Development of adhesion test for coated medical device

High biocompatibility is a basic requirement in medical technology. Polymer coatings can radically improve medical device biocompatibility, especially for surfaces like stainless steel. Adhesion is an important quality in a coating, and this was our rationale for developing a polymer adhesion testing protocol. We compared two biocompatible polymers, polyurethane (PUR) and poly-(DL-lactic-co-glycolic acid) (PDLG). Po lymer layers were created on surface-treated stainless steel. The properties of different la yers were compared. Adhesion of the coatings was characterised by concentration of coating so lution, rate of the contacted surface and surface roughness of the carriers. PUR showed better adhesion under our test conditions

Development of adhesion test for coated medical device

High biocompatibility is a basic requirement in medical technology. Polymer coatings can radically improve medical device biocompatibility, especially for surfaces like stainless steel. Adhesion is an important quality in a coating, and this was our rationale for developing a polymer adhesion testing protocol. We compared two biocompatible polymers, polyurethane (PUR) and poly-(DL-lactic-co-glycolic acid) (PDLG). Polymer layers were created on surface-treated stainless steel. The properties of different layers were compared. Adhesion of the coatings was characterised by concentration of coating solution, rate of the contacted surface and surface roughness of the carriers. PUR showed better adhesion under our test conditions.  DOI: 10.17489/biohun/2013/1/3

SGLT-2-gátló kezelés diabeteses és nem diabeteses vesebetegségben [SGLT-2 inhibitor treatment in diabetic and non-diabetic kidney disease]

A krónikus vesebetegség világszerte népbetegség, prevalenciája az életkorral nő. Hátterében a fejlett országokban leggyakrabban a hipertónia és a diabetes mellitus áll. A diabeteses vesebetegekben gyakran megfigyelhető a krónikus vesebetegséget leggyakrabban jellemző eltérések – a GFR-érték csökkenése és/vagy kóros albuminuria – megjelenése. A nátrium-glükóz kotranszporter-2-gátlók (SGLT-2-gátlók) a vesében lévő SGLT-2-transzporterek gátlásával megakadályozzák a glükóz és a nátrium visszaszívását a proximális tubulusokban, így a glucosuriás hatás által csökkentik a vércukorszintet. A vizelettel történő kalóriavesztés gyakran testsúlycsökkenéshez vezet, emellett az SGLT-2-gátlók a vérnyomást is kedvezően befolyá-solják, jelentős részük igazolt kardiovaszkuláris protektív hatással rendelkezik. A dapa- és az empagliflozin esetében CVOT vizsgálatokból származó adatok ezen felül vesevédő hatást is igazoltak, sőt a dapagliflozin előnyös renális hatását már nem diabeteses vesebetegség esetén is igazolták. Egy az EMPA-REG, a CANVAS és a DECLARE-TIMI vizsgálatokat értékelő meta-analízis alapján az SGLT-2-gátlók a vesevégpont szempontjából mind a CV szempontok szerint primer, mind a szekunder CV prevenciós populációban hatékonynak bizonyultak. A kifejezetten vesevégpontokra tervezett DAPA-CKD és az EMPA-KIDNEY vizsgálatokba már diabeteses vesebetegek mellett egyéb etiológiájú, azaz nem diabeteses eredetű vesebetegségben szenvedő betegeket is bevontak. Egyelőre a DAPA-CKD vizsgálat eredményei ismertek: itt a primer végpont, amely a renális kimenetel mellett a CV halálozást is tartalmazta, jelentősen ritkábban fordult elő a dapagliflozinnal kezeltekben. A tisztán renális összevont végpont (eGFR 50%-os csökkenése, végstádiumú vesebetegség vagy renális halálozás) kockázata is alacsonyabb volt dapagliflozin mellett. Az eGFR éves csökkenésének mértéke itt is kisebb volt az SGLT-2-gátló mellett. A ko-rábbi vizsgálatokhoz hasonlóan itt is azt látjuk, hogy az SGLT-2-gátló kezelés megkezdését követően az eGFR értéke átme-netileg lecsökken (ez általában 3–4 ml/min/1,73 m2 körüli), azonban ezt követően a GFR-csökkenés lelassul, és a vizsgálatot jobban megtartott vesefunkcióval fejezik be az SGLT-2-gátló ágon lévő betegek. Az SGLT-2-gátlók vesevédő hatásában sze-repe van a glikémiás hatásnak, a vérnyomás- és testsúlycsökkentő hatásnak, a diuretikus hatásnak, az antifibrotikus hatásnak, az eritropoetinnek, de mindenekelőtt a tubuloglomeruláris feedback helyreállításának. Ezen túlmenően a kardiorenális mechanizmusok révén a vesevédő hatás hozzájárul a CV kockázat csökkentéséhez is

Incorporation of Ortho- and Meta-Tyrosine Into Cellular Proteins Leads to Erythropoietin-Resistance in an Erythroid Cell Line

Background/Aims: Erythropoietin-resistance is an unsolved concern in the treatment of renal anaemia. We aimed to investigate the possible role of ortho- and meta-tyrosine - the hydroxyl free radical products of L-phenylalanine - in the development of erythropoietin-resistance. Methods: TF-1 erythroblast cell line was used. Cell concentration was determined on day 1; 2 and 3 by two independent observers simultaneously in Bürker cell counting chambers. Protein concentration was determined with colorimetric method. Para-, ortho- and meta-tyrosine levels were measured using reverse phase-HPLC with fluorescence detection. Using Western blot method activating phosphorylation of STAT5 and ERK1/2 were investigated. Results: We found a time- and concentration-dependent decrease of erythropoietin-induced proliferative activity in case of ortho- and meta-tyrosine treated TF-1 erythroblasts, compared to the para-tyrosine cultured cells. Decreased erythropoietin-response could be regained with a competitive dose of para-tyrosine. Proteins of erythroblasts treated by ortho- or meta-tyrosine had lower para-tyrosine and higher ortho- or meta-tyrosine content. Activating phosphorylation of ERK and STAT5 due to erythropoietin was practically prevented by ortho- or meta-tyrosine treatment. Conclusion: According to this study elevated ortho- and meta-tyrosine content of erythroblasts may lead to the dysfunction of intracellular signaling, resulting in erythropoietin-hyporesponsiveness

Insulin Therapy of Nondiabetic Septic Patients Is Predicted by para

Hydroxyl radical converts Phe to para-, meta-, and ortho-Tyr (p-Tyr, m-Tyr, o-Tyr), while Phe is converted enzymatically to p-Tyr in the kidney and could serve as substrate for gluconeogenesis. Pathological isoforms m- and o-Tyr are supposed to be involved in development of hormone resistances. Role of Phe and the three Tyr isoforms in influencing insulin need was examined in 25 nondiabetic septic patients. Daily insulin dose (DID) and insulin-glucose product (IGP) were calculated. Serum and urinary levels of Phe and Tyr isoforms were determined using a rpHPLC-method. Urinary m-Tyr/p-Tyr ratio was higher in patients with DID and IGP over median compared to those below median (P=0.005 and P=0.01, resp.). Urinary m-Tyr and m-Tyr/p-Tyr ratio showed positive correlation with DID (P=0.009 and P=0.023, resp.) and with IGP (P=0.004 and P=0.008, resp.). Serum Phe was a negative predictor, while serum p-Tyr/Phe ratio was positive predictor of both DID and IGP. Urinary m-Tyr and urinary m-Tyr/p-Tyr, o-Tyr/p-Tyr, and (m-Tyr+o-Tyr)/p-Tyr ratios were positive predictors of both DID and IGP. Phe and Tyr isoforms have a predictive role in carbohydrate metabolism of nondiabetic septic patients. Phe may serve as substrate for renal gluconeogenesis via enzymatically produced p-Tyr, while hydroxyl radical derived Phe products may interfere with insulin action

Exenatide induces aortic vasodilation increasing hydrogen sulphide, carbon monoxide and nitric oxide production

BACKGROUND: It has been reported that GLP-1 agonist exenatide (exendin-4) decreases blood pressure. The dose-dependent vasodilator effect of exendin-4 has previously been demonstrated, although the precise mechanism is not thoroughly described. Here we have aimed to provide in vitro evidence for the hypothesis that exenatide may decrease central (aortic) blood pressure involving three gasotransmitters, namely nitric oxide (NO) carbon monoxide (CO), and hydrogen sulphide (H2S). METHODS: We determined the vasoactive effect of exenatide on isolated thoracic aortic rings of adult rats. Two millimetre-long vessel segments were placed in a wire myograph and preincubated with inhibitors of the enzymes producing the three gasotransmitters, with inhibitors of reactive oxygen species formation, prostaglandin synthesis, inhibitors of protein kinases, potassium channels or with an inhibitor of the Na+/Ca2+-exchanger. RESULTS: Exenatide caused dose-dependent relaxation of rat thoracic aorta, which was evoked via the GLP-1 receptor and was mediated mainly by H2S but also by NO and CO. Prostaglandins and superoxide free radical also play a part in the relaxation. Inhibition of soluble guanylyl cyclase significantly diminished vasorelaxation. We found that ATP-sensitive-, voltage-gated- and calcium-activated large-conductance potassium channels are also involved in the vasodilation, but that seemingly the inhibition of the KCNQ-type voltage-gated potassium channels resulted in the most remarkable decrease in the rate of vasorelaxation. Inhibition of the Na+/Ca2+-exchanger abolished most of the vasodilation. CONCLUSIONS: Exenatide induces vasodilation in rat thoracic aorta with the contribution of all three gasotransmitters. We provide in vitro evidence for the potential ability of exenatide to lower central (aortic) blood pressure, which could have relevant clinical importance