Functional responses of uremic single skeletal muscle fibers to redox imbalances

BACKGROUND: The exact causes of skeletal muscle weakness in chronic kidney disease (CKD) remain unknown with uremic toxicity and redox imbalances being implicated. To understand whether uremic muscle has acquired any sensitivity to acute redox changes we examined the effects of redox disturbances on force generation capacity. METHODS: Permeabilized single psoas fibers (N =37) from surgically induced CKD (UREM) and sham-operated (CON) rabbits were exposed to an oxidizing (10 mM Hydrogen Peroxide, H2O2) and/or a reducing [10 mM Dithiothreitol (DTT)] agent, in a blind design, in two sets of experiments examining: A) the acute effect of the addition of H2O2 on maximal (pCa 4.4) isometric force of actively contracting fibers and the effect of incubation in DTT on subsequent re-activation and force recovery (N =9 CON; N =9 UREM fibers); B) the effect of incubation in H2O2 on both submaximal (pCa 6.2) and maximal (pCa 4.4) calcium activated isometric force generation (N =9 CON; N =10 UREM fibers). RESULTS: Based on cross-sectional area (CSA) calculations, a 14 % atrophy in UREM fibers was revealed; thus forces were evaluated in absolute values and corrected for CSA (specific force) values. A) Addition of H2O2 during activation did not significantly affect force generation in any group or the pool of fibers. Incubation in DTT did not affect the CON fibers but caused a 12 % maximal isometric force decrease in UREM fibers (both in absolute force p =0.024, and specific force, p =0.027). B) Incubation in H2O2 during relaxation lowered subsequent maximal (but not submaximal) isometric forces in the Pool of fibers by 3.5 % (for absolute force p =0.033, for specific force p =0.019) but not in the fiber groups separately. CONCLUSIONS: Force generation capacity of CON and UREM fibers is affected by oxidation similarly. However, DTT significantly lowered force in UREM muscle fibers. This may indicate that at baseline UREM muscle could have already been at a more reduced redox state than physiological. This observation warrants further investigation as it could be linked to disease-induced effects

Effects of redox disturbances on motility, contractility and muscle tissue pathogenesis

CITATION: Karatzaferi, C. et al. 2019. Effects of redox disturbances on motility, contractility and muscle tissue pathogenesis. Oxidative Medicine and Cellular Longevity, 3272035, doi:10.1155/2019/3272035.The original publication is available at https://www.hindawi.comWhether in health or disease, reactive oxygen and nitrogen species (ROS/RNS) affect smooth and striated muscle status and function in ways not always discernible or appreciated. Despite the technological and methodological advancements, some key challenges still exist. On the one hand, one challenge is to appreciate acute effects on contractility and/or bioenergetics within a realistic functional context, effectively linking in vitro observations to in vivo conditions. On the other hand, chronic effects on indices of clinical significance are more difficult to clarify given the interplay of redox status variations with systemic inflammation and autophagy but also with lifestyle factors such as nutrition and physical activity—which impact on systemic health indices, as well as directly on smooth and striated muscles.https://www.hindawi.com/journals/omcl/2019/3272035/Publisher's versio

Socioeconomic impact of restless legs syndrome and inadequate restless legs syndrome management across European settings

Restless legs syndrome (RLS) is one of the most common neurological disorders. It describes an irresistible urge to move the legs, mostly manifested in the evening and at night, which can lead to severe sleep disturbance. As part of the European Brain Council (EBC)-led Value-of-Treatment project, this study aimed at capturing the socioeconomic impact of RLS related to the inadequate diagnosis and treatment across different European healthcare settings. The economic burden of RLS was estimated using the published EBC framework of analysis in three separate European Union healthcare systems (France, Germany, and Italy). The RLS care pathway was mapped to identify the unmet needs of patients. Based on specific patient stories, the economic impact of correctly diagnosing RLS and changing between inadequate and target treatment was calculated using appropriate scenario analysis. RLS proved to be a significant personal and social burden, when epidemiological data, high prevalence of RLS, and its need for treatment are combined. By looking at the savings emerging from the provision of optimal care management (timely and correct diagnosis, evidence-based therapy, avoidance of therapy-related complications such as augmentation), the authors foresee substantial economic savings with the achievement of adequate diagnosis and treatment of RLS. Education about RLS is urgently needed for all subspecialties involved in RLS patient care as well as the general public. Equally important, the search for new causal treatment strategies should be intensified to reduce suffering and substantial societal cost

A 26-Year-Old Male with Mesothelioma Due to Asbestos Exposure

Mesothelioma is a malignancy with poor prognosis, with an average 5-year survival rate being less than 9%. This type of cancer is almost exclusively caused by exposure to asbestos. A long exposure can cause mesothelioma and so can short ones, as each exposure is cumulative. We report a case of a 26-year-old male who was exposed to asbestos during his primary school years from the age of 6 to 12. Although the tumor mainly affects older men who in their youth were occupationally exposed to asbestos, malignant mesothelioma can also occur in young adults. A medical history was carefully taken and asbestos exposure was immediately mentioned by the patient. We conducted biopsy on the right supraclavicular lymph node. The patient was not a candidate for surgery, and chemotherapy treatment was initiated. While patient's chemotherapy is still ongoing, no other similar cases of students or teachers have been traced up to date from his school. The school building was demolished in January 2009

Anti-C1q Autoantibodies Are Frequently Detected in Patients With Systemic Sclerosis Associated With Pulmonary Fibrosis

BACKGROUND: Anti-C1q autoantibodies (autoAbs) are associated with systemic lupus erythematosus (SLE) but their presence in other rheumatic diseases has not been adequately investigated. OBJECTIVE: We aim to assessanti-C1q autoAbs and circulating immune complexes (CICs) in systemic sclerosis (SSc). METHODS: One hundred twenty four patients with SSc (106 females; median age 59.4 years, range 25-81.4; 75(60.5%) with limited cutaneous SSc[lcSSc], and 49(39.5%) with diffuse cutaneous SSc[dcSSc]), were studied. Twenty-five patients with Sjögren\u27s syndrome (SjS), 29 with rheumatoid arthritis (RA), and 38 patients with systemic lupus erythematosus (SLE) and 53 healthy controls (NC) were also included. ELISAs with high and low salt buffers the former allowing IgGFc binding to C1q, the latter not allowing IgGFc binding and anti-C1q Ab binding to C1q were used to measure anti-C1q Abs and CICs. RESULTS: Anti-C1q Abs were present in20/124 (16.1%) SSc patients [5 had high levels (\u3e80 RU/mL) and 10 patients (50%) had moderate levels (40-80 RU/mL)] compared to 1/25 (4%) SjS, 1/29 (3.4%) RA patients (p CONCLUSIONS: Anti-C1q autoAbs were frequently detected in patients with SSc and their high levels predict the co-occurrence of pulmonary fibrosis or pulmonary arterial hypertension

Ground deformation detection of the greater area of Thessaloniki (Northern Greece) using radar interferometry techniques

In the present study SAR interferometric techniques (stacking of conventional interferograms and Permanent Scatterers), using images from satellites ERS-1 and 2, have been applied to the region of Thessaloniki (northern Greece). The period covered by the images is 1992–2000. Both techniques gave good quantitative and qualitative results. The interferometric products were used to study ground surface deformation phenomena that could be related to the local tectonic context, the exploitation of underground water and sediments compaction. <br><br> The city of Thessaloniki shows relatively stable ground conditions. Subsidence in four locations, mainly in the area surrounding the city of Thessaloniki, has been detected and assessed. Two of the sites (Sindos-Kalochori and Langadhas) were already known from previous studies as subsiding areas, using ground base measurements. On the contrary the other two sites in the northern suburbs of Thessaloniki (Oreokastro) and in the south-east (airport area) were unknown as areas of subsidence. A further investigation based on fieldwork is needed in these two areas. Finally, an attempt to interpret the observed deformation, according to the geological regime of the area and its anthropogenic activities, has been carried out

Factors associated with leisure-time physical activity among patients undergoing hemodialysis

Background End-stage renal disease patients are characterized by low levels of physical activity, especially during leisure time. However, the recognition of variables associated with patterns of physical activity in this population has been little explored. Thus, the objective was to assess factors associated with levels of physical activity during leisure time among patients on haemodialysis. Methods Ninety-eight patients (51.6 ± 15.7 years, 57 M/41 F) from two dialysis centres in São Paulo, Brazil participated in this cross-sectional study. Participants were divided into those who never exercised during leisure-time (inactive) and those who exercised at least once a week (active). The independent factors assessed were: socio-demographic data, comorbidities, personal barriers to exercise and physical activity records from childhood to adulthood (tracking of physical activity). Results Only 27 % of patients were engaged in PA during their leisure time at least once a week. Patients who engaged in regular physical activity during adulthood before the initiation of the hemodialysis treatment (adjusted OR: 7.24 95 % IC: 1.99; 26.50), those who developed the renal disease through diseases other than diabetes or hypertension (adjusted OR: 4.82; 95 % IC: 1.48; 15.68), and those who had no cardiovascular diseases (adjusted OR: 11.33; 95 % IC: 1.23; 103.8) where more likely to be active during their leisure-time. Conclusion Comorbidities such as cardiovascular disease, hypertension and diabetes mellitus as well as the level of physical activity prior to end-stage renal disease could predict leisure-time physical activity among patients receiving hemodialysis therapy