Hairy cell leukemia - etiopathogenesis, diagnosis and modern therapeutic approach.

Hairy cell leukemia (HCL) represents 2% of all leukemia cases, with men aged above 55 years being the most affected. The most common symptoms of this type of leukemia include splenomegaly, monocytopenia, and neutropenia. In the basic blood count examination, leukopenia with monocytopenia and granulocytopenia, as well as aplastic anemia and/or thrombocytopenia occur. The mutation of ß-rapidly accelerated fibrosarcoma (BRAF) proto-oncogene, which can be found in nearly 100% of patients, is an important feature of HCL. Immunophenotypic analysis of the HCL cells reveals high expression of B-lineage antigens, including CD19, CD20, and CD22. Additionally, CD11c, CD25, CD103, and CD123 belong to specific markers of HCL. Lactate dehydrogenase activity and ß-2-microglobulin concentration are also important in the patient's assessment. The differential diagnosis between HCL, hairy cell leukemia variant (HCL-V) and splenic marginal zone lymphoma (SMZL) is of first importance. Currently, the main treatment for HCL involves the use of purine analogues, excluding pregnant women, individuals with severe infections, and those with relapsing HCL.

Chitosan-Glycolic Acid Gel Modification of Chloride Ion Transport in Mammalian Skin: An In Vitro Study.

Chitosan, a polyaminosaccharide with high medical and cosmetic potential, can be combined with the beneficial properties of glycolic acid to form a gel that not only moisturizes the skin, but also has a regenerative effect. Its involvement in the activation of biochemical processes may be associated with the activity of skin ion channels. Therefore, the aim of the research was to evaluate the immediate (15 s) and long-term (24 h) effect of chitosan-glycolic acid gel (CGG) on the transepithelial electric potential and the transepithelial electric resistance (R) of skin specimens tested in vitro. Stimulation during immediate and prolonged application of CGG to skin specimens resulted in a significant decrease in the measured minimal transepithelial electric potential (PDmin). The absence of any change in the R after the CGG application indicates that it does not affect the skin transmission, or cause distortion, microdamage or changes in ion permeability. However, the reduction in potential may be due to the increased transport of chloride ions, and thus water, from outside the cell into the cell interior. Increased secretion of chloride ions is achieved by stimulating the action of the CFTR (cystic fibrosis transmembrane conductance). It can be assumed that chitosan gently stimulates the secretion of chlorides, while maintaining a tendency to reduce the transport of sodium ions, without causing deformation or tissue damage.

The Role of Glutathione in Selected Viral Diseases.

During inflammatory processes, immunocompetent cells are exposed to substantial amounts of free radicals and toxic compounds. Glutathione is a cysteine-containing tripeptide that is an important and ubiquitous antioxidant molecule produced in human organs. The intracellular content of GSH regulates the detoxifying capacity of cells, as well as the inflammatory and immune response. GSH is particularly important in the liver, where it serves as the major non-protein thiol involved in cellular antioxidant defense. There are numerous causes of hepatitis. The inflammation of the liver can be caused by a variety of infectious viruses. The relationship between oxidative stress and the hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis E virus (HEV) infection is not fully known. The aim of this study was to examine the relationship between hepatotropic viruses and glutathione status, including reduced glutathione (GSH) and oxidized glutathione (GSSG), as well as antioxidant enzymes, e.g., glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) in liver diseases.

30-Min Exposure to Tobacco Smoke Influences Airway Ion Transport-An In Vitro Study.

Introduction: Smoking is one of the most important causes of cancer in humans. However, it has not been proven how long exposure to cigarette smoke is sufficient to induce cancerogenesis. Cigarette smoke can cause changes in ion and water transport and the maintenance of mucociliary transport. The conducted research concerned the assessment of changes in ion transport in rabbit tracheal specimens after 30 min of exposure to cigarette smoke. Materials and Methods: A modified Ussing chamber was used to measure the transepithelial electrical potential under stationary conditions (PD) and during mechanical stimulation (PDmin), and the transepithelial electrical resistance (R) in control and cigarette smoke-exposed tracheal fragments. Results: Significant changes in PD (-2.53 vs. -3.92 mV) and PDmin (-2.74 vs. -0.39 mV) were noted for the samples exposed to smoke, which can be associated with a rise in reactivity after applying a mechanical stimulus. In addition, the measured R (108 vs. 136 Ω/cm2) indicated no changes in the vitality of the samples, but an increase in their permeability to ions in the experimental conditions. Conclusions: A single 30-min exposure to cigarette smoke has been shown to be associated with increased permeability of the tracheal epithelium to ions and thus to substances emitted during smoking, which might be sufficient to create the possibility of initiating procarcinogenic processes.

Effective Interventions in Obesity: Current Evidence and Concepts.

This Special Issue, entitled "Specialized Diet, Obesity and Associated Metabolic Disorders" in the section "Clinical Nutrition" of Nutrients, addresses the metabolic changes that occur in humans as a result of the so-called western lifestyle [...].

Dietary Interventions in Obesity and Metabolic Syndrome.

Here, we present a Special Issue of Nutrients entitled "Specialized Diet, Obesity and Associated Metabolic Diseases" containing up-to-date scientific data important to both researchers and the public [...].

Nickel ions influence the transepithelial sodium transport in the trachea, intestine and skin.

Measurements of transepithelial potential and resistance in tissue and organ model systems enable the evaluation of the Ni2+ effect on the epithelial sodium channels, aquaporin 3, and the sodium-potassium pump in the epithelial cells. The aim of the presented study was to assess the immediate and prolonged effect of nickel ions on the transport of sodium ions in tissues exposed to direct contact with nickel, including airways, digestive tract and the skin. The influence of 0.1 mM nickel solution was performed on the trachea (n = 34), intestine (n = 44), and skin (n = 51) samples descended from 16 New Zealand albino rabbits. The electrophysiological parameters were measured in a modified Ussing chamber in stationary conditions and during a 15-s mechanical-chemical stimulation. A statistically significant decrease in the electric resistance values and the smallest range of the measured potential were observed for the Ni-treated trachea specimens. The use of nickel solution did not affect the sodium transport in the intestine epithelium. The skin fragments showed altered sodium ion transport, as demonstrated by the lower range and intensity of the measured potential. The gastrointestinal tract seems to be an organ best adapted to contact with nickel ions. In airways, nickel ions most likely enter epithelial cells and the space between them, modifying proteins and the airway surface liquid. The skin turned out to be the most sensitive tissue to the intensification of sodium ion transport through nickel ions.

Evaluation of Serum Iron Parameters among Men Performing Regular Physical Activity-A Preliminary Study.

Iron deficiency anemia is one of the most common issues in clinical practice. It can be caused by intense physical activity, among other things. The aim of the study was to assess serum iron parameters in a group of men who engage in regular physical activity. The study group was composed of 20 men who regularly perform strength or endurance sports, whereas the control group consisted of 20 men without any sports activity. The red blood cell (RBC) parameters, platelet count (PLT), and white blood cell (WBC) count in venous blood samples were assessed with an automated hematology analyzer. The serum concentration of ferritin was determined through an immunology assay. There were no statistically significant differences between groups comparing RBC parameters and WBC. However, statistical analysis showed dissimilarity in PLT count and serum ferritin concentration comparing control and study groups (p < 0.05). It was shown that lower serum ferritin concentration concerns men with regular physical activity, whereas other blood parameters were not affected in this group.

The Impact of Diclofenac Gel on Ion Transport in the Rabbit (Oryctolagus cuniculus) Skin: An In Vitro Study.

Diclofenac belongs to the non-steroidal anti-inflammatory drugs with analgesic, antipyretic and anti-inflammatory effects. Diclofenac administration on the skin may be associated with the appearance of side effects. The study aimed to evaluate the impact of diclofenac gel on transepithelial electrophysiological parameters of the 55 rabbit abdomen skin specimens. The electric parameters were analyzed in a modified Ussing chamber. The resistance (R) of the skin specimens treated with diclofenac gel significantly increased, which could be related to the reduction in the water content in intercellular spaces and, consequently, tighter adhesion of the cells. Increased electric potential (PD) was also observed in the skin specimens treated with diclofenac gel. The increase in both R and PD measured under stationary conditions was most likely caused by a transient and reversible increase in sodium ion transport, as the R and PD values decreased after the diclofenac gel was washed away. However, diclofenac gel did not affect the maximum and minimum PDs measured during stimulations. Therefore, it seems that diclofenac gel does not affect the perception of stimuli in the model system used.

Reduced sodium absorption in the colon under serotonin is a potential factor aggravating secretory diarrhea.

BACKGROUND: Serotonin is a substance with a propulsive effect on the gastrointestinal tract. It stimulates the intestinal secretion of water and electrolytes, and plays an important role in the pathophysiology of secretory diarrhea. However, the influence of serotonin on intestinal absorption is very poorly understood. OBJECTIVES: This study aimed to evaluate the serotonin and selected antagonists of serotonin receptors, i.e., ondansetron (5-HT3) and GR113808 (5-HT4), on electrogenic sodium ion absorption in the colon. MATERIAL AND METHODS: The electrophysiologic method developed by Ussing and modified with a stimulating function on the mucosal side of the isolated colon wall was used. The influence of selected serotonergic compounds on the electrogenic transport of sodium ions under stationary conditions and mechanical stimulation was investigated. For this purpose, experiments were performed on specimens of isolated rabbit colon. Amiloride and bumetanide were used as reagents directly controlling individual ion transport. The data were analyzed using tests for paired samples (paired sample t-test, Wilcoxon signed-rank test and one-sided sign test). RESULTS: Serotonin reduced stationary and stimulated colonic sodium absorption. The 5-HT3 receptor antagonist did not influence the studied phenomenon, while 5-HT4 antagonists acted contrary to serotonin. CONCLUSIONS: Serotonin reduces both stationary and stimulated sodium ion absorption, thus playing an important role in the pathophysiology of secretory diarrhea. The described phenomenon depends on serotonin's action on 5-HT4 receptors.

Effect of Low High-Density Lipoprotein Level on Endothelial Activation and Prothrombotic Processes in Coronary Artery Disease-A Pilot Study.

High-density lipoproteins (HDL) play an important role in the prevention of atherosclerosis. The aim of the study was to assess the relationship between serum HDL-C concentration and proinflammatory/prothrombic activation in coronary artery disease (CAD) patients. The study group included 27 acute myocardial infarction (AMI) patients and 30 stable angina pectoris (SA) patients. The control group consisted of 23 people without cardiac symptoms. In the AMI and SA groups, a lower HDL-C and a higher LDL-C/HDL-C index were observed. The SA patients had lower total cholesterol, LDL-C, sE-selectin ligand, as well as higher triglycerides and CD40 concentration in comparison with both the control and AMI groups. A higher von Willebrand Factor and intercellular adhesion molecule-1 were found in both study groups. Low HDL-C concentration in the CAD patients may intensify pro-inflammatory endothelial activation and prothrombotic processes. A low concentration of HDL-C and a high value of the LDL-C/HDL-C index seem to be better indices of atherogenic processes than the LDL-C concentration alone.

The impact of Morus alba L. leaf extract on intestinal ion transport. An in vitro study.

Morus alba L. (White mulberry), is an important and popular herbal plant of the Moraceae family. It has been widely used due to its therapeutic properties, which include antidiabetic, antibacterial, anti-inflammatory, cardiovascular, and hypolpidemic activity. The present study evaluates the effects of aqueous white mulberry leaf extract on the transepithelial ion pathway in the rabbit colon epithelium (n = 48), using electrophysiological methods. In addition, the antioxidant potential and the chemical composition of the extract were determined. A mechanical-chemical stimulation with white mulberry in RH fluid (MB-RH) caused a statistically significant (p < 0.001) increase in the transepithelial electrical potential difference, from - 0.130 to - 0.685 mV. Gentle washing of the intestine with white mulberry in bumetanide, used as inhibitor of transepithelial chloride pathways, resulted in 14.8% shorter reaction than during MB-RH stimulation. There were no statistically significant differences between the electric potential values measured during stimulation with amiloride solution, used as inhibitor of transepithelial sodium pathways, and white mulberry in amilorid solution (p = 0.485). A short-term application of extract to the colon epithelium is responsible for local and reversible inhibition of chloride ion channels. The extract enhances sodium ion absorption and consequently changes the electrical potential. The effect of white mulberry extract on sodium ion transport may be related to the mechanism of hypoglycaemic activity of mulberry leaves.

Characteristics of Selected Adipokines in Ascites and Blood of Ovarian Cancer Patients.

Ovarian cancer is one of the most common malignancies among women worldwide. The course of the disease is often latent and asymptomatic in the early stages, but as it develops, metastasis occurs, accompanied by accumulation of ascites in the peritoneal cavity. The ascites fluid constitutes a specific microenvironment influencing the processes of carcinogenesis. In ascites, signaling is mediated by various cytokines that control tumor cell proliferation, progression, metastasis, and chemoresistance. Adipokines, secreted into ascites and also appearing in blood, may be markers of ongoing processes related to the development of neoplastic disease. Moreover, a significant influence of adipocyte lipids on the growth of tumors, for which they are one of energy sources, is observed. Adiponectin, interleukin 6 (IL-6), interleukin 8 (IL-8), monocyte chemotactic protein-1 (MCP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1), discussed in the present review, were found to mediate the effects of omentum metastasis through homing, migration and invasion of ovarian cancer cells. Further research on those adipokines seem to be a natural consequence, allowing for a better understanding of the mechanisms of neoplastic disease and determination of the treatment procedure.

The influence of hydration status on ion transport in the rabbit (Oryctolagus cuniculus) skin-An in vitro study.

The preservation of physiological transport of ions and water content is particularly important for maintaining the skin barrier, touch and pain stimuli, as well as the initiation of skin regeneration processes, especially after treatments associated with breaking skin continuity and wound healing difficulties. The aim of the study was to assess changes in ion transport, measured as values of transepithelial electric resistance and potential difference in stationary conditions and during mechanical-chemical stimulations, depending on the hydration status of isolated rabbit skin specimens. The specimens were divided into five groups: control (n = 22), dehydrated in 10% NaCl (n = 30), rehydrated after dehydration (n = 26), dried at 37°C (n = 26), and rehydrated after drying (n = 25). Dehydrated tissue samples showed altered resistance compared to the control; this change was maintained regardless of rehydration. In the dehydrated samples, changes in the measured electric potential were also noted, which returned to values comparable with the control after rehydration. Dehydrated skin, regardless of the cause of dehydration, responds with changes in the transport of sodium and chloride ions and the altered cellular microenvironment. It could influence the perception of stimuli, particularly pain, and slow down the regeneration processes.

Pyrethroids: How They Affect Human and Animal Health?

Pyrethroids are pesticides commonly used in crop protection; in the forestry, wood, and textile industries; as well as in medicine and veterinary medicine to treat parasitic crustacean infestations. They have been found to be relatively safe for humans and animals. Pyrethroids are recommended for personal protection against malaria and virus Zika by the World Health Organization. Pyrethroids act on voltage-gated sodium channels, which cause an influx of sodium ions into the nerve cells and permanent depolarization. They also influence activities of enzymes, especially in nerve and liver cells. Contact of pyrethroids with the skin, digestive tract, and respiratory tract results in their penetration into the body. Due to the importance of the subject, a summary of the current state of knowledge on the toxic effects of pyrethroids was presented in the comprehensive review by Chrustek et al, published in journal Medicina. Particular attention was paid to nephrotoxic, hepatotoxic, cardiotoxic, immunotoxic, neurotoxic, and behavioral effects of pyrethroids on human and animal bodies. It could be added that pyrethroids generate oxidative stress, which modifies DNA, RNA, protein, lipid and carbohydrate molecules. However, public awareness of the possible negative effects of the use of insecticides is still low. Further research should be carried out to clarify the molecular basis of the pathomechanism of pyrethroid detrimental action. Proper dissemination of the results seems to be of first importance for public health.

Analysis of changes in sodium and chloride ion transport in the skin.

The measurement of electric potential and resistance reflect the transport of sodium and chloride ions which take place in keratinocytes and is associated with skin response to stimuli arising from external and internal environment. The aim of the study was to assess changes in electrical resistance and the transport of chloride and sodium ions, under iso-osmotic conditions and following the use of inhibitors affecting these ions' transport, namely amiloride (A) and bumetanide (B). The experiment was performed on 104 fragments of rabbit skin, divided into three groups: control (n = 35), A-inhibited sodium transport (n = 33) and B-inhibited chloride transport (n = 36). Measurement of electrical resistance (R) and electrical potential (PD) confirmed tissue viability during the experiment, no statistically significant differences in relation to control conditions were noted. The minimal and maximal PD measured during stimulation confirmed the repeatability of the recorded reactions to the mechanical and mechanical-chemical stimulus for all examined groups. Measurement of PD during stimulation showed differences in the transport of sodium and chloride ions in each of the analyzed groups relative to the control. The statistical analysis of the PD measured in stationary conditions and during mechanical and/or mechanical-chemical stimulation proved that changes in sodium and chloride ion transport constitute the physiological response of keratinocytes to changes in environmental conditions for all applied experimental conditions. Assessment of transdermal ion transport changes may be a useful tool for assessing the skin condition with tendency to pain hyperactivity and hypersensitivity to xenobiotics.

Cisplatin influences the skin ion transport - An in vitro study.

Platinum-based drugs, used in treating tumors, cause numerous undesirable effects in patients, like neuropathic pain, hypersensitivity, reddening, pruritus and rash. Changes in Na+ transport modify local osmolality and contribute to the initiation of hypersensitivity and allergy. They are also associated with stimulation of C-fibres and hyperalgesia. Cl- transport is essential for regulation of sweat composition and the migration of immunocompetent cells. The aim of the conducted study was to assess the effect of a cisplatin solution on the electrophysiological parameters of the isolated rabbit skin specimens. The difference in transepithelial electrical potential (PD) and resistance (R) in stationary conditions and during 15 s mechanical-chemical stimulation (PDmin and PDmax), were measured. Measurement of R revealed that tissue samples were live, and their permeability to ions were stable. Control specimens had PD -0.22 mV (median). The PD of specimens treated by cisplatin was -0.55 mV (median), to for cisplatin and bumetanide 0 mV (median). Treatment with cisplatin did not change the continuous transport of Na+ and K+ ions, but did change that of Cl- ions. Stimulation of samples with the transport blockers of Cl-, Na+ and both induced repeatable and measurable reactions in the transport of the appropriate ions. It was shown that absorption of Na+ ions and release of Cl- ions was intensified than in the untreated specimens. It was proven in the study that cisplatin influences the Na+ and Cl- transport in the skin cells. Restoring the balance in ion flow can prevent side effects of use cisplatin-based drugs.

2'-(1H-phenanthro[9,10-d]imidazol-2-yl)-phenyl-4-carboxylic acid N-hydroxysuccinimide ester: A new phenanthroimidazole derivative as a fluorescent probe for medical imaging applications.

In this study a new probe (2'-(1H-phenanthro[9,10-d]imidazol-2-yl)-phenyl-4-carboxylic acid N-hydroxysuccinimide ester, PB1-1) was synthesized and presented, containing the ester group as reactive group for medical imaging applications. The tests included a comparison to the PB1 probe with the aldehyde group described earlier. Also, the photophysics of PB1 and PB1-1 when conjugated to albumin (HSA) and concanavalin A (Con A) was studied. The fluorescence anisotropy measurements and the method of fluorescence quenching of protein were used to examine these interactions. The results showed that both dyes are highly bound to the studied proteins, especially PB1-1. In the present study we also compared the stability of prepared conjugates. The in vitro study have shown that all tested compounds presented to be usable in the case of fixated cell staining. PB1-1-ConA and PB1-1-HSA were characterized with the lowest cytotoxicity during the MTT assay, and thus should be more suitable for live imaging applications than PB1-ConA and PB1-HSA. The results obtained in this work confirmed the theses presented in in silico studies as to the correctness of the choice of ester group as actively binding to the protein. At the same time, we have experimentally demonstrated the significant influence of a probe-protein linker on the spectral properties of conjugates used in medical imaging. We have clearly indicated that a detailed analysis of derivatives with different reactive group allows for proper probe selection. We also pointed out that based on the geometric skeleton of one dye, a whole range of fluorescent probes with different absorption and fluorescence spectra can be obtained for in vitro tests in medical imaging.

Female Volleyball Players Are More Prone to Cortisol Anticipatory Stress Response than Sedentary Women.

Background and Objectives: Top-level sports performance places heavy physical and psychological demands on elite-level athletes, which can be a source of increased levels of stress. Therefore, high-level volleyball players may present altered cardiovascular and endocrinological stress response during stressful events. Although many previous studies have examined the response to stress on athletes, most of them regarded only males, while the impact of the female menstrual cycle has rarely been taken into account. We aimed to study psychophysiological response to anticipatory stressor through analysis of heart rate, self-reported anxiety level, and salivary cortisol in healthy young female athletes by minimalizing the effect of confounders. Materials and Methods: A total of 55 females (25 members of the best league for female volleyball players in Poland and 30 sedentary-lifestyle control subjects) in the follicular phase of their menstrual cycle were exposed to mental arithmetic tasks as an experimental imitation of the stressor. Volleyball players were significantly taller than sedentary individuals (177.1 ± 3.4 cm vs. 173.3 ± 3.4 cm, respectively, p = 0.034), but did not differ in weight (73.6 ± 5.2 kg vs. 70 ± 4.23 kg, respectively, p = 0.081), body mass index (BMI) (23.5 ± 1.13 vs. 24.1 ± 1.45, respectively, p = 0.060), and age (22 ± 1.11 vs. 23 ± 1.14 years, respectively, p = 0.2). Their stress responses were assessed through self-reported anxiety levels and physiological measurements of salivary cortisol concentrations and heart rate (HR). Results: For HR, significant effects of time (F(2,120) = 21.34, p < 0.001, η2 = 0.26) were found, but not for training status (F(1,60) = 2.69, p = 0.106, η2 = 0.04). For cortisol levels, the analysis showed the main effects of time (F(3,180) = 11.73, p < 0.001, η2 = 0.16) and training status (F(1,60) = 4.69, p = 0.034, η2 = 0.07) and a significant interaction between training status and time (F(3,180) = 3.07, p = 0.029, η2 = 0.05). Post-hoc analyses showed higher cortisol concentrations among volleyball players following the math task (all p < 0.001), as well as higher cortisol concentrations in S2, S3, and S4 compared to S1 in volleyball players (all p < 0.001). We observed also a significant increase in state anxiety in both groups (all p < 0.001), but no differences in state anxiety levels between groups. Conclusion: Female volleyball players may not differ in subjective graduation of stressors; however, exposure to training-based stressors seems to promote cortisol response to the anticipated stressor.