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In many pharmaceuticals, a hydrogen atom or hydroxyl group is replaced by a fluorine to increase bioavailability and biostability. The fate of fluorine released from fluorine-containing drugs is not well investigated. The aim of this study was to examine possible fluorination of proteins in rat liver and brain after administration of the fluorinated drug cinacalcet. We assigned 18 Wistar rats to a control group ( n = 6) and a group treated with cinacalcet (2 mg kg -1 /body weight, 5 days/week), divided into 7 day ( n = 6) and 21 day ( n = 6) treatment subgroups. Fluorinated proteins were identified using a free proteomics approach; chromatographic separation and analysis by high-resolution mass spectrometry; peptide/protein identification using the Mascot search algorithm; manual verification of an experimentally generated MS/MS spectrum with the theoretical MS/MS spectrum of identified fluorinated peptides. Three fluorinated proteins (spectrin beta chain; carbamoyl-phosphate synthase [ammonia], mitochondrial; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1) were identified in the liver and four (spectrin beta chain, dihydropyrimidinase-related protein 4, prominin-2, dihydropyrimidinase-related protein 4) in the brain tissue after 21 days of cinacalcet treatment, but not in the control group. Introduction of fluorine into an organism by administration of fluorinated drugs results in tissue-specific fluorination of proteins.

The study aimed to analyze bacterial flora in diabetic foot infection, empiric and targeted antibiotic therapy, and factors influencing wound healing duration. The study we undertook a review analysis of data in 118 cases of diabetic foot among 98 patients who reported to the Wound Care Clinic in Warsaw, Poland between 01/2014 and 12/2018. Collected data included sociodemographic data, wounds information, used treatment, results of the microbiological examination, and empiric and targeted antibiotic therapy. For purposes of identifying the empirical and targeted antibiotic compatibility, the patients were divided into subgroups: ETA+ (compatibility of empiric-targeted antibiotic), ETA- (non-compatibility of empiric-targeted antibiotic), NEA (no empiric antibiotic), and NTA (no targeted antibiotic). The study group consisted of men, N = 71 (72.4%) and women, N = 27 (27.6%). Twenty patients (20.4%) were diagnosed as obese according to the body mass index classification. Staphylococcus aureus and Enterococcus faecalis were identified in most cases [N = 53 (24.4%), and N = 41 (18.9%), respectively]. Sixteen patients (13.6%) received gentamycin locally. Amoxicillin with clavulanic acid, clindamycin, and levofloxacin were the most frequently used antibiotics as empiric therapy; meanwhile, in targeted therapy, amoxicillin with clavulanic acid and levofloxacin were most frequently used. Empiric and targeted antibiotic therapies were compatible in 65 (55.1%) cases. The duration of healing did not differ between selected subgroups, and was longer in obese patients (p = .001). Other variables did not influence the healing time. The use of empiric antibiotic therapy before targeted therapy and the topical use of gentamycin did not reduce the healing time of diabetic foot infection. The healing time of diabetic foot infection was longer in obese patients than in nonobese patients., (Copyright © 2021 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of the study was to analyze bacterial flora in venous leg ulcers, empiric and targeted antibiotic therapy, and factors influencing healing time., Materials and Methods: Data from 30 patients with venous leg ulcers were retrospectively analyzed. Collected data included: sociodemographic data, wounds information, number of comorbidities, results of the microbiological examination, and empiric and targeted antibiotic therapy. To compare the empiric and targeted treatment in terms of their compatibility, the group of patients was divided into the four subgroups: NEA (no empiric antibiotics), NA (no antibiotics), ETA+ (compatibility of empiric and targeted antibiotic), ETA- (no compatibility of empiric and targeted antibiotic)., Results: The average ulcer healing time was 163.4 ± 97.1 (range 51.0 to 426.0) days and increased by 28 days with each additional bacterial strain in the ulcer (p = 0.041). Healing time did not differ between the four groups. Staphylococcus aureus and Pseudomonas aeruginosa were the most frequent bacteria. Amoxicillinium/acidum clavulanicum was the most common empirical antibiotic and amoxicillinium/acidum clavulanicum, and levofloxacinum was the most common targeted antibiotic., Conclusions: Venous leg ulcer healing time was prolonged with each subsequent bacterial strain in the ulcer, and it was independent from systemic antibiotic therapy.

The pathophysiology of rotator cuff tendinopathy is not fully understood, particularly in terms of the local inflammatory process. This study aimed to investigate the expression of selected molecules in the tumour necrosis factor (TNF)-α transduction pathway, including TNF-α, TNF receptor 1 (TNFR1), neutral sphingomyelinase activation associated factor (NSMAF), caspase 3 (Casp3), and interleukin (IL)-8, in patients with rotator cuff tendinopathy that had undergone surgical treatment. We included 44 participants that underwent arthroscopy, due to rotator cuff tendinopathy. Samples from the injured tendon were collected during arthroscopy, and RT-PCR was performed to determine gene expression. Pearson correlation analyses or U-Mann-Whitney test were performed to identify associations with the following parameters: sex, age at admission, body mass index, the presence of night pain, previous treatment (nonsteroidal anti-inflammatory drugs and/or steroids), medical history of the shoulder injury, upper subluxation of the humeral head, and the number of tendons injured. RT-PCR showed that the selected pro-inflammatory factors involved in the TNF-α signalling pathway expression levels were expressed in the tendon tissues. However, the levels of expression varied from patient to patient. Variations were over 250-fold for TNF-α, about 130-fold for TNFR1, NSMAF, and Casp3, and 1000-fold for IL-8. We could not confirm that any of the clinical parameters investigated were associated with the level of gene expression in the TNF-α pathway and IL-8.

We investigated quality of life (WHOQoL-BREF), perceived stress (PSS-10), anxiety and depression (HADS-M), life satisfaction (SWLS), and serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), and cortisol in family caregivers (n = 94) and professional caregivers (n = 48) of demented patients, as well as among noncaregivers (n = 30). Compared with professional caregivers, family caregivers had higher scores in HADS-M depression ( P = .003) and anxiety ( P = .033), lower life satisfaction ( P = .04), and lower quality of life in psychological ( P = .02) and social relationship ( P = .03) domains. There were no differences in serum levels of IL-6, CRP, or cortisol between caregivers and control participants. In multivariable analysis, when family relationship was considered together with the time period of caregiving and results of the Mini-Mental State Examination test in care recipients (n = 118, 12.49 ± 7.99), only family relationship influenced scores in HADS-M depression ( P = .004), SWLS scores ( P = .011), and WHOQoL-BREF scores in psychological ( P = .011) and social relationship ( P = .008) domains. In conclusion, family caregivers are more stressed and have deeper depressive and anxiety disorders, lower life satisfaction, and lower quality of life than professional caregivers.

Introduction: Assessing cognitive function could help to provide appropriate care for nursing home residents. The aim of the study was to identify the factors affecting cognitive function in nursing home residents in Poland and assess how it influenced the mortality rate during a 3-year observational period., Methods: This study included 202 elderly individuals from a nursing home in 2015. The investigation included examination of cognitive function using the MMSE and bioelectrical impedance analysis. Collected data included sex, age, blood pressure (BP), heart rate, number of comorbidities, years spent in the nursing home, educational level, and cigarette-smoking., Results: The mean MMSE score was 21.36 ± 6.35, which was negatively correlated with age and diastolic BP ( p = 0.001 and p = 0.024, respectively) and positively correlated with body mass, BMI, fat-free mass, fat, muscle mass, and education level ( p = 0.004, p = 0.004, p = 002, p = 0.049, p = 0.005, and p ˂ 0.001, respectively). Patients who died during the observational period had lower MMSE scores than those who survived (23.34 ± 5.68 vs. 20.16 ± 6.45; p < 0.001). Smokers had better MMSE results than nonsmokers (23.34 ± 5.98 vs. 20.08 ± 4.94; p < 0.001)., Discussion: Polish nursing home residents had mild cognitive impairment depending on their age, sex, educational level, and nutritional status. Lower MMSE score was a prognostic factor for mortality in the 3-year observational period., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 by S. Karger AG, Basel.)

Objectives: Safe pharmaceutical care (PC) requires an interprofessional team approach, involving physicians, nurses and pharmacists. Nurses' roles however, are not always explicit and clear, complicating interprofessional collaboration. The aim of this study is to describe nurses' practice and interprofessional collaboration in PC, from the viewpoint of nurses, physicians and pharmacists., Design: A cross-sectional survey., Setting: The study was conducted in 17 European countries, each with their own health systems., Participants: Pharmacists, physicians and nurses with an active role in PC were surveyed., Main Outcome Measures: Nurses' involvement in PC, experiences of interprofessional collaboration and communication and views on nurses' competences., Results: A total of 4888 nurses, 974 physicians and 857 pharmacists from 17 European countries responded. Providing patient education and information (PEI), monitoring medicines adherence (MMA), monitoring adverse/therapeutic effects (ME) and prescribing medicines were considered integral to nursing practice by 78%, 73%, 69% and 15% of nurses, respectively. Most respondents were convinced that quality of PC would be improved by increasing nurses' involvement in ME (95%), MMA (95%), PEI (91%) and prescribing (53%). Mean scores for the reported quality of collaboration between nurses and physicians, collaboration between nurses and pharmacists and interprofessional communication were respectively <7/10, ≤4/10, <6/10 for all four aspects of PC., Conclusions: ME, MMA, PEI and prescribing are part of nurses' activities, and most healthcare professionals felt their involvement should be extended. Collaboration between nurses and physicians on PC is limited and between nurses and pharmacists even more., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Organ transplantation has become the treatment of choice for end-stage organ failure, including renal and liver failure. The benefits of patient employment after transplantation are numerous, but factors determining the ability to work among these patients are not clearly defined. The growing interest in these factors has strong practical implications for organizations creating vocational rehabilitation programs. Given the interconnection between psychological and physical functioning in patients after transplantation, the present study examined the impact of anxiety on vocational rehabilitation and its relationship with functional tests. A total of 100 patients after liver or kidney transplantation underwent functional tests, including the 6-minute walking test and 30-second chair stand test (30"CST), and psychological tests, specifically the Inventory of Physical Activity Objectives, Work Ability Index, and State-Train Anxiety Inventory. Working ability was affected by psychological factors. State and trait anxiety exhibited inverse relationships with subjective readiness to occupational activity (P < .001, r = -.59 and P < .001, r = -.56, respectively). The level of anxiety was negatively related to the results of the 30"CST. State-Train Anxiety Inventory, State Anxiety subscale and State-Train Anxiety Inventory, State-Trait Anxiety subscale vs 30"CST: P < .001, r = -.43 P < .001, r = -.44). Thus, state and trait anxiety influence perceived work ability and partially functional status. These observations may indicate the potential benefits of including psychologists in interdisciplinary teams for physical and especially vocational rehabilitation of patients after liver or kidney transplantation.

Objective: The aim of the present study was to assess the employment rate among kidney and liver transplant recipients in Poland and identify the predictors of employment., Settings: The study was based on a self-prepared questionnaire containing five parts: demographic data and professional, medical, physical and psychological factors. This is a multicentre study involving four hospitals in Poland., Participants: The investigated group consisted of 285 individuals (92 women and 185 men; 8 no sex given) aged between 18 and 45 years who underwent kidney or liver transplantation 1-5 years prior. Because of missing data, 279 questionnaires were considered regarding employment status after transplantation and 277 when sex differences were considered., Results: A total of 120 patients (43%) worked full-time, 42 (15%) part-time and 117 (42%) remained unemployed, with a higher employment rate post-transplantation among men than women (60% vs 55%, p=0.04). More women performed white collar work (74% vs 41%, p=0.0003) and had to modify their working position than men (22% vs 7%, p=0.0118). Factors determining employment after transplantation included higher level of education (OR=27.08; p=0.0096), employment 1 year prior to transplantation (OR=11.05; p<0.001) and good psychological adaptation (OR=4.23; p<0.001). Men working the year before transplantation had higher education (OR=9.66; p=0.0356). Among men, more kidney recipients worked compared with liver recipients (OR=3.567; p=0.0417). Among women, age determined employment status (OR=0.89; p=0.0234)., Conclusion: Higher education is the most important predictor of employment after transplantation. Therefore, rehabilitation programmes including vocational activity should be directed to increase the level of education, both pretransplantation and post-transplantation if possible., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Viral infections, including cytomegalovirus (CMV) and Epstein-Barr virus (EBV), play an important role in carcinogenesis and can influence patients' prognosis and condition during cancer treatment.The goal of this study was to investigate CMV and EBV infections in patients receiving radiotherapy or radiochemotherapy due to head and neck cancers to determine the influence of these infections on the risk of death. The observation period was 2 years.Of 41 patients enrolled, 11 received radiotherapy (simultaneous-integrated boost intensity-modulated radiation therapy [SIB-IMRT], 2.25 Gy/fraction, 30 fractions, [n = 7] or IMRT, 2 Gy per fraction, 35 fractions, [n = 4]) and 30 received radiochemotherapy (cisplatin 100 mg/m and SIB-IMRT [n = 13] or IMRT [n = 17]). Plasma CMV and EBV DNA levels were assessed using real-time PCR before or during treatment or 4 weeks posttreatment.The risk of death in the group positive for plasma CMV or EBV deoxyribonucleic acid (DNA) was significantly higher compared to the group without detectable plasma CMV (odd ratio [OR]: 7.5, 95% confidence interval [CI]: 1.11-50.67) or EBV DNA (OR: 10.91, 95% CI: 1.135-104.8). Results were confirmed using the Bayesian method. Plasma positivity for CMV or EBV DNA was associated with a higher risk of death (both P = .04).Viral infections negatively affect the survival of patients with head and neck cancers. Diagnosing and treating these viral infections in patients with positive results should be considered.

Background: The use of alcohol, tobacco, and illicit substances typically first occurs in adolescence. The purpose of this study was to examine alcohol, cigarette, and illicit substance use among adolescents in Poland, including the age of initiation, frequency of use, methods of access, location of use, and parental knowledge and attitude., Methods: An author-derived questionnaire was used to cross-sectionally survey 541 participants aged 13-17 years old. Due to the fact that some answers were lacking, the number of questionnaires analysed was 538 in case of smoking and illicit substances use, and 535 in case of alcohol drinking., Results: The use of alcohol, cigarette, and illicit substance among the investigated group was 36.1, 37.6, and 10.8% respectively. The average age of initiation was 13-14 years old. Parents were aware of alcohol, cigarette, and illicit substance use 49.5, 35.8 and 22.4% of the time, respectively, and the rate of acceptance was 5.7 and 6.7% for alcohol and cigarettes. More than 28% of participants smoked in school, and 32.7% accessed illicit substances in the school's neighborhood., Conclusions: The rate of alcohol, cigarette, and illicit substance use in Poland is high and increasing, despite globally designed preventative actions. Parents' awareness of children's alcohol, cigarette, or illicit substance use is low, and schools hardly fulfil their educational and protective role. Preventative actions are necessary, and local challenges should be considered.

Aging is related to a decline in the function of many organs. The results of blood tests are essential for clinical management and could change over a lifespan reflecting aging. The aim of this study was to examine serum levels of liver, kidney, and bone marrow function and to study their dynamics as a function of age and sex.The cross-sectional study conducted in Poland included 180 healthy individuals (20-90 years) divided into subgroups by sex and decade. These included subgroups of ≥65 or <65 years (men and women). We investigated serum levels of creatinine, estimated glomerular filtration rate, estimated effective renal blood/plasma flow, urine pH, urine neutrophil gelatinase-associated lipocalin (NGAL) as well as serum levels of transaminases, bilirubin, total cholesterol (TC), international normalized ratio (INR), and blood morphology.All parameters were within normal range in all groups. Urine NGAL was higher in men aged ≥65 years than women (25.67 ± 53.65 vs 16.49 ± 34.66, P = .001); serum levels of TC and platelet (PLT) count were higher in women than men aged ≥65 years (221.0 ± 41.7 vs 188.4 ± 48.2 and 250.3 ± 47.8 vs 202.5 ± 57.9, P = .003 and P = .038, respectively). The INR was lower in women (0.97 ± .06 vs 1.19 ± 0.48, P = .03).These blood tests were normal in healthy people aged ≥65 years. Higher PLT and TC and lower INR in women might indicate a higher risk of cardiovascular diseases. These changes in blood tests were not attributed to aging itself.

Objectives: Activities of daily living are currently the simplest form of activity. For many people this is the only activity in which they participate. In this connection, it is important to determine the level of physical activity connected with daily habits including occupational activities. The main goal of the presented study has been to assess the level of activities of daily living in different age groups and its differentiation by season and working (WD) and non-working days (NWD)., Material and Methods: The study group (urban citizens, N = 106) was divided into young (Y) (N = 40), middle-aged (M) (N = 38), and senior (S) (N = 28) participants. The daily step number on 7 consecutive days during 4 seasons between June 2012 and 2013 was counted objectively using pedometers. The long-form of the International Physical Activity Questionnaire (IPAQ) was completed each season as a subjective assessment., Results: The daily step number for the whole group for the year was (median) 6615 (range: 3648-10 709), fewer than recommended. The median (Me) was highest in group M (Me = 6994, range: 3648-10 709) followed by Y (Me = 6957, range: 4094-10 321) and S (Me = 5469, range: 3743-8955). The lowest daily step number occurred in winter (M = 6208, Y = 6063, S = 5242), and the highest in spring (Y = 7385) or summer (M = 7717; S = 6095). All groups had a greater daily step number on WDs compared to NWDs (Y: 8411 vs. 5744, M: 7612 vs. 5839, S: 6327 vs. 4580; p < 0.01 for all). Pedometer-tracked values did not correlate with the IPAQ results., Conclusions: Activity level in Polish urban society is low, especially on NWDs and in colder months. The daily number of steps is highest in the middle-aged group, which may be connected with working status. Objective methods are recommended for assessing physical activity level. Int J Occup Med Environ Health 2018;31(1):47-54., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

Physical exercise causes adaptive changes, mainly in muscles, but it also influences other organs, including liver. Most changes are beneficial; however, strenuous exercise is a strong stressor, and it can result in splanchnic hypoperfusion with subsequent disturbances in liver homeostasis and energy. Cathepsin B is a protease linked to protein turnover and extracellular matrix degradation. It is also involved in autophagy and the activation of proinflammatory and profibrotic pathways. This study investigated the influences of one session of exercise and endurance training on the mRNA, protein level, and activity of cathepsin B in rat liver. Healthy rats were randomly divided into two groups (n = 30, each); one group was untrained and the other received 6-weeks of endurance training with an increasing load. For each group, rats were sacrificed before (controls, n = 10), immediately after (n = 10), and 3 h after (n = 10) an acute bout of intense exercise. Liver gene expression was evaluated with quantitative real-time PCR. Liver protein content was measured with ELISA. Liver enzyme activity was measured fluorometrically. One session of exercise or training did not influence cathepsin B gene expression or protein concentration at any investigated time point. In untrained rats, cathepsin B activity decreased 3 hours after (P = 0.027) one session of exercise. In trained rats, cathepsin B activity increased immediately (P = 0.005) after one session of exercise. Training did not influence baseline cathepsin B activity. In conclusion, one session of exercise differentially influenced cathepsin B activity in the liver, depending on training status.

Aim: Retention of indoxyl sulphate and p-cresol sulphate is associated with many diseases. The aim of the present study was to examine serum levels of indoxyl sulphate and p-cresol sulphate, the dynamics of their changes according to age, and their precursors., Methods: The study included 180 healthy individuals aged 20-90 years (n = 180), divided into subgroups by decade (n = 30 in each subgroup) and into subgroups of ≥65 years (n = 42) or <65 years (n = 138). Serum indoxyl sulphate and p-cresol sulphate, tryptophan, and tyrosine were measured using high-performance liquid chromatography-mass spectrometry., Results: The 70-90 years age group had higher indoxyl sulphate than the 50-59 years age group (P = 0.033). The 70-90 years age group had higher p-cresol sulphate than the 20-29 years (P < 0.001), 30-39 years (P < 0.001), 40-49 years (P = 0.007) and 50-59 years (P = 0.001) age groups; the 60-69 years age group had higher p-cresol sulphate than the 20-29 years (P = 0.043) and 30-39 years (P = 0.011) age groups. Indoxyl sulphate and p-cresol sulphate serum levels were higher in those aged ≥65 years. Indoxyl sulphate and p-cresol sulphate serum levels correlated positively with age, but not with tryptophan and tyrosine, respectively., Conclusions: Healthy aging is associated with indoxyl sulphate and p-cresol sulphate serum level increases, which are not linked to tryptophan and tyrosine serum levels. Geriatr Gerontol Int 2017; 17: 1022-1026., (© 2016 Japan Geriatrics Society.)

We examined the serum levels of IL-6, IL-8, TNF, IL-6R, TNF-R1, and CRP and the dynamics of changes in these levels according to age. The study included healthy individuals of 20-90 years of age. Participants were divided into subgroups based on their decade of life, and into subgroups of ≥65 or <65 years. Serum cytokine levels were assayed by ELISA, and CRP using an immunoturbidimetric method. Serum CRP levels were within the normal range for all subgroups. The 60- to 70-year age group showed higher CRP than the 20- to 30- (p = 0.003), 30- to 40- (p = 0.009), and 40- to 50- (p = 0.030) year age groups. Serum cytokine levels were low. It was greater in the 60- to 70-year age group than in the 20- to 30- (p = 0.008) and 30- to 40- (p = 0.040) year groups, and was greater in the 70- to 90-year group than the 20- to 30-year group (p = 0.043). Serum TNF-R1 level in the 70- to 90-year group was greater than in all other age groups (p = 0.000 for all comparisons). Other measured parameters did not differ between groups. Serum levels of IL-6, CRP, and TNF-R1 were greater in participants ≥65 than <65 years of age. Healthy older people showed low serum levels of CRP and pro-inflammatory cytokines, but higher than in younger population. Therefore, the adjustment of normal ranges in the elderly should be considered. Serum levels of pro-inflammatory cytokines elevated beyond normal ranges indicate particular diseases.

Exercise induces changes in muscle fibers and the extracellular matrix that may depend on elastin content and the activity of proteolytic enzymes. We investigated the influence of endurance training on the gene expression and protein content and/or activity of elastin, elastase, cathepsin K, and plasmin in skeletal and heart muscles and in the aorta. Healthy rats were randomly divided into untrained (n=10) and trained (n=10; 6 weeks of endurance training with increasing load) groups. Gene expression was evaluated via qRT-PCR. Elastin content was measured via enzyme-linked immunosorbent assay and enzyme activity was measured fluorometrically. Elastin content was significantly higher in skeletal (P=0.0014) and heart muscle (P=0.000022) from trained rats versus untrained rats, but not in the aorta. Although mRNA levels in skeletal muscle did not differ between groups, the activities of elastase (P=0.0434), cathepsin K (P=0.0343) and plasmin (P=0.000046) were higher in trained rats. The levels of cathepsin K (P=0.0288) and plasminogen (P=0.0005) mRNA were higher in heart muscle from trained rats, but enzyme activity was not. Enzyme activity in the aorta did not differ between groups. Increased elastin content in muscles may result in better adaption to exercise, as may remodeling of the extracellular matrix in skeletal muscle., (© 2016. Published by The Company of Biologists Ltd.)

Objectives: Monoclonal gammopathy of undetermined significance (MGUS) occurs without other symptoms, although monoclonal proteins can cause kidney injuries. Here, we assessed kidney function and identified the best follow-up parameters in patients with MGUS without kidney damage symptoms., Methodology: Forty-six patients with MGUS were included in the study group. The control group (CRT, n = 23) consisted of healthy subjects matched for age and sex. Serum cystatin C was determined using an immunonephelometric method, serum and urine neutrophil gelatinase-associated lipocalin (NGAL) was measured with an immunoenzymatic method, and cathepsin B activity was determined fluorometrically., Results: Serum cystatin C and urine NGAL were higher, and serum NGAL was lower in MGUS patients compared with CRT. Neither serum cystatin C, nor serum or urine NGAL, correlated with the biomarkers of MGUS. The serum activity of cathepsin B did not differ between groups and did not correlate with serum cystatin C. Serum cystatin C correlated with serum creatinine, while serum NGAL did not correlate with serum creatinine or cystatin C. The estimated glomerular filtration rates (eGFRs) in MGUS were within normal range and correlated with serum cystatin C. The strongest correlation was observed for CKD-EPI. Seven patients presented with albuminuria >30 mg/day. There was a correlation between albuminuria in this group and λ free light chains., Conclusions: The kidney function in MGUS patients is impaired, although there are no clinical and standard laboratory test manifestations. Cystatin C and urine, but not serum, NGAL should be considered markers for kidney injury. CKD-EPI is recommended for eGFR assessment., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Irisin induces the browning of adipose tissue. The goal of this study was to investigate the influence of acute exercise in untrained and trained rats and endurance training on FNDC5 mRNA and irisin levels in white and red skeletal muscle and serum. Rats (n=60) were randomly divided into two groups: untrained and trained (subjected to 6-week endurance training with increasing load). Subgroups of rats from each group were sacrificed before (controls), immediately after, or 3 hours following acute exercise with the same work load. Muscle samples (red and white) and serum were collected. FNDC5 mRNA was evaluated using RT-PCR. Irisin levels were measured using an immunoenzymatic method. Muscle FNDC5 mRNA decreased immediately after acute exercise compared with baseline levels, but not in red muscle in trained rats. Atrend toward a return to baseline appeared 3 hours after the exercise, but only in white muscle in untrained group. Irisin protein levels increased after acute exercise in red muscle 3 hours post-exercise compared with samples taken immediately after exercise, and decreased 3 hours post-exercise compared to pre-exercise level in white muscles. FNDC5 mRNA did not change following training, whereas irisin protein levels increased in red muscle and decreased in white muscle. Serum irisin levels remained unchanged following acute exercise and training. We concluded that changes in irisin mRNA and protein levels in rat muscle after acute exercise are limited and depend on training status and the muscle type. Irisin serum levels remained stable after acute exercise or endurance training.

Renalase is a newly discovered amine oxidase and may lower blood pressure by metabolizing catecholamines. We have hypothesized that exercise and training may regulate renalase expression to control blood pressure. In this study, we investigated changes in renalase expression after exercise and training in white and red portion of the gastrocnemius muscle, kidney, and serum in rats. Rats were either untrained or subjected to six weeks of endurance training, which predominantly recruits red fibers. Rats from each group were sacrificed before (n = 10), immediately after (n = 10), or three hours (n = 10) following exercise. Renalase mRNA and protein levels were measured by RT-PCR and ELISA, respectively. There were no significant changes in renalase expression after prolonged training or acute exercise in the serum or red muscle of rats. However, in white muscle, renalase mRNA and protein levels decreased after acute exercise in untrained rats, whereas, in trained rats, its protein level remained unchanged, despite a decrease in mRNA. Thus, exercise influenced renalase expression only in white muscle fibers that are not predominantly recruited during exercise. The reduction of renalase protein in white muscle suggests that renalase may contribute to blood redistribution between contracting and non-contracting fibers during exercise. In the kidney, renalase protein levels decreased after training, while mRNA levels increased. The reduction in renalase protein levels may contribute to functional kidney hypoperfusion, which has been observed after training. In conclusion, exercise differentially regulates renalase expression in skeletal muscle and kidney.

Colon cancer is currently the third most common cancer disease in men and second in women. Physical exercise of sufficient intensity and duration reduces the risk of colon cancer by as much as 30-50%. Despite many studies the mechanism of this phenomenon remains unclear. However it is known, to be caused by coexistence of various factors. The control of energy balance, body weight and insulin resistance seems to be most important. Myokines also play a very important role. Among them: SPARC that causes inhibition of proliferation and apoptosis and anti-inflammatory cytokines. In addition, physical activity exerts local anti-inflammatory effect by decreased expression of COX-2 and iNOS in the colon mucosa. Physical exercise also improves survival rates after treatment of colon cancer. But it seems that better prognosis is only observed in selected group of patients diagnosed with specific biomarkers of cancer cells. Despite beneficial effects of physical activity, awareness of this fact is very low.

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma-cell proliferative disorder characterized by the presence of a monoclonal immunoglobulin and associated with a life-long average 1% annual risk of developing lymphoproliferative malignancies. The prevalence of MGUS is about 3% in the general population 50 years of age or older. The current diagnostic criteria for MGUS are concentration of monoclonal protein in serum less that 3.0 g/dL, bone marrow plasmacytosis less that 10% and lack of organ damage including hypercalcaemia, renal impairment, anemia and bone lesions. Currently, there are no methods for classification of patients due to the risk of progression to MM, and there is no therapy to prevent the progression, so the standard treatment for patients with MGUS is observation. The increased risk of developing MGUS among first-degree relatives of MGUS patients is observed, however, due to the low absolute risk for MGUS and the lack of available intervention and early disease therapies, familial screening for MGUS is not recommended.

Objectives: Scuba diving is a very specialized, physically demanding activity. The bones of divers are subjected to stress from water pressure, from the forces generated when their muscles resist water pressure, and from weightlessness. Notably, few studies have addressed the effects of diving on bone mineral density (BMD) and bone mineral content (BMC), and the results have been controversial. The goal of the study was to assess BMD and BMC in a group of professional scuba divers., Methods: The study group (diving group [D]) included 16 male professional scuba divers who also worked as firemen. The control group included 14 firemen who did not scuba dive (non-diving group [ND]). The groups were matched by age, weight, and height. The BMD and BMC of the whole skeleton, L1-L4, total hip, and femoral neck were assessed by dual-energy X-ray absorptiometry., Results: There were no differences in BMD or in BMC in the two groups, and the BMD and BMC values were within one standard deviation in terms of Z- and T-scores. There was no correlation between total diving time (hours) and BMD in the D group., Conclusion: Scuba diving does not negatively influence bone turnover., (Copyright © 2011 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Adipose tissue is an important organ that produces and secretes hormones and cytokines, including TGF-β1, PDGF-AA, and VEGF-A. The goal of the present study was to investigate the influence of a single session of acute exercise, as well as the prolonged endurance training on the production of TGF-β1, PDGF-AA, and VEGF-A in the subcutaneous white adipose tissue in rats. Rats were randomly divided into two groups: untrained (UT, n = 30) and trained rats (T, subjected to 6-week endurance training with increasing load, n = 29). Both groups were subjected to an acute exercise session with the same work load. The rats were killed before (UTpre, Tpre), immediately after (UT0h, T0h), or 3 h (UT3h, T3h) after exercise and adipose tissue samples collected. Growth factor mRNA was evaluated using RT-PCR; the protein levels were measured before and after training (UTpre and Tpre) using the immunoenzymatic method. TGF-β1 and PDGF-AA mRNA levels were decreased in the UT3h rats compared to the UTpre rats (P = 0.0001 and P = 0.03, respectively), but the VEGF-A mRNA level remained unchanged in the UT0h and UT3h rats compared to UTpre rats. TGF-β1, PDGF-AA and VEGF-A mRNA levels were decreased in the T3h rats compared to Tpre (P = 0.0002, P = 0.02, and P = 0.03, respectively). TGF-β1, PDGF-AA and VEGF-A mRNA levels significantly increased in the Tpre rats compared to UTpre (all P = 0.0002). However, the protein levels remained constant. In conclusion, prolonged physical exercise increases growth factor mRNA in adipose tissue but not protein levels.

Life expectancy lengthened over the past 165 years. This is one of the reasons, that the prevalence of diseases connected with elderly, including osteoporosis, has increased. A physical activity may be used as prophylactic tool against osteoporosis and improve the skeletal resistance to bone fractures. Mechanotransduction, eg. the response of the cell to mechanical stimuli in bones is particularly relevant, because the mammalian skeleton remodels to adapt to loading environment. It also helps to gain and maintain the maximal BMD. The molecular mechanism of mechanotransduction is complex and depends on integrated activity of osteoblasts and osteocytes. Osteocytes are the cell that posses the ability to sense mechanical load. Shear stress induced in bones canaliculi by fluid flow induces the synthesis of PGE2, NO and activation of integrins, what triggers the Wnt signaling pathway. This pathway is important in osteocytes to prevent apoptosis and transmit the signals to other bone cells, and in osteoblasts for differentiation, proliferation and synthesis of bone matrix. The effectiveness of physical training in osteoporosis prevention depends on strain magnitude, strain rate, cycle number, strain frequency and rest periods, and the increase in BMD is found only in loaded parts of skeleton.

Background: Physical exercise benefits the heart, but the mechanism is not understood. The mechanism of muscle plasticity after physical training is also unclear. The proangiogenic and mitogenic activity of PDGF and VEGF could be involved in both processes. This study investigated the influence of a single bout of acute exercise on the PDGF-AA and VEGF-A expression in skeletal and heart muscle in untrained rats and in those subjected to prolonged endurance training (trained)., Material/methods: Fifty-nine rats were randomly assigned to the untrained (UT) or trained (T, subjected to 6-week endurance training) groups. The groups were subjected to an acute bout of exercise with the same work load a day after final training. Rats of both groups were sacrificed and skeletal and heart muscle samples were collected before, immediately after (0 h), or 3 hours (3 h) after acute exercise., Results: Prolonged training caused an increase in PDGF-AA mRNA (p=0.038) and protein (p=0.016) in rat skeletal muscle (T vs. UT). A similar pattern was observed in VEGF-A, but the changes were not significant. Acute exercise caused a significant decrease in PDGF-AA mRNA after 0 and 3 h (p=0.03 and p=0.04, respectively). In the heart there were no significant changes in either mRNA after acute exercise or after endurance training., Conclusions: Six-week endurance training in rats increases PDGF-AA mRNA and protein in skeletal, but not in heart muscle.

The serum level of the transforming growth factor-beta1 (TGF-beta1) is elevated after acute bouts of exercise and prolonged training, as well as after myocardial infarction. However, the source of this increase remains unclear. Contracting skeletal muscles are known to be the source of many cytokines. To determine whether skeletal or heart muscles produce TGF-beta1 during exercise, we investigated the effect of a single bout of acute exercise on TGF-beta1 generation in skeletal and heart muscles in untrained rats (UT, n=30) and in rats subjected to prolonged (6-week) endurance training (T, n=29). The UT and T (a day after final training) groups were subjected to an acute bout of exercise with the same work load. Rats from both groups were sacrificed and skeletal and heart muscle samples were collected before (pre), immediately after (0 h), or 3 hours (3 h) after acute exercise. TGF-beta1 mRNA was quantified by RT-PCR in these samples, and basal TGF-beta1 protein levels were determined in skeletal muscle in the UTpre and Tpre subgroups by ELISA. Acute exercise caused a non-significant increase in TGF-beta1 mRNA in skeletal muscle in UT0h rats, in compare to UTpre rats. There was a significant decrease of TGF-beta1 mRNA in the T0h group (p=0.0013) in compare to Tpre rats. Prolonged training caused a significant increase in TGF-beta1 mRNA (p=0.02); however, the TGF-beta1 protein level decreased (p=0.02). In heart muscle, there was a significant decrease of TGF-beta1 mRNA in UT0h (p=0.01) and UT3h (p=0.04) compared to UTpre rats. TGF-beta1 mRNA levels were unchanged in T0h and T3h compared to Tpre; basal TGF-beta1 mRNA expression after training was also unchanged (UTpre vs. Tpre). We conclude that physical exercise is a potent stimulus for inducing TGF-beta1 gene expression in skeletal muscle, but does not increase the protein level. Thus, skeletal and heart muscle do not contribute to increased serum levels of TGF-beta1 after physical exercise.

The aim of the study was to compare and investigate the repeatability of two tests for predicting the maximal oxygen uptake: the Kline's walking test and the Astrand-Ryhming nomogram cycle ergometer protocol. Both tests were performed twice on separate days by 15 female students aged 20-25. Medium value of VO2max (ml/min/kg) in the walking test was in first trial 59.46 +/- 3.16, and in second 59.99 +/- 3.36, and in Astrand-Ryhming nomogram cycle ergometer protocol in first trial 41.75 +/- 6.91, and in second 42.18 +/- 6.09. The coefficient of variation was 5.31 and 5.6 in first and second trials of walking test, and 16.54 and 14.43 in first and second trial of Astrand-Ryhming nomogram cycle ergometer protocol. Blind-Altman diagram showed that both tests are acceptable for maximal oxygen uptake prediction. There was no correlation between both tests, and in Astrand-Ryhming nomogram cycle ergometer protocol there was correlation between VO2max and BMI. The results showed that both tests could be used for prediction of VO2max; however the repeatability and precision was better in the walking test, which could be recommended for VO2max prediction, especially in the situation when submaximal tests are preferable. It is not recommended to apply various tests in the same person to detect the changes in VO2max.

Indomethacin is a nonsteroidal anti-inflammatory drug used frequently to control chronic or temporary pain. In the kidney, indomethacin decreases medullary and cortical perfusion, resulting in hypoxia. Kidney hypoxia has many effects, including changes in gene expression, and is a strong stimulus for angiogenesis. Other angiogenic factors include vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2), transforming growth factor beta 1 (TGFbeta1), and platelet-derived growth factor (PDGF). Our goal was to examine the influence of indomethacin on mRNA expression of these factors and their selected receptors in the renal cortex of healthy rats. Groups of 8 healthy, male, six-week-old Wistar rats received either indomethacin (5 mg/kg/day) or placebo orally for three months. RNA from renal cortex biopsies was analyzed by real-time polymerase chain reaction to quantify the mRNA levels of each cytokine. We observed significantly higher mRNA levels for VEGF (1.73-fold), FGF-2 (5.6-fold) and TGFbeta receptor III (2.93-fold), PDGF receptor alpha (2.93-fold) and receptor beta (2.91-fold) in rats receiving indomethacin compared to rats given placebo (p < 0.05). Amounts of mRNA for TGFbeta1, PDGF, FGF receptors 1 and 2 and TGFbeta receptor I did not differ between analysed groups. Our data indicates that indomethacin may regulate the expression of potent angiogenic factors VEGF and FGF-2.

Strenuous physical exercise induces muscle fibers damage and non-specific inflammatory response. Activated by inflammatory process cells may serve as the source of wide spectrum of inflammatory mediators and growth factors. Namely Platelet Derived Growth Factor (PDGF), Transforming Growth Factor-beta (TGF-beta) and Vascular Endothelial Growth Factor (VEGF) could be released. The aim of present study was to assess the impact of physical exercise on growth factors generation in healthy young people. 14 young sportsmen were enrolled into the study. They performed strenuous physical exercise. Blood samples were drawn before, immediately after, and 2 hours after the exercise bout. Serum PDGF, TGF-beta and VEGF concentrations were measured using commercially available ELISA kit based on immunoenzimatic method. Serum level of PDGF increased significantly from 1.7 ng/ml before to 4.64 ng/ml (2.73-fold) immediately after, and to 3.3 ng/ml (1.94-fold) 2 hours after exertion. Serum level of TGF-beta increased significantly from 20.58 ng/ml before to 55.37 ng/ml (2.7-fold) immediately after, and to 40.03 ng/ml (1.95-fold) 2 hours after exertion. Serum level of VEGF increased significantly from 91.83 pg/ml before to 165.61 pg/ml (1.8-fold) immediately after the exercise. Two hours after the exertion serum level of VEGF was 137.22 pg/ml, what is 1.49-fold above the basal level; however not being significantly different. In summery, observed increased level of growth factors could be involved in the process of adaptation of human organism to physical training. In addition, in the context of the role of inflammation in the pathogenesis of various diseases, our results point to the potentially deleterious effect of strenuous physical exercise.

One of the signs of advancing age in humans is sarcopenia. The term is used to define the loss of muscle mass and strength that occurs with ageing. Sarcopenia contributes to the decreased capacity of independent living and increased amounts of traumas. Numbers of mechanisms are proposed as a cause of sarcopenia, including changes in protein metabolism, alterations in hormonal and neural functions, impaired regeneration after contraction-induced injuries, mitochondrial abnormalities, oxidative stress and apoptosis in skeletal muscle fibres. Further studies on the mechanisms leading to sarcopenia could provide the basis for prevention and establishment of therapeutic methods that would contribute to an increase in the standard of living among elderly people.

Wound healing is critical for survival. The damaged tissue is usually replaced by connective tissue, which forms permanent scar. This causes the impairment of organ function. The scar is the effect of synthesis and degradation of extracellular matrix. Many factors are involved in the process of wound healing, among them growth factors: TGF-beta and PDGF and proteolytic enzymes such as elastase and collagenase. Further studies for the mechanisms leading to scar formation, factors that play role in this process and interactions among them could provide basis for the therapeutic modification and outcome of wound healing.

Beta2-microglobulin (beta2M) is the light chain of the class I HLA molecule. The serum level of beta2M is elevated in various diseases including lymphoma, inflammation, viral infections and chronic renal dysfunction. The present study addressed the possible influence of beta2M on T lymphocyte activation in vitro. Peripheral blood mononuclear cells from a group of 17 healthy subjects were examined. Stimulation with OKT3 and fibronectin in combination with 30 mg beta2M/dl resulted in a two-fold increase of cell proliferation. A similar effect was observed when OKT3 and collagen I were applied as well as when OKT3 and collagen IV were used as costimulation to T cells. The CD69 expression, measured by flow cytometry was significantly enhanced above the control level (1.52 +/- 1.03% vs 33.21 +/- 20.26%, p<0.01, control group and 30 mg beta2M/dl, respectively). Together, these observations suggest that beta2M may play a role in modulating lymphocyte proliferation, possibly through modification of the CD69 molecule.