Mammalian brain as well as mouse neuroblastoma (N18TG2) and rat basophilic leukaemia (RBL) cells were previously shown to contain ‘anandamide amidohydrolase’, a membrane-bound enzyme sensitive to ...serine and cysteine protease inhibitors and catalyzing the hydrolysis of the endogenous cannabimimetic metabolite, anandamide (arachidonoyl-ethanolamide). With the aim of developing novel inhibitors of this enzyme, we synthesized three arachidonic acid (AA) analogues, i.e. arachidonoyl-diazo-methyl-ketone (ADMK), arachidonoyl-chloro-methyl-ketone (ACMK) andO-acetyl-arachidonoyl-hydroxamate (AcAHA), by adding to the fatty acid moiety three functional groups previously used to synthesize irreversible inhibitors of serine and cysteine proteases. The three compounds were purified and characterized by proton nuclear magnetic resonance and electron impact mass spectrometry. Their effect was tested on anandamide amidohydrolase partially purified from N18TG2and RBL-1 cells and porcine brain. Pre-treatment of the enzyme with each compound produced a significant inhibition, with ADMK being the most potent (IC50= 3, 2 and 6 μM) and AcAHA the weakest (IC50= 34, 15 and 25 μM) inhibitors. The inactivated enzyme regained its full activity when chromatographed by anion-exchange chromatography, suggesting that none of the compounds inhibited the amidohydrolase in a covalent manner. Accordingly, Lineweaver-Burk profiles showed competitive inhibition by each compound. Conversely, the irreversible inhibitor of cytosolic phospholipase A2, methyl-arachidonoyl-fluoro-phosphonate (MAFP), covalently inhibited the amidohydrolase. MAFP was active at concentrations 103times lower than those reported for phospholipase A2inhibition, and is the most potent anandamide amidohydrolase inhibitor so far described (IC50= 1-3 nM). MAFP, ADMK and ACMK, probably by inhibiting anandamide degradation, produced an apparent increase of thein vitroformation of anandamide from its biosynthetic precursorN-arachidonoyl-phosphatidyl-ethanolamine.
We present a search for the lepton-flavour-violating decays $B^+ \to K^+ \tau^\pm \ell^\mp$, with $\ell = (e, \mu)$, using the full data sample of $772 \times 10^6$ $B\overline{B}$ pairs recorded by ...the Belle detector at the KEKB asymmetric-energy $e^+ e^-$ collider. We use events in which one $B$ meson is fully reconstructed in a hadronic decay mode. We find no evidence for $B^\pm \to K^\pm \tau \ell$ decays and set upper limits on their branching fractions at the 90% confidence level in the $(1$-$3) \times 10^{-5}$ range. The obtained limits are the world's best results.
The first attempts to reproduce dusky grouper (
Epinephelus marginatus, Lowe 1834) under controlled conditions started in 1995, but the egg and larvae quality was very low. Mass production is still ...encountering many difficulties, mainly concentrated in the larval period when very high mortality rates are observed, confirming what has been observed in the rearing of other grouper species. The main bottlenecks have been identified as the difficulty to properly nourish the larvae, stress shock syndrome, and the high deformation rates.
We analysed 633 dusky grouper larvae and juveniles (0.2–7.2 cm total length, TL), sampled during two larval rearing cycles carried out in 2001 and 2002 in Italy. The specimens at different development stages were stained
in toto for bone and cartilage and examined for skeletal anomalies during dusky grouper ontogenesis. The incidence of anomalies in groupers hatched from the same egg batch but reared using two different methods (green waters and semi-intensive rearing) and three stocking densities (8, 16 and 28 larvae/l) was compared, with a view to providing tools for identifying the most appropriate larval rearing method in order to at least limit the onset of skeletal anomalies.
Our results suggest that during development no particular skeletal anomaly patterns (or fate) can be clearly identified as a high variability was observed in malformation typologies and the regions affected.
No significant differences in the morphological quality between groupers reared using semi-intensive (LV02 lot) and green water (GW02-01 lot) methodologies were observed, whilst groupers reared at the highest stocking density (28 larvae/l) showed the highest frequency of deformed individuals (75.8%), the highest malformation charge (average of 5.5 anomalies per deformed individual), the largest range of anomaly typologies (38), and the highest incidence of individuals with at least one severe anomaly (30.9%). Whilst in green waters no evident effects of larvae density were observed on survival rates, the survival rate in large volume reared individuals (17.5%) was considerably higher with respect to those reared in green waters (0.2%) at 7–8 larvae/l. This indicates that the semi-intensive methodology should be considered more effective in enhancing the survival rate of dusky grouper larvae.
En acuicultura, la intensificación de los cultivos para obtener grandes volúmenes de producción conlleva a establecer un ambiente que genera estrés en los organismos. Estas condiciones debilitan su ...sistema inmune lo que incrementa la propagación de enfermedades y generan grandes pérdidas económicas. Uno de los factores responsables de la mortalidad de las especies cultivadas son las infecciones fúngicas. En las granjas de cultivo, los procedimientos de manejo que se realizan durante las etapas de incubación, cría y engorde son importantes para el rendimiento final del producto. Una de las etapas cruciales es la incubación, ya que en esta etapa suele haber un alto grado de mortalidad. Se han realizado diversos estudios que utilizan productos químicos para la profilaxis, desinfección y control de las micosis. Esta utilización ha provocado la resistencia de los agentes patógenos y la acumulación de residuos en los tejidos de los organismos acuáticos o en el ambiente. Por ello, se están desarrollando otras formas de terapia más rentables y con menos efectos deletéreos sobre el medio ambiente. La fitoterapia surge como una alternativa por su comprobada acción ante enfermedades de diversa etiología. En esta revisión se compila y discute la bibliografía existente sobre las enfermedades fúngicas más comunes en los peces, anfibios y crustáceos, se enfatiza en las que afectan a las ovas de los organismos en cultivo y se analizan los antimicóticos naturales utilizados in vitro e in vivo en acuicultura.
Clinical trials indicate that amifostine may confer protection on various normal tissues without attenuating anti-tumor response. When administered prior to chemotherapy or radiotherapy, it may ...provide a broad spectrum of cytoprotection including against alkylating drugs. The mechanism of protection resides in the metabolism at normal tissue site by membrane-bound alkaline phosphatase. Toxicity of this drug is moderate with hypotension, nausea and vomiting, and hypocalcemia being observed. We report a phase II study using amifostine as a protective drug against high-dose cyclophosphamide (HDCY) (7 g/m2), used to mobilize peripheral blood progenitor cells (PBPC) and to reduce tumor burden. We enrolled 29 patients, 22 (75. 9%) affected by aggressive and 7 (24.1%) by indolent non-Hodgkin's lymphoma (NHL), who were submitted to 58 infusions of amifostine and compared them with a historical group (33 patients) affected by aggressive NHL and treated with VACOP-B followed by HDCY. The most important results in favor of amifostine were the reduction of intensity of cardiac, pulmonary and hepatic toxicity, and a significant reduction of frequency and severity of mucositis (P = 0. 04). None of the 29 patients died in the protected group, while in the historical group 2/33 patients died because of cardiac or pulmonary toxicity and 2 patients stopped therapy due to toxicity. Amifostine did not prevent the aplastic phase following HDCY. PBPC collection and hematological recovery were adequate in both groups. The number of CFU-GM (colony-forming units-granulocyte/macrophage) colonies and mononuclear cells in the apheresis products was significantly higher in the amifostine group (P = 0.02 and 0.01, respectively). Side effects were mild and easily controlled. We conclude that amifostine protection should be useful in HDCY to protect normal tissues, with acceptable side effects.
Tissue engineering of parathyroid gland Iovino, F; Armano, G; Auriemma, P P ...
Il Giornale di chirurgia,
2010 Jun-Jul, Letnik:
31, Številka:
6-7
Journal Article
Recenzirano
The postoperative hypoparathyroidism is a not rare complication after total thyroidectomy and/or total parathyroidectomy. Attempts to transplant parathyroid tissue began in 1975 with the work of ...Wells, but still today results are disappointing. However, with the development of tissue engineering techniques, some experimental approaches to build artificial parathyroid are been made. Bioengineered device, actively secreting PTH, for transplant in patients with iatrogenic hypoparathyroidism is unavailable.
Parathyroid cells were obtained from three chronic uremic patients in hemodialysis, operated for secondary hyperparathyroidism. Cell cultures in RPMI medium were subsequently seeded on collagen scaffold (three-dimensional matrix with slow biodegradation). Collagen is the major component of the extracellular matrix and thus is a good substrate for cell adhesion and growth. Culture media, with a low calcium concentration, were optimised to physiologically stimulate parathyroid hormone secretion. Cell cultures were morphologically observed in optical and electron (ESEM) microscopy and metabolically assayed by MTT method until the tenth week. Besides, concentration of parathyroid hormone in the culture medium has been measured for several weeks.
After 24 hours of culture in RPMI, cells extracted from human parathyroid glands were nearly all adherent and organised in clusters to resemble the glandular organization. The cellular population consisted predominantly of parathyroid cells (90-95%). On collagen scaffolds, cells maintains an epithelial-like morphology also after 10 weeks, colonizing the scaffold surface and keeping a good proliferative rate with a discrete production of parathyroid hormone.
The use of parathyroid cells extracted from patients with secondary hyperparathyroidism was certainly an appropriate choice that enabled us to achieve these results, that albeit partial bode well for the experimental in vivo animal model. The bioengineered scaffolds when implanted in the subcutaneous can avoid the dispersion of parathyroid cells, assuring also the possibility to easily remove the implant in case of complications. Our research was aimed primarily to the optimisation of PTH secreting human parathyroid cells cultures and then to the in vitro engineering of human parathyroid glands in three-dimensional collagen scaffolds.
The behaviour of a SiC-fibre-reinforced composite with a graded matrix was investigated in an arc jet facility. The graded matrix was comprised of several layers of silicon carbide that transition to ...a mixed SiC-HfB
2
top layer and was sealed with an HfB
2
-SiC coating. Samples were exposed to maximum specific total enthalpy hypersonic flow between 14 and 17 MJ kg
−1
under stagnation pressures between 2700 and 3050 Pa for hold times of between 137 and 395 s. The resulting sample surface temperatures ranged between 1600 and 1950°C. Spectral emissivity at about
1 μm
was calculated using a pyrometer capable of switching between one and two color modes and was shown to decrease with oxidation and removal of SiO
2
from the surface. The impacts of the surface chemistry changes during oxidation and of active oxidation were investigated.
Performance of the Belle II Silicon Vertex Detector Tanigawa, H.; Adamczyk, K.; Aihara, H. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
08/2020, Letnik:
972
Journal Article
Recenzirano
The Belle II experiment at the SuperKEKB collider of KEK (Japan) started recording physics data in spring 2019 with all its subdetectors installed and with the goal of accumulating 50ab−1 of e+e− ...collision events at the unprecedented instantaneous luminosity of 8×1035cm−2s−1, about 40 times larger than its predecessor. The Belle II vertex detector plays a crucial role in the broad Belle II physics program, especially for time-dependent CP measurements. It consists of two layers of DEPFET-based pixels and four layers of double-sided silicon strip detectors (SVD).
The experience gained from the first period of SVD operation can be summarized as smooth and reliable running of the detector, with high stability of noise levels and calibration parameters obtained from local calibration runs. No major problem has been experienced. The detector even survived a few serious radiation accidents in which the beam was lost due to failure in the machine focusing quadrupoles without any notable damage. The SVD performance were carefully studied with these first physics data. The SVD showed excellent hit and tracking efficiency. Moreover, cluster energy and signal to noise ratio as well as the hit time and spatial resolutions measured on data showed a fair agreement with the expected performance.
•Belle II silicon vertex detector operated during the first year of the experiment.•All sensors worked with stable and excellent hit efficiencies above 99 %.•Signal-to-noise ratios between 15 and 30, cluster time resolution better than 3 ns.•First effects of irradiation visible in leakage currents.
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