascular risk in childhood cancer survivors treated with anthracyclines during childhood.

Nilotinib induces ER stress and cell death in H9c2 cells.

Tyrosine kinases inhibitors (TKi) represent a relatively novel class of anticancer drugs that target cellular pathways overexpressed in certain types of malignancies, such as chronic myeloid leukaemia (CML). Nilotinib, ponatinib and imatinib exhibit cardiotoxic and vascular effects. In this study, we focused on possible cardiotoxicity of nilotinib using H9c2 cells as a suitable cell model. We studied role of endoplasmic reticulum (ER) stress and apoptosis in nilotinib toxicity using a complex approach. Nilotinib impaired mitochondrial function and induced formation of ROS under clinically relevant concentrations. In addition, ability of nilotinib to induce ER stress has been shown. These events result in apoptotic cell death. All these mechanisms contribute to cytotoxic effect of the drug. In addition, involvement of ER stress in nilotinib toxicity may be important in co-treatment with pharmaceuticals affecting ER and ER stress, e.g. beta-blockers or sartans, and should be further investigated.

Different doxorubicin formulations affect plasma 4-hydroxy-2-nonenal and gene expression of aldehyde dehydrogenase 3A1 and thioredoxin reductase 2 in rat.

Increased oxidative stress is indisputably an important mechanism of doxorubicin side effects, especially its cardiotoxicity. To prevent impairment of non-tumorous tissue and to improve the specificity in targeting the tumor tissue, new drug nanotransporters are developed. In many cases preclinical therapeutic advantage has been shown when compared with the administration of conventional drug solution. Three forms of doxorubicin--conventional (DOX), encapsulated in liposomes (lipoDOX) and in apoferritin (apoDOX) were applied to Wistar rats. After 24 h exposition, the plasma level of 4-hydroxy-2-nonenal (4-HNE) as a marker of lipoperoxidation and tissue gene expression of thioredoxin reductase 2 (TXNRD2) and aldehyde dehydrogenase 3A1 (ALDH3A1) as an important part of antioxidative system were determined. Only conventional DOX significantly increases the level of 4-HNE; encapsulated forms on the other hand show significant decrease in plasma levels of 4-HNE in comparison with DOX. They also cause significant decrease in gene expression of ALDH3A1 and TXNRD2 in liver as a main detoxification organ, and a mild influence on the expression of these enzymes in left heart ventricle as a potential target of toxicity. Thus, 4-HNE seems to be a good potential biomarker of oxidative stress induced by various forms of doxorubicin.

Motion artefact in voltage-sensitive fluorescent dye emission during repeated ischemia of isolated heart.

Motion artefact (MA) in voltage-sensitive fluorescent signals causes significant debasement of action potential. During ischemia and reperfusion in isolated rabbit heart, this artefact develops in a manner which may be described by the time of its onset, level, and shape. The MA during ischemia: (a) may become substantial with approximately two minutes delay after establishing global ischemia; (b) may be almost twice as high as the physiological action potential and decreases both with time and repetition of ischemia; (c) the MA shape is unpredictable and depends on individual rabbit.

Application of the optical method in experimental cardiology: action potential and intracellular calcium concentration measurement.

It has been shown that, in addition to conventional contact electrode techniques, optical methods using fluorescent dyes can be successfully used for cardiac signal measurement. In this review, the physical and technical fundamentals of the method are described, as well as the properties of the most common systems for measuring action potentials and intracellular calcium concentration. Special attention is paid to summarizing limitations and trends in developing this method.

Osmotin, a pathogenesis-related protein.

Plants protect themselves from pathogen invasion through the local expression of a variety of pathogenesis-related proteins. They are highly diverse in both primary structure and length, and exhibit different direct antimicrobial activity. This text reviews the knowledge of osmotin, antimicrobial protein involved in innate immunity of plants. Osmotin belongs to the fifth class of the group of pathogenesis-related (PR) proteins and has been found in different plants species, in every case osmotin is cysteine-rich protein involved in plant defense responses to several pathogens and abiotic stresses. The phylogenetic tree of amino acids compositions of osmotins from different plant species is presented and the basic similarities of clusters are discussed in this review. Osmotin gene is activated by different biotic as well as abiotic signals and has many functions. The review summarizes biochemical and structural properties, induction, functions and structural homology between osmotin and other proteins. Recent data about recombinant production in bacterial and plant cells are examined. The article indicates possible ways of osmotin application in research in the field of functional biology, medicine and agriculture.

Restricted feeding regime affects clock gene expression profiles in the suprachiasmatic nucleus of rats exposed to constant light.

The master circadian clock located in the suprachiasmatic nuclei (SCN) is dominantly entrained by external light/dark cycle to run with a period of a solar day, that is, 24 h, and synchronizes various peripheral clocks located in the body's cells and tissues accordingly. A daily restricted normocaloric feeding regime synchronizes the peripheral clocks but has no effect on SCN rhythmicity. The aim of this study was to elucidate whether feeding regime may affect the molecular mechanism generating SCN rhythmicity under conditions in which the rhythmicity is disturbed, as occurs under constant light. The rats were maintained under constant light for 30 days and were either fed ad libitum during the whole period, or their access to food was restricted to only 6 h a day during the last 2 weeks in constant light. Locomotor activity was monitored during the whole experiment. On the last day in constant light, daily expression profiles of the clock genes Per1, Per2, Bmal1, and Rev-erbα were determined in the SCN of both groups by in situ hybridization. Due to their exposure to constant light, the rats fed ad libitum became completely arrhythmic, while those exposed to the restricted feeding were active mostly during the time of food availability. In the SCN of behaviorally arrhythmic rats, no oscillations in Rev-erbα and Bmal1 gene expression were detected, but very low amplitude, borderline significant, oscillations in Per1 and Per2 persisted. Restricted feeding induced significant circadian rhythms in Rev-erbα and Bmal1 gene expression, but did not affect the low amplitude oscillations of Per1 and Per2 expression. These findings demonstrate that, under specific conditions, when the rhythmicity of the SCN is disturbed and other temporal entraining cues are lacking, the SCN molecular clockwork may likely sense temporal signals from changes in metabolic state delivered by normocaloric food.