Manganese Sulfanyl Porphyrazine-MWCNT Nanohybrid Electrode Material as a Catalyst for H2O2 and Glucose Biosensors.

The demetallation reaction of sulfanyl magnesium(II) porphyrazine with N-ethylphthalimide substituents, followed by remetallation with manganese(II) salts, yields the corresponding manganese(III) derivative (Pz3) with high efficiency. This novel manganese(III) sulfanyl porphyrazine was characterized by HPLC and analyzed using UV-Vis, MS, and FT-IR spectroscopy. Electrochemical experiments of Pz3 conducted in dichloromethane revealed electrochemical activity of the new complex due to both manganese and N-ethylphthalimide substituents redox transitions. Subsequently, Pz3 was deposited on multiwalled carbon nanotubes (MWCNTs), and this hybrid material was then applied to glassy carbon electrodes (GC). The resulting hybrid electroactive electrode material, combining manganese(III) porphyrazine with MWCNTs, showed a significant decrease in overpotential of H2O2 oxidation compared to bare GC or GC electrodes modified with only carbon nanotubes (GC/MWCNTs). This improvement, attributed to the electrocatalytic performance of Mn3+, enabled linear response and sensitive detection of H2O2 at neutral pH. Furthermore, a glucose oxidase (GOx)-containing biosensing platform was developed by modifying the prepared GC/MWCNT/Pz3 electrode for the electrochemical detection of glucose. The bioelectrode incorporating the newly designed Pz3 exhibited good activity in the presence of glucose, confirming effective electronic communication between the Pz3, GOx and MWCNT surface. The linear range for glucose detection was 0.2-3.7 mM.

Ashwagandha's Multifaceted Effects on Human Health: Impact on Vascular Endothelium, Inflammation, Lipid Metabolism, and Cardiovascular Outcomes-A Review.

Withania somnifera, commonly known as Ashwagandha, has been popular for many years. Numerous studies have shown that the extract of this plant, due to its wealth of active substances, can induce anti-inflammatory, neuroprotective, immunomodulatory, hepatoprotective, cardioprotective, anti-diabetic, adaptogenic, anti-arthritic, anti-stress, and antimicrobial effects. This review examines the impact of Ashwagandha extract on the vascular endothelium, inflammation, lipid metabolism, and cardiovascular outcomes. Studies have shown that Ashwagandha extracts exhibit an anti-angiogenic effect by inhibiting vascular endothelial growth factor (VEGF)-induced capillary sprouting and formation by lowering the mean density of microvessels. Furthermore, the results of numerous studies highlight the anti-inflammatory role of Ashwagandha extract, as the action of this plant causes a decrease in the expression of pro-inflammatory cytokines. Interestingly, withanolides, present in Ashwagandha root, have shown the ability to inhibit the differentiation of preadipocytes into adipocytes. Research results have also proved that W. somnifera demonstrates cardioprotective effects due to its antioxidant properties and reduces ischemia/reperfusion-induced apoptosis. It seems that this plant can be successfully used as a potential treatment for several conditions, mainly those with increased inflammation. More research is needed to elucidate the exact mechanisms by which the substances contained in W. somnifera extracts can act in the human body.

Can Asiatic Acid from Centella asiatica Be a Potential Remedy in Cancer Therapy?-A Review.

Centella asiatica has been recognized for centuries in Eastern medicine for its pharmacological properties. Due to the increasing prevalence of oncological diseases worldwide, natural substances that could qualify as anticancer therapeutics are becoming increasingly important subjects of research. This review aims to find an innovative use for asiatic acid (AA) in the treatment or support of cancer therapy. It has been demonstrated that AA takes part in inhibiting phosphorylation, inducing cell death, and reducing tumor growth and metastasis by influencing important signaling pathways, such as PI3K, Akt, mTOR, p70S6K, and STAT3, in cancer cells. It is also worth mentioning the high importance of asiatic acid in reducing the expression of markers such as N-cadherin, ß-catenin, claudin-1, and vimentin. Some studies have indicated the potential of asiatic acid to induce autophagy in cancer cells through changes in the levels of specific proteins such as LC3 and p62. It can also act as an anti-tumor immunotherapeutic agent, thanks to its inductive effect on Smad7 in combination with naringenin (an Smad3 inhibitor). It seems that asiatic acid may be a potential anticancer drug or form of adjunctive therapy. Further studies should take into account safety and toxicity issues, as well as limitations related to the pharmacokinetics of AA and its low oral bioavailability.

The Association of Tobacco Smoking and Level of Apoptosis in the Long Head of the Biceps Chronic Tendinopathy-An Immunohistochemical Study.

BACKGROUND: The substances present in cigarette smoke have a negative impact on cellular integrity and metabolism, can reduce blood flow to tissues, and can disrupt collagen synthesis. Ultimately this can lead to cell death, which clinically may result in impaired tendon healing and the onset of chronic tendinopathy. Within the shoulder, the exact association between the extent of apoptosis in the long head of the biceps (LHB) tendon and harmful factors like cigarette smoke remains unclear. OBJECTIVES: The purpose of this study was to investigate the connection between smoking, the degree of apoptosis in LHB tendinopathy, and the long-term outcomes of surgical treatment. DESIGN: Observational, retrospective study. METHODS: This study included 22 consecutive patients who had undergone arthroscopic biceps tenodesis or tenotomy for symptomatic LHB tendinopathy with or without concomitant rotator cuff tears (RCT). The intra-articular LHB tendon remnants were histologically examined by measuring the level of expression of apoptotic cell markers such as BCL2, cleaved caspase 3, and p53. Pre- and postoperative clinical outcomes were analyzed by collecting patient report outcome measures such as the American Shoulder and Elbow Surgeons (ASES) score and the Visual Analogue Scale (VAS) for pain. RESULTS: The smokers group had a mean pack-year history of 13.12 (SD = 9.94), mean number of cigarettes per day of 14.77 (SD = 4.64), and a mean smoking duration of 16.38 (SD = 10.1) years. Among the smoking indexes, the number of cigarettes per day showed a positive correlation with Snyder classification (p = 0.0459, rho = 0.3682). Non-smokers and smokers did not show a statistically significant difference in the expression indexes of BCL2, cleaved caspase 3, or p53 (p = 0.4216, p = 0.5449, p = 0.5613, respectively). However, the cleaved caspase 3 expression index showed a negative correlation with the severity of rotator cuff lesions in the total population (p = 0.0193, rho = -0.4651). CONCLUSIONS: While apoptotic processes in the LHB tendon were observed, no significant association was found between tobacco smoking, the extent of apoptosis, and clinical outcomes. However, the expression of the apoptotic marker cleaved caspase 3 correlated with the severity of rotator cuff pathology. Furthermore, active smoker status was associated with worse clinical outcomes in terms of pain following LHB tenodesis or tenotomy.

Can Ashwagandha Benefit the Endocrine System?-A Review.

Withania somnifera, also known as Ashwagandha, has been used in traditional medicine for thousands of years. Due to the wide range of its activities, there has been interest in its possible beneficial effects on the human body. It is proved that, among others, Ashwagandha has anti-stress, anti-inflammatory, antimicrobial, anti-cancer, anti-diabetic, anti-obesity, cardioprotective, and hypolipidemic properties. Particularly interesting are its properties reported in the field of psychiatry and neurology: in Alzheimer's disease, Parkinson's disease, multiple sclerosis, depression, bipolar disorder, insomnia, anxiety disorders and many others. The aim of this review is to find and summarize the effect that Ashwagandha root extract has on the endocrine system and hormones. The multitude of active substances and the wide hormonal problems faced by modern society sparked our interest in the topic of Ashwagandha's impact on this system. In this work, we also attempted to draw conclusions as to whether W. somnifera can help normalize the functions of the human endocrine system in the future. The search mainly included research published in the years 2010-2023. The results of the research show that Ashwagandha can have a positive effect on the functioning of the endocrine system, including improving the secretory function of the thyroid gland, normalizing adrenal activity, and multidirectional improvement on functioning of the reproductive system. The main mechanism of action in the latter appears to be based on the hypothalamus-pituitary-adrenal (HPA) axis, as a decrease in cortisol levels and an increase in hormones such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in men were found, which results in stress level reduction and improvement in fertility. In turn, other studies prove that active substances from W. somnifera, acting on the body, cause an increase in the secretion of triiodothyronine (T3) and thyroxine (T4) by the thyroid gland and a subsequent decrease in the level of thyroid-stimulating hormone (TSH) in accordance with the hypothalamus-pituitary-thyroid (HPT) axis. In light of these findings, it is clear that Ashwagandha holds significant promise as a natural remedy for various health concerns, especially those related to the endocrine system. Future research may provide new insights into its mechanisms of action and expand its applications in both traditional and modern medicine. The safety and toxicity of Ashwagandha also remain important issues, which may affect its potential use in specific patient groups.

The Association between Acetabulum Fractures and Subsequent Coxarthrosis in a Cohort of 77 Patients-A Retrospective Analysis of Predictors for Secondary Hip Osteoarthritis.

OBJECTIVE: the aim of this study was to document the occurrence of THA after acetabulum surgery and examine the factors that predict its occurrence. METHODS: This study included 77 consecutive patients who were admitted for acetabulum fracture surgery between 2012 and 2019. The inclusion criteria were acetabular fractures and indications for operative management. The exclusion criteria were acetabular fractures treated non-operatively, fractures requiring primary THA, and periprosthetic acetabular fractures. Data concerning demographics, date of injury, date of surgery, surgical approach, stabilization, and further reconstructive surgery were collected retrospectively. The number of patients who underwent THA and their risk factors were recorded. The minimum follow-up for each patient was 2 years of observation. A total of 77 patients with a mean age of 53 years were included. RESULTS: At a mean follow-up of 2 years, THA was performed in 16 (20.8%) patients due to post-traumatic arthritis. An analysis of the surgical approaches showed that the Kocher-Langenbeck approach increased the risk of THA nearly 12 times compared with the ilioinguinal approach (p = 0.016). Furthermore, the duration of the waiting period for surgery significantly impacted the occurrence of THA, with each additional day leading to an 89% increase in the risk of prosthesis usage (p = 0.001). CONCLUSIONS: This study suggests that acetabular fractures may lead to post-traumatic hip osteoarthritis. The surgical approach and the waiting time for surgery are potential factors that may predict secondary hip osteoarthritis and the need for subsequent THA. However, further investigations should be performed to establish predictors for secondary hip osteoarthritis, and especially to determine the impact of the surgical approach.

Therapeutic Drug Monitoring of Direct Oral Anticoagulants in Patients with Extremely Low and High Body Weight-Pilot Study.

Phase III clinical trials for individual direct oral anticoagulants (DOACs) contained a limited representation of subjects with abnormal body weight, which were mostly limited to a BMI > 40 kg/m2, or body weight > 120 kg for obese subjects, and <50 kg for underweight subjects. Although low or high body weight is not a contraindication to DOACs therapy, it can significantly affect the safety and effectiveness of treatment. Due to the limited amount of clinical data on the use of DOACs in extremely abnormal weight ranges, optimal pharmacotherapy in this group of patients is a matter of controversy. The objective of this study was to evaluate the pharmacokinetics of DOAC properties in patients with abnormal body weight beyond the established cut-off points in the phase III studies for rivaroxaban, apixaban, and dabigatran. In total, 38 patients took DOACs for at least 12 months for non-valvular atrial fibrillation in 2019-2021. Blood samples were collected before the planned intake of the drug and 4 h after its administration. The determined concentrations of DOACs were statistically analyzed in relation to body weight, age, and eGFR (estimated Glomerular Filtration Rate). Among subjects taking apixaban, rivaroxaban, and dabigatran, the smallest representation of patients who achieved therapeutic concentrations were those treated with dabigatran. The population of people with abnormal body weight is a potential risk group of patients, in which some of them do not reach the therapeutic range of DOACs.

Current Treatment of Melanoma Brain Metastases.

Melanoma is a type of skin cancer in which there is a strong correlation between its occurrence and exposure to ultraviolet radiation. Although it is not the most common skin cancer, it has the highest mortality rate of all skin cancers. The prognosis of patients is significantly worsened by melanoma metastasis to the brain, which often occurs in patients with advanced disease. The formation and development of melanoma metastases to the brain involve a very complex process, and their mechanisms are not fully understood. One of the ways for metastatic melanoma cells to survive and develop cancer in the brain environment is the presence of oncogenic BRAF mutation, which occurs in up to 50% of metastatic melanoma cases. Before discovering new methods of treating metastases, the overall survival of patients with this disease was 6 months. Currently, research is being conducted on new drugs using immunotherapy (immune checkpoint inhibitors: anti-PD-1, anti-CTLA-4) and targeted therapy (BRAF and MEK inhibitors) to improve the prognosis of patients. In this article, we summarize the current state of knowledge about the results of treating brain metastases with new systemic therapies.

Natural Phytochemicals as SIRT Activators-Focus on Potential Biochemical Mechanisms.

Sirtuins are a family of proteins with enzymatic activity. There are seven mammalian sirtuins (SIRT1-SIRT7) that are found in different cellular compartments. They are a part of crucial cellular pathways and are regulated by many factors, such as chemicals, environmental stress, and phytochemicals. Several in vitro and in vivo studies have presented their involvement in anti-inflammatory, antioxidant, and antiapoptotic processes. Recent findings imply that phytochemicals such as resveratrol, curcumin, quercetin, fisetin, berberine, and kaempferol may regulate the activity of sirtuins. Resveratrol mainly activates SIRT1 and indirectly activates AMPK. Curcumin influences mainly SIRT1 and SIRT3, but its activity is broad, and many pathways in different cells are affected. Quercetin mainly modulates SIRT1, which triggers antioxidant and antiapoptotic responses. Fisetin, through SIRT1 regulation, modifies lipid metabolism and anti-inflammatory processes. Berberine has a wide spectrum of effects and a significant impact on SIRT1 signaling pathways. Finally, kaempferol triggers anti-inflammatory and antioxidant effects through SIRT1 induction. This review aims to summarize recent findings on the properties of phytochemicals in the modulation of sirtuin activity, with a particular focus on biochemical aspects.

Synthesis, Electrochemical and Photochemical Properties of Sulfanyl Porphyrazine with Ferrocenyl Substituents.

Ferrocene is useful in modern organometallic chemistry due to its versatile applications in material sciences, catalysis, medicinal chemistry, and diagnostic applications. The ferrocene moiety can potentially serve many purposes in therapeutics and diagnostics. In the course of this study, (6-bromo-1-oxohexyl)ferrocene was combined with dimercaptomaleonitrile sodium salt to yield a novel maleonitrile derivative. Subsequently, this compound was subjected to an autocyclotetramerization reaction using the Linstead conditions in order to obtain an octaferrocenyl-substituted magnesium(II) sulfanyl porphyrazine. Following that, both compounds-the maleonitrile derivative and the porphyrazine derivative-were subjected to physicochemical characterization using UV-Vis, ES-TOF, MALDI-TOF, and one-dimensional and two-dimensional NMR spectroscopy. Moreover, the sulfanyl porphyrazine was subjected to various photophysical studies, including optical absorption and emission measurements, as well as the evaluation of its photochemical properties. Values of singlet oxygen generation quantum yields were obtained in different organic solvents. The electrochemical properties of the synthesized compounds were studied using cyclic voltammetry. According to the electrochemical results, the presence of electron-withdrawing oxohexyl groups attached to ferrocene afforded significantly more positive oxidation potentials of the ferrocene-based redox process up to 0.34 V vs. Fc+/Fc.

The Use of Cannabidiol in Metabolic Syndrome-An Opportunity to Improve the Patient's Health or Much Ado about Nothing?

Cannabis-derived therapies are gaining popularity in the medical world. More and more perfect forms of cannabinoids are sought, which could be used in the treatment of many common diseases, including metabolic syndrome, whose occurrence is also increasing. The purpose of this review was to investigate the usefulness of cannabinoids, mainly cannabidiol (CBD), in individuals with obesity, impaired glucose and lipid metabolism, high blood pressure, and non-alcoholic fatty liver disease (NAFLD). We summarised the most recent research on the broad topic of cannabis-derived influence on metabolic syndrome components. Since there is a lot of work on the effects of Δ9-THC (Δ9-tetrahydrocannabinol) on metabolism and far less on cannabidiol, we felt it needed to be sorted out and summarised in this review. The research results on the use of cannabidiol in obesity are contraindicatory. When it comes to glucose homeostasis, it appears that CBD maintains it, sensitises adipose tissue to insulin, and reduces fasting glucose levels, so it seems to be a potential target in this kind of metabolic disorder, but some research results are inconclusive. CBD shows some promising results in the treatment of various lipid disorders. Some studies have proven its positive effect by decreasing LDL and increasing HDL as well. Despite their probable efficacy, CBD and its derivatives will likely remain an adjunctive treatment rather than a mainstay of therapy. Studies have also shown that CBD in patients with hypertension has positive effects, even though the hypotensive properties of cannabidiol are small. However, CBD can be used to prevent blood pressure surges, stabilise them, and have a protective effect on blood vessels. Results from preclinical studies have shown that the effect of cannabidiol on NAFLD may be potentially beneficial in the treatment of the metabolic syndrome and its components. Nevertheless, there is limited data on CBD and NAFLD in human studies. Because of the numerous confounding factors, the conclusions are unclear, and more research in this field is required.

Cyclic AMP but Not Calmodulin as a Potential Wasoconstrictor in Simulated Reperfusion.

The phenomena of ischemia and reperfusion are associated with the pathological background of cardiovascular diseases. Ischemia is initiated by ischemia reperfusion injury (IRI), which involves disruption of intracellular signaling pathways and causes cell death. The aim of this study was to assess the reactivity of vascular smooth muscle cells in the conditions of induced ischemia and reperfusion, and to determine the mechanisms leading to contractility disorders. This study was conducted using classical pharmacometric methods on an isolated model of the rat caudal artery. The experiment consisted of the analysis of the final and initial perfusate pressure measurements after induction of arterial contraction with phenylephrine in the presence of forskolin and A7 hydrochloride, two ligands modifying the contractility of vascular smooth muscle cells (VSMC). The pharmacometric analysis showed that in simulated reperfusion, cyclic nucleotides have a vasoconstrictive effect, and calmodulin has a vasodilating effect. The responsiveness of vascular smooth muscle cells to the vasopressor effects of α1-adrenomimetics during reperfusion may change uncontrollably, and the effects of secondary messengers may be counter physiological. Further studies are needed to evaluate the function of other second messengers on VSMCs in the process of ischemia and reperfusion.

Augmentation Therapies as Treatments for Coexisting Somatic Problems in Schizophrenia-A Systematic Review.

The aim of this review is to appraise the data from available randomized clinical trials (RCT) regarding the possible combinations of neuroleptic and non-antipsychotic treatment which could enhance antipsychotic therapy efficacy whilst simultaneously addressing somatic symptoms in individuals with schizophrenia. A systematic search of the PubMed database up to February 2022 was conducted. Inclusion criteria: randomized controlled trials using augmentation therapy in chronic schizophrenia in adults, written in English, and only studies with psychometric assessments of schizophrenia were incorporated. Exclusion criteria: non-clinical, first episode of schizophrenia, patients on medication other than antipsychotics augmented, and not adjunctive therapy. Overall, 37 studies of 1931 patients with schizophrenia who received a combination of antipsychotic medication with other drugs were selected. A statistically significant reduction of negative and positive symptoms of schizophrenia, measured with the PANSS scale, when using a combination of antipsychotic treatment along with aspirin, simvastatin, N-acetylcysteine, or pioglitazone was found. A combination of antipsychotic medication with aspirin, simvastatin, N-acetylcysteine, or pioglitazone seems to be effective in the reduction of symptoms of schizophrenia in adults, but long-term studies are required to confirm this effect.

Does Intense Endurance Workout Have an Impact on Serum Levels of Sex Hormones in Males?

The benefits of physical activity and sports are widely known and proved to be crucial for overall health and well-being. In this research, the authors decided to measure the impact of endurance training in a professional male rowing team on the serum concentration levels of testosterone, estradiol, sex hormone binding globulin (SHBG) and nitric oxide (NO) and apolipoprotein A1 (Apo-A1). Proper levels of the serum concentration are necessary in order to maintain physical effectiveness. Authors analyzed the data and reviewed the former conterminous articles to find the possible mechanisms leading to changes of serum concentration of certain hormones and molecules. The direct effect of physical activity was a decrease in testosterone serum concentration (from 7.12 ± 0.4 to 6.59 ± 0.35 (ng/mL)), sex hormone binding globulin serum concentration (from 39.50 ± 2.48 to 34.27 ± 2.33 (nmol/L)), nitric oxide serum concentration (from 440.21 ± 88.64 to 432 ± 91.89 (ng/mL)), increase in estradiol serum concentration (from 78.2 ± 11.21 to 83.01 ± 13.21 (pg/mL)) and no significant increase in Apo-A1 serum concentration (from 2.63 ± 0.2 to 2.69 ± 0.21 (mg/mL)). Low testosterone concentration in OTS may be a consequence of increased conversion to estradiol, because gonadotropic stimulation is maintained. Apo-A1 serum concentration was measured due to a strong connection with testosterone level and its possible impact of decreasing cardiovascular risk.

Effect of Systemic Prednisone Treatment on Changes of Inflammation Markers in Chronic Rhinosinusitis.

(1) Objective: We aimed to evaluate the effect of treatment with prednisone on nasal and systemic periostin and eotaxin expression, IgE in plasma and eosinophils in tissue. (2) Methods: We compared the values of nasal and systemic periostin, eotaxin, IgE and eosinophils in tissue in patients treated with only nasal steroids before FESS, group 1, with those treated with an oral steroid-prednisone, group 2. (3) Results: A statistically significant decrease in the level of periostin, eotaxin and IgE in plasma was achieved in patients treated with prednisone one week before and after surgery (in sequence: p < 0.0476, p < 0.0006, p < 0.0031). In patients treated with steroids, we also observed a lower level of periostin in the epithelium (p < 0.044), eotaxin in the stroma (p limit value < 0.075) and eosinophils (p < 0.031) in the tissues collected during the operation. (4) Conclusions: Systemic steroid treatment with prednisone distinctly decreases periostin, eotaxin and IgE expression in plasma. We also observed a lower level of periostin in the epithelium, eotaxin in the stroma and eosinophils in the tissues. We need more attempts to find inflammatory markers associated with chronic rhinosinusitis. Identifying drugs that decrease inflammatory parameters would allow for more targeted therapy.

Cholecalciferol supplementation lowers leptin and TMAO but increases NO and VEGF-A levels in obese vitamin D deficient patients: Is it one of the potential cardioprotective mechanisms of vitamin D?

BACKGROUND: Vitamin D deficiency is one of the most common health issues in developed countries. Obese patients are most at risk of having serum 25-hydroxyvitamin D3 (25(OH)D3) levels that are too low due to the accumulation of vitamin D in adipose tissue. While the effects of a deficiency on the skeletal or immune system are known, the effects on the cardiovascular system are not yet clear. Our study investigates the effect of cholecalciferol supplementation in obese patients on selected biomarkers associated with cardiovascular diseases (CVDs). METHODS: The study enrolled 33 obese patients with insufficient 25(OH)D3 levels. For three months, the subjects supplemented with cholecalciferol at a dose of 2000 IU/day. Concentrations of nitric oxide (NO), vascular endothelial growth factor A (VEGF-A), leptin, trimethylamine N-oxide (TMAO) and soluble suppression of tumorigenicity 2 (sST2) were measured in baseline samples using ELISA (BioTek EPOCH). 25(OH)D3 levels measured on Beckman Coulter DXI 800 by chemiluminescence method. RESULTS: After supplementation, 25(OH)D3 levels increased significantly. Normal levels were achieved in most patients. A statistically significant reduction leptin and TMAO levels was observed. At the same time, NO and VEGF-A levels increased statistically significantly. CONCLUSION: This study indicates that restoring normal 25(OH)D3 levels in obese people reduces the concentration of pro-inflammatory factors associated with cardiovascular diseases. Reducing inflammation and the potential impact on vascular reactivity leads to the conclusion that cholecalciferol supplementation in obese patients may benefit the cardiovascular system.

Pulmonary artery targeted therapy in treatment of COVID-19 related ARDS. Literature review.

INTRODUCTION: The most grievous complication of the COVID-19 is the acute respiratory distress syndrome. A specific, rescue treatment for rapidly deteriorating patients should emerge to improve respiratory function and help patients to survive the most challenging period. Drugs used in targeted therapy of pulmonary arterial hypertension (PAH) appears to be suitable for this task and this article describes their potential for treatment of severe cases of COVID-19. METHODS: The authors reviewed the following databases for randomized controlled trials, reviews and meta-analyses published up to July 2020: Pubmed, Scopus, Google Scholar, Cochrane Database and ClinicalKey. The authors included every study contributory to the assessment of the potential of drugs used in targeted PAH therapy in treatment of COVID-19. RESULTS: Endothelin receptor antagonists, phosphodiesterase 5 inhibitors, riociguat and prostacyclin have proven ani-inflammatory effect and reduce pulmonary artery blood pressure, lung oedema and remodelling. Bosentan shows antiviral properties and sildenafil, as well as epoprostenol, inhibits apoptosis of lung epithelial cells. Among patients with lung lesions the decrease of pulmonary blood pressure can lead to increase of ventilation/perfusion mismatch and decrease of blood oxygenation. CONCLUSIONS: Among all assessed drugs bosentan, sildenafil and epoprostenol appear to be most promising and a combination of these drugs should be considered due to synergism. The targeted PAH therapy in treatment of COVID-19 associated ARDS could be a useful tool saving lives of patients with severe SARS-CoV-2 infection, however, its introduction should be investigated and monitored very carefully as it can lead to transient deterioration of patient condition.

Vitamin D Supplementation and Its Impact on Different Types of Bone Fractures.

Vitamin D helps to balance the levels of calcium and phosphorus to maintain proper bone structure. It is also involved in essential biological roles and displays a wide spectrum of potential benefits in the human body. Since there are many types of fractures that occur at specific ages and due to different circumstances, the influence of vitamin D on the frequency of a particular fracture may differ. Thus, the authors investigated the possible preventive effect of vitamin D on the risks of vertebral fractures, hip fractures, stress fractures and pediatric fractures. Additional aspects of vitamin D, especially on recuperation after injures and its impact on the severity of particular fractures, were also discussed. It was suggested that vitamin D supplementation may contribute to a reduction in hip fracture risk due to reduced bone turnover, decreased frequency of falls and improved muscle function. Furthermore, vitamin D appears to lower the risk of stress fractures in athletes and military recruits. Due to a nonunified protocol design, presented investigations show inconsistencies between vitamin D supplementation and a decreased risk of vertebral fractures. However, a vitamin D preventive effect on pediatric fractures seems to be implausible.

The Influence of Body Mass Index on Growth Factor Composition in the Platelet-Rich Plasma in Patients with Knee Osteoarthritis.

BACKGROUND: An abnormally high body mass index is strongly associated with knee osteoarthritis. Usually, obese patients are excluded from clinical trials involving PRP intra-articular injections. Growth factors have been demonstrated to have a disease-modifying effect on KOA treatment, even though data on their influence on treatment effectiveness in obese patients are lacking. PURPOSE: To prospectively compare the level of selected growth factors including transforming growth factor-b (TGF-ß), epidermal growth factor (EGF), fibroblast growth factor, insulin-like growth factor-1 (IGF-1), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and fibroblast growth factor-2 (FGF-2) in platelet-rich plasma (PRP) in obese patients and patients with normal BMI. METHODS: A total of 49 patients were included in the study according to inclusion and exclusion criteria. The groups strongly differed in body mass index (median values 21.6 vs. 32.15). Concentrations of growth factors were measured with an enzyme-linked immunosorbent assay. Statistical significance was determined with the Mann-Whitney U test. The compliance of the distribution of the results with the normal distribution was checked using the Shapiro-Wilk test separately for both groups. RESULTS: There were no statistically significant differences in median marker levels between groups. Statistically significant Pearson correlations were observed between IGF-1 serum level and age (weak negative, r = -0.294, p = 0.041) and gender (moderate positive, r = 0.392, 0.005). CONCLUSIONS: BMI does not influence the level of selected growth factors in patients with knee osteoarthritis. Obese and non-obese patients had similar compositions of PDGF, TGF-ß, EGF, FGF-2, IGF-1, and VEGF. PRP can be used in both groups with similar effects associated with growth factors' influence on articular cartilage.

Therapeutic Drug Monitoring of Carbamazepine: A 20-Year Observational Study.

BACKGROUND: Carbamazepine (CBZ) is a first-generation anticonvulsant drug. Hence, in certain cases, therapeutic drug monitoring (TDM) supports pharmacotherapy. METHODS: The presented research was based on a retrospective analysis including 710 ambulatory and hospitalized patients treated with CBZ between the years 1991 and 2011. The method used for the determination of the CBZ concentration was fluorescence polarization immunoassay (FPIA) performed using an Abbott GmbH TDx automatic analyzer, with the therapeutic range for carbamazepine being 4-12 µg/mL. RESULTS: The therapeutic range was observed more often in patients between 3 and 17 years of age compared with the population ≥18 years of age (73.5% vs. 68.8%). The therapeutic level was exceeded less frequently in the population between 3 and 17 years of age despite them being given a significantly higher dose per kilogram of body weight than in the population ≥18 years of age (13.64 mg/kg vs. 10.43 mg/kg, p < 0.0001). Patients ≥18 years of age were statistically significantly more likely to be in the group with a suspected drug overdose (73.9% vs. 26.1%), and suicide attempts only occurred in elderly patients (100.0% vs. 0.0%, p = 0.003). CONCLUSION: The results of the TDM of CBZ showed that only 71% of all samples were at the therapeutic level. To ensure the maximum efficacy and safety of the therapy, it is necessary to monitor the concentration of CBZ regardless of sex and age.