Levels of biological markers of nitric oxide in serum of patients with squamous cell carcinoma of the oral cavity

The aim of the study was a determination of the levels of nitric oxide（NO）and its biological markers such as malonyldialdehyde（MDA）and nitrotyrosine in the serum of patients with squamous cell carcinoma（SCC）of the oral cavity and identification of the relationships between NO and those markers.These studies were performed on patients with SCC of the oral cavity before and after treatment.Griess reaction was used for the estimation of the total concentration of NO in serum.The nitrotyrosine level in serum was assessed with an enzyme-linked immunosorbent assay（ELISA）kit,and MDA level using a spectrophotometric assay.Higher concentrations of NO in blood serum were determined in patients with stage IV of the disease before treatment in comparison to the control group and patients with stages II and III of the disease.Moreover,higher concentrations of MDA and nitrotyrosine were determined in the serum of patients in all stages of the disease in comparison to healthy people.After treatment,lower concentrations of NO in the serum of patients with stage IV of the disease were observed in comparison to the amounts obtained prior to treatment.In addition,lower levels of nitrotyrosine in the serum of patients with all stages of the disease were recorded,whereas higher concentrations of MDA were determined in these patients in comparison to results obtained before treatment.The compounds formed with the contribution of NO,such as MDA and nitrotyrosine,may lead to cancer progression in patients with SCC of the oral cavity,and contribute to formation of resistance to therapy in these patients as well.Moreover,the lack of a relationship between concentrations of NO and MDA,and between NO and nitrotyrosine in serum suggests that the process of lipid peroxidation and nitration in patients with SCC does not just depend on NO.     

Malnutrition in Older Adults—Effect on Falls and Fractures: A Narrative Review

Malnutrition in older adults impacts health status, increased mortality, and morbidity. Malnutrition may increase the development of geriatric syndromes and contribute to a higher prevalence of falls and osteoporotic fractures that lead to loss of independence and an increased rate of institutionalization. The role of malnutrition in the pathogenesis of other geriatric syndromes seems to be well established. However, the data concerning nutritional interventions are confounding. Moreover, long-term undernutrition seems to be one of the factors that strongly influences the efficacy of interventions. This review outlines the current literature on this topic, and aims to guide physicians to make proper decisions to prevent the vicious cycle of falls, fractures, and their negative outcomes in patients with malnutrition.     

Influence of Amodiaquine on the Antimalarial Activity of Ellagic Acid: Crystallographic and Biological Studies

In the search for new antimalarial drugs, design of hybrid molecules is recommended to improve biological activity and to decrease the risk of parasite resistance development. Ellagic acid, as an inhibitor of Plasmodium glutathione, presents an original mode of action and thus appears as a promising antiplasmodial compound. A new complex (AQ–EA) consisting of the well‐known antimalarial drug, amodiaquine, and ellagic acid was obtained. The studied crystal structure of AQ–EA showed that the triclinic centrosymmetrical unit cell of the crystal contains two molecules of amodiaquine (AQ) and two symmetrically independent molecules of ellagic acid (EA). The packing of the molecules in the crystal is dominated by hydrogen bonds between AQ and EA. The antiplasmodial activity of the hybrid complex AQ–EA was also determined and compared with the values of IC₅₀ for AQ and EA separately. Potentiation assays between both molecules were conducted to understand the pharmacological interactions between AQ and EA against Plasmodium falciparum in vitro. The hybrid complex AQ–EA (IC₅₀ of 47 nm ) showed improved antiplasmodial activity in comparison with EA alone.     

Costs and effects of secondary prevention with perindopril in stable coronary heart disease in Poland: an analysis of the EUROPA study including 1251 Polish patients

OBJECTIVES: To estimate the long-term impact of treatment with perindopril on costs and health effects in patients with stable coronary artery disease in Poland. METHODS: The cost-effectiveness analysis was based on data from a randomized double-blind, placebo-controlled trial. A decision-tree analysis was employed, including Monte Carlo and bootstrapping techniques. This study was a sub-study of the EUROPA (European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease) trial (n = 12 218; mean follow-up 4.2 years). Resource use was based on data from Polish EUROPA study patients (n = 1251), while effectiveness was based on the whole EUROPA study. The health gain of perindopril in life-years was based on overall EUROPA study results, and the adapted Polish life expectancy of patients not dying during the trial. Costs were calculated in new Polish zloty (PLN), year 2003 values; euro1 = PLN4.053. Only direct healthcare costs related to cardiovascular events and medication use were studied. RESULTS: When observed mortality was combined with life expectancy beyond the end of the study, perindopril use showed a gain in life expectancy of 0.182 life-years (SD +/- 0.129) at a cost of PLN1983 (SD +/- 103) with discounting of 5% per annum on costs and no discounting on effects. This resulted in an incremental cost-effectiveness ratio (ICER) of PLN10 896 per life-year gained. The probability that the ICER for perindopril was below the threshold of PLN60 000 was 88%. The overall results were insensitive to discount rates for costs and life-years. CONCLUSIONS: Perindopril leads to a reduction in the risk of coronary events among patients with stable heart disease. When the expected improvement in life expectancy is combined with associated medical costs, there is a high probability that perindopril is cost effective, given the threshold of PLN60 000 per life-year gained.     

Synthesis and Structure–Activity Relationship of 2,6-Disubstituted Thiosemicarbazone Derivatives of Pyridine as Potential Antituberculosis Agents

In this study, six new 2,6-disubstituted thiosemicarbazone derivatives of pyridine were synthesized (4–9), and their tuberculostatic activity was evaluated. All of them showed two- to eightfold higher activity (minimum inhibitory concentration (MIC) 0.5–4 µg/mL) against the resistant strain compared with the reference drug. Compounds 5 and 7, which contained the most basic substituents—pyrrolidine and piperidine—in their structure, strongly inhibited the growth of the standard strain (MIC 2 µg/mL). Furthermore, the same derivatives exhibited activity comparable to that of the reference drugs against some types of Gram-positive bacteria (MIC 0.49 µg/mL) and showed no cytotoxicity (IC50 > 50 µg/mL) in HaCaT cells. The zwitterionic structure of each compound was determined using X-ray crystallography. Absorption, distribution, metabolism, and excretion analyses showed that all compounds are good drug candidates. Thus, compounds 5 and 7 were identified as leading structures for further research on antituberculosis drugs with extended effects.     

Feasibility and clinical utility of real-time tele-echocardiography using personal mobile device-based pocket echocardiograph

IntroductionRecently introduced microUSB ultrasound probe, which can be connected to personal mobile device constitutes a new class of diagnostic pocket size imaging devices (PSID).The aim of this study was to assess the feasibility and clinical utility of real-time tele-echocardiography with the use such device.Material and methodsThe study group comprised 30 patients (18 men and 12 women; mean age: 54 ±14 years; mean body mass index: 27 ±6 kg/m²), admitted to various hospital departments (infectious diseases, internal medicine and cardiology). All patients underwent focused echocardiographic examination performed by an inexperienced operator using PSID and collaborating remotely in real-time with cardiologist by means of tele-consultation. Before commencing the examination, the operators underwent 1 h training in use of the PSID.ResultsIn most of patients PSID imaging provided sufficient diagnostic image quality. The dimensions of left ventricle, left atrium and the aorta obtained during the this examination showed good correlation with standard echocardiography (r = 0.89, r = 0.82, r = 0.92 respectively), but the correlation for TAPSE measurements was less pronounced (r = 0.52). The agreement in detection of pathologies (wall motion abnormalities, morphological and functional valvular abnormalities) between the tele-echocardiography and standard echocardiographic examination was good to very good (κ ranged from 0.648 to 0.823).ConclusionsPocket size imaging devices allows an inexperienced operator to perform a focused echocardiographic examination under a remote supervision of an experienced cardiologist. The introduction of new technology in the form of PSID with tele-echocardiography feature can revolutionize access to this imaging technique.     

Enhanced Production of Biogas Using Biochar–Sulfur Composite in the Methane Fermentation Process

The methane fermentation of organic waste is one way to minimize organic waste, which accounts for 77% of the global municipal waste stream. The use of biochar as an additive for methane fermentation has been shown to increase the production potential of biogas. Sulfur waste has a potential application to synergistic recycling in a form of composites with other materials including biochar. A composite product in the form of a mixture of biochar and molten sulfur has been proposed. In this experiment, additions of the sulfur–biochar composite (SBC) were tested to improve the fermentation process. The biochar was produced from apple chips under the temperature of 500 °C. The ground biochar and sulfur (<1 mm particle size) were mixed in the proportion of 40% biochar and 60% sulfur and heated to 140 °C for sulfur melting. After cooling, the solidified composite was ground. The SBC was added in the dose rate of 10% by dry mass of prepared artificial kitchen waste. Wet anaerobic digestion was carried out in the batch reactors under a temperature of 37 °C for 21 days. As an inoculum, the digestate from Bio-Wat Sp. z. o. o., Świdnica, Poland, was used. The results showed that released biogas reached 672 mL × g_vs⁻¹, and the yield was 4% higher than in the variant without the SBC. Kinetics study indicated that the biogas production constant rate reached 0.214 d⁻¹ and was 4.4% higher than in the variant without the SBC.     

Success of targeted transperineal biopsy in patients on surveillance for grade group 1 prostate cancer

IntroductionWe aimed to determine the minimum cross-sectional ellipsoid area on magnetic resonance (MR) of intraprostatic nodules that best predicts for subsequent targeted biopsies revealing ≥ grade group (GG) 2 disease.MethodsForty-six patients previously diagnosed with GG 1 prostate adenocarcinoma who received cognitively fused, MR-guided, transperineal targeted biopsies in addition to six random biopsies were included in this analysis. A Youden cutpoint analysis was used to determine the ellipsoid area in the axial plane best predicting for ≥GG 2 disease within the targeted biopsy cores and logistic regression used to assess the result.ResultsMedian time from MR imaging to targeted biopsy was 2.4 (1.4–5.5) months. Forty of 46 (87%) patients had one nodule and 6/46 (13%) had two separate nodules on MR that received targeted biopsy. Of the 52 nodules, five (10%), 33 (63%), and 14 (27%) were Prostate Imaging-Reporting and Data System (PI-RADS) 3, 4, and 5, respectively. Thirteen (25%), six (12%), and 33 (64%) were in the anterior, medial, and posterior regions of the prostate, respectively. Median area was 0.72 (0.49–1.29) cm² (average diameter 9.5 mm). Fifteen of 46 (33%) patients had ≥1 random biopsy and 20/52 (38%) nodules had ≥1 targeted biopsy revealing ≥GG 2 disease. The optimal area cutpoint was ≥0.7 cm², with an area under the curve of 0.671 (0.510–0.832). On logistic regression, area ≥0.7 cm² was solely predictive of targeted biopsy revealing ≥GG 2 disease (odds ratio 6.5, 1.3–32.4, p=0.022).ConclusionsNodule area ≥0.7 cm² may predict for transperineal-based targeted biopsies being positive for ≥GG 2 disease when 1–2 cores are taken.     

Catabolic/Anabolic Imbalance Is Accompanied by Changes of Left Ventricular Steroid Nuclear Receptor Expression in Tachycardia-Induced Systolic Heart Failure in Male Pigs

BackgroundSteroid hormones play an important role in heart failure (HF) pathogenesis, and clinical data have revealed disordered steroidogenesis in male patients with HF. However, there is still a lack of studies on steroid hormones and their receptors during HF progression. Therefore, a porcine model of tachycardia-induced cardiomyopathy corresponding to HF was used to assess steroid hormone concentrations in serum and their nuclear receptor levels in heart tissue during the consecutive stages of HF.Methods and ResultsMale pigs underwent right ventricular pacing and developed a clinical picture of mild, moderate, or severe HF. Serum concentrations of dehydroepiandrosterone, testosterone, dihydrotestosterone, estradiol, aldosterone, and cortisol were assessed by enzyme-linked immunosorbent assay. Androgen receptor, estrogen receptor alpha, mineralocorticoid receptor, and glucocorticoid receptor messenger RNA levels in the left ventricle were determined by qPCR.The androgen level decreased in moderate and severe HF animals, while the corticosteroid level increased. The estradiol concentration remained stable. The quantitative real-time polymerase chain reaction revealed the downregulation of androgen receptor in consecutive stages of HF and increased expression of mineralocorticoid receptor messenger RNA under these conditions.ConclusionsIn the HF pig model, deteriorated catabolic/anabolic balance, manifested by upregulation of aldosterone and cortisol and downregulation of androgen signaling on the ligand level, was augmented by changes in steroid hormone receptor expression in the heart tissue.