11,619 research outputs found
Alpha2-adrenoceptor mediated co-release of dopamine and noradrenaline from noradrenergic neurons in the cerebral cortex
No full textPrevious results suggest that extracellular dopamine (DA) in
the rat cerebral cortex originates from dopaminergic and
noradrenergic terminals. To further clarify this issue, dialysate
DA, dihydroxyphenylacetic acid (DOPAC) and noradrenaline
(NA) were measured both in the medial prefrontal cortex
(mPFC) and in the occipital cortex (OCC), with dense and
scarce dopaminergic projections, respectively. Moreover, the
effect of the a2-adrenoceptor antagonist RS 79948 and the
D2-receptor antagonist haloperidol on extracellular DA, DOPAC
and NA was investigated. Extracellular DA and DOPAC
concentrations in the OCC were 43% and 9%, respectively,
those in the mPFC. Haloperidol (0.1 mg/kg i.p.) increased DA
and DOPAC (by 35% and 150%, respectively) in the mPFC,
but was ineffective in the OCC. In contrast, RS 79948
(1.5 mg/kg i.p.) increased NA, DA and DOPAC, both in the
mPFC (by approximately 50%, 60% and 130%, respectively)
and the OCC (by approximately 50%, 80% and 200%,
respectively). Locally perfused, the DA transporter blocker
GBR 12909 (10 lM) was ineffective in either cortex, whereas
desipramine (DMI, 100 lM) markedly increased extracellular
NA and DA in both cortices. The weak haloperidol effect on
DA efflux was not enhanced after DA- and NA-transporter
blockade, whereas after DMI, RS 79948 markedly increased
extracellular NA, and especially DA and DOPAC in both cortices.
The results support the hypothesis that most extracellular
DA in the cortex is co-released with NA from
noradrenergic terminals, such co-release being primarily
controlled by a2-adrenoceptors
Interferon regulatory factor 5 is a potential target of autoimmune response triggered by Epstein-barr virus and Mycobacterium avium subsp. paratuberculosis in rheumatoid arthritis: investigating a mechanism of molecular mimicry
No full textMirtazapine-induced corelease of dopamine and noradrenaline from noradrenergic neurons in the medial prefrontal and occipital cortex
No full textThe novel antidepressant mirtazapine has been shown to increase extracellular noradrenaline and dopamine in the medial prefrontal
cortex. Our previous studies indicate that extracellular dopamine in the cerebral cortex originates largely from noradrenergic terminals, such
release being controlled by a2-adrenoceptors. Because mirtazapine inhibits a2-adrenoceptors, the possibility that it might corelease dopamine
and noradrenaline was investigated. By means of microdialysis, the effect of mirtazapine on extracellular dopamine, 3,4-dihydroxyphenylacetic
acid (DOPAC) and noradrenaline in the medial prefrontal cortex, densely innervated by dopaminergic and noradrenergic neurons, and
in the occipital cortex, receiving equal noradrenergic but scarce dopaminergic projections, was compared. Basal extracellular concentration of
noradrenaline was similar in both cortices, while dopamine in the occipital cortex was only about 50% lower than in the medial prefrontal
cortex, reflecting noradrenergic rather than dopaminergic projections. The intraperitoneal (i.p.) administration of mirtazapine (5 and 10 mg/
kg) increased extracellular dopamine, DOPAC and noradrenaline to approximately the same extent in both cortices, an effect totally
suppressed by the a2-adrenoceptors agonist clonidine (0.15 mg/kg, i.p.). To exclude the possibility that mirtazapine-induced increase in
dopamine might result from reduced dopamine removal from extracellular space, noradrenaline and dopamine uptake mechanisms were
blocked by perfusing 100 AM desipramine into either cortex. The combined i.p. administration of mirtazapine (5 mg/kg) and the local
perfusion of desipramine produced an additional increase in extracellular dopamine, DOPAC and noradrenaline in the medial prefrontal
cortex and occipital cortex compared with the increase produced by either drug given alone. The results suggest that mirtazapine by inhibiting
a2-adrenoceptors produces a corelease of noradrenaline and dopamine from noradrenergic terminals in the cerebral cortex.
D 2004 Elsevier B.V. All rights reserved
Potentially beneficial cardiovascular effects of melatonin administration in women.
No full textThe cardiovascular effects induced by the daytime administration of melatonin (1 mg) were compared to those of placebo in 12 young women. In order to eliminate cardiovascular effects due to fluctuating endogenous sex steroids, all women were taking a fixed dose of monophasic contraceptive pill. In comparison to placebo, the administration of melatonin reduced, within 90 min, the pulsatility index of the internal carotid artery, evaluated by color Doppler ultrasound (P < 0.01), as well as both systolic and diastolic blood pressure evaluated in supine position (P < 0.01). Supine catecholamine levels were not significantly modified, but norepinephrine levels evaluated after 5 min of standing position were significantly reduced (P < 0.02). These data suggest that in women the administration of 1 mg of melatonin may exert beneficial effects on blood vessels
Mycobacterium tuberculosis lipoarabinomannan antibodies are associated to rheumatoid arthritis in Sardinian patients
No full textLittle is known regarding the environmental factors at play in igniting rheumatoid arthritis (RA) autoimmunity, although an association between Mycobacteria and RA has been documented. This pilot study focused on examining a possible involvement of Mycobacterium tuberculosis (MTB) and Mycobacterium avium ss. paratuberculosis (MAP) in RA. We measured out the serum levels of IgG antibody against different mycobacterial antigens in Sardinian patients and controls, by an enzyme-linked immunosorbent assay. The population study was composed of 61 RA patients under different therapies and 52 healthy controls, whereas the antigens tested were MTB lipoarabinomannan (ManLAM), MAP heath shock protein 70, and MAP protein tyrosine phosphatase. The frequencies of anti-ManLAM antibodies were higher in the RA group (23 %) compared to the healthy controls (5.7 %) (AUC = 0.7; p < 0.0001), whereas serum reactivity to MAP antigens was not observed. ManLAM antigen was also detected in the plasma of three RA patients (which were anti-ManLAM antibody positive) by Western blot analysis using anti-Man-LAM monoclonal antibodies. The data produced corroborate the hypothesis of a potential association between MTB ManLAM and RA disease, but so far, further studies are necessary to understand its role in RA pathogenesis
Study on the Mg-Li-Zn ternary alloy system with improved mechanical properties, good degradation performance and different responses to cells
No full textNovel Mg-(3.5, 6.5wt%)Li-(0.5, 2, 4wt%)Zn ternary alloys were developed as new kinds of biodegradable metallic materials with potential for stent application. Their mechanical properties, degradation behavior, cytocompatibility and hemocompatibility were studied. These potential biomaterials showed higher ultimate tensile strength than previously reported binary Mg-Li alloys and ternary Mg-Li-X (X=Al, Y, Ce, Sc, Mn and Ag) alloys. Among the alloys studied, the Mg-3.5Li-2Zn and Mg-6.5Li-2Zn alloys exhibited comparable corrosion resistance in Hank's solution to pure magnesium and better corrosion resistance in a cell culture medium than pure magnesium. Corrosion products observed on the corroded surface were composed of Mg(OH)2, MgCO3 and Ca-free Mg/P inorganics and Ca/P inorganics. In vitro cytotoxicity assay revealed different behaviors of Human Umbilical Vein Endothelial Cells (HUVECs) and Human Aorta Vascular Smooth Muscle Cells (VSMCs) to material extracts. HUVECs showed increasing nitric oxide (NO) release and tolerable toxicity, whereas VSMCs exhibited limited decreasing viability with time. Platelet adhesion, hemolysis and coagulation tests of these Mg-Li-Zn alloys showed different degrees of activation behavior, in which the hemolysis of the Mg-3.5Li-2Zn alloy was lower than 5%. These results indicated the potential of the Mg-Li-Zn alloys as good candidate materials for cardiovascular stent applications. Statement of significance: Mg-Li alloys are promising as absorbable metallic biomaterials, which however have not received significant attention since the low strength, controversial corrosion performance and the doubts in Li toxicity. The Mg-Li-Zn alloy in the present study revealed much improved mechanical properties higher than most reported binary Mg-Li and ternary Mg-Li-X alloys, with superior corrosion resistance in cell culture media. Surprisingly, the addition of Li and Zn showed increased nitric oxide release. The present study indicates good potential of Mg-Li-Zn alloy as absorbable cardiovascular stent material.Accepted Author ManuscriptBiomaterials & Tissue Biomechanic
Antiphospholipid syndrome nephropathy (APSN) in patients with lupus nephritis: a retrospective clinical and renal pathology study.
No full textData about clinical-laboratory features and outcome of antiphospholipid syndrome nephropathy (APSN) in the course of lupus nephritis (LN) are scarce. To determine prevalence, clinical correlations and outcome of APSN in patients with LN, retrospective analysis of renal specimens and review of medical records from 48 LN patients were performed. APSN was found in 12/48 (25 %) of LN. Positivity for lupus anticoagulant (LAC) and double antiphospholipids positivity [LAC plus anticardiolipin (aCL)] were significantly more frequent in APSN-LN (p = 0.02 and p = 0.01, respectively) than in LN, while single aCL positivity was not. Overt antiphospholipid syndrome appeared more frequent in patients with APSN-LN (p = 0.05). There were no statistically significant differences between APSN-LN and LN in the proportion of each World Health Organization class of LN (with the exception of a trend toward fewer Class III LN in APS-LN) and in the systemic lupus erythematosus (SLE) disease duration and severity. At the time of renal biopsy, patients with APSN-LN had median serum creatinine levels significantly higher than patients with LN [1.45 (0.6-6.6) vs. 1.00 (0.7-3.0), p = 0.02]. Double antiphospholipid positivity was the only variable significantly associated with APSN-LN at multivariate regression analysis (OR 8, 95 % CI 1.7-37, p = 0,008). APSN-LN and LN did not differ significantly as regards the rate of complete (25 vs. 19.4 %, p = 0.72) and partial treatment response (25 vs. 29 %, p = 0.82) at 6 months and the progression to end-stage renal disease after a median follow-up of 8.1 ± 3.6 years (16.6 vs. 13.8 %, p = 0.82). APSN was demonstrated in a quart of LN, appeared to be independent from underlying LN class and SLE severity, and did not seem to confer a worse prognosis to LN. The findings of higher creatinine and more interstitial fibrosis in APSN should be confirmed in future prospective larger studies
Granuloma anulare sclerodermiforme e sclerosi sistemica: a proposito di una diagnosi differenziale complessa
No full text“Mg” Bone: Ink extrusion-based additive manufacturing of Mg implants
No full textThe treatment of largy bone defect remains challenging in clinics. All the clinically available bone grafts have their own limitations and are not ideal for the treatment. Therefore, developing a new generation of suitable bone substitutes is urgently needed. In the recent years, porous magnesium (Mg) has been extensively studied for orthopedic applications owing to its biodegradability, favorable mechanical properties, and osteopromotive ability. The recent advances in additive manufacturing (AM) provide unprecedented opportunities to design and fabricate porous Mg scaffolds with interconnected porous structures that are favorable for the adhesion and proliferation of bone cells. However, powder bed fusion AM, which is the most commonly used AM technique for fabricating metal structures, has encountered many difficulties in manufacturing Mg due to safety concerns, excessive oxidation, and undesirable compositional variation due to the low boiling temperature of Mg. To alleviate these difficulties, alternative AM techniques that can create highly porous structures at room temperature are highly sought after. The aim of this research was to develop a room-temperature AM technique for manufacturing porous Mg and to characterize the fabricated Mg-based scaffolds in different aspects relevant to their potential applications as bone implants.In this thesis work, we, for the first time, successfully employed extrusion-based 3D printing techniques to fabricate biodegradable porous Mg and Mg-based scaffolds for application in orthopedics. We started with the optimization of the formulated binder system, the printing process, and the subsequent liquid-phase sintering process for the AM of Mg and Mg-based scaffolds. On this basis, a series of Mg and Mg-based porous scaffolds, including Mg alloy and Mg matrix composite scaffolds were successfully fabricated. Then, we conducted comprehensive studies on the microstructure, geometrical characteristics, in vitro biodegradation behavior, mechanical properties, and the in vitro biodegradation and the responses of preosteoblast MC3T3-E1 cells to the fabricated scaffolds to evaluate the ability of the fabricated scaffolds to satisfy the requirements of ideal bone-substituting biomaterials. By modifying the alloy composition and adding bioceramic components, the properties of the Mg scaffolds required were significantly improved as compared to those of the pure Mg specimens. The fabricated Mg-matrix composite scaffolds were shown to be the most promising materials to be further developed for bone substitution. Surface modification could also contribute to bringing the fabricated Mg scaffolds closer to meeting the requirements. Therefore, with proper material design and surface modification, the Mg-based scaffolds fabricated using extrusion-based 3D printing technique constitute a new category of porous Mg-based biomaterials that hold great promise for application as bone substitutes
Extrusion-based additive manufacturing of Mg-Zn alloy scaffolds
No full textPorous biodegradable Mg and its alloys are considered to have a great potential to serve as ideal bone substitutes. The recent progress in additive manufacturing (AM) has prompted its application to fabricate Mg scaffolds with geometrically ordered porous structures. Extrusion-based AM, followed by debinding and sintering, has been recently demonstrated as a powerful approach to fabricating such Mg scaffolds, which can avoid some crucial problems encountered when applying powder bed fusion AM techniques. However, such pure Mg scaffolds exhibit a too high rate of in vitro biodegradation. In the present research, alloying through a pre-alloyed Mg-Zn powder was ultilized to enhance the corrosion resistance and mechanical properties of AM geometrically ordered Mg-Zn scaffolds simultaneously. The in vitro biodegradation behavior, mechanical properties, and electrochemical response of the fabricated Mg-Zn scaffolds were evaluated. Moreover, the response of preosteoblasts to these scaffolds was systematically evaluated and compared with their response to pure Mg scaffolds. The Mg-Zn scaffolds with a porosity of 50.3% and strut density of 93.1% were composed of the Mg matrix and MgZn2 second phase particles. The in vitro biodegradation rate of the Mg-Zn scaffolds decreased by 81% at day 1, as compared to pure Mg scaffolds. Over 28 days of static immersion in modified simulated body fluid, the corrosion rate of the Mg-Zn scaffolds decreased from 2.3 ± 0.9 mm/y to 0.7 ± 0.1 mm/y. The yield strength and Young's modulus of the Mg-Zn scaffolds were about 3 times as high as those of pure Mg scaffolds and remained within the range of those of trabecular bone throughout the biodegradation tests. Indirect culture of MC3T3-E1 preosteoblasts in Mg-Zn extracts indicated favorable cytocompatibility. In direct cell culture, some cells could spread and form filopodia on the surface of the Mg-Zn scaffolds. Overall, this study demonstrates the great potential of the extrusion-based AM Mg-Zn scaffolds to be further developed as biodegradable bone-substituting biomaterials.Biomaterials & Tissue BiomechanicsTeam Peyman TaheriTeam Arjan Mo
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