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Objectives: Evaluate the prevalence of genetic factors in a large population of infertile subjects and define the seminological, hormonal, and ultrasonographic features for each alteration. Methods: This single-center retrospective study included male partners of infertile couples undergoing genetic investigations due to oligozoospermia or azoospermia evaluated from January 2012 to January 2022. The genetic investigations consist of karyotype, CFTR gene mutations plus variant of the IVS8-5T polymorphic trait, Y chromosome microdeletion, and Next Generation Sequencing panel to analyze genes implicated in congenital hypogonadotropic hypogonadism (CHH). Results: Overall, 15.4% (72/466) of patients received a diagnosis of genetic cause of infertility. Specifically, 23 patients (31.9%) harbor mutations in the CFTR gene, 22 (30.6%) have a 47, XXY karyotype, 14 (19.4%) patients show a Y chromosome microdeletion, 7 (9.7%) have structural chromosomal anomalies, and 6 (8.3%) have CHH. Overall, 80.6% of patients were azoospermic and 19.4% oligozoospermic (sperm concentration 3.5 ± 3.8 million/mL). Almost all patients presented hormonal alterations related to the specific genotype, while the main ultrasound alterations were testicular hypoplasia, calcifications/microcalcifications, and enlarged/hyperechoic epididymis. Conclusions: The prevalence of genetic abnormalities in males of infertile couples was 15.4% in our Center. CFTR gene disease-causing variants resulted in more frequent, with various clinical features, highlighting the complexity and heterogeneity of the presentation. Other investigations are needed to understand if conditions like ring chromosomes and other translocations are related to infertility or are incidental factors.
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The aim of this study is to evaluate the predictive role of specific clinical factors for the diagnosis of Multiple Endocrine Neoplasia type-1 (MEN1) and type-4 (MEN4) in patients with an initial diagnosis of gastrointestinal, bronchial, or thymic neuroendocrine tumor (NET). METHODS: Patients referred to the NET Unit between June 2021 and December 2022 with a diagnosis of NET and at least one clinical criterion of suspicion for MEN1 and MEN4 underwent molecular analysis of the MEN1 and CDKN1B genes. Phenotypic criteria were: (1) age ≤ 40 years; (2) NET multifocality; (3) MEN1/4-associated manifestations other than NETs; and (4) endocrine syndrome related to NETs or pituitary/adrenal tumors. RESULTS: A total of 22 patients were studied. In 18 patients (81.8%), the first-level genetic test was negative (Group A), while four patients (25%) were positive for MEN1 (Group B). No patient was positive for MEN4. In Group A, 10 cases had only one clinical criterion, and three patients met three criteria. In Group B, three patients had three criteria, and one met all criteria. CONCLUSION: These preliminary data show that a diagnosis of NET in patients with a negative family history is suggestive of MEN1 in the presence of ≥three positive phenotypic criteria, including early age, multifocality, multiple MEN-associated manifestations, and endocrine syndromes. This indication may allow optimization of the diagnosis of MEN in patients with NET.
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Neoplasia Endocrina Múltiple Tipo 1 , Tumores Neuroendocrinos , Neoplasias Hipofisarias , Humanos , Adulto , Neoplasia Endocrina Múltiple Tipo 1/diagnóstico , Neoplasia Endocrina Múltiple Tipo 1/genética , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/patología , Neoplasias Hipofisarias/genética , Pruebas Genéticas , Tracto Gastrointestinal/patologíaRESUMEN
ACM is a rare hereditary heart disease characterized by a progressive fibro-fatty replacement of the myocardium that can affect either the right or the left ventricle or both. It is mainly caused by variants in the desmosome genes with autosomal dominant transmission and incomplete penetrance. The disease shows a wide spectrum of clinical manifestations, including ventricular arrhythmias, HF and myocarditis. The latter is considered a 'hot phase' in the natural history of the disease and must therefore be distinguished from the isolated AM, which is frequently due to viral infections. Our case report is an example of how an AM, as the first manifestation of the disease, helped to reach a diagnosis of ACM through the genetic analysis. In fact, the multi-parametric investigation, which also included CMR and EMB, revealed controversial aspects that led us to perform the genetic test. The latter revealed a heterozygous pathogenic variant in the PKP2 that was considered definitive proof of ACM.
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Background and Objectives: The aim of this study was to evaluate the impact of medications on oxidative stress, inflammatory biomarkers and semen characteristics in males with idiopathic infertility. Materials and Methods: In this observational case-control clinical study, 50 men with idiopathic infertility were enrolled, of whom 38 (the study group) were on pharmacological treatment and 12 made up the control group. The study group was clustered according to the medications (Group A: anti-hypertensive, n = 10; Group B: thyroxine, n = 6; Group C: non-steroidal anti-inflammatory drugs, n = 13; Group D: miscellaneous, n = 6; Group E: lipid-lowering drugs, n = 4). Semen analyses were performed according to WHO 2010 guidelines. Interleukins (IL)-10, IL-1 beta, IL-4, IL-6, Tumor Necrosis Factor- alpha (TNF-alpha) and IL-1 alpha were determined using a solid-phase sandwich immunoassay. The diacron reactive oxygen metabolites, d-ROMs test, was performed by means of a colorimetric determination of reactive oxygen metabolites and measured with a spectrophotometer. Beta-2-microglobulin and cystatin-C were measured with an immunoturbidimetric analyzer. Results: No differences between the study and control groups for age and macroscopic and microscopic semen characteristics were found, nor were any differences found after clustering according to the drug categories. IL-1 alpha and IL-10 were significantly lower in the study group compared with the control group; IL-10 was significantly lower in groups A, B, C and D compared with the control group. Furthermore, a direct correlation between IL-1 alpha, IL-10 and TNF-alpha and leukocytes was found. Conclusions: Despite the sample size limitations, the data suggest a correlation between drug use and activation of the inflammatory response. This could clarify the pathogenic mechanism of action for several pharmacological classes on male infertility.
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Infertilidad Masculina , Semen , Masculino , Humanos , Interleucina-1alfa/metabolismo , Factor de Necrosis Tumoral alfa/análisis , Interleucina-10/metabolismo , Infertilidad Masculina/tratamiento farmacológico , Estrés Oxidativo , Oxígeno/metabolismoRESUMEN
Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease, characterized by the presence of unexplained left ventricular hypertrophy. This condition is often associated with electrocardiographic abnormalities including QTc prolongation occurring in 13% of patients. The main explanation for prolonged QTc in HCM is myocardial hypertrophy and the related structural damage. However, other mechanisms, including long QT syndrome (LQTS) genes mutations, may be involved. In the present study we explored the hypothesis of a distinct genetic basis underlying QTc prolongation in HCM by investigating the potential co-inheritance of pathogenic gene variants associated with LQTS and HCM. For this purpose, starting from a cohort of 150 HCM patients carrying pathogenic variants in sarcomere genes, we selected 25 patients carrying a QTc prolongation unexplained by any other cause. The QTc was considered prolonged if greater than 450â ms in males and greater than 470â ms in females. The NGS analysis was performed with Illumina TrueSight Cardio panel genes on Illumina MiniSeq platform. We identified pathogenic/likely pathogenic variants in the KCNQ1 in two patients (c.1781G > A, p. Arg594Gln; c.532G > A, p. Ala178Thr) (8%). Variants of uncertain significance were identified in SCN5A, KCNJ5, AKAP9 and ANK2 in four patients (16%). Although the results are limited by the small number of patients included in the study, they highlight a minor contribution of LQTS genes for QTc prolongation in HCM patients. The screening for ion channel genes mutations may be considered in HCM patients with prolonged QTc unexplained by any other cause. This in-depth molecular diagnosis may contribute to improve risk stratification and treatment planning.
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Mitochondrial dysfunction, causing increased reactive oxygen species (ROS) production, is a molecular feature of heart failure (HF). A defective antioxidant response and mitophagic flux were reported in circulating leucocytes of patients with chronic HF and reduced ejection fraction (HFrEF). Atrial natriuretic peptide (ANP) exerts many cardiac beneficial effects, including the ability to protect cardiomyocytes by promoting autophagy. We tested the impact of ANP on autophagy/mitophagy, altered mitochondrial structure and function and increased oxidative stress in HFrEF patients by both ex vivo and in vivo approaches. The ex vivo study included thirteen HFrEF patients whose peripheral blood mononuclear cells (PBMCs) were isolated and treated with αANP (10-11 M) for 4 h. The in vivo study included six HFrEF patients who received sacubitril/valsartan for two months. PBMCs were characterized before and after treatment. Both approaches analyzed mitochondrial structure and functionality. We found that levels of αANP increased upon sacubitril/valsartan, whereas levels of NT-proBNP decreased. Both the ex vivo direct exposure to αANP and the higher αANP level upon in vivo treatment with sacubitril/valsartan caused: (i) improvement of mitochondrial membrane potential; (ii) stimulation of the autophagic process; (iii) significant reduction of mitochondrial mass-index of mitophagy stimulation-and upregulation of mitophagy-related genes; (iv) reduction of mitochondrial damage with increased inner mitochondrial membrane (IMM)/outer mitochondrial membrane (OMM) index and reduced ROS generation. Herein we demonstrate that αANP stimulates both autophagy and mitophagy responses, counteracts mitochondrial dysfunction, and damages ultimately reducing mitochondrial oxidative stress generation in PBMCs from chronic HF patients. These properties were confirmed upon sacubitril/valsartan administration, a pivotal drug in HFrEF treatment.
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Insuficiencia Cardíaca , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Factor Natriurético Atrial , Tetrazoles/farmacología , Tetrazoles/uso terapéutico , Mitofagia , Leucocitos Mononucleares , Especies Reactivas de Oxígeno , Volumen Sistólico , Antagonistas de Receptores de Angiotensina/farmacología , Antagonistas de Receptores de Angiotensina/uso terapéutico , Valsartán/farmacología , Valsartán/uso terapéutico , MitocondriasRESUMEN
Both genetic and environmental factors contribute to the development of dilated cardiomyopathy. Among the genes involved, TTN mutations, including truncated variants, explain 25% of DCM cases. We performed genetic counseling and analysis on a 57-year-old woman diagnosed with severe DCM and presenting relevant acquired risk factors for DCM (hypertension, diabetes, smoking habit, and/or previous alcohol and cocaine abuse) and with a family history of both DCM and sudden cardiac death. The left ventricular systolic function, as assessed by standard echocardiography, was 20%. The genetic analysis performed using TruSight Cardio panel, including 174 genes related to cardiac genetic diseases, revealed a novel nonsense TTN variant (TTN:c.103591A > T, p.Lys34531*), falling within the M-band region of the titin protein. This region is known for its important role in maintaining the structure of the sarcomere and in promoting sarcomerogenesis. The identified variant was classified as likely pathogenic based on ACMG criteria. The current results support the need of genetic analysis in the presence of a family history, even when relevant acquired risk factors for DCM may have contributed to the severity of the disease.
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Actinic keratosis (AK) is a preneoplastic skin disorder which can rapidly progress to cutaneous squamous cell carcinomas (SCCs). In light of our previous findings, indicating a possible oncogenic role of the mesenchymal isoform of FGFR2 (FGFR2c) aberrantly expressed in AK keratinocytes, we analyzed the possible tumor-promoting role of this receptor in the stromal AK counterpart in this work. Molecular analysis showed that, particularly in early AK lesions, FGFR2c dermal upregulation is accompanied by the downregulation of the cancer-associated fibroblasts (CAF) transcription repressor CSL, the upregulation of the CAF activator ULK3, and the consequent CAF gene induction. Immunofluorescence and molecular analysis, coupled with silencing approaches by siRNA, applied on primary cultures of KIN I-derived fibroblasts, indicated that FGFR2c upregulation contribute to CAF signature and the increased autophagy in response to FGF2. Magnetic bead-based multiplex assay, combined with FGFR2 signaling shut-off approaches, indicated that, especially in response to FGF2, IL-6 secretion could depend on FGFR2c high expression and signaling, suggesting the possible establishment of FGFR2c-dependent secretory autophagy, contributing to tumor-promoting factor release. Overall, our results identified FGFR2c as a signaling molecule involved in controlling precancerous/stromal cell oncogenic crosstalk, pointing to this receptor as a possible early molecular marker predictive for AK's rapid malignant progression.
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ABSTRACT: Perroni, F, Castagna, C, Amatori, S, Gobbi, E, Vetrano, M, Visco, V, Guidetti, L, Baldari, C, Luigi Rocchi, MB, and Sisti, D. Use of exploratory factor analysis to assess the fitness performance of youth football players. J Strength Cond Res 37(7): e430-e437, 2023-Football performance involves several physical abilities that range in aerobic, anaerobic, and neuromuscular domains; however, little is known about their interplay in profiling individual physical attributes. This study aimed to profile physical performance in youth football players according to their training status. One hundred seven young male soccer players (age 13.5 ± 1.4 years; height 168 ± 7 cm; body mass 57.4 ± 9.6 kg; and body mass index 20.2 ± 2.1 kg·m -2 ) volunteered for this study. Players' physical performance was assessed with football-relevant field tests for sprinting (10 m sprint), vertical jump (countermovement jump), intermittent high-intensity endurance (Yo-Yo Intermittent Recovery Test Level 1, YYIRT1), and repeated sprint ability (RSA). The training status was assumed as testosterone and cortisol saliva concentrations; biological maturation was estimated using the Pubertal Development Scale. Exploratory factor analysis (EFA) revealed 3 main variables depicting anthropometric (D1, 24.9%), physical performance (D2, 18.8%), and training status (D3, 13.3%), accounting for 57.0% of total variance altogether. The level of significance was set at p ≤ 0.05. The RSA and YYIRT1 performances were largely associated with D2, suggesting the relevance of endurance in youth football. This study revealed that for youth football players, a 3-component model should be considered to evaluate youth soccer players. The EFA approach may help to disclose interindividual differences useful to talent identification and selection.
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Rendimiento Atlético , Fútbol , Humanos , Masculino , Adolescente , Niño , Aptitud Física , Prueba de EsfuerzoRESUMEN
Juvenile polyposis syndrome (JPS) is an autosomal dominant disorder characterized by hyperplastic polyps in the upper and lower gastrointestinal (GI) tract with a high risk of developing GI cancers. We have described a three-generation Italian family with all the spectrum of SMAD4 phenotype. A multigene panel test was performed on the genomic DNA of the proband by next-generation sequencing, including genes related to hereditary GI tumor syndromes. Molecular analysis revealed the presence of the c.1140-2A>G substitution in the SMAD4 gene, a novel splice variant that has never been described before. Our family is remarkable in that it illustrates the variable expressivity of the SMAD4 phenotype within the same family. The possibility of phenotype variability should also be considered within family members carrying the same mutation. In JPS, a timely genetic diagnosis allows clinicians to better manage patients and to provide early surveillance and intervention for their asymptomatic mutated relatives in the early decades of life.
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We report here a case of a patient affected by B-cell chronic lymphocytic leukemia (CLL) that developed COVID-19 during the actual SARS-CoV-2 outbreak. The coexistence of CLL and COVID-19 raises many questions regarding the possible increased risk of developing COVID-19 among patients with CLL, the problems in managing therapies for both diseases and, above all, the difficulties in diagnosing COVID-19 in patients affected by CLL. In our patient, an 84-year-old man, the recognition of COVID-19 was delayed because of its atypical clinical presentation and technical problems related to the methods used for the diagnosis. Based on the symptoms and the radiological aspect of the lung, the occurrence of COVID-19 was suspected. Repeated tests on oro/nasopharyngeal swabs gave negative results, causing a delay in the diagnosis. Moreover, different methods used to identify the SARS-CoV-2 antibodies in serum gave conflicting results, and only two tests were able to identify SARS-CoV-2 Abs of the IgG type. During the clinical course of unrecognized COVID-19, our patient developed severe complications and did not receive any specific treatment for the two diseases. Recognition of COVID-19 in patients with CLL is a challenging task and the most accurate methods are necessary to overcome the diagnostic difficulties encountered.
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This pilot study explores the effects of a post-operative physical exercise program on the quality of life (QoL) and functional and nutritional parameters of patients that underwent laparoscopic colorectal cancer surgery, compared to usual care alone. The intervention group (IG) attended a 2-month-long supervised and combined exercise-training program during the post-operative period. Both IG and control group (CG) participated in the QoL, functional, and nutritional assessments before exercise training (T0), 2 months after the beginning of the exercise (end of treatment) (T1), and 2 (T2) and 4 (T3) months from the end of treatment. Eleven patients with colorectal cancer that underwent laparoscopic surgery were enrolled (six intervention; five control). The IG showed significant improvements compared to the CG in "Physical functioning" (PF2) (p = 0.030), "Cognitive functioning" (CF) (p = 0.018), and "Fatigue" (FA) (p = 0.017) of the European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) at T1; in SMWT (p = 0.022) at T1; in PF2 (p = 0.018) and FA (p = 0.045) of EORTC QLQ-C30 at T2, in phase angle (PhA) of bioelectrical impedance analysis (p = 0.022) at T3. This pilot study shows that a post-operative, combined, and supervised physical exercise program may have positive effects in improving the QoL, functional capacity, and nutritional status in patients that undergo laparoscopic colorectal cancer surgery.
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Neoplasias Colorrectales , Laparoscopía , Neoplasias Colorrectales/cirugía , Fatiga , Humanos , Proyectos Piloto , Calidad de VidaRESUMEN
Military personnel of all armed forces receive multiple vaccinations and have been doing so since long ago, but relatively few studies have investigated the possible negative or positive interference of simultaneous vaccinations. As a contribution to fill this gap, we analyzed the response to the live trivalent measles/mumps/rubella (MMR), the inactivated hepatitis A virus (HAV), the inactivated trivalent polio, and the trivalent subunits influenza vaccines in two cohorts of Italian military personnel. The first cohort was represented by 108 students from military schools and the second by 72 soldiers engaged in a nine-month mission abroad. MMR and HAV vaccines had never been administered before, whereas inactivated polio was administered to adults primed at infancy with a live trivalent oral polio vaccine. Accordingly, nearly all subjects had baseline antibodies to polio types 1 and 3, but unexpectedly, anti-measles/-mumps/-rubella antibodies were present in 82%, 82%, and 73.5% of subjects, respectively (43% for all of the antigens). Finally, anti-HAV antibodies were detectable in 14% and anti-influenza (H1/H3/B) in 18% of the study population. At mine months post-vaccination, 92% of subjects had protective antibody levels for all MMR antigens, 96% for HAV, 69% for the three influenza antigens, and 100% for polio types 1 and 3. An inverse relationship between baseline and post-vaccination antibody levels was noticed with all the vaccines. An excellent vaccine immunogenicity, a calculated long antibody persistence, and apparent lack of vaccine interference were observed.
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We previously examined the safety and immunogenicity of multiple vaccines administered to a military cohort, divided into two groups, the first composed of students at military schools, thus operating inside the national borders for at least 3 years, and the other formed of soldiers periodically engaged in a 9-month-long mission abroad (Lebanon). In the current study, we analyzed 112 individuals of this cohort, 50 pertaining to the first group and 62 to the second group, in order to examine the possible late appearance of side effects and to calculate the half-life of the induced antibodies. Moreover, the possible involvement of B-cell polyclonal activation as a pathogenetic mechanism for long term antibody persistence has even been explored. No late side effects, as far as autoimmunity and/or lymphoproliferation appearance, have been noticed. The long duration of the vaccine induced anti-HAV antibodies has been confirmed, whereas the antibodies induced by tetravalent meningococcal polysaccharide vaccine have been found to persist above the threshold for putative protection for a longer time, and anti-tetanus, diphtheria, and polio 1 and 3 for a shorter time than previously estimated. No signs of polyclonal B-cell activation have been found, as a possible mechanism to understand the long antibody persistence.
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The study aimed to investigate the correlations among immune, haematological, endocrinological markers and fitness parameters, and assess if the physiological parameters could be a predictor of fitness values. Anthropometric, physical evaluations (countermovement jump-CMJ, 10 m sprint, VO2max, repeated sprint ability-RSA total time and index) and determination of blood (IL-6, IL-10, IL-17A and tumour necrosis factor) and salivary (testosterone and cortisol) samples parameters in 28 young male soccer players (age: 13.0 ± 0.2 years, body mass index (BMI): 19.5 ± 2.2 kg/m2) were analysed. To evaluate the dependence of the variables related to athletic performance, multiple linear regression with backward stepwise elimination was considered. A significant regression equation was found in CMJ (F(5,16) = 9.86, p < 0.001, R2 adjusted = 0.679) and in the RSA index (F(5,16) = 15.39, p < 0.001, R2 adjusted = 0.774) considering only five variables, in a 10 m sprint (F(4,17) = 20.25, p < 0.001, R2 adjusted = 0.786) and in the RSA total time (F(4,17) = 15.31, p < 0.001, R2 adjusted = 0.732) considering only four variables and in VO2max (F(9,12) = 32.09, p < 0.001, R2 adjusted = 0.930) considering nine variables. Our study suggests the use of regression equations to predict the fitness values of youth soccer players by blood and saliva samples, during different phases of the season, short periods of match congestion or recovery from an injury.
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Biomarcadores , Aptitud Física , Carrera , Fútbol , Adolescente , Niño , Prueba de Esfuerzo , Humanos , Masculino , Proyectos PilotoRESUMEN
Novel strategies have been proposed for articular cartilage damage occurring during osteoarthritis (OA) and -among these- Extracorporeal Shock Wave Therapy (ESWT), intra-articular injections of Platelet-Rich Plasma (PRP) or Hyaluronic Acid (HA) revealed encouraging results. To investigate the possible mechanisms responsible for those clinical benefits, we established primary cultures of human chondrocytes derived from cartilage explants and measured the in vitro effects of ESW, PRP and HA therapies. After molecular/morphological cell characterization, we assessed those effects on the functional activities of the chondrocyte cell cultures, at the protein and molecular levels. ESWT significantly prevented the progressive dedifferentiation that spontaneously occurs during prolonged chondrocyte culture. We then attested the efficiency of all such treatments to stimulate the expression of markers of chondrogenic potential such as SOX9 and COL2A, to increase the Ki67 proliferation index as well as to antagonize the traditional marker of chondrosenescence p16INK4a (known as Cdkn2a). Furthermore, all our samples showed an ESW- and HA-mediated enhancement of migratory and anti-inflammatory activity onto the cytokine-rich environment characterizing OA. Taken together, those results suggest a regenerative effect of such therapies on primary human chondrocytes in vitro. Moreover, we also show for the first time that ESW treatment induces the surface expression of major hyaluronan cell receptor CD44 allowing the increase of COL2A/COL1A ratio upon HA administration. Therefore, this work suggests that ESW-induced CD44 overexpression enhances the in vitro cell susceptibility of human chondrocytes to HA, presumably favouring the repair of degenerated cartilage.
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Condrocitos/fisiología , Receptores de Hialuranos/metabolismo , Ácido Hialurónico/administración & dosificación , Osteoartritis/terapia , Plasma Rico en Plaquetas/química , Regeneración , Anciano , Cartílago Articular/citología , Cartílago Articular/efectos de los fármacos , Cartílago Articular/fisiología , Células Cultivadas , Condrocitos/citología , Condrocitos/efectos de los fármacos , Técnicas de Cocultivo , Tratamiento con Ondas de Choque Extracorpóreas , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Ácido Hialurónico/farmacología , Inyecciones Intraarticulares , Persona de Mediana Edad , Osteoartritis/inmunologíaRESUMEN
Extracorporeal shock wave therapy (ESWT) is a non-invasive and innovative technology for the management of specific tendinopathies. In order to elucidate the ESWT-mediated clinical benefits, human Tendon-derived Stem/Progenitor cells (hTSPCs) explanted from 5 healthy semitendinosus (ST) and 5 ruptured Achilles (AT) tendons were established. While hTSPCs from the two groups showed similar proliferation rates and stem cell surface marker profiles, we found that the clonogenic potential was maintained only in cells derived from healthy donors. Interestingly, ESWT significantly accelerated hTSPCs differentiation, suggesting that the clinical benefits of ESWT may be ascribed to increased efficiency of tendon repair after injury.
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Diferenciación Celular/fisiología , Proliferación Celular/fisiología , Ondas de Choque de Alta Energía , Células Madre/citología , Traumatismos de los Tendones/patología , Tendones/citología , Adipogénesis/efectos de la radiación , Diferenciación Celular/efectos de la radiación , Proliferación Celular/efectos de la radiación , Células Cultivadas , Técnica del Anticuerpo Fluorescente , Humanos , Técnicas In Vitro , Osteogénesis/efectos de la radiación , Células Madre/fisiología , Células Madre/efectos de la radiación , Traumatismos de los Tendones/radioterapia , Tendones/fisiología , Tendones/efectos de la radiaciónRESUMEN
Encouraging results using extracorporeal shock wave therapy (ESWT) for treating chronic tendinopathies were recently obtained, although the specific mechanisms by which it induces therapeutic effects remain largely unknown. In order to provide possible explications of such clinical efficacy, several reports have investigated the effects of ESWT on animal models and different kind of cultured cells. Our contribute in establishing the potential outcome of ESWT on human primary cultured tenocytes, derived from healthy compared to ruptured tendons, have supported the growing evidence that shock waves may supply faster post-injury recovery. The purpose of this review was to summarize and evaluate the available basic scientific evidences for using ESWT in tendon pathologies, suggesting possible shock waves-induced mechanisms of tissue repair.
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We investigated the hypothesis that patients developing high-grade erythema of the breast skin during radiation treatment could be more likely to present increased levels of proinflammatory cytokines which may lead, in turn, to associated fatigue. Forty women with early stage breast cancer who received adjuvant radiotherapy were enrolled from 2007 to 2010. Fatigue symptoms, erythema, and cytokine levels (IL-1ß, IL-2, IL6, IL-8, TNF-α, and MCP-1) were registered at baseline, during treatment, and after radiotherapy completion. Seven (17.5%) patients presented fatigue without associated depression/anxiety. Grade ≥2 erythema was observed in 5 of these 7 patients. IL-1ß, IL-2, IL-6, and TNF-α were statistically increased 4 weeks after radiotherapy (P < 0.05). After the Heckman two-step analysis, a statistically significant influence of skin erythema on proinflammatory markers increase (P = 0.00001) was recorded; in the second step, these blood markers showed a significant impact on fatigue (P = 0.026). A seeming increase of fatigue, erythema, and proinflammatory markers was observed between the fourth and the fifth week of treatment followed by a decrease after RT. There were no significant effects of hormone therapy, breast volume, and anemia on fatigue. Our study seems to suggest that fatigue is related to high-grade breast skin erythema during radiotherapy through the increase of cytokines levels.