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BACKGROUND: We aimed to identify the target of deprescribing, i.e. the 24-hour SBP increase needed to achieve the greatest reduction of SBP drops. METHOD: Forty hypertensive patients (mean age 73.6 ± 9.3 years, 26 females) with reflex syncope and SBP drops on a screening ABPM were advised to withdraw or to reduce their therapy. The study objective was the reduction of SBP drops <90 mmHg and <100 mmHg on a second ABPM performed within 3 months. RESULTS: Out of a total of 98 drugs taken during ABPM 1, 44 were withdrawn, 16 had a dose reduction and 38 remained unchanged at the time of ABPM 2. 24-hour SBP increased from 119.7 ± 10.1 mmHg to 129.4 ± 13.2 mmHg during ABPM2. Total disappearance of daytime SBP drops <100 mmHg was achieved in 20 (50 %) patients who had 24-hour SBP of 134±13 mmHg and an increase from ABPM 1 of 12 (IQR 5-20) mmHg. Compared with the 20 patients who had persistence of drops, these patients had a greater reduction of the number of hypotensive drugs (67 % versus 19 %, p = 0.002) and a greater rate of withdrawals (62 % versus 29 %, p = 0.003). CONCLUSION: In hypertensive patients with reflex syncope, an increase of 12 mmHg and an absolute value of 24-hour SBP of 134 mmHg appear to represent the optimal goals aimed to prevent SBP drops. Drugs withdrawal, rather than simply dose reduction, is mostly required to achieve the above target.
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AIMS: Systolic blood pressure (SBP) drops recorded by 24-h ambulatory blood pressure (BP) monitoring (ABPM) identify patients with susceptibility to reflex syncope and orthostatic intolerance. We tested the hypothesis that treatments aimed to increase BP (reassurance, education, and lifestyle measures plus pharmacological strategies) can reduce SBP drops. METHODS AND RESULTS: This was a multicentre, observational proof-of-concept study performed in patients with reflex syncope and/or orthostatic intolerance and with SBP drops on a screening ABPM. Among 144 eligible patients, 111 underwent a second ABPM on average 2.5 months after start of treatment. Overall, mean 24-h SBP increased from 114.1 ± 12.1 to 121.4 ± 14.5â mmHg (P < 0.0001). The number of SBP drops <90 and <100â mmHg decreased by 61%, 46% during daytime, and by 48% and 37% during 24-h period, respectively (P < 0.0001 for all). The dose-response relationship between difference in 24-h average SBP increase and reduction in number of SBP drops reached a plateau around â¼15â mmHg increase of 24-h SBP. The reduction in SBP drop rate was consistent and significant in patients who underwent deprescription of hypotensive medications (n = 44) and in patients who received BP-rising drugs (n = 67). CONCLUSION: In patients with reflex syncope and/or orthostatic intolerance, an increase in average 24-h SBP, regardless of the implemented strategy, significantly reduced the number of SBP drops and symptom burden. A 13â mmHg increase in 24-h SBP appears to represent the optimal goal for aborting the maximal number of SBP drops, representing a possible target for future interventions. ClincalTrials.gov identifier: NCT05729724.
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Hipertensión , Hipotensión , Intolerancia Ortostática , Síncope Vasovagal , Humanos , Antihipertensivos/uso terapéutico , Presión Sanguínea , Monitoreo Ambulatorio de la Presión Arterial , Hipertensión/tratamiento farmacológico , Intolerancia Ortostática/diagnóstico , Intolerancia Ortostática/tratamiento farmacológico , Reflejo , Síncope Vasovagal/diagnóstico , Síncope Vasovagal/prevención & control , Prueba de Estudio ConceptualRESUMEN
Microbiota changes during allogeneic hematopoietic stem cell transplantation has several known causes: conditioning chemotherapy and radiation, broad-spectrum antibiotic administration, modification in nutrition status and diet, and graft-versus-host disease. This article aims to review the current knowledge about the close link between microbiota and allogeneic stem cell transplantation setting. The PubMed search engine was used to perform this review. We analyzed data on microbiota dysbiosis related to the above-mentioned affecting factors. We also looked at treatments aimed at modifying gut dysbiosis and applications of fecal microbiota transplantation in the allogeneic stem cell transplant field, with particular interest in fecal microbiota transplantation for graft-versus-host disease (GvHD), multidrug-resistant and clostridium difficile infections, and microbiota restoration after chemotherapy and antibiotic therapy.
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Gonadotropin-Releasing Hormone (GnRH) is a decapeptide responsible for the control of the reproductive functions. It shows C- and N-terminal aminoacid modifications and two other distinct isoforms have been so far identified. The biological effects of GnRH are mediated by binding to high-affinity G-protein couple receptors (GnRHR), showing characteristic very short C tail. In mammals, including humans, GnRH-producing neurons originate in the embryonic nasal compartment and during early embryogenesis they undergo rapid migration towards the hypothalamus; the increasing knowledge of such mechanisms improved diagnostic and therapeutic approaches to infertility. The pharmacological use of GnRH, or its synthetic peptide and non-peptide agonists or antagonists, provides a valid tool for reproductive disorders and assisted reproduction technology (ART). The presence of GnRHR in several organs and tissues indicates additional functions of the peptide. The identification of a GnRH/GnRHR system in the human endometrium, ovary, and prostate has extended the functions of the peptide to the physiology and tumor transformation of such tissues. Likely, the activity of a GnRH/GnRHR system at the level of the hippocampus, as well as its decreased expression in mice brain aging, raised interest in its possible involvement in neurogenesis and neuronal functions. In conclusion, GnRH/GnRHR appears to be a fascinating biological system that exerts several possibly integrated pleiotropic actions in the complex control of reproductive functions, tumor growth, neurogenesis, and neuroprotection. This review aims to provide an overview of the physiology of GnRH and the pharmacological applications of its synthetic analogs in the management of reproductive and non-reproductive diseases.
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Hormona Liberadora de Gonadotropina , Neoplasias , Masculino , Ratones , Femenino , Animales , Humanos , Hormona Liberadora de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Reproducción , Ovario/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Mamíferos/metabolismoRESUMEN
BACKGROUND: Conduction system pacing (CSP) using His bundle pacing (HBP) or left bundle branch area pacing (LBBAP) has emerged as an alternative to right ventricular pacing (RVP). Comparative data on the risk of complications between CSP and RVP are lacking. OBJECTIVE: This prospective, multicenter, observational study aimed to compare the long-term risk of device-related complications between CSP and RVP. METHODS: A total of 1029 consecutive patients undergoing pacemaker implantation with CSP (including HBP and LBBAP) or RVP were enrolled. Propensity score matching for baseline characteristics yielded 201 matched pairs. The rate and nature of device-related complications occurring during follow-up were prospectively collected and compared between the 2 groups. RESULTS: During a mean follow-up duration of 18 months, device-related complications were observed in 19 patients: 7 in RVP (3.5%) and 12 in CSP (6.0%) (P = .240). On dividing the matched cohort into 3 groups with similar baseline characteristics according to pacing modality (RVP, n = 201; HBP, n = 128; LBBAP, n = 73), patients with HBP showed a significantly higher rate of device-related complications than did patients with RVP (8.6% vs 3.5%; P = .047) and patients with LBBAP (8.6% vs 1.3%; P = .034). Patients with LBBAP showed a rate of device-related complications similar to that of patients with RVP (1.3% vs 3.5%; P = .358). Most of the complications observed in patients with HBP (63.6%) were lead related. CONCLUSION: Globally, CSP was associated with a risk of complications similar to that of RVP. Considering HBP and LBBAP separately, HBP showed a significantly higher risk of complications than did both RVP and LBBAP whereas LBBAP showed a risk of complications similar to that of RVP.
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Fascículo Atrioventricular , Estimulación Cardíaca Artificial , Humanos , Estudios Prospectivos , Puntaje de Propensión , Estimulación Cardíaca Artificial/efectos adversos , Estimulación Cardíaca Artificial/métodos , Electrocardiografía/métodos , Trastorno del Sistema de Conducción Cardíaco , Resultado del TratamientoRESUMEN
An Implantable Cardioverter-Defibrillator was implanted in an asymptomatic 56-year-old man, with type 2 Brugada pattern on ECG, inducible ventricular fibrillation at elective electrophysiological study, and a family history of sudden cardiac death. Seventeen years later, the patient was admitted to the hospital due to palpitations related to a typical atrial flutter. A transthoracic echocardiogram unexpectedly revealed a clinically manifest hypertrophic cardiomyopathy.
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Síndrome de Brugada , Cardiomiopatía Hipertrófica , Desfibriladores Implantables , Masculino , Humanos , Persona de Mediana Edad , Electrocardiografía , Arritmias Cardíacas , Muerte Súbita Cardíaca , Cardiomiopatía Hipertrófica/complicaciones , Cardiomiopatía Hipertrófica/diagnóstico , Síndrome de Brugada/complicaciones , Síndrome de Brugada/diagnósticoRESUMEN
The impairment of development/migration of hypothalamic gonadotropin-releasing hormone (GnRH) neurons is the main cause of Kallmann's syndrome (KS), an inherited disorder characterized by hypogonadism, anosmia, and other developmental defects. Olfactorin is an extracellular matrix protein encoded by the UMODL1 (uromodulin-like 1) gene expressed in the mouse olfactory region along the migratory route of GnRH neurons. It shares a combination of WAP and FNIII repeats, expressed in complementary domains, with anosmin-1, the product of the ANOS1 gene, identified as the causative of KS. In the present study, we have investigated the effects of olfactorin in vitro and in vivo models. The results show that olfactorin exerts an anosmin-1-like strong chemoattractant effect on mouse-immortalized GnRH neurons (GN11 cells) through the activation of the FGFR and MAPK pathways. In silico analysis of olfactorin and anosmin-1 reveals a satisfactory similarity at the N-terminal region for the overall arrangement of corresponding WAP and FNIII domains and marked similarities between WAP domains' binding modes of interaction with the resolved FGFR1-FGF2 complex. Finally, in vivo experiments show that the down-modulation of the zebrafish z-umodl1 gene (orthologous of UMODL1) in both GnRH3:GFP and omp 2k :gap-CFP rw034 transgenic zebrafish strains leads to a clear disorganization and altered fasciculation of the neurites of GnRH3:GFP neurons crossing at the anterior commissure and a significant increase in olfactory CFP + fibers with altered trajectory. Thus, our study shows olfactorin as an additional factor involved in the development of olfactory and GnRH systems and proposes UMODL1 as a gene worthy of diagnostic investigation in KS.
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Environmental stimuli, including sex hormones and oxidative stress (OS), affect bone balance, modifying the epigenetic profiles of key osteogenic genes. Nonetheless, the interplay between sex steroids, epigenome and OS has yet be fully elucidated. This paper aims to study in vitro the role of sex steroids in OS-induced alteration in bone cells' homeostasis, and to assess the possible contribution of epigenetic modifications. Toward this purpose, osteoblast (MC3T3-E1) and osteocyte (MLOY-4) cell lines were exposed to two different sources of free oxygen radicals, i.e., tert-butyl hydroperoxide and dexamethasone, and the protective effect of pre-treatment with androgens and estrogens was evaluated. In particular, we analyzed parameters that reflect bone cell homeostasis such as cell viability, cell migration, transcriptomic profile, transcriptional activity, and epigenetic signature. Our findings indicate that estrogens and androgens counteract OS effects. Using partially overlapping strategies, they reduce OS outcomes regarding cell viability, cell migration, the transcriptomic profile of gene families involved in bone remodeling, and epigenetic profile, i.e., H3K4me3 level. Additionally, we demonstrated that the protective effect of steroids against OS on bone homeostasis is partially mediated by the Akt pathway. Overall, these results suggest that the hormonal milieu may influence the mechanisms of age-related bone disease.
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Osteocitos , Estrés Oxidativo , Antioxidantes , Hormonas Esteroides Gonadales , Humanos , OsteoblastosRESUMEN
Many of the recent advances in our understanding of human reproductive biology and its genetic basis have arisen directly via the genetic investigation of patients with Kallmann syndrome and their families. The disease is characterised by the association of an isolated defect in the secretion (or, less commonly, action) of gonadotropin-releasing hormone (GnRH) and consequent infertility, with anosmia and potentially other associated non-reproductive features. GnRH-producing neurons are located in the hypothalamic brain region after a peculiar migration during embryonic life. To date, different genes affecting GnRH neuron development/migration have so far been implicated in Kallmann syndrome, but our knowledge of the genetic basis of the syndrome remains incomplete. From a clinical point of view, the disease has suffered from a lack of definitive diagnosis and treatment, and although progress has been made in terms of timely diagnosis and evidence-based treatment of patients, implementation remains inconsistent. These aspects will be discussed in this review, which examines new strategies for arriving at more evidence-based and patient-centred medical practice in Kallmann syndrome.
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We present the case of a professional soccer player affected by right bundle branch block and symptomatic 2:1 atrio-ventricular block during effort, due to progressive cardiac conduction disease (Lev-Lenegre disease), who received successful left bundle branch area pacing after a failed attempt at His bundle pacing. The electrocardiographic outcome of paced QRS was consistent with a rapid electrical activation of the left ventricle through the Purkinje system. The pursue of physiological pacing was preferred over conventional, given the young age of our patient and the expectedly high burden of stimulation, to reduce the long-term risk of pacing-induced cardiomyopathy.
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Fascículo Atrioventricular , Estimulación Cardíaca Artificial , Atletas , Bloqueo de Rama/diagnóstico , Bloqueo de Rama/terapia , Electrocardiografía , HumanosRESUMEN
AIMS: Indications, methodology, and diagnostic criteria for carotid sinus massage (CSM) and tilt testing (TT) have been standardized by the 2018 Guidelines on Syncope of the European Society of Cardiology. Aim of this study was to assess their effectiveness in a large cohort which reflects the performance under 'real-world' conditions. METHODS AND RESULTS: We analysed all patients who had undergone CSM and TT in the years 2003-2019 for suspected reflex syncope. Carotid sinus massage was performed according to the 'Method of Symptoms'. Tilt testing was performed according to the 'Italian protocol' which consists of a passive phase followed by a sublingual nitroglycerine phase. For both tests, positive test was defined as reproduction of spontaneous symptoms in the presence of bradycardia and/or hypotension. Among 3293 patients (mean age 73 ± 12 years, 48% males), 2019 (61%) had at least one test positive. A bradycardic phenotype was found in 420 patients (13%); of these, 60% were identified by CSM, 37% by TT, and 3% had both test positive. A hypotensive phenotype was found in 1733 patients (53%); of these, 98% were identified by TT and 2% had both TT and CSM positive. CONCLUSION: The overall diagnostic yield of the tests in patients >40-year-old with suspected reflex syncope was 61%. Both CSM and TT are useful for identifying those patients with a bradycardic phenotype, whereas CSM has a limited value for identifying the hypotensive phenotype. Since the overlap of responses between tests is minimal, both CSM and TT should be performed in every patient over 40 years receiving investigation for unexplained but possible reflex syncope.
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Seno Carotídeo , Pruebas de Mesa Inclinada , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Italia , Masculino , Masaje , Persona de Mediana Edad , Reflejo , Síncope/diagnósticoRESUMEN
Bone remodeling and repair require osteogenic cells to reach the sites that need to be rebuilt, indicating that stimulation of osteoblast migration could be a promising osteoanabolic strategy. We showed that purified δ-tocotrienol (δ-TT, 10 µg/mL), isolated from commercial palm oil (Elaeis guineensis) fraction, stimulates the migration of both MC3T3-E1 osteoblast-like cells and primary human bone marrow mesenchymal stem cells (BMSC) as detected by wound healing assay or Boyden chamber assay respectively. The ability of δ-TT to promote MC3T3-E1 cells migration is dependent on Akt phosphorylation detected by Western blotting and involves Wnt/ß-catenin signalling pathway activation. In fact, δ-TT increased ß-catenin transcriptional activity, measured using a Nano luciferase assay and pretreatment with procaine (2 µM), an inhibitor of the Wnt/ß-catenin signalling pathway, reducing the wound healing activity of δ-TT on MC3T3-E1 cells. Moreover, δ-TT treatment increased the expression of ß-catenin specific target genes, such as Osteocalcin and Bone Morphogenetic Protein-2, involved in osteoblast differentiation and migration, and increased alkaline phosphatase and collagen content, osteoblast differentiation markers. The ability of δ-TT to enhance the recruitment of BMSC, and to promote MC3T3-E1 differentiation and migratory behavior, indicates that δ-TT could be considered a promising natural anabolic compound.
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Movimiento Celular/efectos de los fármacos , Osteoblastos/efectos de los fármacos , Vitamina E/análogos & derivados , Animales , Ciclo Celular/efectos de los fármacos , Línea Celular , Evaluación Preclínica de Medicamentos , Histona Acetiltransferasas/metabolismo , Ratones , Activación Transcripcional/efectos de los fármacos , Vitamina E/farmacología , beta Catenina/metabolismoRESUMEN
AIMS: The reproducibility of carotid sinus massage (CSM) is debated. The aim of this study was to assess the reproducibility according to the methodology and diagnostic criteria defined by the guidelines on syncope of the European Society of Cardiology. METHOD: Among 2800 patients with syncope who underwent CSM in the years 2005-2019, 109 patients (62 males; mean age 76 ± 10 years) had performed a second CSM after a median of 28 months. Carotid sinus hypersensitivity (CSH) was diagnosed when CSM elicited a pause of >3 s and/or a fall in systolic blood pressure >50 mm Hg without reproduction of spontaneous symptoms. Carotid sinus syndrome (CSS) was established when spontaneous symptoms were reproduced in the presence of bradycardia and/or hypotension. RESULTS: The reproducibility of CSM was 78% for 18 CSS patients, 41% for 29 CSH patients, and 77% for 62 negative patients. The corresponding interrater agreement was good for CSS (kappa = 0.66), moderate for negative CSM (kappa = 0.42), and poor for CSH (kappa = 0.30). Combining CSH and negative tests, their reproducibility rose to 90% with kappa = 0.66. CONCLUSION: CSS but not CSH has a good reproducibility. About half of patients with CSH had a negative response at the second test, thus suggesting a great overlap between them.
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Seno Carotídeo/fisiopatología , Síncope/diagnóstico , Síncope/fisiopatología , Anciano , Femenino , Humanos , Italia , Masculino , Reproducibilidad de los ResultadosRESUMEN
Hartsfield syndrome (HS) is an ultrarare developmental disorder mainly featuring holoprosencephaly and ectrodactyly. It is caused by heterozygous or biallelic variants in FGFR1. Recently, a dominant-negative effect was suggested for FGFR1 variants associated with HS. Here, exome sequencing analysis in a 12-year-old boy with HS disclosed a novel de novo heterozygous variant c.1934C>T in FGFR1 predicted to cause the p.(Ala645Val) amino-acid substitution. In order to evaluate whether the variant, changing a highly conserved residue of the kinase domain, affects FGFR1 function, biochemical studies were employed. We measured the FGFR1 receptor activity in FGF2-treated cell lines exogenously expressing wild-type or Ala645Val FGFR1 by monitoring the activation status of FGF2/FGFR1 downstream pathways. Our analysis highlighted that RAS/ERK1/2 signaling was significantly perturbed in cells expressing mutated FGFR1, in comparison with control cells. We also provided preliminary evidence showing a modulation of the autophagic process in cells expressing mutated FGFR1. This study expands the FGFR1 mutational spectrum associated with HS, provides functional evidence further supporting a dominant-negative effect of this category of FGFR1 variants and offers initial insights on dysregulation of autophagy in HS.
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Labio Leporino , Fisura del Paladar , Dedos/anomalías , Deformidades Congénitas de la Mano , Holoprosencefalia , Discapacidad Intelectual , Sistema de Señalización de MAP Quinasas , Mutación Missense , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos , Sustitución de Aminoácidos , Labio Leporino/genética , Labio Leporino/metabolismo , Labio Leporino/patología , Fisura del Paladar/genética , Fisura del Paladar/metabolismo , Fisura del Paladar/patología , Femenino , Dedos/patología , Genes Dominantes , Deformidades Congénitas de la Mano/genética , Deformidades Congénitas de la Mano/metabolismo , Deformidades Congénitas de la Mano/patología , Holoprosencefalia/genética , Holoprosencefalia/metabolismo , Holoprosencefalia/patología , Humanos , Discapacidad Intelectual/genética , Discapacidad Intelectual/metabolismo , Discapacidad Intelectual/patología , Masculino , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/genética , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Proteínas ras/genética , Proteínas ras/metabolismoRESUMEN
Gonadotropin-releasing hormone (GnRH) is recognized as the central regulator of the functions of the pituitary-gonadal axis. The increasing knowledge on the mechanisms controlling the development and the function of GnRH-producing neurons is leading to a better diagnostic and therapeutic approach for hypogonadotropic hypogonadisms and for alterations of the puberty onset. During female life span, the function of the GnRH pulse generator may be affected by a number of inputs from other neuronal systems, offering alternative strategies for diagnostic and therapeutic interventions. Moreover, the identification of a GnRH/GnRH receptor system in both human ovary and endometrium has widened the spectrum of action of the peptide outside its hypothalamic functions. The pharmacological use of GnRH itself or its synthetic analogs (agonists and antagonists) provides a valid tool to either stimulate or block gonadotropin secretion and to modulate the female fertility in several reproductive disorders and in assisted reproduction technology. The use of GnRH agonists in young female patients undergoing chemotherapy is also considered a promising therapeutic approach to counteract iatrogenic ovarian failure.
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Hormona Liberadora de Gonadotropina/metabolismo , Sistema Hipotálamo-Hipofisario/fisiología , Modelos Biológicos , Células Neuroendocrinas/fisiología , Ovario/fisiología , Precursores de Proteínas/metabolismo , Receptores LHRH/agonistas , Reproducción , Animales , Endometrio/efectos de los fármacos , Endometrio/crecimiento & desarrollo , Endometrio/fisiología , Endometrio/fisiopatología , Femenino , Fármacos para la Fertilidad Femenina/farmacología , Fármacos para la Fertilidad Femenina/uso terapéutico , Preservación de la Fertilidad/tendencias , Hormona Liberadora de Gonadotropina/química , Humanos , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/crecimiento & desarrollo , Sistema Hipotálamo-Hipofisario/fisiopatología , Infertilidad Femenina/tratamiento farmacológico , Infertilidad Femenina/patología , Infertilidad Femenina/fisiopatología , Infertilidad Femenina/terapia , Ciclo Menstrual/efectos de los fármacos , Células Neuroendocrinas/citología , Células Neuroendocrinas/metabolismo , Células Neuroendocrinas/patología , Ovario/efectos de los fármacos , Ovario/crecimiento & desarrollo , Ovario/fisiopatología , Embarazo , Insuficiencia Ovárica Primaria/tratamiento farmacológico , Insuficiencia Ovárica Primaria/patología , Insuficiencia Ovárica Primaria/fisiopatología , Isoformas de Proteínas/agonistas , Isoformas de Proteínas/metabolismo , Precursores de Proteínas/química , Pubertad/efectos de los fármacos , Receptores LHRH/antagonistas & inhibidores , Receptores LHRH/metabolismo , Receptores LHRH/uso terapéutico , Reproducción/efectos de los fármacos , Transducción de Señal/efectos de los fármacosRESUMEN
The activation of nicotinic cholinergic receptors (nAChR) inhibits the reproductive axis; however, it is not clear whether nicotine may directly modulate the release of hypothalamic gonadotropin-releasing hormone (GnRH). Experiments carried out in GT1-1 immortalized GnRH neurons reveal the presence of a single class of high affinity α4ß2 and α7 nAchR subtypes. The exposure of GT1-1 cells to nicotine does not modify the basal accumulation of GnRH. However, nicotine was found to modify GnRH pulsatility in perifusion experiments and inhibits, the release of GnRH induced by prostaglandin E1 or by K+-induced cell depolarization; these effects were reversed by D-tubocurarine and α-bungarotoxin. In conclusion, the results reported here indicate that: functional nAChRs are present on GT1-1 cells, the activation of the α-bungarotoxin-sensitive subclass (α7) produces an inhibitory effect on the release of GnRH and that the direct action of nicotine on GnRH neurons may be involved in reducing fertility of smokers.
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Hormona Liberadora de Gonadotropina/metabolismo , Nicotina/farmacología , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo , Alprostadil/metabolismo , Línea Celular , AMP Cíclico/metabolismo , Humanos , Potasio/farmacologíaRESUMEN
It is accepted that confusion regarding the description of genetic variants occurs when researchers do not use standard nomenclature. The Human Genome Organization Gene Nomenclature Committee contacted a panel of consultants, all working on the KAL1 gene, to propose an update of the nomenclature of the gene, as there was a convention in the literature of using the 'KAL1' symbol, when referring to the gene, but using the name 'anosmin-1' when referring to the protein. The new name, ANOS1, reflects protein name and is more transferrable across species.
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Proteínas de la Matriz Extracelular/genética , Síndrome de Kallmann/genética , Proteínas del Tejido Nervioso/genética , Terminología como Asunto , Animales , Proteínas de la Matriz Extracelular/química , Proteínas de la Matriz Extracelular/metabolismo , Humanos , Proteínas del Tejido Nervioso/química , Proteínas del Tejido Nervioso/metabolismoRESUMEN
INTRODUCTION: The aim of this study was to assess long-term results after single and multiple procedures of catheter ablation of ventricular tachycardia (VT). While it is generally accepted that multiple procedures are sometimes necessary in order to achieve long-term clinical success, the literature on this issue displays wide variability. METHODS: We assessed the outcome of 160 consecutive patients who underwent 214 ablation procedures in the period 2008 to May 2015: 93 had overt structural heart disease (SHD) (previous myocardial infarction in 74 cases) and 67 had no SHD. RESULTS: After the first procedure, the 1-year actuarial recurrence rates were 25% in patients with SHD and 5% in those without. However, recurrences increased progressively after the first year, reaching 46% and 35%, respectively, at 5 years. Overall, VT recurred in 35/93 (38%) patients with SHD and 22/67 (33%) patients without. Redo (1 to 4) procedures were performed in 28 (20%) patients with SHD and 18 (27%) patients without. After the last procedure, the 1-year actuarial recurrence rates were 5% in patients with SHD and 7% in those without, and the corresponding rates at 5 years were 23% and 7%. During follow-up, 21 patients died (all in the SHD group): no death was related to VT recurrence. CONCLUSIONS: During long-term follow-up, VT frequently recurs after the first procedure, both in patients with SHD and in those without; multiple procedures are needed in order to increase the success rate.