28 results on '"De Santi, F."'
Search Results
2. Diffusion of gravity waves by random space inhomogeneities in pancake-ice fields. Theory and validation with wave buoys and synthetic aperture radar
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Olla P., De Carolis G., and De Santi F.
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Ghiaccio marino ,Onde di gravita` ,Telerilevamento ,Physics::Atmospheric and Oceanic Physics - Abstract
We study the diffusion of ocean waves by ice bodies much smaller than a wavelength, such as pancakes and small ice floes. We argue that inhomogeneities in the ice cover at scales comparable to that of the wavelength significantly increase diffusion, producing a contribution to wave attenuation comparable to what is observed in the field and usually explained by viscous effects. The resulting attenuation spectrum is characterized by a peak at the scale of the inhomogeneities in the ice cover, which could explain the rollover of the attenuation profile at small wavelengths observed in field experiments. The proposed attenuation mechanism leads to the same behaviors that would be produced by a viscous wave model with effective viscosity linearly dependent on the ice thickness. This may explain recent findings that viscous wave models require a thickness-dependent viscosity to fit experimental attenuation data. Experimental validation is carried out using wave buoy attenuation data and synthetic aperture radar image analysis.
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- 2021
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3. On the Analysis of SAR Derived Wind and Sea Surface Currents
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Zamparelli, V., primary, De Santi, F., additional, De Carolis, G., additional, and Fornaro, G., additional
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- 2020
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4. The Operation Of Thyrotomy, With A Short Account Of The Cases In Which It Has Been Performed At St. Bartholomew's Hospital During The Last Fifteen Years
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de Santi, F.
- Published
- 1895
5. Type 2 diabetes is associated with an increased prevalence of respiratory symptoms as compared to the general population
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De Santi, F., primary, Zoppini, G., additional, Locatelli, F., additional, Finocchio, E., additional, Cappa, V., additional, Dauriz, M., additional, and Verlato, G., additional
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- 2017
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6. Integrazione di metodologie di rilievo per la creazione di modelli tridimensionali necessari per l’analisi dello stato di danno sismico
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Menin, Andrea, Bragagnolo, Denis, and DE SANTI, F.
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- 2010
7. Cento anni dalla nascita di Umberto Mastroianni.Umberto Matroianni nell’architettura: un fruttuoso rapporto tra scultura e spazio del costruito
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Villata, A., DE SANTI, F., Mignone, A., Mistrangelo, A., Barbero, G., Sanfo, V., Michelone, G., BRUNOZZI TINI BRUNOTTI, F., Giacomini, MARIA VITTORIA, and Scaroina, F.
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Umberto Mastroianni - Published
- 2010
8. Energy and water vapor transport across a simplified cloud-clear air interface
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Gallana, L, primary, Di Savino, S, additional, De Santi, F, additional, Iovieno, M, additional, and Tordella, D, additional
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- 2014
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9. Microwave Thermal Ablation of Thyroid Nodules with the MONTREAL Technique: Preliminary Clinical Results.
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Mazzucco M, Mattarello MJ, De Santi F, Peron C, Mazzucco A, Terni T, and Tosoratti N
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Ultrasound-guided percutaneous Microwave Thermoablation (MWA) is an increasingly popular minimally invasive therapy for the treatment of benign thyroid nodules due to its remarkable heating velocity and resilience to heat sinking. We present a cohort of 26 patients (17 F, 9M, mean age 56.2yy) with 20 goiters (mean volume 34.9cc, min 6.5cc-max 84cc) and 6 autonomously functioning nodules (AFTNs, mean volume 11.6cc, min 3.5cc-max 24cc) treated with MWA, using the moving shot technique and a novel energy delivery algorithm (MONTREAL), based on intra-operative real-time reflectivity measurements: each moving shot was automatically terminated when reflectivity was observed to ramp up. 17G or 18G internally cooled 2.45 GHz applicators were used (AMICA-PROBE, HS HOSPITAL SERVICE SpA), operated at 15-30W. On average, each treatment deposited 9.9±5.5kJ during 696±325s, through 26.7±14.4 moving shots: the mean moving shot duration was 28.1±9.0s, yielding a mean ablation time per unit nodule volume of 34.3±19.1s/cc. No mild nor severe complications were recorded. Post-MWA ultrasound follow-up showed a mean volume reduction ratio of 59.1±10.2% [min 44% - max 80%] at 3 months and of 70.1±8.5% [min 53% - max 91%] at 6 months, with slightly better outcomes in the AFTNs sub-group (volume reduction of 65.3±10.2%/76.0±4.0% at 3/6 months and, in all cases, normal TSH values at 3 months upon pharmacological therapy suspension). MWA treatments of benign nodules with the MONTREAL technique appeared to be safe, fast, and effective. Further research is warranted to confirm these preliminary results., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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- 2024
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10. Thermoablation Using Radiofrequency and Microwaves of Autonomous Thyroid Nodules: Our Experience
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Mattarello MJ, De Santi F, Mingardi R, Peron C, and Mazzucco M
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Introduction: Significant results have been achieved using ultrasound-guided and ultrasound-assisted ablative techniques, such as Laser Thermal Ablation (LTA), Radiofrequency Ablation (RFA), High-Intensity Focused Ultrasound (HIFU), and Microwave Ablation (MWA). These techniques are ideally suited for the treatment of normally functioning benign thyroid nodes with local compressive symptoms or aesthetic problems. These treatments have been applied to hyperfunctioning “hot” nodes. LTA and RFA are the most commonly used. From January 2021 to July 2023 at our Center, a total of 160 patients with benign thyroid nodules were treated, of which 35 had autonomous nodules [1-4]. Our analysis focused on evaluating the locoregional treatment of the latter. Based on the volume and ultrasound-vascular characteristics, patients were selected for thermoablative treatment with either RFA or MWA (Amica Gen HS - Hospital Service) starting in July 2022., Results: No complications were documented. However, one patient was referred for surgery and 1 patient was re-treated with MWA., Conclusion: In the light of personal experience ultrasound-guided thermal ablation treatment with RFA in patients with a single pretoxic or toxic thyroid nodule with or without associated compressive or aesthetic symptoms has proven to be very effective and satisfactory. The treatment must be preceded by adequate information regarding the advantages and disadvantages of the various procedures and the methods of the treatment session. MWA proved to be more effective than RFA with no functional recovery of the treated nodules even if they were relatively larger in size. We obtained the suspension of thyrostatic therapy with normalization of the TSH level in the third month after treatment.
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- 2024
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11. Venlafaxine increases aromatization, reduces apical V-ATPase in clear cells and induces increased number of mast cells and smooth muscle cells death in rat cauda epididymis.
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da Silva AAS, de Santi F, Hinton BT, Cerri PS, and Sasso-Cerri E
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- Rats, Male, Animals, Venlafaxine Hydrochloride pharmacology, Venlafaxine Hydrochloride metabolism, Aromatase, Connexin 43 metabolism, Mast Cells metabolism, Epidermal Growth Factor metabolism, Estrogens pharmacology, Myocytes, Smooth Muscle metabolism, Epididymis, Vacuolar Proton-Translocating ATPases metabolism, Vacuolar Proton-Translocating ATPases pharmacology
- Abstract
Depressive disorders (DD) have affected millions of people worldwide. Venlafaxine, antidepressant of the class of serotonin and norepinephrine reuptake inhibitors, has been prescribed for the treatment of DD. In rat testes, venlafaxine induces testosterone (T) aromatization and increases estrogen levels. Aromatase is a key enzyme for the formation of estrogen in the epididymis, an essential organ for male fertility. We investigated the impact of serotonergic/noradrenergic venlafaxine effect on the epididymal cauda region, focusing on aromatase, V-ATPase and EGF epithelial immunoexpression, smooth muscle (SM) integrity and mast cells number (MCN). Male rats were distributed into control (CG; n = 10) and venlafaxine (VFG, n = 10) groups. VFG received 30 mg/kg b.w. of venlafaxine for 35 days. The epididymal cauda was processed for light and transmission electron microscopy (TEM). The expression of connexin 43 (Cx43) and estrogen alpha (Esr1), adrenergic (Adra1a) and serotonergic (Htr1b) receptors were analyzed. Clear cells (CCs) area, SM thickness, viable spermatozoa (VS) and MCN were evaluated. Apoptosis was confirmed by TUNEL and TEM. The following immunoreactions were performed: T, aromatase, T/aromatase co-localization, V-ATPase, EGF, Cx43 and PCNA. The increased Adra1a and reduced Htr1b expressions confirmed the noradrenergic and serotonergic venlafaxine effects, respectively, corroborating the increased MCN, apoptosis and atrophy of SM. In VFG, the epithelial EGF increased, explaining Cx43 overexpression and basal cells mitotic activity. T aromatization and Esr1 downregulation indicate high estrogen levels, explaining CCs hypertrophy and changes in the V-ATPase localization, corroborating VS reduction. Thus, in addition to serotonergic/noradrenergic effects, T/estrogen imbalance, induced by venlafaxine, impairs epididymal structure and function., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (Copyright © 2022. Published by Elsevier Inc.)
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- 2023
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12. Venlafaxine-induced adrenergic signaling stimulates Leydig cells steroidogenesis via Nur77 overexpression: A possible role of EGF.
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de Santi F, Beltrame FL, Rodrigues BM, Scaramele NF, Lopes FL, Cerri PS, and Sasso-Cerri E
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- Animals, Male, Rats, Epidermal Growth Factor metabolism, Gene Expression Regulation drug effects, Leydig Cells metabolism, Nuclear Receptor Subfamily 4, Group A, Member 1 biosynthesis, Venlafaxine Hydrochloride pharmacology
- Abstract
Venlafaxine, a norepinephrine and serotonin reuptake inhibitor, impairs rat sperm parameters, spermatogenesis and causes high intratesticular estrogen and testosterone levels, indicating that Leydig cells (LCs) may be a venlafaxine target. We evaluated the effect of venlafaxine treatment on rat LCs, focusing on adrenergic signaling, EGF immunoexpression and steroidogenesis. Germ cells mitotic/meiotic activity and UCHL1 levels were also evaluated in the seminiferous epithelium. Eighteen adult male rats received 30 mg/kg of venlafaxine (n = 9) or distilled water (n = 9). The seminiferous tubules, epithelium and LCs nuclear areas were measured, and the immunoexpression of Ki-67, UCHL1, StAR, EGF, c-Kit and 17β-HSD was evaluated. UCHL1, StAR and EGF protein levels and Adra1a, Nur77 and Ndrg2 expression were analyzed. Malondialdehyde (MDA) and nitrite testicular levels, and serum estrogen and testosterone levels were measured. Venlafaxine induced LCs hypertrophy and Ndrg2 upregulation in parallel to increased number of Ki-67, c-Kit- and 17β-HSD-positive interstitial cells, indicating that this antidepressant stimulates LCs lineage proliferation and differentiation. Upregulation of Adra1a and Nur77 could explain the high levels of StAR and testosterone levels, as well as aromatization. Enhanced EGF immunoexpression in LCs suggests that this growth fact is involved in adrenergically-induced steroidogenesis, likely via upregulation of Nur77. Slight tubular atrophy and weak Ki-67 immunoexpression in germ cells, in association with high UCHL1 levels, indicate that spermatogenesis is likely impaired by this enzyme under supraphysiological estrogen levels. These data corroborate the unchanged MDA and nitrite levels. Therefore, venlafaxine stimulates LCs steroidogenesis via adrenergic signaling, and EGF may be involved in this process., (Copyright © 2021 Elsevier Inc. All rights reserved.)
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- 2022
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13. Cimetidine-induced androgenic failure causes cell death and changes in actin, EGF and V-ATPase immunoexpression in rat submandibular glands.
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Manzato MC, de Santi F, da Silva AAS, Beltrame FL, Cerri PS, and Sasso-Cerri E
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- Actins metabolism, Animals, Cimetidine pharmacology, Cytochrome P-450 CYP1A2 Inhibitors pharmacology, Drug Evaluation, Preclinical, Epidermal Growth Factor metabolism, Male, Rats, Sprague-Dawley, Submandibular Gland metabolism, Testosterone metabolism, Vacuolar Proton-Translocating ATPases metabolism, Rats, Cimetidine therapeutic use, Cytochrome P-450 CYP1A2 Inhibitors therapeutic use, Receptors, Androgen metabolism, Submandibular Gland drug effects
- Abstract
Submandibular gland (SMG) is responsive to androgens via androgen receptor (AR). We verified whether cimetidine induces androgenic dysfunction in SMG, and evaluated the structural integrity, cell death and immunoexpression of actin, EGF and V-ATPase in androgen-deficient SMG. Male rats received cimetidine (CMTG) and control animals (CG) received saline. Granular convoluted tubules (GCTs) diameter and number of acinar cell nuclei were evaluated. TUNEL and immunofluorescence reactions for detection of AR, testosterone, actin, EGF and V-ATPase were quantitatively analysed. In CG, testosterone immunolabelling was detected in acinar and ductal cells cytoplasm. AR-immunolabelled nuclei were observed in acinar cells whereas ductal cells showed AR-immunostained cytoplasm, indicating a non-genomic AR action. In CMTG, the weak testosterone and AR immunoexpression confirmed cimetidine-induced androgenic failure. A high cell death index was correlated with decreased number of acinar cells, GCTs diameter and EGF immunoexpression under androgenic dysfunction. Actin immunofluorescence decreased in the SMG cells, but an increased and diffuse cytoplasmic V-ATPase immunolabelling was observed in striated ducts, suggesting a disruption in the actin-dependent V-ATPase recycling due to androgenic failure. Our findings reinforce the androgenic role in the maintenance of SMG histophysiology, and point to a potential clinical use of cimetidine against androgen-dependent glandular tumour cells., (© 2021 Anatomical Society.)
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- 2021
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14. Hot moments and hotspots of cyanobacteria hyperblooms in the Curonian Lagoon (SE Baltic Sea) revealed via remote sensing-based retrospective analysis.
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Vaičiūtė D, Bučas M, Bresciani M, Dabulevičienė T, Gintauskas J, Mėžinė J, Tiškus E, Umgiesser G, Morkūnas J, De Santi F, and Bartoli M
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- Baltic States, Environmental Monitoring, Eutrophication, Lithuania, Retrospective Studies, Russia, Cyanobacteria, Remote Sensing Technology
- Abstract
A temporally and spatially detailed historical (1985-2018) analysis of cyanobacteria blooms was performed in the Curonian Lagoon (Lithuania, Russia), the largest coastal lagoon in the Baltic Sea. Satellite data allowed the mapping of cyanobacteria surface accumulations, so-called "scums", and of chlorophyll-a concentration. The 34-year time series shows a tendency towards later occurrence (October-November) of the cyanobacteria scum presence, whereas the period of its onset (June-July) remains relatively constant. The periods when scums are present, "hot moments", have been consistently increasing in duration since 2008. The differences in the starting, ending and annual duration of cyanobacteria blooms have been significantly altered by hydro-meteorological conditions (river discharge, water temperature, and wind conditions) and their year-round patterns. The most important environmental factors that determined the temporal changes of the scum presence and area were the standing stock of cyanobacteria and the ambient wind conditions. The "hotspots", the areas where the blooms most likely occur, were distributed in the south-southwestern and central parts of the lagoon. The least affected areas were the northern part, which is connected to the coastal waters of the Baltic Sea, and the Nemunas River delta region. The longstanding, well-established spatial patterns of cyanobacteria blooms were linked to hydrodynamic features, namely water renewal time and current patterns, and to potential nutrient sources that included muddy sediments and the locations of colonies of piscivorous birds. Our findings confirmed that the annual and seasonal variations of cyanobacteria blooms and their regulation are a complex issue due to interactions between multiple factors over spatially and temporally broad scales. Despite great progress in the prevention and control of eutrophication and cyanobacteria blooms, the lagoon is still considered to be in a poor ecological status. This work provides a new and missing understanding on the spatial and temporal extent of cyanobacteria blooms and the factors that govern them. Such an understanding can help in planning management strategies, forecasting the magnitude and severity of blooms under changing nutrient loads and potential climate scenarios., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)
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- 2021
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15. SAR image wave spectra to retrieve the thickness of grease-pancake sea ice using viscous wave propagation models.
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De Carolis G, Olla P, and De Santi F
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Young sea ice composed of grease and pancake ice (GPI), as well as thin floes, considered to be the most common form of sea ice fringing Antarctica, is now becoming the "new normal" also in the Arctic. A study of the rheological properties of GPI is carried out by comparing the predictions of two viscous wave propagation models: the Keller model and the close-packing (CP) model, with the observed wave attenuation obtained by SAR image techniques. In order to fit observations, it is shown that describing GPI as a viscous medium requires the adoption of an ice viscosity which increases with the ice thickness. The consequences regarding the possibility of ice thickness retrieval from remote sensing data of wave attenuation are discussed. We provide examples of GPI thickness retrievals from a Sentinel-1 C band SAR image taken in the Beaufort Sea on 1 November 2015, and three CosmoSkyMed X band SAR images taken in the Weddell Sea on March 2019. The estimated GPI thicknesses are consistent with concurrent SMOS measurements and available local samplings.
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- 2021
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16. Venlafaxine-induced damage to seminiferous epithelium, spermiation, and sperm parameters in rats: A correlation with high estrogen levels.
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de Santi F, Beltrame FL, Rodrigues BM, Junior MJVP, Scaramele NF, Lopes FL, Cerri PS, and Sasso-Cerri E
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- Animals, Aromatase metabolism, Connexin 43 metabolism, Drug Evaluation, Preclinical, Male, Rats, Sprague-Dawley, Seminiferous Epithelium enzymology, Sperm Motility drug effects, Testosterone metabolism, Rats, Estrogens metabolism, Seminiferous Epithelium drug effects, Serotonin and Noradrenaline Reuptake Inhibitors adverse effects, Spermatozoa drug effects, Venlafaxine Hydrochloride adverse effects
- Abstract
Background: Venlafaxine (selective serotonin and norepinephrine reuptake inhibitor) use has increased worldwide. However, the impact of venlafaxine on testes and sperm parameters has not been investigated., Objectives: We evaluated venlafaxine impact on testicular and sperm parameters and verified whether the changes are reversible., Methods: Animals from venlafaxine-35 days and venlafaxine-65 days groups received 30 mg/kg of venlafaxine for 35 days. Control-35 days and control-65 days received distilled water. In control-65 days and venlafaxine-65 days, the treatment was interrupted for 30 days. Sperm concentration, morphology, motility, and mitochondrial activity were analyzed. Number of step 19 spermatids (NLS), frequency of tubules with spermiation failure, Sertoli cells number, and TUNEL-positive germ cells were quantified. Testicular aromatase, connexin 43 (Cx43) immunoexpression, Cx43 protein levels, and Cx43 expression were evaluated. Either intratesticular testosterone or estrogen levels were measured., Results: Venlafaxine impaired sperm morphology, reduced sperm concentration, mitochondrial activity, and sperm motility. The frequency of tubules with spermiation failure and NLS increased in parallel to increased Cx43 immunoexpression; mRNA and protein levels; and aromatase, testosterone, and estrogen levels. An increase in germ cell death and decreased Sertoli cells number were observed. In venlafaxine-65 days, except for sperm motility, mitochondrial activity, Sertoli cells number, and germ cell death, all other parameters were partially or totally recovered., Conclusion: Venlafaxine increases testosterone aromatization and Cx43. This drug, via high estrogen levels, disturbs Sertoli cells, induces germ cell death, and impairs spermiation and sperm parameters. The restoration of spermiation associated with the decreased Cx43 and hormonal levels in venlafaxine-65 days reinforces that high estrogen levels are related to venlafaxine-induced changes. The presence of damaged Sertoli cells, germ cell death, and low sperm motility in venlafaxine-65 days indicates that interruption of treatment for 30 days was insufficient for testicular recovery and points to a long-term estrogen impact on the seminiferous epithelium., (© 2020 American Society of Andrology and European Academy of Andrology.)
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- 2021
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17. Muscular atrophy, impaired epithelial autophagy and UCHL1 increase in androgen-deficient cauda epididymis.
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de Santi F, Lunardi ID, Beltrame FL, Cerri PS, and Sasso-Cerri E
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- Animals, Apoptosis drug effects, Connexin 43 genetics, Connexin 43 metabolism, Epididymis metabolism, Epithelial Cells drug effects, Epithelial Cells metabolism, Male, Membrane Glycoproteins genetics, Membrane Glycoproteins metabolism, Rats, Rats, Sprague-Dawley, Seminal Vesicles drug effects, Seminal Vesicles metabolism, Autophagy drug effects, Cimetidine pharmacology, Cytochrome P-450 CYP1A2 Inhibitors pharmacology, Epididymis drug effects, Muscular Atrophy metabolism, Ubiquitin Thiolesterase metabolism
- Abstract
In epididymis, cimetidine induces androgenic failure due to reduced sex hormone-binding globulin stromal levels and blockade of androgen receptor (AR) nuclear import. UCHL1, a hydrolase of ubiquitin-proteasome system (UPS), seems to play a role in autophagy and apoptotic pathway. However, the role of UPS and autophagy in epididymis has not been clarified. We evaluated UCHL1 and autophagy in epididymal cauda epithelium under androgenic deficiency induced by cimetidine, focusing on the interplay among these processes and apoptosis. The integrity of epididymal muscular layer was also evaluated. Male rats received cimetidine (CMTG) or saline (CG). Seminal vesicles were weighed, the expression of androgen-responsive genes Crisp1 and connexin 43 (Cx43) in cauda epididymis was evaluated, and cauda fragments were processed for light and transmission electron microscopy. The epithelium height and muscular thickness were measured. TUNEL, immunohistochemistry for caspase-3 and Cx43, and immunofluorescence for AR, Bcl-2, UCHL1, MAP LC3A, and p62/SQSTM1 (autophagic markers) were performed. Bcl-2, UCHL1, and Cx43 were detected by Western blot. In CMTG, the reduction in seminal vesicles weight accompanied by downregulation of Crisp1 and Cx43 confirmed epididymal androgenic failure. These results were associated with muscular atrophy, apoptosis and weak Cx43 and AR immunoexpression, supporting the androgenic dependence of muscular integrity. The high UCHL1 levels and reduction in Bcl-2 reinforce UCHL1 role in epithelial cells death. The intense immunoexpression of LC3A and p62/SQSTM1 indicates autophagic disturb, which in association with high UCHL1 levels, points to a role of UPS and autophagy in the regulation of epididymal epithelial cells viability under androgenic control.
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- 2020
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18. Vitamin B 12 Prevents Cimetidine-Induced Androgenic Failure and Damage to Sperm Quality in Rats.
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Beltrame FL, de Santi F, Vendramini V, Cabral REL, Miraglia SM, Cerri PS, and Sasso-Cerri E
- Abstract
Cimetidine, used as an anti-ulcer and adjuvant treatment in cancer therapy, causes disorders in the male reproductive tract, including steroidogenesis. However, its effect on sperm quality and male fertility has been poorly addressed. Since vitamin B
12 has demonstrated to recover spermatogonia number and sperm concentration in cimetidine-treated rats, we evaluated the impact of cimetidine on sperm quality and fertility potential and whether vitamin B12 is able to prevent the harmful effect of this drug on steroidogenesis and sperm parameters. Adult male rats were treated for 52 consecutive days as follows: cimetidine group (100 mg/kg of cimetidine), cimetidine/vitamin B12 group (100 mg/kg of cimetidine + 3 μg vitamin B12 ), vitamin B12 group (3 μg vitamin B12 ) and control group (saline). Serum testosterone levels and immunofluorescence associated to western blot for detection of 17β-HSD6 were performed. Sperm morphology and motility, mitochondrial activity, acrosome integrity, DNA integrity by Comet assay, lipid peroxidation as well as fertility potential were analyzed in all groups. Apoptotic spermatids were also evaluated by caspase-3 immunohistochemistry. In the cimetidine-treated animals, reduced serum testosterone levels, weak 17β-HSD6 levels and impaired spermiogenesis were observed. Low sperm motility and mitochondrial activity were associated with high percentage of sperm tail abnormalities, and the percentage of spermatozoa with damaged acrosome and DNA fragmentation increased. MDA levels were normal in all groups, indicating that the cimetidine-induced changes are associated to androgenic failure. In conclusion, despite the fertility potential of rats was unaffected by the treatment, the sperm quality was significantly impaired. Therefore, considering a possible sperm-mediated transgenerational inheritance, the long term offspring health needs to be investigated. The administration of vitamin B12 to male rats prevents the androgenic failure and counteracts the damage inflicted by cimetidine upon sperm quality, indicating that this vitamin may be used as a therapeutic agent to maintain the androgenic status and the sperm quality in patients exposed to androgen disrupters.- Published
- 2019
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19. Fluoxetine-induced androgenic failure impairs the seminiferous tubules integrity and increases ubiquitin carboxyl-terminal hydrolase L1 (UCHL1): Possible androgenic control of UCHL1 in germ cell death?
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Câmara ML, Almeida TB, de Santi F, Rodrigues BM, Cerri PS, Beltrame FL, and Sasso-Cerri E
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- Animals, Germ Cells metabolism, Hydrolases drug effects, Hydrolases metabolism, In Situ Nick-End Labeling methods, Leydig Cells drug effects, Leydig Cells metabolism, Male, Rats, Seminiferous Tubules metabolism, Sertoli Cells drug effects, Sertoli Cells metabolism, Spermatogenesis drug effects, Testis drug effects, Testis metabolism, Ubiquitins metabolism, Androgens metabolism, Cell Death drug effects, Fluoxetine pharmacology, Germ Cells drug effects, Seminiferous Tubules drug effects, Ubiquitin Thiolesterase metabolism
- Abstract
The selective serotonin reuptake inhibitor fluoxetine has been used for the treatment of depression. Although sexual disorders have been reported in male patients, few studies have demonstrated the fluoxetine effect on the reproductive histophysiology, and the target of this antidepressant in testes is unknown. We evaluated the impact of short-term treatment with fluoxetine on the adult rat testes, focusing on steroidogenesis by Leydig cells (LC) and androgen-dependent testicular parameters, including Sertoli cells (SC) and peritubular myoid cells (PMC). Since UCHL1 (ubiquitincarboxyl-terminal hydrolase L1) seems to control spermatogenesis, the immunoexpression of this hydrolase was also analyzed. Adult male rats received 20 mg/kg BW of fluoxetine (FG) or saline (CG) for eleven days. In historesin-embedded testis sections, the seminiferous tubule (ST) and epithelial (Ep) areas, and the LC nuclear diameter (LCnu) were measured. The number of abnormal ST, androgen-dependent ST, SC and PMC was quantified. Testicular β-tubulin levels and peritubular actin immunofluorescence were evaluated. Serum testosterone levels (STL) and steroidogenesis by 17β-HSD6 immunofluorescence were analyzed, and either UCHL1-immunolabeled or TUNEL-positive germ cells were quantified. In FG, abnormal ST frequency increased whereas ST and Ep areas, androgen-dependent ST number, LCnu, 17β-HSD6 activity and STL reduced significantly. TUNEL-positive PMC and SC was related to decreased number of these cells and reduction in peritubular actin and β-tubulin levels. In FG, uncommon UCHL1-immunoexpression was found in spermatocytes and spermatids, and the number of UCHL1-immunolabeled and TUNEL-positive germ cells increased in this group. These findings indicate that LC may be a fluoxetine target in testes, impairing PMC-SC integrity and disturbing spermatogenesis. The increase of UCHL1 in the damaged tubules associated with high incidence of cell death confirms that this hydrolase regulates germ cell death and may be controlled by androgens. The fertility in association with the androgenic status of patients treated with fluoxetine should be carefully evaluated., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)
- Published
- 2019
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20. Reduced levels of stromal sex hormone-binding globulin and androgen receptor dysfunction in the sperm storage region of the rat epididymis.
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de Santi F, Beltrame FL, Hinton BT, Cerri PS, and Sasso-Cerri E
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- Animals, Cells, Cultured, Epithelial Cells pathology, Male, Rats, Spermatozoa cytology, Stromal Cells pathology, Testosterone metabolism, Epididymis metabolism, Epididymis pathology, Epithelial Cells metabolism, Receptors, Androgen metabolism, Sex Hormone-Binding Globulin metabolism, Spermatozoa physiology, Stromal Cells metabolism
- Abstract
The cauda epididymidis is the major sperm storage region whose androgenic supply, essential for the sperm viability, is provided by the vasculature and is dependent upon testosterone diffusion through the stromal tissue to reach the epithelial cells. We have focused our efforts on examining the regulation of this important epididymal region by evaluating the impact of the androgen disrupter cimetidine on the epithelial-stromal androgenic microenvironment. Male rats received 100 mg/kg cimetidine (CMTG) or saline (CG) for 50 days, serum testosterone levels were measured and the epididymal cauda region was processed for light and transmission electron microscopy. In the proximal cauda region, the duct diameter was measured and birefringent collagen in the stroma was quantified. TUNEL-labeled epithelial cells were quantified, and androgen receptor (AR), karyopherin alpha (KPNA) and sex hormone-binding globulin (SHBG) levels were analyzed by immunofluorescence and Western blot. CMTG showed reduced duct diameter and high number of apoptotic epithelial cells. In the epithelium, the total AR concentration and the KPNA immunoreactivity were reduced, and a weak/absent AR nuclear immunofluorescence was observed in contrast to the enhanced AR immunolabeling observed in the cytoplasm of the epithelial cells. A significant reduction of collagen and SHBG levels in the stroma was also observed. Cimetidine treatment impairs AR nuclear import in the epithelium, causing androgenic dysfunction and subsequent epithelial cell apoptosis and duct atrophy. The connective tissue atrophy and reduction of SHBG stromal levels associated with epithelial androgenic dysfunction indicate a possible role of stromal SHBG in the androgenic supply of the sperm storage region of the epididymis., (© 2018 Society for Reproduction and Fertility.)
- Published
- 2018
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21. Long-Acting GLP-1 Receptor Agonist Exenatide Influence on the Autonomic Cardiac Sympatho-Vagal Balance.
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Cacciatori V, Zoppini G, Bellavere F, Rigolon R, Thomaseth K, Pichiri I, Trombetta M, Dauriz M, De Santi F, Targher G, Santi L, and Bonora E
- Abstract
Long-acting glucagon-like peptide 1 receptor agonists are increasingly used to treat type 2 diabetes. An increase of heart rate (HR) has been observed with their use. To elucidate the role of the cardiac sympatho-vagal balance as a possible mediator of the reported increase in HR, we performed power spectral analysis of HR variability (HRV) in patients receiving exenatide extended-release (ER). Twenty-eight ambulatory patients with type 2 diabetes underwent evaluation at initiation of exenatide-ER and thereafter at 3 and at 6 months. To obtain spectral analyses of HRV, a computerized acquisition of 10 minutes of RR electrocardiogram intervals (mean values of ~700 RR intervals) were recorded both in lying and in standing positions. All patients showed a substantial increase of HR both in lying and in standing positions. Systolic blood pressure, body weight, and glycated hemoglobin A1c significantly decreased both at 3 and 6 months compared with basal levels. The low-frequency/high-frequency ratio varied from 3.05 ± 0.4 to 1.64 ± 0.2 ( P < 0.001) after 3 months and to 1.57 ± 0.3 ( P < 0.001) after 6 months in a lying position and from 4.56 ± 0.8 to 2.24 ± 0.3 ( P < 0.001) after 3 months and to 2.38 ± 0.4 ( P < 0.001) after 6 months in a standing position compared with basal values, respectively. HR variations, induced by exenatide-ER treatment, do not appear to be related to sympathetic autonomic tone. Of note, we observed a relative increase of vagal influence on the heart.
- Published
- 2017
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22. The antineoplastic busulphan impairs peritubular and Leydig cells, and vitamin B 12 stimulates spermatogonia proliferation and prevents busulphan-induced germ cell death.
- Author
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Sasso-Cerri E, Oliveira B, de Santi F, Beltrame FL, Caneguim BH, and Cerri PS
- Subjects
- Animals, Cell Death drug effects, Cell Proliferation drug effects, In Situ Nick-End Labeling, Leydig Cells drug effects, Male, Rats, Rats, Sprague-Dawley, Seminiferous Tubules drug effects, Spermatogenesis drug effects, Testis drug effects, Testosterone blood, Vitamin B Complex pharmacology, Antineoplastic Agents, Alkylating toxicity, Busulfan toxicity, Spermatogonia drug effects, Vitamin B 12 pharmacology
- Abstract
Busulphan (Bu), an alkylating agent used for bone marrow and spermatogonial stem cell transplantation (SSCT), impairs Sertoli (SC) cells, which are necessary for the spermatogonial stem cell (SSC) homing during transplantation. As Leydig (LC) and peritubular myoid (PMC) cells are essential for SC support and maintenance of spermatogonial niche, we evaluated the impact of Bu on the LC and PMC structural integrity. Vitamin B
12 (B12 ) has demonstrated beneficial effects against drug-induced testicular changes; thus, we also examined whether this vitamin is able to stimulate spermatogonia mitotic activity and prevent Bu-induced germ cell death. Rats received 10mg/kg of Bu in the 1st and 4th days, and daily B12 supplementation during Bu treatment and for 6days after the last injection of Bu (Bu-6d), totaling 10days of treatment. Other animals received the same treatment as Bu-6d, and B12 supplementation (Bu+7dB12 ) or saline (Bu+7dS) for 7 more days, totaling 17days of treatment. Serum testosterone levels were measured. In the historesin-embedded testis sections, the seminiferous tubule and epithelial areas were measured, and the number of spermatogonia and PMC was quantified. Actin and 17β-HSD6 immunofluorescence was detected, and the number of TUNEL-positive LC and germ cells was computed. In Bu-6d, PMC number reduced, and a weak actin immunoexpression and death in these cells was observed. The testosterone levels reduced, and the interstitial tissue showed a weak 17β-HSD6 immunoexpression and increased number of TUNEL-positive LC. In Bu+7dB12 , the number of spermatogonia was higher than in Bu-6d and Bu+7dS, and the number of TUNEL-positive germ cells was significantly lower than in Bu+7dS. Bu exerts a harmful impact on PMC and LC, reducing the testosterone levels. Vitamin B12 prevents significantly Bu-induced germ cell death and stimulates spermatogonia proliferation, being a useful strategy for the enrichment of SSC in vitro and an adjuvant therapy for spermatogenesis recovery in oncologic patients., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)- Published
- 2017
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23. Limit regimes of ice formation in turbulent supercooled water.
- Author
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De Santi F and Olla P
- Abstract
A study of ice formation in stationary turbulent conditions is carried out in various limit regimes of crystal growth, supercooling, and ice entrainment at the water surface. Analytical expressions for the temperature, salinity, and ice concentration mean profiles are provided, and the role of fluctuations in ice production is numerically quantified. Lower bounds on the ratio of sensible heat flux to latent heat flux to the atmosphere are derived and their dependence on key parameters such as salt rejection in freezing and ice entrainment in the water column is elucidated.
- Published
- 2017
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24. Seminiferous epithelium damage after short period of busulphan treatment in adult rats and vitamin B 12 efficacy in the recovery of spermatogonial germ cells.
- Author
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Vasiliausha SR, Beltrame FL, de Santi F, Cerri PS, Caneguim BH, and Sasso-Cerri E
- Subjects
- Adult Germline Stem Cells pathology, Animals, Body Weight drug effects, Leukopenia chemically induced, Leukopenia prevention & control, Male, Organ Size drug effects, Rats, Sprague-Dawley, Seminiferous Epithelium pathology, Sertoli Cells drug effects, Sertoli Cells pathology, Spermatogenesis drug effects, Testis drug effects, Testis metabolism, Testis pathology, Thrombocytopenia chemically induced, Thrombocytopenia prevention & control, Vimentin metabolism, Adult Germline Stem Cells drug effects, Antineoplastic Agents, Alkylating toxicity, Busulfan toxicity, Seminiferous Epithelium drug effects, Vitamin B 12 pharmacology
- Abstract
Several different strategies have been adopted in attempt to recover from chemotherapy-damaged spermatogenesis that is often seen in oncologic patients. In this study, we have evaluated the impact of short period of exposure to busulphan on the haemogram and seminiferous epithelium of adult rats, focusing on spermatogonial depletion and Sertoli cell (SC) integrity. We then examined whether vitamin B
12 supplementation improves the haematological parameters and spermatogonia number. The animals received 10 mg/kg of busulphan (BuG) or busulfan+vitamin B12 (Bu/B12 G) on the first and fourth days of treatment. In H.E.-stained testicular sections, the areas of the seminiferous tubule (ST) and seminiferous epithelium were measured. The number of spermatogonia in H.E-stained and PCNA-immunolabelled testicular sections was quantified. The frequency of tubules with abnormal SC nuclei or TUNEL-positive SC was evaluated. Vimentin immunofluorescence in ST was also evaluated. In BuG and Bu/B12 G, the animals showed leukopenia and thrombocytopenia, but the body weight reduced only in BuG. The areas of ST and seminiferous epithelium decreased in Bu/B12 G and BuG. In BuG, the number of H.E.-stained and PCNA-immunolabelled spermatogonia reduced significantly. The frequency of tubules containing abnormal SC nuclei and TUNEL-positive SC increased and the vimentin immunoexpression pattern changed. In Bu/B12 G, the number of H.E.-stained or PCNA-immunolabelled spermatogonia increased fourfold in comparison with BuG. The structural changes in ST after 6 days of busulphan exposure may be associated with the potential effect of this anti-neoplastic agent on SC. The increased number of spermatogonia in the busulphan-treated animals receiving vitamin B12 indicates that this vitamin can be an adjuvant therapy to improve the fertility in male cancer patients., (© 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.)- Published
- 2016
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25. Dispersive-to-nondispersive transition and phase-velocity transient for linear waves in plane wake and channel flows.
- Author
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De Santi F, Fraternale F, and Tordella D
- Abstract
In this study we analyze the phase and group velocity of three-dimensional linear traveling waves in two sheared flows: the plane channel and the wake flows. This was carried out by varying the wave number over a large interval of values at a given Reynolds number inside the ranges 20-100, 1000-8000, for the wake and channel flow, respectively. Evidence is given about the possible presence of both dispersive and nondispersive effects which are associated with the long and short ranges of wavelength. We solved the Orr-Sommerfeld and Squire eigenvalue problem and observed the least stable mode. It is evident that, at low wave numbers, the least stable eigenmodes in the left branch of the spectrum behave in a dispersive manner. By contrast, if the wave number is above a specific threshold, a sharp dispersive-to-nondispersive transition can be observed. Beyond this transition, the dominant mode belongs to the right branch of the spectrum. The transient behavior of the phase velocity of small three-dimensional traveling waves was also considered. Having chosen the initial conditions, we then show that the shape of the transient highly depends on the transition wavelength threshold value. We show that the phase velocity can oscillate with a frequency which is equal to the frequency width of the eigenvalue spectrum. Furthermore, evidence of intermediate self-similarity is given for the perturbation field.
- Published
- 2016
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26. Lower levels of 25-hydroxyvitamin D3 are associated with a higher prevalence of microvascular complications in patients with type 2 diabetes.
- Author
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Zoppini G, Galletti A, Targher G, Brangani C, Pichiri I, Trombetta M, Negri C, De Santi F, Stoico V, Cacciatori V, and Bonora E
- Abstract
Objective: Low levels of serum 25-hydroxyvitamin D [25(OH)D] are commonly found in type 2 diabetes. We examined whether there is an association between circulating 25(OH)D concentrations and the presence of microvascular complications in people with type 2 diabetes., Research Design and Methods: We studied 715 outpatients with type 2 diabetes who regularly attended our clinic. Participants were evaluated for the presence of microvascular complications (namely retinopathy and/or nephropathy) by clinical evaluation, fundus examination, urine examination and biochemical tests. Serum 25(OH)D levels were also measured for each participant., Results: Hypovitaminosis D (ie, a serum 25(OH)D level <30 ng/mL) was found in 75.4%, while deficiency (ie, a 25(OH)D level <20 ng/mL) was found in 36.6% of these patients. Serum 25(OH)D levels decreased significantly in relation to the severity of either retinopathy or nephropathy or both. In multivariate logistic regression analysis, lower 25(OH)D levels were independently associated with the presence of microvascular complications (considered as a composite end point; OR 0.758; 95% CI 0.607 to 0.947, p=0.015). Notably, this association remained significant even after excluding those with an estimated glomerular filtration rate <60 mL/min/1.73 m(2)., Conclusions: We found an inverse and independent relationship between circulating 25(OH)D levels and the prevalence of microvascular complications in patients with type 2 diabetes. However, vitamin D may be simply a marker and causality cannot be implied from our cross-sectional study. Whether vitamin D supplementation in patients with type 2 diabetes may have beneficial effects on the risk of microvascular complications remains to be investigated.
- Published
- 2015
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27. Comparison of two creatinine-based estimating equations in predicting all-cause and cardiovascular mortality in patients with type 2 diabetes.
- Author
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Targher G, Zoppini G, Mantovani W, Chonchol M, Negri C, Stoico V, Mantovani A, De Santi F, and Bonora E
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Glomerular Filtration Rate physiology, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Cardiovascular Diseases metabolism, Cardiovascular Diseases mortality, Creatinine metabolism, Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Type 2 mortality
- Abstract
Objective: To compare the performance of two glomerular filtration rate (GFR)-estimating equations in predicting the risk of all-cause and cardiovascular mortality in type 2 diabetic patients., Research Design and Methods: We followed 2,823 type 2 diabetic outpatients for a period of 6 years for the occurrence of all-cause and cardiovascular mortality. GFR was estimated using the four-variable Modification of Diet in Renal Disease (MDRD) study equation and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation., Results: At baseline, an estimated GFR (eGFR) <60 mL/min/1.73 m(2) was present in 22.0 and 20.2% of patients using the MDRD study equation and the CKD-EPI equation, respectively. A total of 309 patients died during the follow-up (152 patients from cardiovascular causes). Both creatinine-based equations were associated with an increased risk of all-cause and cardiovascular mortality. However, the CKD-EPI equation provided a more accurate risk prediction of mortality than the MDRD study equation. Receiving operating characteristic curves showed that the areas under the curve (AUCs) for all-cause mortality (AUC 0.712 [95% CI 0.682-0.741]) and cardiovascular mortality (0.771 [0.734-0.808]) using eGFR(CKD-EPI) were significantly greater (P < 0.0001 by the z statistic) than those obtained by using eGFR(MDRD) (0.679 [0.647-0.711] for all-cause mortality and 0.739 [0.698-0.783] for cardiovascular mortality)., Conclusions: Our findings suggest that the estimation of GFR using the CKD-EPI equation more appropriately stratifies patients with type 2 diabetes according to the risk of all-cause and cardiovascular mortality compared with the MDRD study equation.
- Published
- 2012
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28. Validation of the treadmill Six-Minute Walk Test in people following cardiac surgery.
- Author
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Olper L, Cervi P, De Santi F, Meloni C, and Gatti R
- Subjects
- Heart Diseases surgery, Humans, Postoperative Period, Reproducibility of Results, Cardiac Surgical Procedures rehabilitation, Exercise Test methods, Exercise Tolerance, Heart Diseases rehabilitation
- Abstract
Background: The Six-Minute Walk Test (6MWT) often is used to measure exercise capacity in people with cardiopulmonary diseases but has some disadvantages. The 6MWT administered on a treadmill (Tr6MWT) requires less physical space and allows for easier monitoring of vital parameters than the traditional 6MWT., Objective: The objectives of this study were: (1) to analyze the validity of the Tr6MWT in people who underwent cardiac surgery; (2) to compare the reliability, responsiveness, and people's tolerance of the Tr6MWT with those of the 6MWT; and (3) to evaluate the agreement between the 2 tests., Design: This study was designed to assess reliability and validity., Methods: Twenty-six participants who were inpatients were assessed before a 2-week rehabilitation program. Twenty of them also were assessed after rehabilitation. All participants performed 3 Tr6MWT trials and 3 6MWT trials that were randomly assigned on 2 consecutive days., Results: The Pearson r correlation coefficient between the Tr6MWT and the 6MWT was .72, indicating satisfactory concurrent validity. The Tr6MWT was as well tolerated as the 6MWT. The Tr6MWT produced reproducible results after 2 practice tests, whereas the 6MWT did so after only 1 practice test. Both tests showed high test-retest reliability (intraclass correlation coefficient of >.94; standard errors of measurement of 23 m for the Tr6MWT and 18.5 m for the 6MWT). The Tr6MWT showed better responsiveness than the 6MWT (effect sizes of 0.9 for the Tr6MWT and 0.6 for the 6MWT). The distance covered during the Tr6MWT was significantly shorter (X=62 m, SD=91) before rehabilitation but not after rehabilitation., Limitations: A crossover randomized procedure could have improved the reliability of the Tr6MWT in people who performed the 6MWT first., Conclusions: The Tr6MWT appears to be an instrument with adequate concurrent validity and to be tolerable, reliable, and responsive for the evaluation of exercise capacity in people after cardiac surgery even though it is not interchangeable with the 6MWT.
- Published
- 2011
- Full Text
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