1,721,009 research outputs found
Polyunsaturated fatty acids and renal fibrosis:pathophysiologic link and potential clinical implications
The role of polyunsaturated fatty acids in renal fibrosis. Several studies suggest a close relationship between polyunsaturated fatty acids (PUFA) and renal inflammation and fibrosis, which are crucial stages in chronic kidney disease (CKD). Beneficial effects of n-3 PUFA on the course of experimental and human nephropathies have been reported. PUFA can ameliorate chronic, progressive renal injury beyond the simple reduction of serum lipid levels. These pleiotropic effects of PUFA are due to their properties of interfering with the synthesis of a variety of inflammatory factors and events, through effects related both to the modulation of the balance of n-6 and n-3-derived eicosanoids and to direct action on the cellular production of the major cytokine mediators of inflammation and on endothelium function. The mechanisms by which PUFA can favorably interfere with some stages in renal fibrosis processes, such as mesangial cell activation and proliferation and extracellular matrix protein synthesis, include the regulation of some pro-inflammatory cytokine production, renin and nitric oxide (NO) systems and peroxisome proliferator-activated receptor gene expression. An optimal n-6/n-3 PUFA ratio dietary intake could offer new therapeutic strategies aimed at interrupting the irreversible process of renal fibrosis and ameliorating chronic renal injury. However, further experimental, epidemiological and clinical investigations are needed to confirm the role of PUFA in the renal fibrosis pathway and the natural history of chronic nephropathies
È possibile migliorare i test antigenici rapidi Covid-19? Considerazioni da un'esperienza padovana
Background. The early identification of positive patients is a major challenge in the containment of a pandemic. In the case of coronavirus disease Covid-19, the gold standard for SARS-CoV-2 detection is the molecular technique. Antigen tests have the advantage of providing quick results and reducing costs.
The aim of this work was to compare the procedures of different commercially available rapid tests for Covid-19 Ag screening in order to highlight some critical issues and possibly ameliorate performances as well as procedures.
Methods. We have analyzed 187 subjects with a total of 778 tests by mean of a total of 7 different commercially available antigen tests. Positives at the rapid test were confirmed by RT-PCR. Results. Dissimilarities among products were found at each step of the recommended procedures. Conclusions. Small differences may not be relevant to the result, but more consistency across methods would make the tests easier and less operator-dependent. In particular, the type of specimen and the way it is collected are crucial to the reliability of the outcome and must be kept consistent across all manufacturers. We invite companies to agree upon a common protocol that will simplify healthcare professional tasks in the interest of the population well-being, without depriving them of any profit
Effects of unsaturated free fatty acids on adhesion and on gene expression of extracellular matrix macromolecules in human osteoblast-like cultures
To investigate the possible role for unsaturated free fatty acids in osteoblast adhesion, the effects of two polyunsaturated fatty acids (PUFAs), arachidonic (AA) and eicosapentaenoic (EPA) acids, and of one monounsaturated fatty acid, oleic acid (OA), on adhesion to the substrate and on gene expression of three extracellular matrix macromolecules were investigated in an in vitro model system--cultured osteoblast-like human cells. AA, but neither EPA nor OA, diminished bone cell adhesion, whereas both EPA and OA, but not AA, increased gene expression of type I collagen and fibronectin via a transforming growth factor-beta-independent mechanism. These results extend previous evidence for unsaturated fatty acids in bone cell metabolism
EPA and DHA suppress AngII- and arachidonic acid-induced expression of profibrotic genes in human mesangial cells.
BACKGROUND:
There is some evidence suggesting a close relationship between polyunsaturated fatty acids (PUFAs) and renal inflammation and fibrosis, which are crucial stages in chronic kidney disease.
METHODS:
To verify the role of PUFAs in renal fibrosis processes, we investigated the effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) on the gene expression of TGFbeta, fibronectin (FN), connective tissue growth factor (CTGF) and type IV collagen (COLIV) in human mesangial cells, in the absence or presence of angiotensin II (AngII), using reverse transcriptase PCR.
RESULTS:
The addition of AA to mesangial cell cultures induced a significant up-regulation of TGFbeta, FN, CTGF and COLIV expression, similar to that induced by AngII, while EPA and DHA had no stimulatory effects. The coincubation of cells with AngII and AA potentiated AngII-induced gene expression; on the contrary, the coexposure of cells to EPA or DHA suppressed the AngII- and AA-induced up-regulation of TGFbeta, FN, CTGF and COLIV.
CONCLUSION:
We conclude that the PUFAs have different effects, dependent on their chemical structure, on the AngII-TGFbeta system, a major regulator of the renal fibrotic process. Our in vitro results may provide new therapeutic options toward interrupting the irreversible process of renal fibrosis and ameliorating chronic renal injury
Eicosapentaenoic acid modulates CyA-induced proinflammatory cytokine over-expression in osteoblastic cells in vitro
Several adverse outcomes are reported in subjects undergoing long term Cyclosporin A (CyA) treatment. Severe osteopenia has been described in clinical and experimental reports, while beneficial effects of n-3 polyunsaturated fatty acids (PUFAs) on bone metabolism are recognized. In the present study we investigated the effects of n-3 versus n-6 PUFAs on osteoblastic cells treated with CyA, evaluating the expression of interleukin (IL)-1ß, interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in two different experimental protocols and the production of IL-6, IL-1ß, and tumor necrosis factor alpha (TNFalpha) in cells challenged simultaneously with CyA and eicosapentaenoic acid (EPA) for 48h. IL-1ß and IL-6 up-regulation, induced by CyA, was counteracted by the addition of EPA in both protocols; on the contrary, arachidonic acid (AA) magnified CyA the effects. COX-2 and iNOS levels were not modified by CyA treatment. These in vitro results, that substantiate clinical reports of CyA-induced osteopenia, demonstrate a beneficial effect of EPA on CyA-altered cytokine profile, opening new perspectives in the non-pharmacological management of adverse outcomes in CyA-treated patients
Fatty acids and cytokine mRNA expression in human osteoblastic cells: a specific effect of arachidonic acid
Epidemiological, clinical and experimental evidence suggests that fatty acids have a modulatory effect on bone metabolism in animals and humans. To investigate this hypothesis, we evaluated the effects of three different fatty acids, arachidonic acid (AA), eicosapentaenoic acid (EPA) and oleic acid (OA), on the expression of cytokines involved in bone remodelling. Cytokine mRNAs in the human osteoblast-like cell line MG-63 were quantified by reverse transcription-PCR. AA induced increased expression of interleukin-1alpha, interleukin-1beta, tumour necrosis factor-alpha and macrophage colony-stimulating factor mRNAs in a time- and dose-dependent manner. EPA and CA had no stimulatory effects, but instead caused a significant inhibition of AA-induced cytokine mRNA expression. Cell treatment with calphostin C, an inhibitor of protein kinase C (PKC), and cellular PKC down-regulation experiments independently resulted in significant inhibition of AA-induced cytokine expression, suggesting that a PKC-dependent mechanism accounts for the effects of AA on cytokine production. In conclusion, our study demonstrates specific effects of fatty acids on cytokine gene expression in human osteoblast-like cells. The clinical relevance of our findings requires further investigation
Pazienti affetti da malattie croniche, situazioni critiche e strategie di reazione: uno studio qualitativo tra i pazienti affetti da quattro tipi di malattie croniche, seguiti in centri del nord-est d’Italia
Living with a chronic condition represents a strenuous experience that often could be lived as a sequence of waiting and crisis times. Therapeutic path incidents could represent however a catalysts and revelatory time, useful to patients to discover their own resources. A qualitative study according to the phenomenological hermeneutic perspective was conducted to understand the kind of skills expressed by the patients during a difficult episode, and the characteristics that identify patients who can overcome them better. From September 2019 to August 2020 twenty-three patients followed-up in four Hospital Units of Northeastern of Italy were enrolled. All the patients described an episode linked whit their pathological condition; they mentioned mainly supportive, reactive, or behavioral strategies and an acceptance attitude. The sample characteristics may explain the recurring acceptance attitude; however, the younger individuals, those with a higher level of education and those who faced precedent negative life experiences seem to better overcome challenging events. It can’t be taken for granted that patients possess all the skills necessary to overcome the frequent challenging episodes they have to face; for this reason, healthcare professionals should assess their learning and reactive attitude in order to tailor for them therapeutic education paths.Vivere con una malattia cronica rappresenta un’esperienza stressante che spesso può essere vissuta come un alternarsi di momenti di crisi e di attesa di nuove crisi. Gli incidenti critici presenti nel percorso terapeutico possono comunque rappresentare un momento catalizzatore e rivelatore, utile ai pazienti per scoprire le proprie risorse. È stato condotto uno studio qualitativo secondo la prospettiva della fenomenologia ermeneutica con l’obiettivo di comprendere il tipo di abilità espresse dai pazienti durante un episodio sfidante e le caratteristiche che identificano i pazienti capaci di superarlo meglio. Da settembre 2019 ad agosto 2020 sono stati arruolati nello studio ventitré pazienti seguiti in quattro Unità Ospedaliere del Nordest d’Italia. Tutti i pazienti hanno descritto un episodio legato alla loro condizione patologica; hanno menzionato principalmente strategie di ricerca di supporto, di tipo reattivo o comportamentale e un generale atteggiamento di accettazione. Le caratteristiche del campione possono spiegare il ricorrente atteggiamento di accettazione; tuttavia, gli individui più giovani, quelli con un livello di istruzione più elevato e coloro che hanno affrontato precedenti esperienze di vita negative sembrano superare meglio degli altri alcuni eventi difficili. Non è scontato che i pazienti possiedano tutte le competenze necessarie per superare i frequenti episodi sfidanti che devono affrontare; per questo motivo, gli operatori sanitari dovrebbero preventivamente valutare le loro capacità di apprendimento e le loro strategie di coping al fine di personalizzare i percorsi di educazione terapeutica
Arachidonic acid-induced IL-6 expression is mediated by PKCalpha activation in osteoblastic cells
There are several pieces of evidence supporting the important role that essential fatty acids (EFAs) and their metabolites play in regulating calcium and bone metabolism, and their relevance to the pathobiology of bone disease, with particular reference to modulating effects on cytokines. We found that arachidonic acid (AA) triggers a cell signal in osteoblasts and leads to the expression of IL-6. To explore the biochemical pathways involved in AA induction of cytokine gene expression, we evaluated the potential protein kinase C (PKC) dependent mechanism accounting for the AA effect on IL-6 gene expression. The osteoblast-like cell line MG-63 was pretreated with calphostin C, a PKC inhibitor, or phorbol 12-myristate 13-acetate (PMA) for an extended period, a condition which causes PKC downregulation, and subsequently with AA. After these treatments, IL-6 gene expression was no longer evident. We also showed that PKC and, in particular, PKC cc, which are both recruited to the particulate fraction, undergo proteolysis and autophosphorylation; all of these steps are required for PKC activation and, subsequently, for AA-induced signaling. It is interesting that other unsaturated fatty acids, such as oleic acid (OA) or eicosapentaenoic acid (EPA), are unable to induce either PKC activation or IL-6 gene expression
Protective action of a new benzofuran derivative on lipid peroxidation and sulphydryl groups oxidation.
The antioxidant properties of a novel water-soluble antioxidant of the benzofuran family (5-hydroxy-4,6,7-trimethyl-2,3-dihydrobenzofuran-2-acetic acid, BFA) were studied. In rat liver mitochondria BFA increases the lag-time and decreases the extent of lipid peroxidation induced by ascorbate/Fe2+; an IC50 value of about 12 microM was observed. In rat liver microsomes it inhibits the lipid peroxidation induced both by NADPH/Fe2+/ADP (iron-dependent) and by cumene hydroperoxide (iron-independent), showing IC50 values of 25 and 30 microM respectively. The antioxidant efficiency of BFA is slightly higher than that of the congener compound Trolox C. BFA is also able to inhibit the oxidation of protein sulphydryl groups consequent to microsomal lipid peroxidation induced by NADPH/Fe2+/ADP. The antioxidant properties of BFA are discussed considering its hydrophilic character and pharmacological features
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