Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

CELEBREX IN TREATMENT OF VERTEBRAL PAIN SYNDROME IN SYSTEMICV LUPUS ERYTHEMATOSUS

Objective. То study of tizol efficacy for local therapy of rheumatoid arthritis (RA). Materials and methods. 90 pts with active RA (2-3 stage of activity) age 41-54 (m=18, f—72). The method оГ double blind controlled comparison of 10 - days therapy with pure tizol, tizol with diclophenac (1%) and placebo (vaseline) was used. In order to evaluate skin permeability of tizol mass-spectrometry of synovial liquid was used. Results. Positive dynamic of joint syndrome under tizol and tizol with diclophenac therapy were showed. There were reduction of arthalgia, decreasing of morning stiffness, increasing of grip strenght. Erythrocyte sedimentation rate didn’t change. Adding of diclophenac to tizol amplified it's analgetic properties. Mass spectrum analysis showed that concentration of titanium in synovial fluid came approximately 10 times higher after 10 days of tizol therapy. Conclusion. The efficacy of local tizol and it’s compounds in inflammatory joint syndrome was showed. Diclophenac intensified analgetic effect of tizol. Efficacy and convenience of treatment, absens of side-effects, low price allow to recommend tizol - gel compounds for local treatment of inflammatory joint diseases

For half of a century together

В течение второй половины 20 века и начала 21 века терапевтические клиники Ярославского государственного медицинского института (с 1994 года – Ярославская государственная медицинская академия) занимаются изучением клиники, патогенеза, диагностики и лечения ревматических заболеваний. Все эти годы работа проводилась в тесной связи с ведущим учреждением России в области ревматологии – Институтом ревматологии РАМН

CELEBREX IN TREATMENT OF VERTEBRAL PAIN SYNDROME IN SYSTEMICV LUPUS ERYTHEMATOSUS

Celebrex in dosage of 100-200mg/day for 14-20 days was prescribed to 36 SLE pts with symptoms of chronic painful vertebrogenic syndrome. Considerable or moderate lessening of pain syndrome was noticed in 91% of cases (up to 1-3 point by VAS with initial pain more than 4 points). Analgetic effect of the drug was demonstrated already on the 2nd day, the safety was good. Celebrex was recommended for long-term treatment of chronic painful vertebrogenic syndrome in pts with systemic lesions of connective tissue

DIAGNOSTIC MARKERS AND CYTOKINE PROFILE IN PATIENTS WITH RHEUMATOID ARTHRITIS RECEIVING DMARDS

Objective — to evaluate the relationship between antibody titers against modified citrullinated vimentin (AMCV), IgM rheumatoid factor (RF), interleukin (IL) 4, IL6 and IL8, and their correlation with rheumatoid arthritis (RA) activity indicators, systemic manifestations, evolution of disease activity and functional status in patients treated with methotrexate (MT). Material and methods. 76 RA patients were evaluated: 44 — were on MT, 32 — were not receiving DMARDs for &lt;3 months. Serum IgM RF and C-reactive protein (CRP) levels were measured by immunonephelometry, AMCV, IL6, IL8 (ng/Ml) — by solid-phase immunoenzyme analysis. Results. There was no correlation between AMCV levels and RA activity measures (p&gt;0,05). Higher AMCV titers were detected in patients with systemic manifestations vs patients without such symptoms (p=0,002). In subgroup of patients with baseline AMCV &gt;500 U/Ml a significantly lower level of IL6 was observed (p=0,03) with a tendency for AMCV level reduction (p=0,06) and an increase in DAS28 scores after 12 mo of MT therapy (p&gt;0,05). IgM RF titers were significantly higher in patients with high disease activity (p=0,0006) and in patients with systemic manifestations (p=0,04). Significantly higher IL6 levels (p=0,01) and a tendency to DAS28 measures reduction after 12 mo of MT therapy was observed in patients with baseline IgM RF &gt;100 IU/Ml (p&gt;0,05)

Oscular system changes and functional state of endothelium in systemic vasculitides

Objective. To assess by noninvasive methods degree, character and relationship of structural and functional endothelium state disturbances in different regions of vascular bed in systemic vasculitides. Material and methods. 65 pts with systemic vasculitides were examined: 20 with hemorrhagic vasculitis (HV), 20 — with thromboangitis obliterans (TO), 10 — with polyarteritis nodosa (PN), 15 — with Takayasu arteritis (ТА). 30 conditionally healthy persons were included in the control group. Carotid angioscanning with intima-media complex thickness (IMT) measurement and functional tests on brachial artery under sonographic control using SONOS-1500 apparatus with assessment of endothelium-dependent and endothelium- independent vasodilatation were performed. Intracutaneous blood flow was examined by laser Doppler flowmetry with functional tests using LAKK-01 apparatus. Results. Examination of common carotid arteries showed significant increase of IMP in pts with PN and ТА. Pts with HV and TO did not differ from control. Endothelium-dependent vasodilatation was decreased in all groups of pts. The most prominent changes were revealed in ТА and TO. Response to nitroglycerine was normal only in pts with TO. In other groups it was decreased. Endothelium sensitivity to reactive hyperemia was decreased. Hyperemic type of microcirculation prevailed in groups with systemic vasculitides but in HV group microcirculation was mainly normal. Capillary blood flow reserve was significantly lower in PN and TO. Correlation relationship was revealed between main IMP, brachial artery reactivity measures and skin microcirculation. Conclusion. Structural and functional endothelium state disturbances of different regions of vascular bed revealed in systemic vasculitides are interconnected what proves their participation in endothelium damage in these diseases