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BACKGROUND: Short stature (SS) is defined as height more than 2 standard deviations below the mean for age and sex. Hypothyroidism, celiac disease, growth hormone deficiency, hormonal abnormalities, and genetic conditions are among its causes. A wide range of conditions often due to largely unknown genetic variants can elude conventional diagnostic workup. AIM: We used next-generation sequencing (NGS) to better understand the etiology of SS in a cohort of Italian children. PATIENTS AND METHODS: The study sample was 125 children with SS of unknown origin referred to our Institute between 2015 and 2021. All had undergone complete auxological and hormonal investigations to exclude common causes of SS. Genetic analysis was performed using a NGS panel of 104 genes. Clinical data were reviewed to clarify the pathogenicity of the variants detected. RESULTS: In this cohort, 43 potentially causing variants were identified in 38 children. A syndromic genetic condition was diagnosed in 7: Noonan syndrome in 3, Leri-Weill syndrome in 3, and hypochondroplasia in 1. Moreover, 8 benign variants and other 37 like benign variants were found. In 88 children, 179 variants of uncertain significance (VUS) were identified. No variant was found in 16 children. CONCLUSION: Genetic analysis is a useful tool in the diagnostic workup of patients with SS, in adapting management and treatment, and in identifying syndromes with mild atypical clinical features. The role of VUS should not be underestimated, particularly when multiple VUS with possible mutual worsening effects are present in the same child.
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Energy can be transferred between two quantum systems in two forms: unitary energy-that can be used to drive another system-and correlation energy-that reflects past correlations. We propose and implement experimental protocols to access these energy transfers in interactions between a quantum emitter and light fields. Upon spontaneous emission, we measure the unitary energy transfer from the emitter to the light field and show that it never exceeds half the total energy transfer and is reduced when introducing decoherence. We then study the interference of the emitted field and a coherent laser field at a beam splitter and show that the nature of the energy transfer quantitatively depends on the quantum purity of the emitted field.
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Qubits are physical, a quantum gate thus not only acts on the information carried by the qubit but also on its energy. What is then the corresponding flow of energy between the qubit and the controller that implements the gate? Here we exploit a superconducting platform to answer this question in the case of a quantum gate realized by a resonant drive field. During the gate, the superconducting qubit becomes entangled with the microwave drive pulse so that there is a quantum superposition between energy flows. We measure the energy change in the drive field conditioned on the outcome of a projective qubit measurement. We demonstrate that the drive's energy change associated with the measurement backaction can exceed by far the energy that can be extracted by the qubit. This can be understood by considering the qubit as a weak measurement apparatus of the driving field.
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PURPOSE: Treatment of muscle-invasive bladder cancer (MIBC) remains challenging, especially for elderly and/or comorbid patients. Patients who are unfit for or refuse surgery should receive bladder-preserving multimodality treatment (BPMT), consisting of transurethral resection of the bladder tumor (TURB) followed by combined chemoradiotherapy (CRT). We aimed to investigate the effectiveness of vinorelbine, a chemotherapeutic agent not routinely used for MIBC, in patients referred to CRT who are unfit for standard chemotherapy and would thus rely solely on radiotherapy (RT). METHODS: We retrospectively analyzed 52 consecutive patients with MIBC who received standard CRT with cisplatin (nâ¯= 14), CRT with vinorelbine (nâ¯= 26), or RT alone (nâ¯= 12). Primary endpoints were median overall survival (OS) and median cancer-specific survival (CSS). Secondary endpoints were median local control (LC), median distant control (DC), and OS, CSS, LC, and DC after 1, 2, and 3 years, respectively. RESULTS: Median OS and CSS were significantly higher for patients who received vinorelbine as compared to RT alone (OS 8 vs. 22 months, pâ¯= 0.003; CSS 11 months vs. not reached, pâ¯= 0.001). Median LC and DC did not differ significantly between groups. Vinorelbine was well tolerated with no reported side effects >gradeâ¯II. CONCLUSION: Our results suggest that CRT with vinorelbine is well tolerated and superior to RT alone in terms of OS and CSS. Therefore, this treatment regime might constitute a new treatment option for patients with MIBC who are unfit for or refuse surgery or standard chemotherapy. This study encourages a randomized controlled trial to compare this new regime to current standard therapies.
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Neoplasias da Bexiga Urinária , Idoso , Cisplatino/uso terapêutico , Humanos , Músculos/patologia , Invasividade Neoplásica , Estudos Retrospectivos , Resultado do Tratamento , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia , VinorelbinaRESUMO
PURPOSE: The alpha7 nicotinic acetylcholine receptor (α7nAChR), involved in the modulation of inflammation and insulin sensitivity, is downregulated in white adipose tissue (WAT) of obese patients. This study aims to test the ability of a selective synthetic α7nAChR agonist, the spirocyclic Δ2-isoxazoline derivative (R)-(-)-ICH3 (ICH3), to counteract acute inflammation and obesity-associated modifications in WAT. METHODS: We employed the LPS-septic shock murine model, human primary adipocytes and diet-induced obese (DIO) mice. Inflammatory factor expression was assessed by ELISA and quantitative real-time PCR. Flow cytometry was employed to define WAT inflammatory infiltrate. Insulin signaling was monitored by quantification of AKT phosphorylation. RESULTS: In the septic shock model, ICH3 revealed antipyretic action and reduced the surge of circulating cytokines. In vitro, ICH3 stimulation (10 µM) preserved viability of human adipocytes, decreased IL-6 mRNA (P < 0.05) and blunted LPS-induced peak of TNFα (P < 0.05) and IL-6 (P < 0.01). Chronic administration of ICH3 to DIO mice was associated with lower numbers of CD8+ T cells (P < 0.05) and to changed WAT expression of inflammatory factors (Hp, P < 0.05; CD301/MGL1, P < 0.01; Arg-1, P < 0.05). As compared to untreated, ICH3 DIO mice exhibited improved insulin signaling in the skeletal muscle (P < 0.01) mirrored by an improved response to glucose load (ipGTT: P < 0.05 at 120 min). CONCLUSIONS: We proved that ICH3 is an anti-inflammatory drug, able to reduce inflammatory cytokines in human adipocytes and to blunt the effects of obesity on WAT inflammatory profile, on glucose tolerance and on tissue insulin sensitivity.
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Tecido Adiposo Branco/efeitos dos fármacos , Agonistas Colinérgicos/farmacologia , Fumaratos/farmacologia , Obesidade/complicações , Paniculite/etiologia , Paniculite/prevenção & controle , Acetilcolina/agonistas , Acetilcolina/análogos & derivados , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipócitos/patologia , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/patologia , Animais , Temperatura Corporal/efeitos dos fármacos , Células Cultivadas , Agonistas Colinérgicos/uso terapêutico , Citocinas/metabolismo , Dieta Hiperlipídica , Fumaratos/uso terapêutico , Glucose/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Camundongos , Camundongos Obesos , Obesidade/tratamento farmacológico , Compostos de Espiro , Receptor Nicotínico de Acetilcolina alfa7/agonistasRESUMO
The plant phenolic compound (E)-chalcone has been previously found to induce noticeable seedling size reduction and progressive de-greening (bleaching) in shoots of Arabidopsis thaliana seedlings. In this work, we demonstrate that this progressive de-greening occurring on Arabidopsis shoots after (E)-chalcone treatment, is directly linked to early plasma membrane depolarization and dramatic effects on chloroplasts structure and function. Later effects in chalcone-treated seedlings included ROS accumulation, pigment degradation, reduced photosynthetic activity, bleaching, and eventually cell death. De-greening and pigment degradation induced by (E)-chalcone were partially reversed when NaCl was added together with chalcone, which could be related to restoration of altered pH gradients. All these results suggest that rapid alteration of plasma membrane potential after chalcone treatment is a major component of the mode of action of (E)-chalcone on Arabidopsis metabolism.
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Arabidopsis/fisiologia , Membrana Celular/fisiologia , Chalcona/metabolismo , Fotossíntese/fisiologia , Cloroplastos/fisiologia , Potenciais da Membrana , Folhas de Planta/fisiologia , Plântula/fisiologiaRESUMO
BACKGROUND/OBJECTIVES: In lipodystrophy (LD) adipose tissue function to store lipids is impaired, leading to metabolic syndrome, similar to that found in obesity. Emerging evidence links dysmetabolism with disorders of the immune system. Our aim is to investigate whether T-cell populations with regulatory function and monocyte-derived macrophages (MDMs) are affected by LD and obesity. SUBJECTS/METHODS: Blood was collected from 16 LD, 16 obese (OB, BMI>30 kg m-2) and 16 healthy normal-weight women (CNT). Physical parameters, plasma lipid profile, glucose, HbA1c, leptin levels were determined. Flow cytometry was employed to assess the number of circulating CD4+/CD25hi regulatory T cells (Tregs) and invariant natural killer T (iNKT) cells. Characterization of MDMs included: 1. morphological/oil-Red-O staining analyses to define two morphotypes: lipid laden (LL) and spindle-like (sp) MDM; 2. gene expression studies; 3. use of conditioned medium from MDMs (MDMs CM) on human SGBS cells. RESULTS: As compared to CNT, LD and, to a lesser extent, obesity were associated with reduced Tregs and iNKTs (P<0.001 and P<0.01 for LD and OB, respectively), higher number of LL-MDMs (P<0.001 and P<0.01 for LD and OB, respectively), lower number of sp-MDMs (P<0.001 for both LD and OB), which correlated with increased paracrine stimulation of lipid accumulation in cells (P<0.001 and P<0.01 for LD and OB, respectively). LD MDMs showed decreased and increased expression for anti-inflammatory (IL10 and CD163) and pro-inflammatory (CD68 and CCL20) marker genes, respectively. Analysis of correlation indicated that Tregs are directly related with HDL (P<0.01) and inversely related with LL-MDM (P<0.001) and that LL-MDM are directly related with triglycerides (P<0.01) and oxidized LDL (P<0.01). CONCLUSIONS: LD and obesity are associated with changes in the immune system: a significant reduction in the number of T cells with regulatory function and a shift of MDM towards lipid accumulation. Lipid profile of the patients correlates with these changes.
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Tecido Adiposo/metabolismo , Lipodistrofia/imunologia , Macrófagos/imunologia , Obesidade/imunologia , Linfócitos T/citologia , Adulto , Feminino , Citometria de Fluxo , Hemoglobinas Glicadas , Humanos , Lipídeos/imunologia , Lipodistrofia/metabolismo , Lipodistrofia/patologia , Lipodistrofia/fisiopatologia , Contagem de Linfócitos , Ativação de Macrófagos , Obesidade/metabolismo , Obesidade/patologia , Obesidade/fisiopatologia , Fenótipo , Linfócitos T/imunologiaRESUMO
BACKGROUND: While it is now accepted that genes and their products affect food intake, the concept that locomotor behavior or the propensity for physical activity is controlled by neuro hum oral regulators is frequently underappreciated. In mammals, complex interactions have developed to allow the cross-talk between fuel homeostasis and physical activity. AIM: The aim of this review is to provide a synopsis of the influence of the leptin-melanocortin pathway, a well-studied pivotal player in body weight regulation, on locomotor behaviors. CONCLUSIONS: In rodents, reductions in leptin levels that physiologically occur following acute food deprivation or a reduction of the fat mass consequent to prolonged caloric restrictions are associated with a decrease in total locomotor activity and simultaneous increase in food-anticipatory activity, a locomotor behavior which reflects a foraging attitude. These actions can be prevented by leptin administration and are at least partially mediated by the neurons of the melanocortin pathway. In humans, twin studies have attributed to genetic factors approximately 50% of the variance of physical activity. An elevated number of the genes or loci which may affect physical activity are involved in body weight homeostasis. Polymorphisms of the melanocortin-4 and leptin receptors have repeatedly been associated with the level of physical activity. Unraveling the complexity of the regulation of locomotor behavior and the interconnections with the pathways involved in energy homeostasis may help explain the substantial individual variability in physical activities in humans and disentangle the harmful effects of sedentary lifestyle, which may be distinct from the detrimental effects of obesity.
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Homeostase/fisiologia , Leptina/fisiologia , Melanocortinas/fisiologia , Atividade Motora/fisiologia , Transdução de Sinais/fisiologia , Animais , HumanosRESUMO
AIM: Notwithstanding the widely accepted idea that following disuse skeletal muscles become faster, an increase in shortening velocity was previously observed mostly in fibres containing type 1 myosin, whereas a decrease was generally found in fibres containing type 2B myosin. In this study, unloaded shortening velocity of pure type 1 and 2B fibres from hindlimb unloaded mice was determined and a decrease in type 2B fibres was found. METHODS: To clarify whether the decrease in shortening velocity could depend on alterations of myosin motor function, an in vitro motility assay approach was applied to study pure type 1 and pure type 2B myosin from hindlimb unloaded mice. The latter approach, assessing actin sliding velocity on isolated myosin in the absence of other myofibrillar proteins, enabled to directly investigate myosin motor function. RESULTS: Actin sliding velocity was significantly lower on type 2B myosin following unloading (2.70 ± 0.32 µm s(-1)) than in control conditions (4.11 ± 0.35 µm s(-1)), whereas actin sliding velocity of type 1 myosin was not different following unloading (0.89 ± 0.04 µm s(-1)) compared with control conditions (0.84 ± 0.17 µm s(-1)). Myosin light chain (MLC) isoform composition of type 2B myosin from hindlimb unloaded and control mice was not different. No oxidation of either type 1 or 2B myosin was observed. Higher phosphorylation of regulatory MLC in type 2B myosin after unloading was found. CONCLUSION: Results suggest that the observed lower shortening velocity of type 2B fibres following unloading could be related to slowing of acto-myosin kinetics in the presence of MLC phosphorylation.
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Actinas/química , Contração Muscular/fisiologia , Músculo Esquelético/química , Músculo Esquelético/fisiologia , Atrofia Muscular/fisiopatologia , Miosinas/química , Actinas/fisiologia , Animais , Elevação dos Membros Posteriores , Cinética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Motores Moleculares/química , Proteínas Motores Moleculares/fisiologia , Movimento (Física) , Miosinas/fisiologiaRESUMO
BACKGROUND: GPR7, the endogenous coupled receptor for neuropeptide B and neuropeptide W, is expressed in several regions of the central nervous system, which are involved in the regulation of feeding behavior. GPR7 affects the regulation of energy balance through a mechanism independent of leptin and melanocortin pathways. AIM: Aim of this study was to investigate whether GPR7 gene mutations can be detected in human subjects and, in that event, if they are differently distributed among lean and obese subjects. SUBJECTS AND METHODS: The coding region of GPR7 were sequenced in 150 obese patients and 100 normal-weight unrelated controls. Functional studies of the allelic variants were performed. RESULTS: One genetic GPR7 variant was found (Tyr135Phe - rs33977775) in obese subjects (13.3%) and lean control (25%). Functional studies did not reveal significant differences between the wild type and the Tyr135Phe allelic variants in their NPW-mediated capacity to inhibit forskolin-induced cAMP production. CONCLUSIONS: Screening of GPR7 gene mutations among lean and obese subjects revealed a Tyr135Phe allelic variant that was fairly common in the study population. As indicated by in vitro and in silico studies, this variant is unlikely to cause a functional derangement of the receptor.
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Obesidade/genética , Receptores Acoplados a Proteínas G/genética , Receptores de Neuropeptídeos/genética , Magreza/genética , Adulto , Alelos , Substituição de Aminoácidos , Animais , Células COS , Chlorocebus aethiops , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores Acoplados a Proteínas G/fisiologia , Receptores de Neuropeptídeos/fisiologiaRESUMO
OBJECTIVE: Bariatric surgery represents a powerful tool for morbid obesity treatment. However, after stabilization of weight loss that follows surgical interventions, ex-obese patients face the problem of residual tissues removal. Actually, it is unknown whether the characteristics of this residual subcutaneous adipose tissue (SAT) are 'restored' with regard to molecular and morphological features. DESIGN: To clarify this issue, we compared the SAT gene expression profile of ex-obese patients (ExOB-SAT, mean body mass index (BMI): 27.2±1.3 kg m(-2)) with that of lean (normal weight, NW-SAT, mean BMI: 22.6±1.1 kg m(-2)), overweight (OW-SAT, BMI: 27.65±0.2 kg m(-2)) and obese patients, according to BMI classes (OB1-SAT: 30 > or = BMI < or = 34.9, OB2-SAT: 35 > or = BMI < or = 39.9, OB3-SAT: BMI > or = 40). SUBJECTS AND METHODS: A total of 58 samples of SAT were collected during surgical interventions. Gene expression levels were assessed by microarrays and significant genes were validated by RT-qPCR. Adipocyte hypertrophy, inflammatory infiltration and fibrosis were assessed by morphological techniques. RESULTS: Global gene expression in ExOB-SAT was closely related to gene expression of OB3-SAT by hierarchical clustering procedures, in spite of different BMI. Metallothioneins (MT1A and MT2A) were the key over-expressed genes in both groups. At morphologic level, adipocyte hypertrophy and inflammatory infiltration improved after weight loss in ExOB-SAT, despite a persistence of fibrosis. CONCLUSIONS: Taken together, these results demonstrate that SAT gene expression is not fully restored, even after an extensive and stable weight loss. The persistence of 'obesity molecular features' in ExOB-SAT suggests that the molecular signature of adipose tissue is not solely dependent on weight loss and may need longer time period to completely disappear.
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Adipócitos/patologia , Derivação Gástrica , Inflamação/patologia , Obesidade Mórbida/patologia , Gordura Subcutânea/patologia , Magreza/patologia , Redução de Peso , Adulto , Índice de Massa Corporal , Procedimentos Cirúrgicos Eletivos , Feminino , Regulação da Expressão Gênica , Humanos , Hipertrofia , Itália/epidemiologia , Masculino , Metalotioneína/genética , Metalotioneína/metabolismo , Pessoa de Meia-Idade , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/genética , Obesidade Mórbida/cirurgia , RNA Mensageiro/metabolismo , Magreza/epidemiologia , Magreza/genética , Magreza/cirurgia , Fatores de Tempo , Resultado do Tratamento , Redução de Peso/genéticaRESUMO
AIM: In the present study, we have evaluated whether physical exercise affect low osteocalcin concentrations observed in patients with subclinical hypercortisolism. SUBJECTS AND METHODS: Sixteen patients (10 men and 6 women, age 38-55 yr) with adrenal incidentaloma were studied. Fifteen healthy volunteers matched for age (range 35-47 yr) were used as controls. Subjects were submitted to a 8-week exercise-training program with cycle-ergometer for 1 h/day 3-4 days/week at 60% of their individual VO2 max. Before and after this period, resting venous serum osteocalcin and GH concentrations were measured in the same batch. The blood sampling after 8 weeks of the training program were performed after resting for one day. All patients and controls underwent also the following endocrine evaluation: serum cortisol, plasma ACTH. RESULTS: Our results demonstrate a significant increase of osteocalcin after physical exercise and a positive correlation between osteocalcin and GH. This later might suggest a role of GH in the increased osteocalcin secretion. CONCLUSIONS: The data of the present study suggest a positive effect of physical exercise on bone metabolism in patients with adrenal incidentaloma.
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Neoplasias das Glândulas Suprarrenais/sangue , Neoplasias das Glândulas Suprarrenais/terapia , Exercício Físico/fisiologia , Osteocalcina/sangue , Adulto , Biomarcadores/sangue , Terapia por Exercício/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora/fisiologiaRESUMO
Vegetative state (VS) and minimally conscious state (MCS) are considered different clinical entities but their differential diagnosis remains challenging. Some VS patients can show an MCS-like activation in functional magnetic resonance imaging (fMRI) studies that seems to predict recovery from VS. We studied fMRI activation with an affective speech paradigm in a cohort of non-communicative brain-injured individuals consecutively admitted to a post-acute neurorehabilitation facility in five years. Among 93 eligible subjects, 65 met the clinical criteria for VS and 28 for MCS. Because of exclusion criteria, activation studies were performed in only 30 cases out of 93 and analysed in only 24 (about » of the eligible cases): 19 VS and five MCS patients. The passive acoustic stimulus consisted in a familiar voice narrating a significant episode in the patient's life, administered by nonmagnetic earphones. All the MCS patients showed an activation spread to secondary associative cortices but also 52.7% of the VS patients displayed an "atypical" large-scale activation pattern. Regarding the clinical outcome, 80% of the patients with large-scale network activation (LSNA) had some recovery of consciousness. Our results confirm that the VS patients with LSNA at fMRI study have potential for further recovery of consciousness, whereas no patient without activation or only typical activation improved. fMRI study with an affective speech paradigm, when applicable, seems to have a valuable prognostic value in VS patients, even if there are major limitations in terms of applicability.
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OBJECTIVES: Oral fields of visually normal and non-dysplastic mucosa (ODFs) may represent the precursors of oral potentially malignant lesions (OPMLs). Aim of the study was to provide new evidence for the concept of the "field carcinogenesis" model by comparing the ODF and OPML genomic aberration profiles obtained by high resolution DNA flow cytometry (hr DNA-FCM) and array-Comparative Genomic Hybridization (a-CGH). A second aim was to investigate if specific CGH aberrations were associated with DNA aneuploidy. METHODS: Nineteen patients with single OPMLs were recruited for the study. In parallel with obtaining samples of OPML tissue from 11 leukoplakias without dysplasia (nd-OPMLs) and 8 with dysplasia (d-OPMLs), we also obtained samples from distant ODFs. DNA aneuploid nuclei detected by hr DNA-FCM were physically separated, based on DNA content, from the DNA diploid components with a DNA-FCM-Sorter. These relatively pure subpopulations of epithelial nuclei were then submitted to DNA extraction and a-CGH for a genome-wide analysis of DNA copy number aberrations (CNAs). RESULTS: The frequencies of DNA aneuploidy (DI ≠ 1) among ODFs and OPMLs were respectively 5.3% and 32%. The DI aneuploid values of ODFs and nd-OPMLs were all near-diploid (DI ≠ 1 and DI ≤ 1.4), while for d-OPMLs were high-aneuploid (DI > 1.4) in 40% of the cases. CNA averages were 1.9 in ODFs and 6.5 in OPMLs. The gain of the chromosomal region 20q13.33-qter was observed in 37% of both ODFs and corresponding OPMLs. Additional common regions included 7p22.2-pter, 11p15.5-pter and 16p13.3-pter where gains were observed. Furthermore, gains of 20q13.31-q13.33 and of 5p13.33-pter and loss of 9p21.3 were detected at high frequency (respectively, at 62.5%, 50% and 50%) only in d-OPMLs. In particular, loss at 9p21.3, gain at 5p13.33-pter and gain of 20q13.31-q13.33 were associated with DNA aneuploidy (p = 0.00004; p = 0.0005; p = 0.01). CONCLUSIONS: ODFs and OPMLs showed common CNAs in specific chromosomal regions suggesting that they may represent early events of the natural history of oral carcinogenesis according to the field effect cancerization and may contribute to the ODF-OPML transition. In addition, loss at 9p21.3 and gains at 5p13.33-pter and 20q13.31-q13.33 may contribute to DNA aneuploidization.
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Aberrações Cromossômicas , Genoma Humano/genética , Mucosa Bucal/patologia , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Adulto , Idoso , Aneuploidia , Cromossomos Humanos/genética , Hibridização Genômica Comparativa , Variações do Número de Cópias de DNA/genética , DNA de Neoplasias/genética , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The effect of an i. v. infusion of somatostatin (SRIH) 4.1 µg/min×90 min on the basal secretion of NPY and on the NPY response to physical exercise was studied in normal men. Basal NPY secretion was not modified by SRIH infusion, whereas the NPY response to physical exercise was significantly lower in the presence of SRIH. These data suggest the involvement of a somatostatinergic mechanism in the regulation of NPY response to physical exercise.
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Exercício Físico , Neuropeptídeo Y/sangue , Somatostatina/metabolismo , Adulto , Regulação para Baixo , Humanos , Infusões Intravenosas , Masculino , Somatostatina/administração & dosagem , Adulto JovemRESUMO
The present study was undertaken in order to establish the possible involvement of serotonergic receptors in the control of physical exercise-stimulated vasopressin secretion. Twenty-one healthy men (divided in three groups of seven) underwent bicycle-ergometer tests until exhaustion: exercise control test (n=21), exercise plus ondansetron, selective 5-HT3 antagonist (n=7), exercise plus buspirone, selective 5-HT1A receptor agonist (n=7), exercise plus sumatriptan, selective 5-HT1D receptor agonist (n=7). AVP levels, physiological and biochemical variables were measured and compared during tests. Results showed that exercise-induced AVP rise did not change after the administration of buspirone and sumatriptan. In contrast, the administration of ondansetron significantly reduced physical exercise-induced AVP rise. Mean peak levels during physical exercise were 4.9 times higher than basal values in the control test and 2.6 times higher than basal values in the ondansetron plus exercise test. These data demonstrate that 5-HT3 serotonergic receptors at least partially mediate the AVP response to physical exercise. On the other hand, 5-HT1A and 5-HT1D serotonergic receptors do not appear to be involved in the control of AVP secretion during exercise.
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Arginina Vasopressina/sangue , Exercício Físico/fisiologia , Agonistas do Receptor de Serotonina/farmacologia , Serotonina/fisiologia , Adulto , Glicemia/metabolismo , Buspirona/farmacologia , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Ondansetron/farmacologia , Concentração Osmolar , Sumatriptana/farmacologia , Adulto JovemRESUMO
To establish whether ethanol and/or endogenous opioids play a role in the control of arginine-vasopressin (AVP) response to physical exercise, six healthy men underwent six bicycle-ergometer tests until exhaustion [exercise control test; exercise plus ethanol (50 of 110 ml proof whiskey orally), exercise plus naloxone (2 mg injected plus 5 mg infused or 4 mg injected plus 10 mg infused intravenously] or exercise plus ethanol plus naloxone). Plasma AVP levels, physiological and biochemical variables were measured during tests. Physiological and biochemical variables were similar in all tests. During the control test, exercise significantly increased plasma AVP levels, with a peak value five times higher than baseline. The AVP response to exercise was similar in the presence of naloxone, whereas it was abolished by ethanol. When ethanol tests were repeated in the presence of naloxone, at both lower and higher dose, ethanol inhibition on AVP secretion was only partial, with mean peak responses 2.5 times higher than basal values. Results indicate an ethanol involvement in regulation of the AVP response to physical exercise. Furthermore, naloxone-sensitive endogenous opioids appear to play a role in the mechanism underlying ethanol inhibitory action, but not in mediation of the AVP response to physical exercise.