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Healthcare workers (HCWs) can be considered at an increased risk of developing occupational contact dermatitis (OCD) due to repetitive hand washing with soaps and disinfectants and extended use of gloves for many hours during the day. The aim of this study was to summarize the incidence of OCD in HCWs. We searched the databases PubMed/MEDLINE (1980-present), EMBASE (1980-present) and Cochrane Library (1992-present) through May 2020 using the search term 'incidence of contact dermatitis in HCWs' according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Overall, 16 studies (six cohorts; 10 register-based) with follow-up periods between 1987 and 2013 fulfilled the inclusion criteria. The incidence of OCD reported in studies using registers of occupational diseases ranged from 0.6 to 6.7 per 10 000 person-years. The cohort studies reported incidence from 15.9 to 780.0 per 10 000 person-years; the incidence was higher in studies which included apprentice nurses. A higher incidence was also observed amongst dental practitioners, particularly dental technicians and nurses, compared to other HCWs. Studies reporting incidence data are very scarce and results differed by study design, type of contact dermatitis and investigated HCWs. Our study highlighted the dearth of high-quality data on the incidence of OCD and the possible underestimation of disease burden. Prospective cohort studies with harmonized designs, especially exposure assessment and outcome ascertainment, are required to provide more accurate, valid and recent estimates of the incidence of OCD. A high incidence amongst specific occupational groups suggests the need to undertake intervention studies with a focus on prevention, particularly during pandemics such as COVID-19.
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COVID-19 , Dermatitis Profesional , Enfermedades Profesionales , Exposición Profesional , Odontólogos , Dermatitis Profesional/epidemiología , Dermatitis Profesional/etiología , Personal de Salud , Humanos , Incidencia , Rol Profesional , Estudios Prospectivos , SARS-CoV-2RESUMEN
Minimally invasive Heller myotomy is considered the gold standard surgical approach for symptomatic achalasia because it is a safe and effective procedure. Over the last years, several studies comparing the laparoscopic and robotic approach for Heller myotomy have been published. Although the robotic approach appears to have some advantages over standard laparoscopy, data on this topic are still controversial and no definite conclusions have been drawn. This metanalysis has been designed to systematically evaluate and compare the effectiveness and safety of the robot-assisted Heller myotomy as compared to the standard laparoscopic approach. According to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a systematic search on both laparoscopic and robotic Heller myotomy was performed in all the major electronic databases (PubMed, Web of Science, Scopus, EMBASE), using the following search string: (achalasia OR Dor) AND robotic. Six articles were included in the final analysis. A metaregression analysis was performed to assess the possible effects of demographic variables (age, gender, body mass indes (BMI)) and previous abdominal surgery or endoscopic intervention on the analyzed outcomes. No statistical difference was observed in operative times (mean difference (MD) = 20.79, P = 0.19, 95% confidence interval (CI) -10.05,51,62), estimated blood loss (MD = -17.10, P = 0.13, 95% CI -40.48,5.08), conversion rate to open surgery (risk difference (RD) = -0.01, P = 0.33, 95% CI -0.05,0.02), length of hospital stay (MD = -0.73, P = 0.15, 95% CI -1.71,0.25) and long-term recurrence (odds ratio (OR) = 0.59, P = 0.45, 95% CI 0.15,2.33). On the contrary, the robotic approach was found to be associated with a significantly significant lower rate of intraoperative esophageal perforations (OR = 0.13, P < 0.001, 95% CI 0.04, 0.45). Our results suggest that the robotic approach is safer than the laparoscopic Heller myotomy, encouraging the use of robot-assisted surgery. However, our analysis is limited because of the exiguous number of comparative studies and because most of the included studies were statistically underpowered, given the small sample size. Moreover, a high degree of heterogeneity was observed in most of published studies. Taking in consideration the additional costs of robot-assisted procedures, larger Randomized Controlled Trials (RCTs) are advocated to confirm the safety and effectiveness of the robotic approach, and its advantages over standard laparoscopic surgery. In conclusion, well-designed prospective trials and RCTs with homogeneous parameters are needed to draw definitive conclusions about the best surgical approach to pursue in treating symptomatic achalasia.
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Acalasia del Esófago/cirugía , Miotomía de Heller/estadística & datos numéricos , Laparoscopía/estadística & datos numéricos , Procedimientos Quirúrgicos Robotizados/estadística & datos numéricos , Conversión a Cirugía Abierta/estadística & datos numéricos , Femenino , Miotomía de Heller/métodos , Humanos , Laparoscopía/métodos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Tempo Operativo , Procedimientos Quirúrgicos Robotizados/métodos , Resultado del TratamientoRESUMEN
In addition to the well-known involvement of macrophages and neutrophils, other cell types have been recently reported to substantially contribute to the onset and progression of inflammatory bowel diseases (IBD). Enteric glial cells (EGC) are the equivalent cell type of astrocyte in the central nervous system (CNS) and share with them many neurotrophic and neuro-immunomodulatory properties. This short review highlights the role of EGC in IBD, describing the role played by these cells in the maintenance of gut homeostasis, and their modulation of enteric neuronal activities. In pathological conditions, EGC have been reported to trigger and support bowel inflammation through the specific over-secretion of S100B protein, a pivotal neurotrophic factor able to induce chronic inflammatory changes in gut mucosa. New pharmacological tools that may improve the current therapeutic strategies for inflammatory bowel diseases (IBD), lowering side effects (i.e. corticosteroids) and costs (i.e. anti-TNFα monoclonal antibodies) represent a very important challenge for gastroenterologists and pharmacologists. Novel drugs capable to modulate enteric glia reactivity, limiting the pro-inflammatory release of S100B, may thus represent a significant innovation in the field of pharmacological interventions for inflammatory bowel diseases.
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Enfermedades Inflamatorias del Intestino/etiología , Intestinos/inervación , Neuroglía/fisiología , Animales , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Neuroglía/efectos de los fármacos , Óxido Nítrico/fisiología , Subunidad beta de la Proteína de Unión al Calcio S100/fisiologíaRESUMEN
In order to evaluate the impact of cigarettes smoking and smokers' clinical characteristics on skin microvascular function, we measured the skin forearm blood flux, basally and during post-occlusive reactive hyperaemia, in 100 current smokers (mean age 51±11 years; range: 18 to 86 years) and in 66 healthy never-smokers matched for age and sex, by using laser Doppler fluximetry (LDF). Basal and post-ischemic LDF tracings were analyzed in the frequency domain within 0.009-0.02 Hz, 0.021-0.06 Hz and 0.061-0.2 Hz ranges, related to endothelial-dependent, sympathetic-dependent and myogenic-dependent vasomotion, respectively, using an adapted version of the Fourier analysis. The post-ischemic percentage change from baseline of the area under the LDF curve (AUC%) was significantly lower in smokers than in never-smokers [162.5% (139.3-183.0) vs 190.1% (156.3-216.8); p=0.00016]. Compared to controls, smokers also showed a reduced basal power spectral density (PSD) in the myogenic-dependent vasomotion (p=0.0034) and a reduced post-ischemic percentage increase in PSD of the endothelial-dependent vasomotion (p=0.0010) and sympathetic-dependent vasomotion (p=0.0016). An inverse relationship was observed in smokers between AUC% and smoking exposure duration (r=0.23, p=0.018), pack-years (r=0.33, p=0.0007), age (r=0.26, p=0.008) and body mass index (r=0.21, p=0.037). In the multiple linear regression model, pack-years was the only variable independently associated with AUC% (r=0.21, p=0.03). This study confirms that smoking is associated with cutaneous microvascular dysfunction and shows that the severity of this impairment is independently related to the duration and intensity of the exposure to smoking.
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Microcirculación , Microvasos/fisiopatología , Piel/irrigación sanguínea , Fumar/efectos adversos , Enfermedades Vasculares/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Velocidad del Flujo Sanguíneo , Estudios de Casos y Controles , Femenino , Análisis de Fourier , Hábitos , Humanos , Hiperemia/fisiopatología , Flujometría por Láser-Doppler , Modelos Lineales , Masculino , Persona de Mediana Edad , Flujo Sanguíneo Regional , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Enfermedades Vasculares/diagnóstico , Enfermedades Vasculares/fisiopatología , Adulto JovenRESUMEN
BACKGROUND: Recent lines of research have boosted awareness of the immunological facets of schizophrenia. However, associations with protein tyrosine phosphatase regulators have never been reported. The aim of our study was to investigate the expression and promoter status methylation of phosphatase SHP-1, a key negative regulator of the inflammatory process, in Peripheral blood mononuclear cells (PBMCs) of Schizophrenic patients. METHODS: We enrolled fifty-four (28 men and 26 women) unmedicated first episode subjects (SC) who met DSM-IV and thirty-eight (22 men and 16 women) healthy controls (HC). The SC psychopathological status was assessed using the Positive and Negative Syndrome Scale. We evaluated SHP-1 expression by Quantitative Real-time PCR (qPCR) and Western blotting (WB) methods and promoter status methylation through PCR bisulfate. IKK/NFkB signaling was detected by WB, and medium and plasma levels of pro-inflammatory cytokines (IL-1ß, IL-2, and TNF-α) by the ELISA method. SHP-1 was silenced by treating cells with specific siRNA. RESULTS: We found a significantly lower level of SHP-1 gene expression in PBMCs from SC vs. HC, consistently with which the promoter region analyzed presented significant hypermethylation. Silencing of SHP-1 expression induced higher activation of IKK/NF-kB signaling and pro-inflammatory cytokine production in ex vivo PBMCs from both SC and HC. Linear regression among patients generated a model in which SHP-1 expression explained 30% of the clinical negative symptom variance (adjusted R(2)=0.30, ANOVA p<0.001). CONCLUSIONS: Our findings are the first to suggest that impairment of SHP-1 expression is involved in the physiopathology of schizophrenia, opening fruitful new avenues for ameliorating treatment at least of negative symptoms.
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Citocinas/biosíntesis , Proteína Tirosina Fosfatasa no Receptora Tipo 6/fisiología , Esquizofrenia/enzimología , Adulto , Proteína C-Reactiva/análisis , Citocinas/genética , Metilación de ADN , Femenino , Humanos , Quinasa I-kappa B/metabolismo , Leucocitos Mononucleares/enzimología , Masculino , Persona de Mediana Edad , FN-kappa B/metabolismo , Regiones Promotoras Genéticas , Proteína Tirosina Fosfatasa no Receptora Tipo 6/antagonistas & inhibidores , Proteína Tirosina Fosfatasa no Receptora Tipo 6/biosíntesis , Proteína Tirosina Fosfatasa no Receptora Tipo 6/genética , Interferencia de ARN , ARN Mensajero/biosíntesis , ARN Interferente Pequeño/farmacología , Esquizofrenia/genética , Esquizofrenia/inmunología , Esquizofrenia/fisiopatología , Psicología del Esquizofrénico , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: The number and projections of cancer survivors are necessary to meet the healthcare needs of patients, while data on cure prevalence, that is, the percentage of patients who will not die of cancer by time since diagnosis, are lacking. MATERIALS AND METHODS: Data from Italian cancer registries (duration of registration ranged from 9 to 40 years, with a median of 22 years) covering 47% of the population were used to calculate the limited-duration prevalence, the complete prevalence in 2018, projections to 2030, and cure prevalence, by cancer type, sex, age, and time since diagnosis. RESULTS: A total of 3 347 809 people were alive in Italy in 2018 after a cancer diagnosis, corresponding to 5.6% of the resident population. They will increase by 1.5% per year to 4 012 376 in 2030, corresponding to 6.9% of the resident population, 7.6% of women and â¼22% after age 75 years. In 2030, more than one-half of all prevalent cases (2 million) will have been diagnosed by ≥10 years. Those with breast (1.05 million), prostate (0.56 million), or colorectal cancers (0.47 million) will be 52% of all prevalent patients. Cure prevalence was 86% for all patients alive in 2018 (87% for patients with breast cancer and 99% for patients with thyroid or testicular cancer), increasing with time since diagnosis to 93% for patients alive after 5 years and 96% after 10 years. Among patients who survived at least 5 years, the excess risk of death (1 - cure prevalence) was <5% for patients with most cancer types except for those with cancers of the breast (8.3%), lung (11.1%), kidney (13.2%), and bladder (15.5%). CONCLUSIONS: Study findings encourage the implementation of evidence-based policies aimed at improving long-term clinical follow-up and rehabilitation of people living after cancer diagnosis throughout the course of the disease. Updated estimates of complete prevalence are important to enhance data-driven cancer control planning.
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Neoplasias , Humanos , Italia/epidemiología , Femenino , Masculino , Prevalencia , Neoplasias/epidemiología , Neoplasias/terapia , Anciano , Persona de Mediana Edad , Adulto , Adolescente , Adulto Joven , Niño , Anciano de 80 o más Años , Sistema de Registros , Supervivientes de Cáncer/estadística & datos numéricos , Preescolar , Lactante , Predicción , Recién NacidoRESUMEN
Heart failure (HF) is a common clinical syndrome with frequent exacerbations requiring hospitalization. Among the various mechanisms that underlie the pathogenesis of HF, the activation of the immune system leads to a progressive and redundant release of proinflammatory cytokines responsible for a variety of deleterious effects in heart failure, such as endothelial dysfunction, apoptosis of myocytes, activation of MMPs (Matrix Metallo Proteinases) and oxidative stress, with the result of decreased inotropism and clinical syndrome such as pulmonary edema,. The condition of oxidative stress induces the expression of genes coding for the proteins inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1). Twenty-five hospitalized cardiology patients with symptomatic acute congestive HF (NYHA Class III-IV) and impaired left ventricular (LV) function (ejection fraction less than 35 percent) were included in the study. The aim of this study was to evaluate the cytokines plasma concentrations and the expression and activity of iNOS and HO-1 proteins in peripheral blood mononuclear cell (PBMC) extracted from patients in comparison to control group. In ACHF; left ventricular ejection fraction (LVEF) percent was reduced. Furthermore; iNOS and HO-1 expression and cytokines plasma levels were significantly higher in patients with ACHF as compared to controls group. Moreover the enzyme activity presents an opposite trend compared to that obtained in the analysis of the transcript and proteins. Our studies suggest a negative feedback interaction between iNOS and HO-1 important in the physiopathology of heart failure that could be considered a good candidate as a future therapeutic target for the development of new drugs.
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Insuficiencia Cardíaca/fisiopatología , Hemo-Oxigenasa 1/fisiología , Leucocitos Mononucleares/metabolismo , Óxido Nítrico Sintasa de Tipo II/fisiología , Enfermedad Aguda , Anciano , Retroalimentación Fisiológica , Femenino , Humanos , Masculino , Persona de Mediana Edad , FN-kappa B/metabolismo , Función Ventricular IzquierdaRESUMEN
Ozone (O3) is one of the most harmful urban pollutants, but its biological mechanisms have not been fully elucidated yet. Human bronchial epithelial cells (HBEpC) and human macrophage cells (differentiated human monocytic cell line) were exposed to O3 at the concentration of 240 µg/m3 (120 ppb), corresponding to the European Union alert threshold. Cell viability, reactive oxygen species (ROS) production, and pro-inflammatory cytokines release (IL-8 and TNF-α) were evaluated. Results indicated that O3 exposure increases ROS production in both cell types and enhances cytokines release in macrophages. O3 stimulated IL-8 and TNF-α in HBEpC when the cells were pretreated with Lipopolysaccharide, used to mimic a pre-existing inflammatory condition. Proteomics analysis revealed that, in HBEpC, O3 caused the up-regulation of aldo-keto reductase family 1 member B10, a recognized critical protein in lung carcinogenesis. In conclusion, our results show that 120 ppb O3 can lead to potential damage to human health suggesting the need for a revision of the actual alert levels.
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Ozono , Humanos , Ozono/toxicidad , Ozono/metabolismo , Interleucina-8 , Factor de Necrosis Tumoral alfa/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteómica , Células Epiteliales/metabolismo , Pulmón/metabolismo , Macrófagos/metabolismoRESUMEN
BACKGROUND: The present study investigates whether epigenetic differences emerge in the heart of patients undergoing cardiac surgery for an aortic valvular replacement (AVR) or coronary artery bypass graft (CABG). An algorithm is also established to determine how the pathophysiological condition might influence the human biological cardiac age. RESULTS: Blood samples and cardiac auricles were collected from patients who underwent cardiac procedures: 94 AVR and 289 CABG. The CpGs from three independent blood-derived biological clocks were selected to design a new blood- and the first cardiac-specific clocks. Specifically, 31 CpGs from six age-related genes, ELOVL2, EDARADD, ITGA2B, ASPA, PDE4C, and FHL2, were used to construct the tissue-tailored clocks. The best-fitting variables were combined to define new cardiac- and blood-tailored clocks validated through neural network analysis and elastic regression. In addition, telomere length (TL) was measured by qPCR. These new methods revealed a similarity between chronological and biological age in the blood and heart; the average TL was significantly higher in the heart than in the blood. In addition, the cardiac clock discriminated well between AVR and CABG and was sensitive to cardiovascular risk factors such as obesity and smoking. Moreover, the cardiac-specific clock identified an AVR patient's subgroup whose accelerated bioage correlated with the altered ventricular parameters, including left ventricular diastolic and systolic volume. CONCLUSION: This study reports on applying a method to evaluate the cardiac biological age revealing epigenetic features that separate subgroups of AVR and CABG.
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Metilación de ADN , Implantación de Prótesis de Válvulas Cardíacas , Humanos , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/métodos , Resultado del Tratamiento , Válvula Aórtica/cirugía , Epigénesis GenéticaRESUMEN
Cigarette smoke exposure represents a well-established ovotoxic exogenous stress, but the molecular mechanisms underlying of this effect are still unclear. Cigarette smoke upregulates inflammatory genes in the female reproductive organs, therefore an abnormal inflammation response may contribute to the impairment of female fertility. In this study we investigated for the first time the effect of cigarette smoke exposure on NOS and COX expression and activity and on their transcription factors (CREB and NF-kB) in human GCs and on the release of NO and PGE2 in the FF in smoking and non-smoking patients undergoing IVF treatment. In addition, correlation analysis between AMH serum levels, an index of ovarian reserve, and smoking exposure or iNOS and COX-2 protein expression levels were performed using a Pearson correlation method. Cigarette smoke exposure resulted in a significant increase of iNOS and COX-2 protein expression together with an increase of iNOS activity and PGE2 levels. pNF-kB and pCREB protein expression were upregulated in the GCs of smokers compared to non-smokers. The habit of smoking was negatively correlated with serum AMH levels, and positively correlated with iNOS and COX-2 protein expression levels. The data presented in the current study revealed a novel molecular mechanism underlying the toxic effects of cigarette smoke on fertility. Additional pathways mediating the effects of cigarette smoke exposure in human GCs cannot be excluded and should be investigated in future studies.
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Fumar Cigarrillos , FN-kappa B , Ciclooxigenasa 2/genética , Dinoprostona , Femenino , Fertilización In Vitro , Células de la Granulosa , Humanos , Óxido Nítrico Sintasa , Nicotiana , Regulación hacia ArribaRESUMEN
During the past decade, a great deal of data has accumulated supporting the notion that cytokines interact to regulate several aspects of social and emotional behaviour. There are reports of a positive correlation between cytokine levels and aggressive behaviour in healthy populations, and clinical reports describe an increase of aggressive traits in patients who receive cytokine immunotherapy. Interleukin-1beta released during an immune response acts as messenger that helps to modulate behaviour by influencing relevant neurotransmitter systems, and in some cases, by directly acting within the brain. In this site, IL-1beta exerts its actions by acting through 5-HT2 and IL-1 Type I receptors in hypothalamus or by potentially indirect routes, including activation of sensory afferents, and stimulation of cytokine release by brain endothelial cells. This review reports research investigating the relationship between IL-1beta, and the immune and central nervous systems involving or potentially involving defensive aggressive behaviour.
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Agresión , Mecanismos de Defensa , Hipotálamo/inmunología , Interleucina-1beta/inmunología , Receptores Tipo I de Interleucina-1/inmunología , Serotonina/inmunología , Transmisión Sináptica/inmunología , Humanos , Hipotálamo/metabolismo , Interleucina-1beta/metabolismo , Receptores Tipo I de Interleucina-1/metabolismo , Serotonina/metabolismoRESUMEN
BACKGROUND: Extremely low frequency (ELF) electromagnetic fields (EMF) are known to produce a variety of biological effects. Clinical studies are ongoing using EMF in healing of bone fractures and skin wounds. However, little is known about the mechanisms of action of ELF-EMF. Several studies have demonstrated that expression and regulation of nitric oxide synthase (NOS) and cyclooxygenase-2 (COX-2) are vital for wound healing; however, no reports have demonstrated a direct action of ELF-EMF in the modulation of these inflammatory molecules in human keratinocytes. OBJECTIVES: The present study analysed the effect of ELF-EMF on the human keratinocyte cell line HaCaT in order to assess the mechanisms of action of ELF-EMF and to provide further support for their therapeutic use in wound healing. METHODS: Exposed HaCaT cells were compared with unexposed control cells. At different exposure times, expression of inducible NOS (iNOS), endothelial NOS (eNOS) and COX-2 was evaluated by Western blot analysis. Modulation of iNOS and eNOS was monitored by evaluation of NOS activities, production of nitric oxide (NO) and O(2)(-) and expression of activator protein 1 (AP-1). In addition, catalase activity and prostaglandin (PG) E(2) production were determined. Effects of ELF-EMF on cell growth and viability were monitored. RESULTS: The exposure of HaCaT cells to ELF-EMF increased iNOS and eNOS expression levels. These ELF-EMF-dependent increased expression levels were paralled by increased NOS activities, and increased NO production. In addition, higher levels of AP-1 expression as well as a higher cell proliferation rate were associated with ELF-EMF exposure. In contrast, ELF-EMF decreased COX-2 expression, PGE(2) production, catalase activity and O(2)(-) production. CONCLUSIONS: Mediators of inflammation, such as reactive nitrogen and PGE(2), and keratinocyte proliferation are critical for the tissue regenerative processes. The ability of ELF-EMF to upmodulate NOS activities, thus nitrogen intermediates, as well as cell proliferation, and to downregulate COX-2 expression and the downstream intermediate PGE(2), highlights the potential therapeutic role of ELF-EMF in wound healing processes.
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Ciclooxigenasa 2/metabolismo , Queratinocitos/metabolismo , Magnetoterapia/métodos , Óxido Nítrico Sintasa de Tipo III/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Cicatrización de Heridas , Línea Celular , Proliferación Celular , Campos Electromagnéticos , HumanosRESUMEN
Verbascum mallophorum is part of a large family of Scrophulariaceae consisting of more than 360 species. Verbascum mallophorums contains diverse polysaccharides, iroid glycosides, flavonoids, saponins, volatile oils and phenylentanoids. Verbascum has been used in popular medicine for treating wounds, chilblains, respiratory ailments, acne and arthritic disturbances. Inducible nitric oxide synthase (iNOS) represents one of the three isoforms that produce nitric oxide using L-arginine as a substrate in response to an increase in superoxide anion activated by NF-kappaB. It is implicated in different pathophysiological events and its expression increases greatly during an inflammatory process due to oxidative stress. In our study we reproduced an inflammatory state by treating THP-1 cells (human myelomonocytic leukaemia) with pro-inflammatory stimuli, such as LPS and IFN-gamma, obtaining an up-regulation both in the expression and in the activity of iNOS. The aim of our work is to investigate the possible antiinflammatory action of verbascoside extract from Verbascum mallophorum using a concentration of 100 muM. Our results show a significant decrease in the expression and activity of iNOS and extracellular O2- when cells were treated with verbascoside. Based on these results we hypothesize that verbascoside extract from Verbascum mallophorum has anti-inflammatory properties since it reduces the production of superoxide radicals and consequently reduces the activity of iNOS.
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Antiinflamatorios/farmacología , Verbascum/química , Western Blotting , Línea Celular , Citrulina/biosíntesis , Densitometría , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Glucósidos/farmacología , Humanos , Interferón gamma/farmacología , Lipopolisacáridos/farmacología , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Fenoles/farmacología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Superóxidos/metabolismoRESUMEN
Preclinical and clinical evidences have demonstrated that astroglial-derived S100B protein is a key element in neuroinflammation underlying the pathogenesis of Parkinson's disease (PD), so much as that S100B inhibitors have been proposed as promising candidates for PD targeted therapy. Pentamidine, an old-developed antiprotozoal drug, currently used for pneumocystis carinii is one of the most potent inhibitors of S100B activity, but despite this effect, is limited by its low capability to cross blood brain barrier (BBB). To overcome this problem, we developed a non-invasive intranasal delivery system, chitosan coated niosomes with entrapped pentamidine (inPentasomes), in the attempt to provide a novel pharmacological approach to ameliorate parkinsonism induced by subchronic MPTP administration in C57BL-6â¯J mice. inPentasomes, prepared by evaporation method was administered daily by intranasal route in subchronic MPTP-intoxicated rodents and resulted in a dose-dependent manner (0.001-0.004â¯mg/kg) capable for a significant Tyrosine Hydroxylase (TH) positive neuronal density rescue in both striatum and substantia nigra of parkinsonian mice. In parallel, inPentasomes significantly decreased the extent of glial-related neuroinflammation through the reduction of specific gliotic markers (Iba-1, GFAP, COX-2, iNOS) with consequent PGE2 and NO2- release reduction, in nigrostriatal system. inPentasomes-mediated S100B inhibition resulted in a RAGE/NF-κB pathway downstream inhibition in the nigrostriatal circuit, causing a marked amelioration of motor performances in intoxicated mice. On the basis of our results, chitosan coated niosomes loaded with pentamidine, the inPentasome system, self-candidates as a promising new intranasal approach to mitigate parkinsonism in humans and possibly paves the way for a possible clinical repositioning of pentamidine as anti-PD drug.
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Antiinflamatorios/administración & dosificación , Antiparkinsonianos/administración & dosificación , Quitosano/administración & dosificación , Trastornos Parkinsonianos/tratamiento farmacológico , Pentamidina/administración & dosificación , Administración Intranasal , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacocinética , Antiparkinsonianos/química , Antiparkinsonianos/farmacocinética , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Quitosano/química , Quitosano/farmacocinética , Dopamina/metabolismo , Liberación de Fármacos , Liposomas , Masculino , Ratones Endogámicos C57BL , Mucosa Nasal/metabolismo , Trastornos Parkinsonianos/metabolismo , Trastornos Parkinsonianos/patología , Pentamidina/química , Pentamidina/farmacocinéticaRESUMEN
Background: Treatment options for achalasia include endoscopic and surgical techniques that carry the risk of esophageal bleeding and perforation. The rare coexistence of esophageal varices has only been anecdotally described and treatment is presumed to carry additional risk. Methods: Experience from physicians/surgeons treating this rare combination of disorders was sought through the International Manometry Working Group. Results: Fourteen patients with achalasia and varices from seven international centers were collected (mean age 61 ± 9 years). Five patients were treated with botulinum toxin injections (BTI), four had dilation, three received peroral endoscopic myotomy (POEM), one had POEM then dilation, and one patient underwent BTI followed by Heller's myotomy. Variceal eradication preceded achalasia treatment in three patients. All patients experienced a significant symptomatic improvement (median Eckardt score 7 vs 1; p < 0.0001) at 6 months follow-up, with treatment outcomes resembling those of 20 non-cirrhotic achalasia patients who underwent similar therapy. No patients had recorded complications of bleeding or perforation. Conclusion: This study shows an excellent short-term symptomatic response in patients with esophageal achalasia and varices and demonstrates that the therapeutic outcomes and complications, other than transient encephalopathy in both patients who had a portosystemic shunt, did not differ to disease-matched patients without varices.
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Acalasia del Esófago/terapia , Várices Esofágicas y Gástricas/terapia , Anciano , Toxinas Botulínicas/administración & dosificación , Dilatación/estadística & datos numéricos , Acalasia del Esófago/complicaciones , Esfínter Esofágico Inferior/efectos de los fármacos , Esfínter Esofágico Inferior/cirugía , Várices Esofágicas y Gástricas/complicaciones , Esofagoscopía/métodos , Femenino , Estudios de Seguimiento , Miotomía de Heller/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Erectile dysfunction (ED) is a common medical condition that affects the sexual life of millions of men worldwide. Numerous physical and psychological factors are involved in normal erectile function, including neurological, vascular, hormonal and cavernous functions. The current therapy for the condition is pharmacological and psychotherapeutic which regulates the erectile function and amplifies the NO-mediated response. The aim of this work is to test the action of three common phosphodiesterase inhibitors: Tadalafil, Sildenafil Citrate and Vardenafil at 0.05 microM on human monocytes, analyzing the expression of iNOS protein and mRNA by Western blot and rt-PCR, and production of NO by conversion of L-(2,3,4,5)-[3H]Arginine to L-(3H) citrulline. We also tested the efficiency of the antioxidant network by spectrophotometer (SOD, CAT, GPx and Gr), under normal conditions and after stimulation with LPS. The results showed an increase in ROS levels, similar for all the molecules with regard to the antioxidant enzymes. In all cases the treatment determines a response to the limited efficiency, arriving at a situation in which phosphodiesterase inhibitors + LPS clearly show oxidative stress.
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Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5/efectos de los fármacos , Estrés Oxidativo , Inhibidores de Fosfodiesterasa/farmacología , Secuencia de Bases , Western Blotting , Catalasa/metabolismo , Cartilla de ADN , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Humanos , Óxido Nítrico Sintasa de Tipo II/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Superóxido Dismutasa/metabolismo , Superóxidos/metabolismoRESUMEN
There is high confidence that the anthropogenic increase of atmospheric greenhouse gases (GHGs) is causing modifications in the Earth's climate. Coastal waterbodies such as estuaries, bays and lagoons are among those most affected by the ongoing changes in climate. Being located at the land-sea interface, such waterbodies are subjected to the combined changes in the physical-chemical processes of atmosphere, upstream land and coastal waters. Particularly, climate change is expected to alter phytoplankton communities by changing their environmental drivers (especially climate-related), thus exacerbating the symptoms of eutrophication events, such as hypoxia, harmful algal blooms (HAB) and loss of habitat. A better understanding of the links between climate-related drivers and phytoplankton is therefore necessary for projecting climate change impacts on aquatic ecosystems. Here we present the case study of the Zero river basin in Italy, one of the main contributors of freshwater and nutrient to the salt-marsh Palude di Cona, a coastal waterbody belonging to the lagoon of Venice. To project the impacts of climate change on freshwater inputs, nutrient loadings and their effects on the phytoplankton community of the receiving waterbody, we formulated and applied an integrated modelling approach made of: climate simulations derived by coupling a General Circulation Model (GCM) and a Regional Climate Model (RCM) under alternative emission scenarios, the hydrological model Soil and Water Assessment Tool (SWAT) and the ecological model AQUATOX. Climate projections point out an increase of precipitations in the winter period and a decrease in the summer months, while temperature shows a significant increase over the whole year. Water discharge and nutrient loads simulated by SWAT show a tendency to increase (decrease) in the winter (summer) period. AQUATOX projects changes in the concentration of nutrients in the salt-marsh Palude di Cona, and variations in the biomass and species of the phytoplankton community.
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Saliva collection is considered a non-invasive method to detect inflammatory markers in response to emotional states within natural social contexts. Numerous studies have prompted an important role of cytokines in modulating distinct aspects of social and emotional behavior. The aim of this study was to investigate the reliability of plasma and saliva as investigative tools for measure some inflammatory marker levels (CRP, IL-1ß, IL-18, and IL-6). At the same time, the relationships between these markers and emotional states in response to a socio-cognitive stress (Academic Exam, AE), were considered. It was demonstrated that the plasma and saliva concentrations of all immune-mediators analyzed were significantly related across the socio-cognitive stress. In addition, when there was a close correlation to AE, the anger state, the IL-1ß, the IL-18 salivary and plasmatic concentrations were significantly higher, while they decreased during the AE. On the other hand, the anxiety state and the IL-6 levels significantly increased throughout the AE. The IL-1ß and IL-6 were positively associated to the anger and the anxiety state, respectively. In conclusion, our data highlight that different immune markers are similarly detectable in plasma and saliva during socio-cognitive stress. Also, they could be related to different emotional responses.
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Emociones/fisiología , Interleucinas/sangre , Interleucinas/metabolismo , Saliva/metabolismo , Adulto , Biomarcadores/análisis , Proteína C-Reactiva/metabolismo , Citocinas/sangre , Humanos , Interleucina-18/sangre , Interleucina-18/metabolismo , Interleucina-1beta/sangre , Interleucina-1beta/metabolismo , Interleucina-6/sangre , Interleucina-6/metabolismo , Masculino , Reproducibilidad de los Resultados , Estrés Psicológico/sangre , Estrés Psicológico/metabolismo , Estrés Psicológico/psicología , Adulto JovenRESUMEN
OBJECTIVES: In our previous reports, we have demonstrated that extremely low-frequency electromagnetic fields (ELF-EMF) exposure enhances the proliferation of keratinocyte. The present study aimed to clarify effects of ELF-EMF on wound healing and molecular mechanisms involved, using a scratch in vitro model. MATERIALS AND METHODS: The wounded monolayer cultures of human immortalized keratinocytes (HaCaT), at different ELF-EMF and Sham exposure times were monitored under an inverted microscope. The production and expression of IL-1ß, TNF-α, IL-18 and IL-18BP were measured by enzyme-linked immunosorbent assay and quantitative real-time PCR. The activity and the expression of matrix metalloproteinases (MMP)-2/9 was evaluated by zymography and Western blot analysis, respectively. Signal transduction proteins expression (Akt and ERK) was measured by Western blot. RESULTS: The results of wound healing in vitro assay revealed a significant reduction of cell-free area time-dependent in ELF-EMF-exposed cells compared to Sham condition. Gene expression and release of cytokines analysed were significantly increased in ELF-EMF-exposed cells. Our results further showed that ELF-EMF exposure induced the activity and expressions of MMP-9. Molecular data showed that effects of ELF-EMF might be mediated via Akt and ERK signal pathway, as demonstrated using their specific inhibitors. CONCLUSIONS: Our results highlight ability of ELF-EMF to modulate inflammation mediators and keratinocyte proliferation/migration, playing an important role in wound repair. The ELF-EMF accelerates wound healing modulating expression of the MMP-9 via Akt/ERK pathway.
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Citocinas/metabolismo , Campos Electromagnéticos , Queratinocitos/metabolismo , Sistema de Señalización de MAP Quinasas , Metaloproteinasa 9 de la Matriz/metabolismo , Cicatrización de Heridas , Línea Celular Transformada , Humanos , Inflamación/metabolismo , Inflamación/patología , Inflamación/terapia , Queratinocitos/patologíaRESUMEN
In this paper we examined the variations of plasmatic concentrations of hypoxanthine and xanthine, and their relation with other important indicators of muscular stress creatine-kinase (CK), myoglobin, uric acid, leucocytes, in prolonged, isokynetic physical exercise, performed in a concentric mode at different joint excursion. Twenty healthy male subjects performed isokinetic exercises in concentric-concentric mode, with joint excursion of 30, 60, 90 deg/sec. Blood samples were drawn at rest, immediately after exercise and after 45 min of recovery. The plasmatic concentration of hypoxanthine increased at the end of physical exercise, compared to the rest value of about 1,5 micromol/L, up to a level of greater than 19 micromol/L; the values were higher after a period of recovery of 45 min and the increase varies considerably according to the type of exercise that was performed. Myoglobin has a slight but sensible increment too, with the same trend as hypoxanthine, while CK increase without correlation to the type of exercises. The relation with other indicators of muscular activity demonstrates that in none of the different isokinetic exercises, performed at concentric mode, was there ultrastructural damage, while it is possible to come across a considerable metabolic stress, which is dissimilar in the different kinds of exercises. The results suggest that hypoxanthine can be useful in monitoring the effectiveness of a work load and the metabolic stress consequences on the muscle tissue in training or rehabilitation programs. The results also suggest that even myoglobin, at small concentrations, can have the same function.