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1.
Hum Reprod ; 38(1): 103-112, 2023 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-36367827

RESUMEN

STUDY QUESTION: Does LH addition to FSH in vitro recover the human primary granulosa lutein cell (hGLC) sub/poor-response? SUMMARY ANSWER: A picomolar concentration of LH may recover the FSH-induced cAMP and progesterone production of hGLC from sub/poor-responder women. WHAT IS KNOWN ALREADY: Clinical studies suggested that FSH and LH co-treatment may be beneficial for the ovarian response of sub/poor-responders undergoing ovarian stimulation during ART. STUDY DESIGN, SIZE, DURATION: hGLC samples from 286 anonymous women undergoing oocyte retrieval for ART were collected from October 2017 to February 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: hGLCs from women undergoing ovarian stimulation during ART were blindly purified, cultured, genotyped and treated in vitro by increasing concentrations of FSH (nM) ±0.5 nM LH. cAMP and progesterone levels produced after 3 and 24 h, respectively, were measured. In vitro data were stratified a posteriori, according to the donors' ovarian response, into normo-, sub- and poor-responder groups and statistically compared. The effects of LH addition to FSH were compared with those obtained by FSH alone in all the groups as well. MAIN RESULTS AND THE ROLE OF CHANCE: hGLCs from normo-responders were shown to have higher sensitivity to FSH treatment than sub-/poor-responders in vitro. Equimolar FSH concentrations induced higher cAMP (about 2.5- to 4.2-fold), and progesterone plateau levels (1.2- to 2.1-fold), in cells from normo-responder women than those from sub-/poor-responders (ANOVA; P < 0.05). The addition of LH to the cell treatment significantly increased overall FSH efficacy, indicated by cAMP and progesterone levels, within all groups (P > 0.05). Interestingly, these in vitro endpoints, collected from the normo-responder group treated with FSH alone, were similar to those obtained in the sub-/poor-responder group under FSH + LH treatment. No different allele frequencies and FSH receptor (FSHR) gene expression levels between groups were found, excluding genetics of gonadotropin and their receptors as a factor linked to the normo-, sub- and poor-response. In conclusion, FSH elicits phenotype-specific ovarian lutein cell response. Most importantly, LH addition may fill the gap between cAMP and steroid production patterns between normo- and sub/poor-responders. LIMITATIONS, REASONS FOR CAUTION: Although the number of experimental replicates is overall high for an in vitro study, clinical trials are required to demonstrate if the endpoints evaluated herein reflect parameters of successful ART. hGLC retrieved after ovarian stimulation may not fully reproduce the response to hormones of granulosa cells from the antral follicular stage. WIDER IMPLICATIONS OF THE FINDINGS: This in vitro assay may describe the individual response to personalize ART stimulation protocol, according to the normo-, sub- and poor-responder status. Moreover, this in vitro study supports the need to conduct optimally designed, randomized clinical trials exploring the personalized use of LH in assisted reproduction. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by Merck KGaA. M.L. and C.C. are employees of Merck KGaA or of the affiliate Merck Serono SpA. Other authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.


Asunto(s)
Hormona Folículo Estimulante , Células Lúteas , Humanos , Femenino , Hormona Folículo Estimulante/uso terapéutico , Células Lúteas/metabolismo , Progesterona , Gonadotropinas , Reproducción , Inducción de la Ovulación/métodos , Fertilización In Vitro/métodos
2.
J Autoimmun ; 125: 102744, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34781162

RESUMEN

Autoimmune systemic diseases (ASD) may show impaired immunogenicity to COVID-19 vaccines. Our prospective observational multicenter study aimed to evaluate the seroconversion after the vaccination cycle and at 6-12-month follow-up, as well the safety and efficacy of vaccines in preventing COVID-19. The study included 478 unselected ASD patients (mean age 59 ± 15 years), namely 101 rheumatoid arthritis (RA), 38 systemic lupus erythematosus (SLE), 265 systemic sclerosis (SSc), 61 cryoglobulinemic vasculitis (CV), and a miscellanea of 13 systemic vasculitis. The control group included 502 individuals from the general population (mean age 59 ± 14SD years). The immunogenicity of mRNA COVID-19 vaccines (BNT162b2 and mRNA-1273) was evaluated by measuring serum IgG-neutralizing antibody (NAb) (SARS-CoV-2 IgG II Quant antibody test kit; Abbott Laboratories, Chicago, IL) on samples obtained within 3 weeks after vaccination cycle. The short-term results of our prospective study revealed significantly lower NAb levels in ASD series compared to controls [286 (53-1203) vs 825 (451-1542) BAU/mL, p < 0.0001], as well as between single ASD subgroups and controls. More interestingly, higher percentage of non-responders to vaccine was recorded in ASD patients compared to controls [13.2% (63/478), vs 2.8% (14/502); p < 0.0001]. Increased prevalence of non-response to vaccine was also observed in different ASD subgroups, in patients with ASD-related interstitial lung disease (p = 0.009), and in those treated with glucocorticoids (p = 0.002), mycophenolate-mofetil (p < 0.0001), or rituximab (p < 0.0001). Comparable percentages of vaccine-related adverse effects were recorded among responder and non-responder ASD patients. Patients with weak/absent seroconversion, believed to be immune to SARS-CoV-2 infection, are at high risk to develop COVID-19. Early determination of serum NAb after vaccination cycle may allow to identify three main groups of ASD patients: responders, subjects with suboptimal response, non-responders. Patients with suboptimal response should be prioritized for a booster-dose of vaccine, while a different type of vaccine could be administered to non-responder individuals.


Asunto(s)
Vacuna nCoV-2019 mRNA-1273/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/inmunología , Vacuna BNT162/inmunología , COVID-19/prevención & control , Femenino , Humanos , Italia , Lupus Eritematoso Sistémico/inmunología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , SARS-CoV-2/inmunología , Esclerodermia Sistémica/inmunología , Vasculitis Sistémica/inmunología , Vacunación , Potencia de la Vacuna
3.
Ophthalmic Res ; 63(1): 18-24, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31430744

RESUMEN

PURPOSE: To assess closure rate and visual outcome of a court of patients with macular hole (MH) who underwent surgical repair with intraoperative optical coherence tomography (iOCT)-confirmed MH closure and short-term postoperative face-down posturing (FDP). Secondary aim was to assess the correlation between iOCT and postoperative OCT at day 1. METHODS: Retrospective clinical study conducted in the Miulli Hospital Acquaviva delle Fonti (Italy), enrolling patients with idiopathic MH who underwent 25-G pars plana vitrectomy plus internal limiting membrane peeling. During surgery, closure of MH was confirmed by iOCT and short-term FDP (12-24 h, until day-1 visit) was prescribed. All patients had measurement of best-corrected visual acuity (BCVA) and spectral domain-OCT before the surgery and during follow-up (at 1 day, 1 month, 3 months). RESULTS: Twenty-nine eyes of 29 patients (14 males, 62.1%) were enrolled in the study. MH mean size was 451.7 ± 139.7 µm and baseline BCVA was 0.77 ± 0.26 logarithm of the minimum angle of resolution (LogMAR). MH was confirmed to be closed in 100% of patients intraoperatively (iOCT) and at OCT during early follow-up (1-3 days). Mean time of FDP was 18 ± 2.6 h. At 3 months, MH closure rate was 93%; 2 eyes -underwent secondary MH repair surgery. Final BCVA was 0.39 ± 0.22 LogMAR (p < 0.0001). CONCLUSION: iOCT-based confirmation of MH closure could be a safe and useful tool for prescribing short-term FDP after surgery, with high closure rate and no additional complication. The execution of an OCT in the immediate postoperative days could be potentially unnecessary.


Asunto(s)
Posición Prona , Perforaciones de la Retina/cirugía , Cirugía Asistida por Computador/métodos , Tomografía de Coherencia Óptica/métodos , Vitrectomía/métodos , Anciano , Anciano de 80 o más Años , Endotaponamiento/métodos , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Perforaciones de la Retina/diagnóstico por imagen , Estudios Retrospectivos , Agudeza Visual/fisiología
4.
Retina ; 38(9): 1770-1776, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-28723849

RESUMEN

PURPOSE: To determine whether internal limiting membrane (ILM) peeling during pars plana vitrectomy for rhegmatogenous retinal detachment reduces the incidence of epiretinal membrane (ERM) formation. METHODS: In this retrospective study, preoperative, intraoperative, and postoperative data from all eyes undergoing pars plana vitrectomy for rhegmatogenous retinal detachment between January 2007 and December 2013 was analyzed. All cases with at least 1-year of follow-up were included. Data collection included vision, intraoperative complications, occurrence of ERM, and spectral domain optical coherence tomography characteristics. The OCTs were retrieved for all eyes and were graded by a single masked grader. RESULTS: Out of 159 eyes recruited, ILM peeling was done in 78 eyes (49%). Overall occurrence of ERM was 20%. Seven eyes (9%) in ILM peeling group and 25 eyes in the non-ILM peeling group (31%) showed ERM (P = 0.001). Postoperative vision was significantly better in eyes that had ILM peeling (0.48 ± 0.4 logarithm of the minimum angle of resolution [20/63] vs. 0.77 ± 0.6 logarithm of the minimum angle of resolution [20/125], P = 0.003). In multivariable models adjusting for type of tamponade, ILM peeling reduced the likelihood of ERM formation by 75% (P = 0.01). CONCLUSION: Internal limiting membrane peeling during pars plana vitrectomy for rhegmatogenous retinal detachment significantly reduces ERM formation in the postoperative period and is associated with better visual and anatomical outcomes.


Asunto(s)
Membrana Basal/cirugía , Membrana Epirretinal/prevención & control , Complicaciones Posoperatorias/prevención & control , Desprendimiento de Retina/cirugía , Tomografía de Coherencia Óptica/métodos , Agudeza Visual , Vitrectomía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Membrana Basal/patología , Membrana Epirretinal/epidemiología , Estudios de Seguimiento , Humanos , Incidencia , Italia/epidemiología , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Desprendimiento de Retina/diagnóstico , Desprendimiento de Retina/fisiopatología , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
5.
Exp Eye Res ; 120: 109-17, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24486457

RESUMEN

The study was designed to investigate the effects of a new ophthalmic solution containing 0.05% vitamin B12 0.05% on corneal nerve regeneration in rats after corneal injury. Eyes of anesthetized male Wistar rats were subjected to corneal injury by removing the corneal epithelium with corneal brush (Algerbrush). After the epithelial debridement, the right eye of each animal received the instillation of one drop of the ophthalmic solution containing vitamin B12 0.05% plus taurine 0.5% and sodium hyaluronate 0.5% four time per day for 10 or 30 days. Left eyes were used as control and treated with solution containing taurine 0.5% and sodium hyaluronate 0.5% alone following the same regimen. Fluorescein staining by slit-lamp and morphological analysis was used to determine corneal wound healing. Immunohistochemistry, immunoblot and confocal microscopy were used to examine corneal re-innervation. Slit-lamp and histological analyses showed that re-epithelization of the corneas was accelerated in rats treated with vitamin B12. A clear-cut difference between the two groups of rats was seen after 10 days of treatment, whereas a near-to-complete re-epithelization was observed in both groups at 30 days. Vitamin B12 treatment had also a remarkable effect on corneal re-innervation, as shown by substantial increased in the expression of neurofilament 160 and ß-III tubulin at both 10 and 30 days. The presence of SV2A-positive nerve endings suggests the presence of synapse-like specialized structures in corneal epithelium of the eye treated with vitamin B12. Our findings suggest that vitamin B12 treatment represents a powerful strategy to accelerate not only re-epithelization but also corneal re-innervation after mechanical injury.


Asunto(s)
Córnea/inervación , Lesiones Oculares/fisiopatología , Regeneración Nerviosa/efectos de los fármacos , Nervio Oftálmico/fisiología , Vitamina B 12/farmacología , Complejo Vitamínico B/farmacología , Heridas no Penetrantes/fisiopatología , Animales , Lesiones de la Cornea , Fluorofotometría , Concentración de Iones de Hidrógeno , Immunoblotting , Inmunohistoquímica , Masculino , Microscopía Confocal , Proteínas de Neurofilamentos/metabolismo , Soluciones Oftálmicas , Concentración Osmolar , Ratas , Ratas Wistar , Taurina/farmacología , Tubulina (Proteína)/metabolismo
7.
Eur Heart J Case Rep ; 8(9): ytae457, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39420959

RESUMEN

Background: The sudden onset of heart failure in high-risk transcatheter aortic valve implantation (TAVI) candidates poses significant challenges, necessitating meticulous planning and consideration of mechanical circulatory support options. Nevertheless, existing data on the efficacy and safety of mechanical circulatory support in this context are limited, along with criteria for patient selection. Case summary: An 87-year-old patient, with severe low-flow low-gradient aortic stenosis, presented with acute heart failure and concurrent COVID-19 pneumonia. Despite initial conservative management, her clinical condition deteriorated, requiring inotropic support. The decision was made to perform a rescue TAVI procedure with veno-arterial extracorporeal membrane oxygenation (ECMO) support. The patient underwent successful TAVI while managing complications, including cardiac arrest, with haemodynamic support from veno-arterial ECMO. Post-procedure, the patient showed improved cardiac function and was discharged in stable condition. Discussion: This case underscores the significance of strategic patient selection, proactive haemodynamic management, and the judicious use of veno-arterial ECMO in high-risk TAVI, particularly in complex scenarios involving acute heart failure and respiratory insufficiency, exacerbated by COVID-19. It highlights the challenges and critical decision points in TAVI planning, emphasizing the need for further research and standardized guidelines to refine indications for prophylactic mechanical circulatory support in TAVI procedures.

8.
Environ Sci Pollut Res Int ; 31(40): 52963-52979, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39167142

RESUMEN

Italy is the leading rice producer in Europe and the second in the Mediterranean basin (after Egypt), with most of the production concentrated in a large paddy area between the Lombardy and Piedmont regions (northern Italy). In this area, irrigation of rice was traditionally carried out by wet seeding and continuous flooding; in the last fifteen years, this technique has been gradually replaced by dry seeding followed by a delayed flooding (DFL) or by an alternation of flooding and dry periods (FTI), which are economically more advantageous. This study presents the results of an extensive monitoring campaign designed and carried out in 2021 in a representative paddy district of the Lomellina area (Pavia, northern Italy) to assess the impact of the actual rice cropping strategies on surface water and groundwater quality, with particular attention to two widely used herbicides (MCPA and clomazone) and to nutrient losses (e.g., N, P, K). Results show that MCPA and clomazone concentrations detected in surface water and groundwater are always below the RAC (Regulatory Acceptable Concentration) values. As to nutrients, they do not show significant trends along the season in surface water and groundwater: this may be due to the fact that nutrient sources are many. Concerning the concentrations, nitrates may pose a problem for the area, especially for groundwater. However, further studies would be needed to understand to which extent rice cropping can be considered the major source of contamination for water resources.


Asunto(s)
Monitoreo del Ambiente , Agua Subterránea , Herbicidas , Oryza , Contaminantes Químicos del Agua , Agua Subterránea/química , Italia , Herbicidas/análisis , Contaminantes Químicos del Agua/análisis , Agricultura , Nutrientes/análisis
9.
Int J Cardiol ; 414: 132411, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39094635

RESUMEN

BACKGROUND: Cardiogenic Shock (CS) complicating acute myocardial infarction (AMI) poses a significant mortality risk, suggesting the opportunity to implement effective mechanical circulatory support strategies. The comparative efficacy of Intra-Aortic Balloon Pump (IABP) and Impella in managing CS-AMI remains a subject of investigation. OBJECTIVE: This meta-analysis aims to evaluate the comparative effectiveness of Impella and IABP in managing CS-AMI, exploring mortality and adverse events. METHODS: A systematic search of major databases from inception to November 2023 identified eight studies, comprising 10,628 patients, comparing Impella and IABP in CS-AMI. Retrospective studies (preferably Propensity-matched) and Randomized Clinical Trials (RCTs) were included. RESULTS: Impella use exhibited significantly higher mortality (57% vs. 46%; OR: 1.44, 95% CI: 1.29-1.60; p < 0.001) and major bleeding (30% vs 15%; OR: 2.93, 95% CI: 1.67-5.13; p < 0.001). CONCLUSIONS: In unselected CS-AMI patients, Impella usage is associated with significantly higher mortality and major bleeding.


Asunto(s)
Corazón Auxiliar , Contrapulsador Intraaórtico , Infarto del Miocardio , Choque Cardiogénico , Humanos , Corazón Auxiliar/efectos adversos , Contrapulsador Intraaórtico/efectos adversos , Contrapulsador Intraaórtico/instrumentación , Contrapulsador Intraaórtico/métodos , Infarto del Miocardio/complicaciones , Infarto del Miocardio/mortalidad , Infarto del Miocardio/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Choque Cardiogénico/terapia , Choque Cardiogénico/mortalidad , Choque Cardiogénico/etiología , Resultado del Tratamiento
10.
Eye (Lond) ; 38(1): 103-111, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37414935

RESUMEN

OBJECTIVES: To evaluate the 1-year effectiveness and safety of the XEN45, either alone or in combination with phacoemulsification, in glaucoma patients. METHODS: This multicentre, prospective, observational study included consecutive eyes of glaucoma patients from the Italian XEN-Glaucoma Treatment Registry (XEN-GTR) who underwent XEN45 alone or in combination with phacoemulsification, with at least 1 year of follow-up. Surgical success was defined as intraocular pressure (IOP) < 18 mmHg and ≥20% reduction from preoperative IOP, over 1 year of follow-up. RESULTS: Two hundred thirty-nine eyes (239 patients) were analyzed, 144 (60.2%) eyes in the XEN-solo and 95 (39.8%) eyes in the XEN+Phaco groups. One hundred-sixty-eight (70.3%) eyes achieved overall success, without statistically significant differences between study groups (p = 0.07). Preoperative IOP dropped from a median (IQR) of 23.0 (20.0-26.0) mmHg to 14.0 (12.0-16.0) mmHg at month 12 (p < 0.001), with overall 39.9 ± 18.3% IOP reduction. The mean number of preoperative ocular hypotensive medications (OHM) was significantly reduced from 2.7 ± 0.9 to 0.5 ± 0.9 at month 12 (p < 0.001). Preoperative IOP < 15 mmHg (HR: 6.63; 95%CI: 2.61-16.84, p < 0.001) and temporal position of the surgeon (HR: 4.25; 95%CI: 2.62-6.88, p < 0.001) were significantly associated with surgery failure. One hundred-forty-six (61.1%) eyes had no intraoperative complications, whereas 91 (38.1%) and 56 (23.4%) eyes experienced at least one complication, respectively early (< month 1) and late (≥ month 1), all self-limiting or successfully treated without sequelae. Needling occurred in 55 (23.0%) eyes at least once during follow-up. CONCLUSION: Over 1-year follow-up, XEN45 alone or in combination with phacoemulsification, had comparable success rates and effectively and safely lowered IOP and the need for OHM.


Asunto(s)
Implantes de Drenaje de Glaucoma , Glaucoma de Ángulo Abierto , Glaucoma , Humanos , Estudios Prospectivos , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Glaucoma de Ángulo Abierto/cirugía , Glaucoma de Ángulo Abierto/complicaciones , Stents , Presión Intraocular , Glaucoma/tratamiento farmacológico , Glaucoma/cirugía , Glaucoma/complicaciones , Resultado del Tratamiento , Estudios Retrospectivos
11.
J Clin Med ; 13(17)2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39274195

RESUMEN

Ranolazine is an anti-anginal medication that has demonstrated antiarrhythmic properties by inhibiting both late sodium and potassium currents. Studies have shown promising results for ranolazine in treating both atrial fibrillation and ventricular arrhythmias, particularly when used in combination with other medications. This review explores ranolazine's mechanisms of action and its potential role in cardiac arrhythmias treatment in light of previous clinical studies.

12.
Sci Rep ; 14(1): 844, 2024 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-38191651

RESUMEN

Steroidogenesis of gonadal cells is tightly regulated by gonadotropins. However, certain polycyclic aromatic hydrocarbons, including Benzo[a]pyrene (BaP), induce reproductive toxicity. Several existing studies have considered higher than environmentally relevant concentrations of BaP on male and female steroidogenesis following long-term exposure. Also, the impact of short-term exposure to BaP on gonadotropin-stimulated cells is understudied. Therefore, we evaluated the effect of 1 nM and 1 µM BaP on luteinizing hormone/choriogonadotropin (LH/hCG)-mediated signalling in two steroidogenic cell models, i.e. the mouse tumor Leydig cell line mLTC1, and the human primary granulosa lutein cells (hGLC) post 8- and 24-h exposure. Cell signalling studies were performed by homogeneous time-resolved fluorescence (HTRF) assay, bioluminescence energy transfer (BRET) and Western blotting, while immunostainings and immunoassays were used for intracellular protein expression and steroidogenesis analyses, respectively. BaP decreased cAMP production in gonadotropin-stimulated mLTC1 interfering with Gαs activation. Therefore, decrease in gonadotropin-mediated CREB phosphorylation in mLTC1 treated with 1 µM BaP was observed, while StAR protein levels in gonadotropin-stimulated mLTC1 cells were unaffected by BaP. Further, BaP decreased LH- and hCG-mediated progesterone production in mLTC1. Contrastingly, BaP failed to mediate any change in cAMP, genes and proteins of steroidogenic machinery and steroidogenesis of gonadotropin-treated hGLC. Our results indicate that short-term exposure to BaP significantly impairs steroidogenic signalling in mLTC1 interfering with Gαs. These findings could have a significant impact on our understanding of the mechanism of reproductive toxicity by endocrine disruptors.


Asunto(s)
Benzo(a)pireno , Células Intersticiales del Testículo , Humanos , Animales , Ratones , Femenino , Masculino , Benzo(a)pireno/toxicidad , Gonadotropina Coriónica/farmacología , Bioensayo , Western Blotting
13.
Retina ; 38(5): e41-e42, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29578941
14.
JACC Case Rep ; 6: 101673, 2023 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-36704054

RESUMEN

Spontaneous coronary intramural hematoma (SCIH) is a rare but underdiagnosed condition, with dynamic evolution. We present a patient with acute chest pain and normal coronary angiogram undergoing work-up for myocardial infarction with nonobstructive coronary arteries. Cardiac magnetic resonance revealed an ischemic pattern, and subsequent angiography revealed coronary occlusion by SCIH. (Level of Difficulty: Intermediate.).

15.
J Clin Med ; 12(1)2023 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-36615178

RESUMEN

Heart failure (HF) is a complex, multifactorial, progressive clinical condition affecting 64.3 million people worldwide, with a strong impact in terms of morbidity, mortality and public health costs. In the last 50 years, along with a better understanding of HF physiopathology and in agreement with the four main models of HF, many therapeutic options have been developed. Recently, the European Society of Cardiology (ESC) HF guidelines enthusiastically introduced inhibitors of the sodium-glucose cotransporter (SGLT2i) as first line therapy for HF with reduced ejection fraction (HFrEF) in order to reduce hospitalizations and mortality. Despite drugs developed as hypoglycemic agents, data from the EMPA-REG OUTCOME trial encouraged the evaluation of the possible cardiovascular effects, showing SGLT2i beneficial effects on loading conditions, neurohormonal axes, heart cells' biochemistry and vascular stiffness, determining an improvement of each HF model. We want to give a boost to their use by increasing the knowledge of SGLT2-I and understanding the probable mechanisms of this new class of drugs, highlighting strengths and weaknesses, and providing a brief comment on major trials that made Gliflozins a cornerstone in HF therapy. Finally, aspects that may hinder SGLT2-i widespread utilization among different types of specialists, despite the guidelines' indications, will be discussed.

16.
Cells ; 12(11)2023 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-37296657

RESUMEN

Bisphenol A (BPA) is a ubiquitous, synthetic chemical proven to induce reproductive disorders in both men and women. The available studies investigated the effects of BPA on male and female steroidogenesis following long-term exposure to the compound at relatively high environmental concentrations. However, the impact of short-term exposure to BPA on reproduction is poorly studied. We evaluated if 8 and 24 h exposure to 1 nM and 1 µM BPA perturbs luteinizing hormone/choriogonadotropin (LH/hCG)-mediated signalling in two steroidogenic cell models, i.e., the mouse tumour Leydig cell line mLTC1, and human primary granulosa lutein cells (hGLC). Cell signalling studies were performed using a homogeneous time-resolved fluorescence (HTRF) assay and Western blotting, while gene expression analysis was carried out using real-time PCR. Immunostainings and an immunoassay were used for intracellular protein expression and steroidogenesis analyses, respectively. The presence of BPA leads to no significant changes in gonadotropin-induced cAMP accumulation, alongside phosphorylation of downstream molecules, such as ERK1/2, CREB and p38 MAPK, in both the cell models. BPA did not impact STARD1, CYP11A1 and CYP19A1 gene expression in hGLC, nor Stard1 and Cyp17a1 expression in mLTC1 treated with LH/hCG. Additionally, the StAR protein expression was unchanged upon exposure to BPA. Progesterone and oestradiol levels in the culture medium, measured by hGLC, as well as the testosterone and progesterone levels in the culture medium, measured by mLTC1, did not change in the presence of BPA combined with LH/hCG. These data suggest that short-term exposure to environmental concentrations of BPA does not compromise the LH/hCG-induced steroidogenic potential of either human granulosa or mouse Leydig cells.


Asunto(s)
Hormona Luteinizante , Progesterona , Ratones , Animales , Femenino , Humanos , Masculino , Progesterona/metabolismo , Testosterona , Fenoles/toxicidad
17.
Eur J Ophthalmol ; : 11206721221143166, 2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36457210

RESUMEN

PURPOSE: To document the effects of intravitreal dexamethasone implant on retinal microvasculature in patients with diabetic retinopathy complicated by center-involving macular edema. METHODS: 35 eyes of 35 patients affected by retinopathy due to type 2 diabetes (15 treatment-naïve and 20 previously treated) were included in this retrospective study with a follow-up of 4 months. Foveal avascular zone (FAZ) area and superficial capillary plexus (SCP) and deep capillary plexus (DCP) densities in the foveal and parafoveal areas were measured by optical coherence tomography angiography (OCTA) at baseline and 2 and 4 months post-injection. Intraocular pressure, morphological and functional parameters were evaluated. RESULTS: a significant difference was found in both groups at 2 months after injection in terms of functional (BCVA, p < 0.05) and morphological (CMT, p < 0.05) parameters. During follow-up, FAZ area, SCP, and DCP in the foveal and parafoveal areas did not change significantly. CONCLUSIONS: intravitreal dexamethasone implant is effective in the treatment of diabetic center-involving macular edema and was associated with significant improvements in BCVA and CMT at 2 months after injection. After a single dexamethasone implant injection, FAZ area and retinal vascular density does not show significant variations in both naive and non-naive DME patients subgroups.

18.
Eur J Ophthalmol ; 32(5): 3116-3120, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35275025

RESUMEN

PURPOSE: Epiretinal membranes (ERM) are a disorder leading to progressive vision loss and metamorphopsia. The ERM is treated through a pars-plana vitrectomy (PPV) with membrane peeling. The aim of this study was to define the success of intraoperative optical coherence tomography (iOCT) in ERM surgery to standard surgical visualization techniques and enhance our current approach to clinical practice. METHODS: This study included 56 eyes of 54 patients who underwent surgical intervention for management of idiopathic ERM. Patients were recruited between February 2018 and March 2020 at "Francesco Miulli" Hospital ophthalmology department in Acquaviva delle Fonti, Bari, Italy. RESULTS: in 28 eyes, ERM peeling was performed without staining and without iOCT; 25% of these eyes peeling ERM (n = 7) was performed easily, while 75% of eyes peeling ERM (n = 21) was not possible without staining and was necessary staining with Brillant Blu G.In 28 eyes ERM peeling were performed with iOCT; in 92.5% of these eyes (n = 26) ERM peeling was easily done without staining, while in 7.5% of this group of eyes (n = 2) ERM peeling was not possible without staining. CONCLUSIONS: Our study shows how iOCT has successfully assisted the surgeon to complete peeling in most of the cases treated without the use of a chromovitrectomy dye; in flat ERM was more difficult and iOCT failed to visualize the inner limiting membrane (ILM).


Asunto(s)
Membrana Epirretinal , Membrana Basal/cirugía , Membrana Epirretinal/diagnóstico , Membrana Epirretinal/cirugía , Humanos , Retina , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodos , Agudeza Visual , Vitrectomía/métodos
19.
J Clin Med ; 11(18)2022 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-36142967

RESUMEN

Background The Italian XEN Glaucoma Treatment Registry (XEN-GTR) was created to acquire a comprehensive prospective dataset that includes the patient characteristics, intraoperative variables, and postoperative management of glaucoma patients undergoing the XEN gel stent implantation. Methods This was a prospective observational, longitudinal clinical study involving 10 centres throughout Italy. The baseline examination included a comprehensive evaluation of demographic parameters (age, sex, ethnicity, and systemic condition), specific ophthalmological parameters, and quality of life questionnaire score collection. Results The baseline data of 273 patients were analysed. The median (IQR) age was 72 (65.0 to 78.0) years. Of the 273 patients, 123 (45%) were female and 150 (55%) were male. A total of 86% of the patients had open-angle glaucoma with a mean intraocular pressure of 24 ± 6 (range 12.0-60.0) mmHg. The mean number of medications was 2.7 ± 0.9 at baseline for the patients with a prevalence of prostaglandin analogues combined with a beta-blocker and anhydrase carbonic inhibitor (31.8%). The mean scores of the NEI-VFQ 25 and GSS questionnaires were 78 ± 18 (range 26.5-100) and 85 ± 14 (range 79-93), respectively. Combined XEN/cataract surgeries were scheduled in 73.7% of the patients. The preferred place for the XEN implant was the supero-nasal quadrant (91.6%). Conclusions Observing the baseline characteristics of the typical Italian candidates for the XEN gel implant shows that they are patients affected by POAG and cataracts, with moderate to severe glaucoma damage, all of which has an impact on their quality of life.

20.
J Med Case Rep ; 15(1): 206, 2021 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-33875008

RESUMEN

BACKGROUND: This report describes the clinical course of choroidal neovascular membrane (CNV) in West Nile virus-associated chorioretinitis. CASE PRESENTATION: A 28-year-old Italian woman was referred to our institution because of reduced visual acuity in the left eye dating back 4 months. A diagnosis of retinal vasculitis in the right eye and chorioretinitis with CNV in the left eye was made. A complete workup for uveitis revealed positivity only for anti-West Nile virus immunoglobulin M (IgM), while immunoglobulin G (IgG) was negative. Whole-body computed tomography and nuclear magnetic resonance imaging of the brain were also negative. Therefore, the patient was treated with a combination of oral prednisone (starting dose 1 mg/kg per day) and three intravitreal injections of bevacizumab 1.25 mg/0.05 ml, 1 month apart. Fourteen days from starting corticosteroid therapy and after the first intravitreal injection, the patient experienced increased visual acuity to 0.4. Response to therapy was monitored by clinical examination, ocular coherence tomography (OCT), OCT angiography and retinal fluorescein angiography. Three months later, resolution of CNV in the left eye was achieved and no signs of retinal vasculitis were detected in the right eye, while serum IgM for West Nile virus turned negative and IgG positive. CONCLUSION: CNV may be a complication of West Nile virus-associated chorioretinitis, and only subclinical retinal vasculitis may also be found even in non-endemic regions.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Bevacizumab/uso terapéutico , Neovascularización Coroidal/tratamiento farmacológico , Prednisona/uso terapéutico , Vasculitis Retiniana/tratamiento farmacológico , Fiebre del Nilo Occidental/complicaciones , Virus del Nilo Occidental , Adulto , Inhibidores de la Angiogénesis/uso terapéutico , Coriorretinitis/diagnóstico , Coriorretinitis/tratamiento farmacológico , Femenino , Humanos , Inyecciones Intravítreas , Vasculitis Retiniana/diagnóstico , Tomografía de Coherencia Óptica
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