1,394 research outputs found
Characterization of a low affinity-binding site for N-6-substituted adenosine derivatives in rat testis membranes
No full textThe binding characteristics of radiolabeled N-6-(cyclohexyl)adenosine ([H-3]CHA), N-6-(R-phenylisopropyl)adenosine ([H-3]R-PIA), 5'-N-ethyl-carboxamidoadenosine ([H-3]NECA), and 2-[4-(2-carboxyethyl)phenyl]ethyl-amino-5'-N-ethylcarboxamidoadenosine ([H-3]CGS 21680), to rat testis membranes were investigated. Specific binding of [H-3]CGS 21680, a selective agonist for the A(2a) adenosine receptor, was very modest whilst the nonselective agonist [H-3]NECA bound to rat testis membranes showing high binding capacity. At least two types of binding sites for [H-3]NECA could be identified in rat testis membranes: high affinity sites and high capacity sites. Selective agonists for the A(1) adenosine receptor, [H-3]CHA and [H-3]R-PIA bound with high affinity to a single class of binding sites. This high affinity binding site showed the typical pharmacological specificity of the A(1) adenosine receptor with a potency order fur agonists of CHA greater than or equal to R-PIA greater than or equal to NECA greater than or equal to N-6-(S-phenylisopropyl)adenosine (S-PIA). In order to detect the presence of the A(3) adenosine receptor in these membranes we selectively blocked the A(1) receptor with a large molar excess of a xanthine antagonist, either 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) or xanthine amine congener (XAC). In the presence of an antagonist a low affinity binding site for [H-3]CHA and [H-3]R-PIA was detected. This low affinity binding site showed a different pharmacological specificity than the high affinity binding site. In fact the potency order for agonists was CHA greater than or equal to NECA = R-PIA > S-PIA. This finding suggests that the low affinity binding site represents the A(3) adenosine receptor
Clinical and biochemical evaluation of two Extended-Depth of Focus (EDOF) intraocular lenses: a prospective randomized trial
No full textIntroduzione: le lenti intraoculari ad aumentata profondità di fuoco (IOL EDOF) rappresentano una promettente tecnologia volta a migliorare la qualità della visione dopo intervento di cataratta. Benché diversi trial clinici siano apparsi in letteratura scientifica negli ultimi anni, ad oggi nessuno studio clinico prospettico randomizzato controllato mette a confronto i modelli AcrySof IQ Vivity e Tecnis Symfony.
Scopo: obiettivo principale del presente studio è valutare la non inferiorità della nuova IOL EDOF AcrySof® IQ Vivity® rispetto alla consolidata Tecnis Symfony®, in termini di risultati refrattivi ed esperienza soggettiva dopo intervento di cataratta. In aggiunta, lo studio si propone di indagare le possibili relazioni tra osservazioni cliniche e misurazioni biochimiche effettuate nei campioni di lacrime dei pazienti, per identificare potenziali fattori predittivi associati alle disfotopsie osservate nel postoperatorio.
Metodi: nel presente studio prospettico, in singolo cieco, randomizzato e controllato, condotto presso l'Ospedale di Stato della Repubblica di San Marino, sono stati inclusi 49 pazienti (98 occhi) randomizzati nel gruppo di intervento Vivity o nel gruppo di controllo Symfony. Prima dell'intervento è stata testata l’acuità visiva monoculare non corretta (UCVA) e con migliore correzione (BCVA) per lontano, intermedio e per vicino. Ai controlli postoperatori ad 1 e 3 mesi sono stati eseguiti: UCVA e BCVA, curve di defocus, sensibilità al contrasto (CS) fotopica e mesopica, e una valutazione della percezione di fenomeni fotici per mezzo del simulatore Halo & Glare. L’esperienza soggettiva dei pazienti è stata valutata mediante la somministrazione dei questionari qualità della visione (QoV) e indipendenza dagli occhiali (SIQ). Infine, prima e dopo l’intervento sono state effettuate misurazioni della concentrazione dei livelli di metalloproteinasi-9 (MMP-9) totale e della lattoferrina (LF) nei campioni di lacrime, mediante utilizzo di appositi kit ELISA.
Risultati: dei 49 pazienti arruolati, 48 hanno terminato i 3 mesi di follow-up. Un paziente si è ritirato dallo studio, richiedendo la sostituzione della IOL Symfony con una monofocale, a causa della percezione di aloni fastidiosi. Non è stata registrata alcuna complicanza intraoperatoria. Ad 1 e a 3 mesi dall’intervento, non sono state rilevate differenze statisticamente significative nei due gruppi in termini di UCVA e BCVA, curve di defocus, e CS in tutte le frequenze esaminate. Tuttavia, la dimensione e l’intensità media degli aloni percepiti è risultata significativamente inferiore nei pazienti del gruppo di intervento Vivity rispetto a quelli del gruppo di controllo Symfony (p=0.00). Considerando l’intera popolazione in studio, livelli preoperatori di MMP-9 totale superiori a 25.38 ng/mg sono stati associati a valori medi inferiori della dimensione degli aloni ad 1 e a 3 mesi dall’intervento (p < 0.01 e p < 0.05, rispettivamente) e a valori medi inferiori di intensità degli aloni ad 1 mese di follow-up (p = 0.03). Inoltre, è stata osservata una correlazione positiva tra i livelli di LF ad 1 mese e le dimensioni (r = 0.45; p = 0.01) e l'intensità degli aloni (r = 0.43; p = 0.02) durante il follow-up corrispondente.
Conclusioni: le due IOL EDOF hanno dimostrato un'efficacia clinica simile ed un elevato grado di indipendenza dagli occhiali e soddisfazione dei pazienti. Tuttavia, la nuova IOL EDOF Vivity ha indotto minori fenomeni fotici in termini di dimensione e intensità degli aloni rispetto alla consolidata TECNIS Symfony ad 1 e a 3 mesi dall’intervento. In aggiunta, i livelli preoperatori di MMP-9 totale nelle lacrime, misurabili nella pratica clinica mediante test quantitativi come Inflammadry®, sono stati associati ad una differente percezione delle disfotopsie nel postoperatorio. Studi multicentrici e con una numerosità campionaria adeguata sono necessari per confermare e approfondire questi risultati.Introduction: Extended depth of focus intraocular lenses (EDOF IOLs) represent a promising technology aimed at improving vision quality after cataract surgery. Although several clinical trials have appeared in the scientific literature in recent years, to date, no prospective randomized controlled clinical study has compared the AcrySof IQ Vivity and Tecnis Symfony models.
Objective: The primary endpoint of the present study was to evaluate the non-inferiority of the new EDOF IOL AcrySof® IQ Vivity® compared to the established Tecnis Symfony®, in terms of refractive outcomes and subjective experience after cataract surgery. In addition, the study aimed to investigate possible relationships between clinical observations and biochemical measurements in tears, to identify potential predictive factors associated with dysphotopsia observed in the postoperative period.
Methods: In this prospective, single-blinded, randomized, controlled study conducted at the State Hospital of the Republic of San Marino, 49 patients (98 eyes) were included and randomized into the Vivity intervention group and Symfony control group. Before the surgery, monocular uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA) for far, intermediate, and near distances were tested. Postoperative assessments at 1 and 3 months included: UCVA and BCVA, defocus curves, photopic and mesopic contrast sensitivity (CS), and an evaluation of the perception of photic phenomena using the Halo & Glare simulator. Patient subjective experience was assessed through the administration of the quality of vision (QoV) and spectacle independence questionnaires (SIQ). Finally, measurements of total metalloproteinase-9 (MMP-9) and lactoferrin (LF) levels in tear samples were conducted before and after the surgery using specific ELISA kits.
Results: Of the 49 enrolled patients, 48 completed the 3-month follow-up. One patient withdrew from the study, requesting the replacement of the Symfony IOL with a monofocal lens, due to the perception of bothersome halos. No intraoperative complications were recorded. At the 1- and 3-month after surgery, no statistically significant differences were observed between the two groups in terms of UCVA and BCVA, defocus curves, and CS at all examined frequencies. However, the average size and intensity of perceived halos were significantly lower in the Vivity intervention group compared to the Symfony control group (p=0.00). Considering the entire study population, preoperative levels of total MMP-9 greater than 25.38 ng/mg were associated with lower average halo size at 1- and 3-month after surgery (p < 0.01 and p < 0.05, respectively) and lower average halo intensity at the 1-month follow-up (p = 0.03). Similarly, total baseline MMP-9 levels higher than 25.38 ng/mg were associated with significantly reduced glare intensity at the 1-month follow-up (p = 0.05). Furthermore, a positive correlation was observed between LF levels at 1 month and halo size (r = 0.45; p = 0.01) and intensity (r = 0.43; p = 0.02) during the corresponding follow-up. A significant but weak negative correlation was found between LF concentration in tears and both glare size (r = -0.36; p = 0.04) and glare intensity (r = -0.37; p = 0.04) at the 3-month follow-up.
Conclusions: the two investigated EDOF IOLs demonstrated similar clinical efficacy and a high degree of spectacle independence and patient satisfaction. However, the Vivity IOL provided lower photic phenomena in terms of size and intensity of the halos than the Symfony at both follow-ups. Furthermore, our research shed new light on the relationship between MMP-9 in tears and dysphotopsia. Indeed, total MMP-9 levels exceeding 25.38 ng/mg at baseline seemed to influence the subjects' postoperative perception of halos. Nonetheless, further prospective multicenter studies with larger sample sizes are needed to deepen our knowledge of the link between baseline tear MMP-9 levels and dysphotopsia
New cyclopentadienyl ligands and their use in organometallic chemistry and catalysis
No full textIn the course of our studies concerning the chemistry of new ester-functionalized Cp ligands, we have disclosed a new procedure for the one pot synthesis of a variety of alkoxycarbonylcyclopentadienides Na[CpCO2(CHR)2OH] (1) [R = H, Me, Ph]. These ligands provided a valuable route to novel sandwich and yhalf-sandwich metal complexes. Among these, the rhodium derivatives [Rh[CpCO2(CHR)2OH](L,L)] (2) [R = H, Me, Ph; L,L = 2CO, NBD], have been tested as hydroformylation and hydrogenation catalysts. The presence in the lateral chain of the Cp ligand of an hydroxyl functionality has been exploited to develop a new route for anchoring the rhodium complexes on the surface of suitable dendrimers and polystyrene resins
Evaluation of radiative heat transfer for interplanetary re-entry under vibrational nonequilibrium conditions
No full textA radiative heat transfer code, based on the Discrete Transfer method, is used in combination with
a spectral radiative database and a thermochemical nonequilibrium Navier–Stokes flowfield solver, to
compute radiative heating under vibrational nonequilibrium conditions for the re-entry test vehicle
FIRE II. The trajectory point under scrutiny refers to a flight velocity of 8.3 km/s, where radiative
equilibrium prevails. Numerical predictions indicate a quite good agreement with experimental data, both
for the radiative intensity along the stagnation streamline and for the total (convective plus absorbed
radiative) heat flux at the stagnation point. The Discrete Transfer method makes the code applicable
to arbitrarily complex geometries, and the vibrational nonequilibrium description allows considering reentry
from lunar or interplanetary return trajectories, as well as from terrestrial orbits
Role of cysteine residues of rat A(2a) adenosine receptors in agonist binding
No full textIn the present study, we investigated the role of disulfide bridges and sulfhydryl groups in A(2a) adenosine receptor binding of the agonist 2-p-(2-carboxyethyl)phenylethylamino)-5'-N-ethylcarboxamidoadenosine (CGS 21680). To evaluate the presence of essential disulfide bridges, rat striatal membranes were incubated with [H-3]CGS 21680 in the presence of dithiothreitol and binding of the agonist to membranes was measured. The amount of [H-3]CGS 21680 which specifically bound, decreased progressively upon pretreatment of membranes with increasing concentrations of dithiothreitol, Pretreatment of rat striatal membranes with 12.5 mM dithiothreitol for 15 min at 25 degrees C resulted in a 2-fold decrease of A(2a) adenosine receptor affinity for [3H]CGS 21680, and a reduction in the maximal number of binding sites. The presence of agonist or antagonist ligands protected the A(2a) adenosine receptor sites from the effect of dithiothreitol. We also examined the susceptibility of A(2a) adenosine receptors to inactivation by the sulfhydryl alkylating reagent, N-ethylmaleimide. When rat striatal membranes were pretreated with N-ethylmaleimide for 30 minutes at 37 degrees C, a decrease in specific [H-3]CGS 21680 binding was observed. Pretreatment of membranes with 1 mM N-ethylmaleimide also resulted in a 2-fold reduction of A(2a) adenosine receptor affinity for [H-3]CGS 21680, as well as a slight decrease in the maximal number of binding sites. Neither agonist nor antagonist ligands were effective in protecting the receptor sites from inactivation by N-ethylmaleimide. protecting the receptor sites from inactivation by N-ethylmaleimide. This protective effect was significant but not complete. Our data suggest that disulfide bridges play a role in the structural integrity of the A(2a) adenosine receptor, furthermore, reduced sulfhydryl groups appear to be important but we do not yet know if they are on the receptor or on the G(s alpha) subunit
TRYPTOPHAN207 IS INVOLVED IN THE GTP-DEPENDENT CONFORMATIONAL SWITCH IN THE ALPHA-SUBUNIT OF THE G-PROTEIN TRANSDUCIN - CHYMOTRYPTIC DIGESTION PATTERNS OF THE GTP-GAMMA-S AND GDP-BOUND FORMS
No full textThe limited proteolytic pattern of transducin, G(t), and its purified subunits with chymotrypsin were analyzed and the cleavage sites on the alpha(t) subunit were identified. The alpha(t) subunit in the GTPgammaS bound form was cleaved into a major 38 kD fragment, whereas alpha(t)-GDP was progressively digested into 38, 23, 21, and 15 kD fragments. The betagamma(t) subunit was not very sensitive to proteolytic digestion with chymotrypsin. The gamma(t) subunit was not cleaved and only a small portion of beta(t) was digested into several fragments. In order to determine which proteolytic fragment of alpha(t) still contained the carboxyl terminal region, chymotrypsinization was carried out using G(t) previously P-32-labeled at Cys347 by petrussis toxin-catalyzed ADP-ribosylation. The P-32-label was mainly associated with the alpha(t) subunit and a 15 kD fragment. The 23 and 21 kD fragments were not P-32-labeled. Analysis of amino terminal sequences of 38, 21, and 15 kD proteolytic bands allowed the identification of the major cleavage sites. Chymotrypsin had two cleavage sites in the amino terminal region of alpha(t), at Leu15 and Leu19. Chymotrypsin removed 15 19 amino acid residues from the amino terminus of alpha(t), generating two peptides (38 kD) which comigrates in gel electrophoresis. Chymotrypsin also cleaved at Trp207 in a conformation-dependent manner. Trp207 of alpha(t)-GTPgammaS was resistant to proteolysis but alpha(t)-GDP and the 38 kD fragments of alpha(t)-GDP produced the 23 and 21 kD fragments, respectively, and a 15 kD fragment containing the carboxyl terminus. This proves that the environment of Trp207 changes when GTP or GTPgammaS is bound, leading to its inaccessibility to chymotrypsin
PGSE NMR studies on DAB-organo-rhodium dendrimers: Evaluation of the molecular size, self-aggregation tendency, and surface metal density
No full textPGSE NMR measurements have been carried out for DAB-dendr-(NH2)(n) [n = 4 (Dab4), 8 (Dab8), 16 (Dab16), 32 (Dab32), and 64 (Dab64)] and DAB-dendr-[NH(O)COCH2CH2OC(O)C5H4Rh(NBD)](n) [n = 4 (Rh-Dab4), 8 (Rh-Dab8), 16 (Rh-Dab16), 32 (Rh-Dab32), and 64 (Rh-Dab64)] in CD2Cl2 and CD3OD as a function of the concentration. The hydrodynamic radius (r(H)) and, consequently, the hydrodynamic volume (V-H) of all the species are determined from the measured translational self-diffusion coefficients (D-t). In CD2Cl2, both Dab and Rh-Dab dendrimers show a tendency toward self-aggregation that increases with the generations. In addition, while the radii r(H) for Dab dendrimers is ca. 20-30% higher in CD3OD than in CD2Cl2, the r(H) values for Rh-Dab dendrimers are only slightly influenced by solvent variation. To estimate the Rh-Rh spatial proximity (d(Rh/Rh)) on the surface, the internal radius (r(int)) of the Dab skeleton in Rh-Dab dendrimers was (i) considered equal to that of the Dab dendrimers (model A) or (ii) evaluated assuming that the additional solvent molecules derived from the attachment of Rh to Dab dendrimers were incorporated into the elongated dendritic skeleton (model B). It was found that dRh/Rh decreases from 17.2-19.8 angstrom (Rh-Dab4) to about 14.0 angstrom (Rh-Dab64) with the increase in dendrimer generation
Immobilization of [Rh(NBD)(C5H4CO2(CH2)2OH)] on polystyrene resins
No full textWe have recently reported that the reaction between the novel [Rh[C5H4CO2(CH2)2O2C-Im](NBD)] (1), obtained from [Rh[C5H4CO2(CH2)2OH](NBD)] (2) and carbonyldiimidazole, and polypropylenimine dendrimers DAB-dendr-(NH2)n (n = 4, 8, 16, 32, 64) leads to the quantitative formation of the new, completely functionalised, organometallic macromolecules of the type DAB-dendr-[NH(O)COCH2CH2OC(O)C5H4Rh(NBD)]n containing up to 64 peripheral alkoxycarbonylcyclopentadienyl complexes of rhodium(I).
Here we report on the extension of this procedure to the direct and quantitative immobilization of [Rh[C5H4CO2(CH2)2O2C-Im](NBD)] (1) on the -NH2 functionalized (aminomethyl)polystyrene resin. The development of an alternative synthetic method toward the grafting of [Rh[C5H4CO2(CH)2OH](NBD)] (2) on an imidazolide carbamates functionalized Wang resin will be also presented and discussed. The new materials have been characterized by means of spectroscopic (IR Microscopy) and analytical Inductively Coupled Plasma – Atomic Emission Spectrometry (ICP-AES) measurements.Studies on the catalytic activity of these supported systems (dendrimers and resins) in the hydroformylation and hydrogenation of 1-hexene and styrene are currently under investigation
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