13 research outputs found
Influence of different atmospheres on molten salt chemistry and its effect on steel corrosion
Crayfish hemocyanin on chitin bone substitute scaffolds promotes the proliferation and osteogenic differentiation of human mesenchymal stem cells
Crustacean chitin-hemocyanin-calcium mineral complexes were designed as bone biomimetics, with emphasis on their ability to bind or release calcium ions. Chitin scaffolds were prepared by dissolving chitin flakes in LiCl/dimethylacetamide, followed by gel formation and freeze-drying. Some of these scaffolds were modified by incorporation of CaCO3. In some of the chitin-CaCO3 scaffolds, macroporosity was introduced by HCl treatment. Hemocyanin from the crayfish Cherax quadricarinatus was used to further modify the chitin scaffolds by dip coating. Cytocompatibility, cellular adherence and proliferation of human mesenchymal stem cells (hMSCs) were evaluated in terms of cell number as reflected in lactate dehydrogenase activity. The chitin, chitin-CaCO3, and porous chitin-CaCO3 scaffolds were all found to facilitate cell attachment. Hemocyanin dip-coating of these scaffolds led to increased initial cell adhesion, enhanced proliferation, and osteogenic differentiation. Since the hemocyanin loading of the scaffolds was impaired by sterilization by gamma-irradiation (as required for biomedical applications), the hemocyanin loading was performed on previously sterilized scaffolds. All scaffolds facilitated osteogenic differentiation of osteoblasts, with the highest cell ALP-activity being found on hemocyanin-modified porous chitin-CaCO3 scaffolds. Thus, chitin-hemocyanin scaffolds enhanced the initial stages of bone cell development and could serve as promising biomaterials for bone regeneration
Crayfish Hemocyanin Promotes the Proliferation and Osteogenic Differentiation of Human Mesenchymal Stem Cells on Chitin Scaffolds
Association of anandamide with altered binocular depth inversion illusion in schizophrenia
Functional MRI detects perfusion impairment in renal allografts with delayed graft function
Aminothiazole-Featured Pirinixic Acid Derivatives As Dual 5‑Lipoxygenase and Microsomal Prostaglandin E<sub>2</sub> Synthase‑1 Inhibitors with Improved Potency and Efficiency in Vivo
Dual
inhibition of microsomal prostaglandin E<sub>2</sub> synthase-1
(mPGES-1) and 5-lipoxygenase (5-LO) is currently pursued as potential
pharmacological strategy for treatment of inflammation and cancer.
Here we present a series of 26 novel 2-aminothiazole-featured pirinixic
acid derivatives as dual 5-LO/mPGES-1 inhibitors with improved potency
(exemplified by compound <b>16</b> (2-[(4-chloro-6-{[4-(naphthalen-2-yl)-1,3-thiazol-2-yl]amino}pyrimidin-2-yl)sulfanyl]octanoic
acid) with IC<sub>50</sub> = 0.3 and 0.4 μM, respectively) and
bioactivity in vivo. Computational analysis presumes binding sites
of <b>16</b> at the tip of the 5-LO catalytic domain and within
a subpocket of the mPGES-1 active site. Compound <b>16</b> (10
μM) hardly suppressed cyclooxygenase (COX)-1/2 activities, failed
to inhibit 12/15-LOs, and is devoid of radical scavenger properties.
Finally, compound <b>16</b> reduced vascular permeability and
inflammatory cell infiltration in a zymosan-induced mouse peritonitis
model accompanied by impaired levels of cysteinyl-leukotrienes and
prostaglandin E<sub>2</sub>. Together, 2-aminothiazole-featured pirinixic
acids represent potent dual 5-LO/mPGES-1 inhibitors with an attractive
pharmacological profile as anti-inflammatory drugs
Safety and efficacy of rasagiline as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomised, double-blind, parallel-group, placebo-controlled, phase 2 trial
Background Rasagiline, a monoamine oxidase B inhibitor with neuroprotective potential in Parkinson's disease, has shown a disease-modifying effect in the SOD1-Gly93Ala low-expressing mouse model of amyotrophic lateral sclerosis, both alone and in combination with riluzole. We sought to test whether or not rasagiline 1 mg/day can prolong survival in patients with amyotrophic lateral sclerosis also receiving riluzole. Methods Patients with possible, probable, or definite amyotrophic lateral sclerosis were enrolled to our randomised, placebo-controlled, parallel-group, double-blind, phase 2 trial from 15 German network for motor neuron diseases (MND-NET) centres (university hospitals or clinics). Eligible patients were aged at least 18 years, had onset of progressive weakness within the 36 months before the study, had disease duration of more than 6 months and less than 3 years, and had a best-sitting slow vital capacity of at least 50%. After a 4-week screening period, eligible patients were randomly assigned (1:1) to receive either rasagiline (1 mg/day) or placebo in addition to riluzole (100 mg/day), after stratification for site of onset (bulbar or spinal) and study centre. Patients and all personnel assessing outcome parameters were masked to treatment allocation. Patients were followed up 2, 6, 12, and 18 months after randomisation. The primary endpoint was survival time, defined as the time to death or time to study cutoff date (ie, the last patient's last visit plus 14 days). Analyses of primary outcome and safety measures were done in all patients who received at least one dose of trial treatment (intention-to-treat population). The trial is registered with ClinicalTrials.gov, number NCT01879241. Findings Between July 2, 2013, and Nov 11, 2014, 273 patients were screened for eligibility, and 252 patients were randomly assigned to receive rasagiline (n=127) or placebo (n=125). 126 patients taking rasagiline and 125 taking placebo were included in the intention-to-treat analysis. For the primary outcome, the survival probability at the end of the study was 0.43 (95% CI 0.25-0.59) in the rasagiline group (n=126) and 0.53 (0.43-0.62) in the placebo group (n=125). The estimated effect size (hazard ratio) was 0.91 (one-sided 97.5% CI -infinity to 1.34; p=0.31). Rasagiline was well tolerated, and most adverse events were due to amyotrophic lateral sclerosis disease progression rather than treatment; the most frequent of these were dysphagia (32 [25%] taking rasagiline vs 24 [19%] taking placebo) and respiratory failure (25 [20%] vs 31 [25%]). Frequency of adverse events were comparable between both groups. Interpretation Rasagiline was safe in patients with amyotrophic lateral sclerosis. There was no difference between groups in the primary outcome of survival, although post-hoc analysis suggested that rasagiline might modify disease progression in patients with an initial slope of Amyotrophic Lateral Sclerosis Functional Rating Scale Revised greater than 0.5 points per month at baseline. This should be confirmed in another clinical trial. Copyright (C) 2018 Elsevier Ltd. All rights reserved