RESUMEN
Anorexia nervosa (AN) is a complex disorder affecting mainly, but not only, teenagers. Researchers agree that AN is deeply associated with a pro-inflammatory state following an impaired immune system, resulting from altered levels of cytokines such as IL-1ß and TNF-α, also impacted by the frequent depressive states. Thus, this case-control study aimed to evaluate the relationship between patients suffering from AN undergoing specialized eating disorder treatment for AN and pro-inflammatory cytokines. To reach our purpose, we assessed eating-related psychopathology and depressive symptoms and measured serum concentration of pro-inflammatory cytokines IL-1ß, IL-6, IL-8, and TNF-α before and after 6 months of integrated therapy (which included psychopharmacotherapy, psychotherapy, and nutritional treatment), to define whether selected pro-inflammatory cytokines could be considered a pathophysiological marker of the disorder. A sample of 16 young female patients with early diagnosis of AN, and without any previous treatment, and 22 healthy controls matched by age, sex, and socioeconomic status were enrolled. After 6 months of integrated therapy, a significant decrease of all selected pro-inflammatory cytokines was detected. In addition, an improvement in the anxiety-depressant aspects was also noted. In conclusion, the results obtained suggest that pro-inflammatory cytokines are indeed related to the pathophysiology of AN. However, further investigations, involving larger samples of patients with distinct subtypes of AN, are essential to confirm the current findings.
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Anorexia Nerviosa , Citocinas , Humanos , Femenino , Anorexia Nerviosa/sangre , Anorexia Nerviosa/terapia , Adolescente , Estudios de Casos y Controles , Citocinas/sangre , Mediadores de Inflamación/sangre , Inflamación/sangreRESUMEN
Background: RASopathies are developmental disorders caused by dysregulation of the RAS-MAPK signalling pathway, which contributes to the modulation of multiple extracellular signals, including hormones and growth factors regulating energetic metabolism, including lipid synthesis, storage, and degradation. Subjects and methods: We evaluated the body composition and lipid profiles of a single-centre cohort of 93 patients with a molecularly confirmed diagnosis of RASopathy by assessing height, BMI, and total cholesterol, HDL, triglycerides, apolipoprotein, fasting glucose, and insulin levels, in the context of a cross sectional and longitudinal study. We specifically investigated and compared anthropometric and haematochemistry data between the Noonan syndrome (NS) and Mazzanti syndrome (NS/LAH) groups. Results: At the first evaluation (9.5 ± 6.2 years), reduced growth (-1.80 ± 1.07 DS) was associated with a slightly reduced BMI (-0.34 DS ± 1.15 DS). Lipid profiling documented low total cholesterol levels (< 5th percentile) in 42.2% of the NS group; in particular, in 48.9% of PTPN11 patients and in 28.6% of NS/LAH patients compared to the general population, with a significant difference between males and females. A high proportion of patients had HDL levels lower than the 26th percentile, when compared to the age- and sex-matched general population. Triglycerides showed an increasing trend with age only in NS females. Genotype-phenotype correlations were also evident, with particularly reduced total cholesterol in about 50% of patients with PTPN11 mutations with LDL-C and HDL-C tending to decrease during puberty. Similarly, apolipoprotein A1 and apolipoprotein B deficits were documented, with differences in prevalence associated with the genotype for apolipoprotein A1. Fasting glucose levels and HOMA-IR were within the normal range. Conclusion: The present findings document an unfavourable lipid profile in subjects with NS, in particular PTPN11 mutated patients, and NS/LAH. Further studies are required to delineate the dysregulation of lipid metabolism in RASopathies more systematically and confirm the occurrence of previously unappreciated genotype-phenotype correlations involving the metabolic profile of these disorders.
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Apolipoproteína A-I , Síndrome de Noonan , Humanos , Femenino , Masculino , Estudios Transversales , Estudios Longitudinales , Síndrome de Noonan/genética , Genotipo , Glucosa , ColesterolRESUMEN
The evaluation of endocrine involvement in RASopathies is important for the care and follow-up of patients affected by these conditions. Short stature is a cardinal feature of RASopathies and correlates with multiple factors. Growth hormone treatment is a therapeutic possibility to improve height and quality of life. Assessment of growth rate and growth laboratory parameters is routine, but age at start of therapy, dose and effects of growth hormone on final height need to be clarified. Puberty disorders and gonadal dysfunction, in particular in males, are other endocrinological areas to evaluate for their effects on growth and development. Thyroid dysfunction, autoimmune disease and bone involvement have also been reported in RASopathies. In this brief review, we describe the current knowledge on growth, growth hormone therapy, endocrinological involvement in patients affected by RASopathies.
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Hormona de Crecimiento Humana , Calidad de Vida , Masculino , Humanos , Hormona del Crecimiento/farmacología , Hormona del Crecimiento/uso terapéutico , Hormona de Crecimiento Humana/uso terapéutico , Pubertad , EstaturaRESUMEN
Background: The inter-individual differences in taste perception find a possible rationale in genetic variations. We verified whether the presence of four different single nucleotide polymorphisms (SNPs) in genes encoding for bitter (TAS2R38; 145G > C; 785T > C) and sweet (TAS1R3; −1572C > T; −1266C > T) taste receptors influenced the recognition of the basic tastes. Furthermore, we tested if the allelic distribution of such SNPs varied according to BMI and whether the associations between SNPs and taste recognition were influenced by the presence of overweight/obesity. Methods: DNA of 85 overweight/obese patients and 57 normal weight volunteers was used to investigate the SNPs. For the taste test, filter paper strips were applied. Each of the basic tastes (sweet, sour, salty, bitter) plus pure rapeseed oil, and water were tested. Results: Individuals carrying the AV/AV diplotype of the TAS2R38 gene (A49P G/G and V262 T/T) were less sensitive to sweet taste recognition. These alterations remained significant after adjustment for gender and BMI. Moreover, a significant decrease in overall taste recognition associated with BMI and age was found. There was no significant difference in allelic distribution for the investigated polymorphisms between normal and overweight/obese patients. Conclusions: Our findings suggest that overall taste recognition depends on age and BMI. In the total population, the inter-individual ability to identify the sweet taste at different concentrations was related to the presence of at least one genetic variant for the bitter receptor gene but not to the BMI.
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Receptores Acoplados a Proteínas G/genética , Percepción del Gusto , Gusto , Humanos , Obesidad/genética , Sobrepeso , Polimorfismo de Nucleótido Simple , Gusto/genéticaRESUMEN
We previously molecularly and clinically characterized Mazzanti syndrome, a RASopathy related to Noonan syndrome that is mostly caused by a single recurrent missense variant (c.4A > G, p.Ser2Gly) in SHOC2, which encodes a leucine-rich repeat-containing protein facilitating signal flow through the RAS-mitogen-associated protein kinase (MAPK) pathway. We also documented that the pathogenic p.Ser2Gly substitution causes upregulation of MAPK signaling and constitutive targeting of SHOC2 to the plasma membrane due to the introduction of an N-myristoylation recognition motif. The almost invariant occurrence of the pathogenic c.4A > G missense change in SHOC2 is mirrored by a relatively homogeneous clinical phenotype of Mazzanti syndrome. Here, we provide new data on the clinical spectrum and molecular diversity of this disorder and functionally characterize new pathogenic variants. The clinical phenotype of six unrelated individuals carrying novel disease-causing SHOC2 variants is delineated, and public and newly collected clinical data are utilized to profile the disorder. In silico, in vitro and in vivo characterization of the newly identified variants provides evidence that the consequences of these missense changes on SHOC2 functional behavior differ from what had been observed for the canonical p.Ser2Gly change but converge toward an enhanced activation of the RAS-MAPK pathway. Our findings expand the molecular spectrum of pathogenic SHOC2 variants, provide a more accurate picture of the phenotypic expression associated with variants in this gene and definitively establish a gain-of-function behavior as the mechanism of disease.
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Anomalías Múltiples , Péptidos y Proteínas de Señalización Intracelular , Síndrome del Cabello Anágeno Suelto , Anomalías Múltiples/genética , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Síndrome del Cabello Anágeno Suelto/genética , Fenotipo , Proteínas ras/genética , Proteínas ras/metabolismoRESUMEN
Pasta is one of the components of the Mediterranean Diet, despite considerable attention given, its use is still debated. Several studies encouraged the consumption of whole grain because of its many properties and the positive association between refined carbohydrates and insulin resistance, by measuring the Glycaemic Index (GI), an indicator of the physiological effects of a carbohydrate meal. In this study, the GI and polyphenol content of Senatore Cappelli (Triticum turgidum ssp. durum) pasta were evaluated. Using spectrophotometric methods, total polyphenols and flavonoids were found to be 113.5 mg/100 g and 52.96 mg/100 g, respectively. To measure the GI, a standard assay was performed, and values of 47.9 ± 5.2 for long format pasta and 68.5 ± 4.6 for short format pasta were obtained. The present study confirms the presence of polyphenols and flavonoids in pasta Senatore Cappelli. The value of GI is influenced by the pasta shape. These informations could provide valuable data for practitioners preparing personalised diets.
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Triticum , Granos Enteros , Harina/análisis , Valor Nutritivo , PolifenolesRESUMEN
Bone dysplasias (osteochondrodysplasias) are a large group of conditions associated with short stature, skeletal disproportion, and radiographic abnormalities of skeletal elements. Nearly all are genetic in origin. We report a series of seven children with similar findings of chondrodysplasia and growth failure following early hematopoietic stem cell transplantation (HSCT) for pediatric non-oncologic disease: hemophagocytic lymphohistiocytosis or HLH (five children, three with biallelic HLH-associated variants [in PRF1 and UNC13D] and one with HLH secondary to visceral Leishmaniasis), one child with severe combined immunodeficiency and one with Omenn syndrome (both children had biallelic RAG1 pathogenic variants). All children had normal growth and no sign of chondrodysplasia at birth and prior to their primary disease. After HSCT, all children developed growth failure, with standard deviation scores for height at or below -3. Radiographically, all children had changes in the spine, metaphyses and epiphyses, compatible with a spondyloepimetaphyseal dysplasia. Genomic sequencing failed to detect pathogenic variants in genes associated with osteochondrodysplasias. We propose that such chondrodysplasia with growth failure is a novel, rare, but clinically important complication following early HSCT for non-oncologic pediatric diseases. The pathogenesis is unknown but could possibly involve loss or perturbation of the cartilage-bone stem cell population.
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Trasplante de Células Madre Hematopoyéticas/efectos adversos , Linfohistiocitosis Hemofagocítica/genética , Osteocondrodisplasias/genética , Niño , Preescolar , Femenino , Humanos , Linfohistiocitosis Hemofagocítica/complicaciones , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/terapia , Masculino , Proteínas de la Membrana/genética , Osteocondrodisplasias/complicaciones , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/terapia , Perforina/genética , Resultado del TratamientoRESUMEN
Objectives: Growth impairment is a common manifestation in Noonan syndrome (NS). Recombinant human GH (rhGH) treatment has been shown to increase growth and adult height (AH) in a few studies. We aimed to evaluate the growth trajectory towards the AH, and the effects of rhGH treatment in a large cohort of NS children. Methods: Retrospective, multicenter, cohort study including subjects with genetic diagnosis of NS. A total of 228 NS patients, 154 with PTPN11 mutations, 94 who reached AH, were recruited. Auxological data were collected at 2, 5, and 10 years, at pubertal onset, at AH. Sixty-eight NS subjects affected with GH deficiency (GHD) were treated with rhGH at a mean dose of 0.24 mg/kg per week until AH achievement. Results: ANOVA analysis showed a significant difference between birth length and height standard deviation scores (HSDS) at the different key ages (p<0.001), while no significant differences were found between HSDS measurements at 2, 5, and 10 years, at pubertal onset, and at AH. HSDS increased from -3.10 ± 0.84 to -2.31 ± 0.99 during rhGH treatment, with a total height gain of 0.79 ± 0.74, and no significant difference between untreated and treated NS at AH. Conclusions: rhGH treatment at the standard dose used for children with GH idiopathic deficiency is effective in improving growth and AH in NS with GHD. Further studies are needed to assess genotype-specific response to rhGH treatment in the different pathogenic variants of PTPN11 gene and in the less common genotypes.
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Estatura/efectos de los fármacos , Hormona de Crecimiento Humana/uso terapéutico , Síndrome de Noonan/tratamiento farmacológico , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios RetrospectivosRESUMEN
RASopathies are caused by variants in genes encoding components or modulators of the RAS/MAPK signaling pathway. Noonan syndrome is the most common entity among this group of disorders and is characterized by heart defects, short stature, variable developmental delay, and typical facial features. Heterozygous variants in SOS2, encoding a guanine nucleotide exchange factor for RAS, have recently been identified in patients with Noonan syndrome. The number of published cases with SOS2-related Noonan syndrome is still limited and little is known about genotype-phenotype correlations. We collected previously unpublished clinical and genotype data from 17 individuals carrying a disease-causing SOS2 variant. Most individuals had one of the previously reported dominant pathogenic variants; only four had novel changes at the established hotspots for variants that affect protein function. The overall phenotype of the 17 patients fits well into the spectrum of Noonan syndrome and is most similar to the phenotype observed in patients with SOS1-related Noonan syndrome, with ectodermal anomalies as common features and short stature and learning disabilities as relatively infrequent findings compared to the average Noonan syndrome phenotype. The spectrum of heart defects in SOS2-related Noonan syndrome was consistent with the known spectrum of cardiac anomalies in RASopathies, but no specific heart defect was particularly predominating. Notably, lymphatic anomalies were extraordinarily frequent, affecting more than half of the patients. We therefore conclude that SOS2-related Noonan syndrome is associated with a particularly high risk of lymphatic complications that may have a significant impact on morbidity and quality of life.
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Sistema Linfático/patología , Síndrome de Noonan/genética , Fenotipo , Proteínas Son Of Sevenless/genética , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Mutación , Síndrome de Noonan/patologíaRESUMEN
Coronavirus disease 2019 (COVID-19) is often associated with interstitial pneumonia. However, there is insufficient knowledge on the presence of autoimmune serological markers in patients with COVID-19. We analyzed the presence and role of autoantibodies in patients with COVID-19-associated pneumonia. We prospectively studied 33 consecutive patients with COVID-19, 31 (94%) of whom had interstitial pneumonia, and 25 age-matched and sex-matched patients with fever and/or pneumonia with etiologies other than COVID-19 as the pathological control group. All patients were tested for the presence of antinuclear antibodies (ANAs), anti-antiphospholipid antibodies, and anti-cytoplasmic neutrophil antibodies (ANCAs). Clinical, biochemical, and radiological parameters were also collected. Fifteen of 33 patients (45%) tested positive for at least one autoantibody, including 11 who tested positive for ANAs (33%), 8 who tested positive for anti-cardiolipin antibodies (immunoglobulin (Ig)G and/or IgM; 24%), and 3 who tested positive for anti-ß2-glycoprotein antibodies (IgG and/or IgM; 9%). ANCA reactivity was not detected in any patient. Patients that tested positive for auto-antibodies had a significantly more severe prognosis than other patients did: 6 of 15 patients (40%) with auto-antibodies died due to COVID-19 complications during hospitalization, whereas only 1 of 18 patients (5.5%) who did not have auto-antibodies died (P = 0.03). Patients with poor prognosis (death due to COVID-19 complications) had a significantly higher respiratory rate at admission (23 breaths per minute vs. 17 breaths per minute; P = 0.03) and a higher frequency of auto-antibodies (86% vs. 27%; P = 0.008). In conclusion, auto-antibodies are frequently detected in patients with COVID-19 possibly reflecting a pathogenetic role of immune dysregulation. However, given the small number of patients, the association of auto-antibodies with an unfavorable prognosis requires further multicenter studies.
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Autoanticuerpos/fisiología , COVID-19/inmunología , Enfermedades del Sistema Inmune/etiología , SARS-CoV-2 , Adulto , Anciano , Anciano de 80 o más Años , Autoanticuerpos/sangre , COVID-19/patología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Signal transduction through the RAF-MEK-ERK pathway, the first described mitogen-associated protein kinase (MAPK) cascade, mediates multiple cellular processes and participates in early and late developmental programs. Aberrant signaling through this cascade contributes to oncogenesis and underlies the RASopathies, a family of cancer-prone disorders. Here, we report that de novo missense variants in MAPK1, encoding the mitogen-activated protein kinase 1 (i.e., extracellular signal-regulated protein kinase 2, ERK2), cause a neurodevelopmental disease within the RASopathy phenotypic spectrum, reminiscent of Noonan syndrome in some subjects. Pathogenic variants promote increased phosphorylation of the kinase, which enhances translocation to the nucleus and boosts MAPK signaling in vitro and in vivo. Two variant classes are identified, one of which directly disrupts binding to MKP3, a dual-specificity protein phosphatase negatively regulating ERK function. Importantly, signal dysregulation driven by pathogenic MAPK1 variants is stimulus reliant and retains dependence on MEK activity. Our data support a model in which the identified pathogenic variants operate with counteracting effects on MAPK1 function by differentially impacting the ability of the kinase to interact with regulators and substrates, which likely explains the minor role of these variants as driver events contributing to oncogenesis. After nearly 20 years from the discovery of the first gene implicated in Noonan syndrome, PTPN11, the last tier of the MAPK cascade joins the group of genes mutated in RASopathies.
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Carcinogénesis/genética , Proteína Quinasa 1 Activada por Mitógenos/genética , Trastornos del Neurodesarrollo/genética , Síndrome de Noonan/genética , Preescolar , Femenino , Humanos , Sistema de Señalización de MAP Quinasas/genética , Masculino , Mutación Missense/genética , Trastornos del Neurodesarrollo/patología , Síndrome de Noonan/fisiopatología , Fenotipo , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética , Transducción de Señal , Secuenciación del Exoma , Proteínas ras/genéticaRESUMEN
Type 2 diabetes mellitus (T2DM) has a very high impact on quality of life as it is characterized by disabling complications. There is little evidence about taste alterations in diabetes. Since many individual factors are involved in the onset of diabetes, the purpose of our study is to search a possible link between diabetes and individual taste function. Thirty-two participants with T2DM and 32 volunteers without T2DM (healthy controls) were recruited. Four concentrations of each of the four basic tastes (sweet, sour, salty, bitter), and pure rapeseed oil and water, were applied with cotton pads to the protruded tongue, immediately posterior to its first third, either to the left or right side. The results showed significant differences between groups in the ability to recognize sour, bitter, sweet, and water. Taste scores were lower in subjects with T2DM than in healthy controls, and an age-related decline in taste function was found. The taste function reduction associated with T2DM was not related to gender, disease duration, and glycemic control. In conclusion, it can be hypothesized that a general alteration of taste function can lead patients with type 2 diabetes to search for foods richer in sugars, as in a vicious circle, thus decreasing the likelihood of remission of diabetes mellitus.
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Diabetes Mellitus Tipo 2/fisiopatología , Gusto , Adolescente , Adulto , Anciano , Envejecimiento/fisiología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Dieta para Diabéticos , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
In this randomized, double-blind, single-center trial (ANZCTR number ACTRN12619000436178) we aimed to investigate changes in endothelium-dependent vasodilation induced by ubiquinol, the reduced form of coenzyme Q10 (CoQ10), in healthy subjects with moderate dyslipidemia. Fifty-one subjects with low-density lipoprotein (LDL) cholesterol levels of 130-200 mg/dL, not taking statins or other lipid lowering treatments, moderate (2.5%-6.0%) endothelial dysfunction as measured by flow-mediated dilation (FMD) of the brachial artery, and no clinical signs of cardiovascular disease were randomized to receive either ubiquinol (200 or 100 mg/day) or placebo for 8 weeks. The primary outcome measure was the effect of ubiquinol supplementation on FMD at the end of the study. Secondary outcomes included changes in FMD on week 4, changes in total and oxidized plasma CoQ10 on week 4 and week 8, and changes in serum nitrate and nitrite levels (NOx), and plasma LDL susceptibility to oxidation in vitro on week 8. Analysis of the data of the 48 participants who completed the study demonstrated a significantly increased FMD in both treated groups compared with the placebo group (200 mg/day, +1.28% ± 0.90%; 100 mg/day, +1.34% ± 1.44%; p < 0.001) and a marked increase in plasma CoQ10, either total (p < 0.001) and reduced (p < 0.001). Serum NOx increased significantly and dose-dependently in all treated subjects (p = 0.016), while LDL oxidation lag time improved significantly in those receiving 200 mg/day (p = 0.017). Ubiquinol significantly ameliorated dyslipidemia-related endothelial dysfunction. This effect was strongly related to increased nitric oxide bioavailability and was partly mediated by enhanced LDL antioxidant protection.
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Dislipidemias/tratamiento farmacológico , Dislipidemias/fisiopatología , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiopatología , Ubiquinona/análogos & derivados , Vasodilatación/efectos de los fármacos , Adulto , Anciano , Antioxidantes , Disponibilidad Biológica , Arteria Braquial/fisiopatología , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico/sangre , Óxido Nítrico/metabolismo , Índice de Severidad de la Enfermedad , Ubiquinona/administración & dosificación , Ubiquinona/farmacologíaRESUMEN
PURPOSE: Taste changes due to chemotherapy may contribute to the high prevalence of malnutrition in cancer patients. It is believed that 50-70% of patients with cancer suffer from taste disorders. The aim of the present study was to analyze the taste alterations in patient population compared with that in controls, also in relation to gender. In this way, it could open to a new approach for a personalized diet to prevent and/or reduce taste alterations and malnutrition in cancer patients. METHODS: Forty-five cancer patients undergoing chemotherapy were compared with healthy controls (n = 32). Taste function test was used to determine taste sensitivity. Different concentrations for each of the four basic tastes (salty, sweet, sour, bitter) and also fat and water tastes were evaluated. RESULTS: A significant difference in taste sensitivity between patients and control group was found, in line with previous similar studies. As in the control group, taste perception in patients was better in females than in males, suggesting interaction effect between group and gender. CONCLUSIONS: Coping strategies regarding subjective taste impairment should be provided since alterations in taste sensitivity influence food preferences and appetite. Clinicians could thus have the potential to underpin changes in dietary intake and consequently in nutritional status; understanding the extent of the contribution of each taste would help in the development of effective interventions in future. Consequently, patients can adopt appropriate appetizing strategies and, based on that, change their feeding habits.
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Antineoplásicos/efectos adversos , Disgeusia/diagnóstico , Neoplasias/patología , Trastornos del Gusto/fisiopatología , Percepción del Gusto/fisiología , Adulto , Antineoplásicos/uso terapéutico , Apetito , Dieta , Femenino , Preferencias Alimentarias , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Caracteres Sexuales , GustoRESUMEN
Alzheimer's disease (AD) is the most common cause of dementia accounting for 60-70% of all demented cases and one of the leading sources of morbidity and mortality in the aging population. Most of the recent literature regards the relationship between plasma oxidative stress and AD, showing that markers of lipid peroxidation are significantly higher in AD and Mild Cognitive Impairment (MCI) patients with respect to control subjects. The increased generation of reactive oxygen species that occurs in AD may be also responsible for oxidative injury to erythrocyte membranes. Since erythrocyte membrane serves as a variable barrier to oxygen transport, changes in its stability can induce cellular hypoxia and the consequence brain tissue oxygenation. In this study, plasma oxygen radical absorbance capacity (ORAC) and erythrocyte membrane fluidity have been evaluated in control, MCI and AD patients. Moreover erythrocyte membrane acetylcholinesterase (AchE) activity has been measured in control and AD patients. Plasma ORAC significantly decreased in MCI and AD subjects with respect to the controls, while a decrease in erythrocyte membrane fluidity has been observed only in MCI patients. No significant differences were detected in erythrocyte AchE activity between control subjects and AD patients.
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Enfermedad de Alzheimer/sangre , Disfunción Cognitiva/sangre , Membrana Eritrocítica/fisiología , Fluidez de la Membrana , Acetilcolinesterasa/metabolismo , Anciano , Anciano de 80 o más Años , Antioxidantes/metabolismo , Femenino , Fluorescencia , Humanos , Masculino , Estrés OxidativoRESUMEN
An adequate placental vascularization allows the proper development of the fetus and it is crucial for the gestational success. A number of factors regulate angiogenesis, including vascular endothelial growth factor (VEGF), which induces the synthesis of nitric oxide (NO), a potent vasodilator produced by three different nitric oxide synthase (NOS) isoforms. NO is essential to maintain a low vascular resistance in the fetoplacental circulation, although at high concentrations, it may combine with excess superoxide to produce peroxynitrite, which reacts with proteins giving rise to nitrotyrosine. Since obesity, whose incidence is increasing worldwide, is characterized by a low-grade inflammatory state and increased levels of oxidative and nitrative stress, both affecting placental function, our aim was to evaluate the expression of VEGF, eNOS, and iNOS in full-term placentas obtained from normal weight and pre-pregnancy obese women by means of immunohistochemistry and real-time PCR. Moreover, we assessed the NO levels and the nitrotyrosine immunoexpression in the same sample groups. Our results show a significantly higher immunohistochemical expression of VEGF and eNOS in the endothelium of placentas from obese women than in controls, whereas the immunoexpression of iNOS was comparable in the two groups. These data agree with those of the gene expression analysis, thus suggesting the possible existence of a compensatory mechanism for changes in placental blood flow associated with obesity. As concerns nitrotyrosine and NO levels, we observed a significant increase in placental tissue from obese women which may contribute to the development of metabolic and cardiovascular diseases both in the mother and the offspring.
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Óxido Nítrico Sintasa/genética , Obesidad/metabolismo , Placenta/química , Factores de Crecimiento Endotelial Vascular/genética , Adulto , Femenino , Humanos , Inmunohistoquímica , Óxido Nítrico/análisis , Óxido Nítrico Sintasa/metabolismo , Placenta/metabolismo , Embarazo , Reacción en Cadena en Tiempo Real de la Polimerasa , Tirosina/análogos & derivados , Tirosina/análisis , Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
KBG syndrome is an autosomal dominant disorder caused by pathogenic variants within ANKRD11 or deletions of 16q24.3 which include ANKRD11. It is characterized by distinctive facial features, developmental delay, short stature, and skeletal anomalies. We report 12 unrelated patients where a clinical diagnosis of KBG was suspected and confirmed by targeted analyses. Nine patients showed a point mutation in ANKRD11 (none of which were previously reported) and 3 carried a 16q24.3 deletion. All patients presented with typical facial features and macrodontia. Skeletal abnormalities were constant, and the majority of patients showed joint stiffness. Three patients required growth hormone treatment with a significant increase of height velocity. Brain malformations were identified in 8 patients. All patients showed behavioral abnormalities and most had developmental delay. Two patients had hematological abnormalities. We emphasize that genetic analysis of ANKRD11 can easily reach a detection rate higher than 50% thanks to clinical phenotyping, although it is known that a subset of ANKRD11-mutated patients show very mild features and will be more easily identified through the implementation of gene panels or exome sequencing. Joint stiffness was reported previously in few patients, but it seems to be a common feature and can be helpful for the diagnosis. Hematological abnormalities could be present and warrant a specific follow-up.
RESUMEN
The aim of this study was to compare the oral health status and salivary antioxidant system between patients diagnosed with anorexia nervosa (AN) and healthy controls. A total of 25 female AN patients and 25 matched healthy controls were enrolled. Clinical parameters and saliva samples were collected for each patient. Two questionnaires to investigate oral health and hygiene were administered. Superoxide Dismutase (SOD) activity and High Reactive Oxygen Species (hROS) were evaluated. Salivary concentration of SOD was significantly higher in subjects with AN compared with control group (1.010 ± 0.462 vs. 0.579 ± 0.296 U/mL; p = 0.0003). No significant differences between groups were identified for hROS (233.72 ± 88.27 vs. 199.49 ± 74.72; p = 0.15). Data from questionnaires indicated that, although most of the patients recognized the oral hygiene importance in maintaining a good oral health, more than half of them had poor oral hygiene. Altered biochemical composition of saliva in patients with AN could be interpreted as an effective defence mechanism against oxidative stress. Moreover, despite the discrepancy between clinical findings and perception of the oral health in AN population arose, the quality of life of these patients appears not to be significantly affected by their dental condition.