Wpływ treningu fizycznego wykonywanego na powierzchniach niestabilnych z wykorzystaniem elastycznych taśm do ćwiczeń oporowych na sprawność funkcjonalną oraz jakość życia osób starszych

Aim of the study. The authors tried to evaluate the effectiveness of physical exercises, particularly exercises on unstable surfaces, in improving functional efficiency and self-evaluation of quality of life in elderly people. Material and methods. The experiment was completed by a group of 37 out of 45 participants who had fulfilled selection criteria. Age range was from 65 to 90 years, and the average age was 79.5 + 12 years. The following tests were administered: manipulation test, Get Up And Go Test, Tinetti Balance and Walking Test, Single Leg Stance with Eyes Open and Closed, The Sit-And-Reach Test and measurement of back muscles strength. For subjective quality of life evaluation, psychometric testing was employed: SF-36 Health Questionnaire Survey and Life Satisfaction Index. The participants performed physical exercises 3 times a week for 3 months, attending 33 sessions of 45 minutes duration each. The exercises defined in the training schedule were performed individually and under supervision of the physiotherapist. Use of special tools (the Swiss ball, the sensory pillow, and the elastic band) enabled performance of sensorimotor and resistance exercises whilst encouraging a sense of play, which facilitates achieving the aims of therapy. Results. Statistically significant improvement following the physical training was noticed only in the strength of back muscles (p<0.001), in the manipulation ability test (p<0.01), and in the Single Leg Stance with Eyes Open test (p<0.05). In physical categories of quality of life in the SF-36 test, statistically significant improvement was confined to the categories: "role limitations due to physical problems" (p<0.05) and "general health selfperception" (p<0.001). Among all mental categories of the SF-36 test, statistically significant difference was found only in "role limitations due to emotional problems" (p<0.01) and in "vitality" (p<0.05). Conclusions. The applied physical exercise programme positively influences the results of two out of seven tests describing physical performance of elderly people. Higher self-evaluation of quality of life was reported by these people in two physical categories and in two mental categories of the SF-36 test.Cel pracy. Autorzy przedstawili próbę oceny skuteczności treningu fizycznego, uwzględniającego szczególnie ćwiczenia na powierzchniach niestabilnych, na sprawność funkcjonalną oraz samoocenę jakości życia osób starszych. Materiał i metody. Eksperyment ukończyła grupa 37 osób z pośród 45, które spełniały kryteria kwalifikacyjne. Wiek badanych wahał się w granicach od 65 do 90 lat. Średnia wieku wynosiła 79,5 ± 12 lat. Kryterium oceny sprawności funkcjonalnej stanowiły testy: sprawności manipulacyjnej, wstań i idź, równowagi wg Tinetti, chodu wg Tinetti, stania na jednej nodze z oczami otwartymi i zamkniętymi, wysięgu w siadzie oraz badanie momentu siły mięśni grzbietu. Dla subiektywnej oceny jakości życia wykorzystano testy psychometryczne: SF - 36 oraz Indeks Satysfakcji z życia. Osoby biorące udział w eksperymencie, wykonywały ćwiczenia fizyczne 3 razy w tygodniu przez okres 3-ch miesięcy, uczestnicząc w 33 sesjach, trwających po 45 minut. Ćwiczenia określone harmonogramem treningowym były prowadzone indywidualnie pod nadzorem fizjoterapeuty. Zastosowanie do ćwiczeń przyborów (piłka szwajcarska, poduszka rehabilitacyjna i elastyczna taśma) umożliwiało wykonywanie ćwiczeń sensomotorycznych oraz oporowych, zapewniając jednocześnie efekt zabawy, ułatwiający osiąganie zamierzonych celów terapii. Wyniki. We testach charakteryzujących sprawność funkcjonalną istotną statystycznie poprawę średnich wyników na poziomie p < 0,001 zaobserwowano w pomiarze momentów siły mięśni grzbietu, na poziomie p < 0,01 w ocenie sprawności manipulacyjnej oraz na poziomie p < 0,05 w próbie stania na jednej nodze z otwartymi oczami. W ocenie komponenty fizycznej jakości życia testem SF - 36, istotną statystycznie poprawę średnich wyników stwierdzono tylko w przypadku kategorii „ograniczenia wynikające ze stanu zdrowia” (p < 0,05) oraz "percepcji własnego stanu zdrowia" (p < 0,001). W ocenie komponenty mentalnej istotną statystycznie poprawę średnich wyników zaobserwowano w przypadku kategorii „ograniczenia wynikające z problemów emocjonalnych” (p < 0,01) oraz "witalność" (p < 0,05). Wnioski. Znamiennie skuteczny wpływ zastosowanego treningu fizycznego odnosi się tylko do dwóch z siedmiu badanych cech sprawności funkcjonalnej osób starszych. Wyższą samoocenę jakości życia po programie treningowym zaobserwowano w przypadku dwóch kategorii komponenty fizycznej oraz dwóch kategorii komponenty mentalnej testu SF- 36

Tnfa signaling through Tnfr2 protects skin against oxidative stress-induced inflammation

14 páginas, 8 figuras.-- Sergio Candel ... et al.-- This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.TNFα overexpression has been associated with several chronic inflammatory diseases, including psoriasis, lichen planus, rheumatoid arthritis, and inflammatory bowel disease. Paradoxically, numerous studies have reported new-onset psoriasis and lichen planus following TNFα antagonist therapy. Here, we show that genetic inhibition of Tnfa and Tnfr2 in zebrafish results in the mobilization of neutrophils to the skin. Using combinations of fluorescent reporter transgenes, fluorescence microscopy, and flow cytometry, we identified the local production of dual oxidase 1 (Duox1)-derived H2O2 by Tnfa- and Tnfr2-deficient keratinocytes as a trigger for the activation of the master inflammation transcription factor NF-κB, which then promotes the induction of genes encoding pro-inflammatory molecules. In addition, pharmacological inhibition of Duox1 completely abrogated skin inflammation, placing Duox1-derived H2O2 upstream of this positive feedback inflammatory loop. Strikingly, DUOX1 was drastically induced in the skin lesions of psoriasis and lichen planus patients. These results reveal a crucial role for TNFα/TNFR2 axis in the protection of the skin against DUOX1-mediated oxidative stress and could establish new therapeutic targets for skin inflammatory disordersThis work was supported by the Spanish Ministry of Science and Innovation (grants BIO2011-23400 and CSD2007-00002 to VM, and PhD fellowship to SC, all co-funded with Fondos Europeos de Desarrollo Regional/European Regional Development Funds), the Fundación Séneca-Murcia (grant 04538/GERM/06 to VM and PhD fellowship to RE-P), Fundação para a Ciência e Tecnologia (PhD fellowship to SdO, SFRH/BD/62674/2009), a Medical Research Council Senior Clinical fellowship to SAR (G0701932), and the European 7th Framework Initial Training Network FishForPharma (PhD fellowship to SDT, PITG-GA-2011-289209).Peer reviewe

Próba oceny wpływu leczenia infliximabem na sprawność ruchową chorych z reumatoidalnym zapaleniem stawów : badania wstępne

Wstęp: W patogenezie reumatoidalnego zapalenia stawów (RZS) ważną rolę odgrywa czynnik martwicy guzów alfa (TNFa). Lekiem neutralizującym biologiczną aktywność TNFa jest infliximab (Remicade) Celem pracy było określenie dynamiki zmian sprawności ruchowej pacjentów chorych na RZS w trakcie leczenia infliximabem. Metodyka: Infliximab podawano w dawkach 3 mg/kg w postaci 2 godzinnego wlewu dożylnego przez 14 tygodni; początkowo stosowano infuzje co 2 tygodnie, następnie co 4 tygodnie. Grupę badawczą stanowiło 8 kobiet ze średnio zaawansowanym, lub zaawansowanym RZS (IIo i IIIo gr wg Steinbrockera) leczonych na Oddziale Reumatologii Szpitala im J Dietla w Krakowie. Średnia wartość CRP w surowicy tych chorych wynosiła 3,15 mg%, a OB 55,5 po 1 godz. Zakres ruchów badano za pomocą Mechanical Joint Score (MJS), oceniając ruchomość w stawach rąk, nadgarstkowych, oraz w stawach łokciowych, barkowych, biodrowych, kolanowych i skokowych. Oceniano siłę chwytu rąk przy pomocy mankietu do pomiaru ciśnień, oraz nasilenie procesu zapalnego, ból i sztywność stawów używając kwestionariuszy Western Ontario Mc Master University Index (WOMAC) oraz Rheumatoid Arthritis Disease Activity Index (RADAI). Wyniki: Już po pierwszych 2 tygodniach leczenia nastąpiła istotna statystycznie poprawa sprawności ruchowej w stawach mierzona za pomocą MJS, oraz jakości życia mierzona kwestionariuszami RADAI i WOMAC. Wyraźnie zmniejszyły się dolegliwości bólowe i znaczącej poprawie uległa siła chwytu rąk. Zaobserwowano normalizację wartości CRP i OB. Największą poprawę wszystkich parametrów zaobserwowano po pierwszym wlewie infliximabu. W ciągu kolejnych tygodni poprawa postępowała znacznie wolniej. W 14 tygodniu leczenia stwierdzono wyraźne zaostrzenie procesu chorobowego, związane prawdopodobnie z dłuższym odstępem pomiędzy kolejnymi dawkami leku, nie osiągające jednak nasilenia takiego jak przed rozpoczęciem leczenia.Introduction: Tumour necrosis factor alpha (TNFa) plays an important role in the pathogenesis of rheumatoid arthritis (RA). Infliximab (Remicade) is an agent with neutralising effects on the TNFa biological activity. The aim of the study was to assess the dynamics of changes in motor function of patients with RA during infliximab treatment. Methods: Infliximab was administered at doses of 3 mg/kg in a 2-hour intravenous infusion for 14 weeks; initially, the infusions were given every 2 weeks, subsequently every 4 weeks. Eight women at moderately advanced or advanced stages of RA (stages IIş and IIIş according to Steinbrocker Staging System) hospitalised in the Rheumatology Ward of the Józef Dietl Hospital in Cracow were enrolled in the study. Mean serum CRP level in these patients was 3.15 mg%, and the 1-hour sedimentation rate was 55.5. The range of motion was evaluated using the Mechanical Joint Score (MJS) via mobility assessment in the joints of the hands, wrists, and in the elbow, shoulder, hip, knee and ankle joints. Grasp force of the hands was assessed by means of a sphygmomanometer cuff, and the intensity of the inflammatory process, pain and joint stiffness using the questionnaires Western Ontario Mc Master University Index (WOMAC) and Rheumatoid Arthritis Disease Activity Index (RADAI). Results: Statistically significant improvement in the motor function of the joints assessed using MJS and in the quality of life measured by means of RADAI and WOMAC occurred as early as after 2 weeks of the therapy. Pain was markedly alleviated and the grasp force of the hands significantly improved. Normalisation of the CRP concentration and the sedimentaion rate was observed. The most pronounced improvement of all parameters was demonstrated after the first infliximab infusion. During the subsequent weeks, the improvement was significantly slower. In the 14th week of treatment, a marked exacerbation of the disease, yet not exceeding the pre-treatment intensity, was noted, likely due to the increased interval between the successive doses of the preparation. Conclusions: Administration of infliximab in patients with RA induces a quick and significant improvement in patients’ motor function; however, beneficial effects of this agent were attenuated during the subsequent phases of infliximab therapy. This effect may have been caused by the reduction of administration frequency of the preparation (initially every 2 weeks, then every 4 weeks). Therapy-associated occurrence of infliximab-neutralising antibodies resulting in a reduced efficacy of the treatment with this agent cannot be excluded either

Applying plant lectins to assay the effect of environmental pollution on the glycosylation of human placenta

Our study was designed to establish whether air pollution in urbanized industrial centers of southern Poland affects the process of glycosylation in a full-term human placenta. This process of glycosylation was analyzed by the quantitative determination of the binding of WGA and LCA lectins to placental villi. The study was performed on human placentas collected in 1990-91 and 2000-01 in regions of southern Poland differing in their degree of environmental pollution: the highly polluted areas of Upper Silesia and Cracow agglomeration. The Bieszczady area with low pollution was considered the control. The concentrations of nitrogen and sulfur oxides and the concentration of aerosols were used as markers of the degree of air pollution. The direct immunofluorescence reaction of the placenta tissues with fluorescein-labeled (FITC) lec-tins was used. The staining of the placenta tissues was examined under a fluorescence microscope linked to an analysis system. A microdensytometric method was used to assay the amount of tissue-bound lectins. The results showed no significant effect of the three main air pollutants in the study areas in southern Poland, i.e. nitrogen and sulfur oxides and high level of aerosols, on the structure of WGA-and LCA-specific glycoconjugates in human placenta. However, the marked quantitative changes in th

cGMP via PKG activates 26S proteasomes and enhances degradation of proteins, including ones that cause neurodegenerative diseases.

Because raising cAMP enhances 26S proteasome activity and the degradation of cell proteins, including the selective breakdown of misfolded proteins, we investigated whether agents that raise cGMP may also regulate protein degradation. Treating various cell lines with inhibitors of phosphodiesterase 5 or stimulators of soluble guanylyl cyclase rapidly enhanced multiple proteasome activities and cellular levels of ubiquitinated proteins by activating protein kinase G (PKG). PKG stimulated purified 26S proteasomes by phosphorylating a different 26S component than is modified by protein kinase A. In cells and cell extracts, raising cGMP also enhanced within minutes ubiquitin conjugation to cell proteins. Raising cGMP, like raising cAMP, stimulated the degradation of short-lived cell proteins, but unlike cAMP, also markedly increased proteasomal degradation of long-lived proteins (the bulk of cell proteins) without affecting lysosomal proteolysis. We also tested if raising cGMP, like cAMP, can promote the degradation of mutant proteins that cause neurodegenerative diseases. Treating zebrafish models of tauopathies or Huntington's disease with a PDE5 inhibitor reduced the levels of the mutant huntingtin and tau proteins, cell death, and the resulting morphological abnormalities. Thus, PKG rapidly activates cytosolic proteasomes, protein ubiquitination, and overall protein degradation, and agents that raise cGMP may help combat the progression of neurodegenerative diseases

A zebrafish model of Ifih1-driven Aicardi–Goutières syndrome reproduces the interferon signature and the exacerbated inflammation of patients

Type I interferonopathies are a heterogenic group of rare diseases associated with an increase in type I interferon (IFN). The main challenge for the study of Type I interferonopathies is the lack of a well-founded animal model to better characterize the phenotype as well as to perform fast and large drug screenings to offer the best treatment options. In this study, we report the development of a transgenic zebrafish model of Type I interferonopathy overexpressing ifih1 carrying the mutation p.Arg742His (Tg(ifih1_mut)), corresponding to the human mutation p.Arg779His. RNA sequence analysis from Tg(ifih1_mut) larvae revealed a systemic inflammation and IFN signature upon a suboptimal poly I:C induction compared with wild-type larvae, confirming the phenotype observed in patients suffering from Type I interferonopathies. More interestingly, the phenotype was manifested in the zebrafish inflammation and Type I IFN reporters nfkb:eGFP and isg15:eGFP, respectively, making this zebrafish model suitable for future high-throughput chemical screening (HTS). Using the unique advantages of the zebrafish model for gene editing, we have generated Tg(ifih1_mut) knocked down for mavs and ikbke, which completely abrogated the Poly I:C induction and activation of the GFP of the reporters. Finally, we used an FDA-approved drug, Baricitinib (Jak1/Jak2 inhibitor), which was able to reduce the inflammation and the ISG expression. Our results demonstrate the potential of this model to further understand AGS pathological mechanisms and to identify novel therapeutic drugs by HTS

TNFα Impairs Rhabdoviral Clearance by Inhibiting the Host Autophagic Antiviral Response.

TNFα is a pleiotropic pro-inflammatory cytokine with a key role in the activation of the immune system to fight viral infections. Despite its antiviral role, a few viruses might utilize the host produced TNFα to their benefit. Some recent reports have shown that anti-TNFα therapies could be utilized to treat certain viral infections. However, the underlying mechanisms by which TNFα can favor virus replication have not been identified. Here, a rhabdoviral infection model in zebrafish allowed us to identify the mechanism of action by which Tnfa has a deleterious role for the host to combat certain viral infections. Our results demonstrate that Tnfa signals through its receptor Tnfr2 to enhance viral replication. Mechanistically, Tnfa does not affect viral adhesion and delivery from endosomes to the cytosol. In addition, the host interferon response was also unaffected by Tnfa levels. However, Tnfa blocks the host autophagic response, which is required for viral clearance. This mechanism of action provides new therapeutic targets for the treatment of SVCV-infected fish, and advances our understanding of the previously enigmatic deleterious role of TNFα in certain viral infections

Zebrafish Infection: From Pathogenesis to Cell Biology

The study of host–pathogen interactions has illuminated fundamental research avenues in both infection and cell biology. Zebrafish (Danio rerio) larvae are genetically tractable, optically accessible, and present a fully functional innate immune system with macrophages and neutrophils that mimic their mammalian counterparts. A wide variety of pathogenic bacteria have been investigated using zebrafish models, providing unprecedented resolution of the cellular response to infection in vivo. In this review, we illustrate how zebrafish models have contributed to our understanding of cellular microbiology by providing an in vivo platform to study host–pathogen interactions from the single cell to whole animal level. We also highlight discoveries made from zebrafish infection that hold great promise for translation into novel therapies for humans

Tnfa Signaling Through Tnfr2 Protects Skin Against Oxidative Stress-Induced Inflammation

TNFα overexpression has been associated with several chronic inflammatory diseases, including psoriasis, lichen planus, rheumatoid arthritis, and inflammatory bowel disease. Paradoxically, numerous studies have reported new-onset psoriasis and lichen planus following TNFα antagonist therapy. Here, we show that genetic inhibition of Tnfa and Tnfr2 in zebrafish results in the mobilization of neutrophils to the skin. Using combinations of fluorescent reporter transgenes, fluorescence microscopy, and flow cytometry, we identified the local production of dual oxidase 1 (Duox1)-derived H2O2 by Tnfa- and Tnfr2-deficient keratinocytes as a trigger for the activation of the master inflammation transcription factor NF-κB, which then promotes the induction of genes encoding pro-inflammatory molecules. In addition, pharmacological inhibition of Duox1 completely abrogated skin inflammation, placing Duox1-derived H2O2 upstream of this positive feedback inflammatory loop. Strikingly, DUOX1 was drastically induced in the skin lesions of psoriasis and lichen planus patients. These results reveal a crucial role for TNFα/TNFR2 axis in the protection of the skin against DUOX1-mediated oxidative stress and could establish new therapeutic targets for skin inflammatory disorders

The molecular, functional and phylogenetic characterization of PGE2 receptors reveals their different roles in the immune response of the teleost fish gilthead seabream (Sparus aurata L.)

Prostaglandin E2 (PGE2) plays an important role in immune activities in teleost fish, including seabream. However, receptors involved in PGE2 signaling, as well as the pathways activated downstream, are largely unknown. In this study, one ortholog of mammalian PTGER1, PTGER3 and PTGER4, and two of PTGER2 (Ptger2a and Ptger2b) were identified and characterized in gilthead seabream. In silico analysis showed that all these receptors possessed the organization domain of G protein-coupled receptors, with the exception of Ptger2b. The corresponding in vivo studies revealed that they were expressed in all the tissues examined, the highest mRNA levels of ptger1 and ptger3 being observed in the spleen and of ptger2a and ptger4 in the blood. Bacterial infection induced higher mRNA levels of ptger2a, ptger3 and ptger4 in peritoneal exudate (the site of bacterial injection). In addition, head kidney acidophilic granulocytes and macrophages displayed different ptger1, ptger2a, ptger3 and ptger4 expression profiles. Furthermore, in macrophages the expression of the receptors was weakly affected by stimulation with bacterial DNA or with PGE2, while in acidophilic granulocytes stimulation resulted in the upregulation of ptger2a and ptger4. Taken together, these results suggest different roles for seabream PGE2 receptors in the regulation of the immune responses.Versión del editor3,26