RESUMO
The commonest form of thyroid dysfunction seen in subjects with TM is primary hypothyroidism due to abnormalities of the thyroid gland. Central hypothyroidism (CH) has been reported as an uncommon clinical entity in TM patients although the anterior pituitary gland is particularly sensitive to free radical oxidative stresses. Diagnosis is usually made on a biochemical basis showing low circulating concentrations of thyroid hormone associated with an inappropriately low TSH levels. The diagnosis is not clinically obvious and a basal normal TSH level does not exclude the diagnosis of CH. Therefore, it is important that clinicians accurately interpret thyroid function tests. In TM patients, CH prevalence differs at different ages is unknown and it is not easy to diagnose because most of the symptoms of symptoms of CH are non specific and are frequently attributed to anaemia or other associated complications . We performed a cross-sectional analysis on a large database using the clinical records of our TM patients to explore the prevalence of CH in prepubertal (<11 years: 25 patients; 13 males) peripubertal (between 11 and 16 years: 9 patients; 3 males), and pubertal TM subjects (>16 years: 305 patients; 164 males). Central hypothyroidism was present in 26 (7,6%) TM patients. Their mean age was 29.9 ± 8.4 years, 14 (53.8%) were males and 12 (46.1%) were females. The prevalence of CH was 6% in patients with a chronological age below 21 years and 7.9% in those above 21 years. Clinicians should be alert for the diagnosis of CH through accurate interpretation of thyroid function tests. We recommend L-thyroxine therapy if the level of FT4 is consistently low provided that the patient has normal cortisol levels.
Assuntos
Hipotireoidismo/epidemiologia , Talassemia beta/complicações , Adolescente , Adulto , Criança , Estudos Transversais , Feminino , Seguimentos , Saúde Global , Humanos , Hipotireoidismo/etiologia , Lactente , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Triage is a complex and dynamic decisional process composed of sequential actions and necessary evaluations in order to establish the priority of access to medical attention in emergency care. In the Triage not only medical-biological knowledge is important but also the methods that together are inspired by ethical models. Following the historical considerations and after having brought out the methods and practice used in various countries and also having underlined the personal experience of the Emergency Department of the Emergency Department of the University Policlinic of the "Sapienza" University of Rome (Italy), the biggest hospital in Europe, the authors emphasized the nursing care in the "triage" and support the necessity of an adequate training period not only to acquired the technical knowledge required but also the psychological and social interaction as well as moral and practical competence. By "practical" we intend it to be explicitly a dimension in which moral competence has been acquired in using concrete first person action in a virtuous way towards the betterment of the sick person using the best modes of justice.
Assuntos
Serviço Hospitalar de Emergência/ética , Serviço Hospitalar de Emergência/normas , Triagem/ética , Triagem/normas , HumanosRESUMO
Physiological signalling by the epidermal growth factor receptor (EGFR) controls developmental processes and tissue homeostasis, whereas aberrant EGFR activity drives oncogenic cell transformation. Under normal conditions, the EGFR must therefore generate outputs of defined strength and duration. To this aim, cells balance EGFR activity via different modalities of negative signalling. Increasing attention is being drawn on transcriptionally controlled feedback inhibitors of EGFR, namely RALT/MIG6, LRIG1, SOCS4 and SOCS5. Genetic studies in mice have revealed the essential role of Ralt/Mig6 in regulating Egfr-driven skin morphogenesis and tumour formation, yet the mechanisms through which RALT abrogates EGFR activity are still undefined. We report that RALT suppresses EGFR function by inhibiting its catalytic activity. The evolutionarily conserved ErbB-binding region (EBR) is necessary and sufficient to carry out RALT-dependent suppression of EGFR kinase activity in vitro and in intact cells. The mechanism involves binding of the EBR to the 953RYLVIQ958 sequence, which is located in the alphaI helix of the EGFR kinase and has been shown to participate in allosteric control of EGFR catalytic activity. Our results uncover a novel mechanism of temporal regulation of EGFR activity in vertebrate organisms.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Receptores ErbB/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/química , Animais , Sítios de Ligação , Catálise , Células Cultivadas , Sequência Conservada , Receptores ErbB/química , Receptores ErbB/metabolismo , Evolução Molecular , Retroalimentação Fisiológica , Humanos , Camundongos , Fosforilação , Estrutura Terciária de Proteína , Transdução de Sinais , Proteínas Supressoras de TumorRESUMO
The purpose of the study was to investigate determinants of acute mountain sickness after rapid ascent to high altitude. A total of 21 climbers were studied ascending from <1,200 m to Capanna Regina Margherita, a hut in the Alps at 4,559 m, within <24 h. During their overnight stay at 4,559 m, breathing patterns and ventilation were recorded by calibrated respiratory inductive plethysmography along with pulse oximetry. In the following morning, acute mountain sickness was assessed. Altogether, 11 mountaineers developed pronounced symptoms of acute mountain sickness (Lake Louise score > or =5) and 10 did not (controls). Compared to controls, subjects with acute mountain sickness had lower nocturnal oxygen saturation (mean+/-SD 59+/-13% versus 73+/-6%), higher minute ventilation (7.94+/-2.35 versus 6.06+/-1.34 L x min(-1)), and greater mean inspiratory flow, a measure of respiratory centre drive (0.29+/-0.09 versus 0.22+/-0.05 L x s(-1)). Periodic respiration was prevalent but not significantly different among the two groups (apnoea/hypopnea index 60.1+/-34.6 versus 47.1+/-42.6 events per h). The data suggest that pronounced nocturnal hypoxemia, which was not related to hypoventilation, may have promoted acute mountain sickness. Periodic breathing seems not to play a predominant role in the pathogenesis of acute mountain sickness.
Assuntos
Doença da Altitude/diagnóstico , Hipoventilação/diagnóstico , Hipóxia/diagnóstico , Mecânica Respiratória/fisiologia , Doença Aguda , Adulto , Altitude , Doença da Altitude/epidemiologia , Gasometria , Estudos de Casos e Controles , Feminino , Humanos , Hipoventilação/epidemiologia , Hipóxia/epidemiologia , Incidência , Masculino , Montanhismo , Pletismografia , Prognóstico , Troca Gasosa Pulmonar , Medição de Risco , Índice de Gravidade de Doença , SuíçaRESUMO
Hepatocyte growth factor/scatter factor (HGF/SF) is a growth factor with pleiotropic effects on different cell types. It acts as a mitogen and motility factor for many epithelial cells. HGF/SF and its receptor Met are present in the developing and adult mammalian brain and control neuritogenesis of sympathetic and sensory neurons. We report that the striatal progenitor ST14A cells express the Met receptor, which is activated after binding with HGF/SF. The interaction between Met and HGF/SF triggers a signaling cascade that leads to increased levels of c-Jun, c-Fos, and Egr-1 proteins, in agreement with data reported on the signaling events evoked by HGF in other cellular types. We also studied the effects of the exposure of ST14A cells to HGF/SF. By time-lapse photography, we observed that a 24-hr treatment with 50 ng/ml HGF/SF induced modification in cell morphology, with a decrease in cell-cell interactions and increase of cell motility. In contrast, no effect on cell proliferation was observed. To investigate which intracellular pathway is primarily involved we used PD98059 and LY294002, two specific inhibitors of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAP-kinase/ERK-kinase) and phosphoinositide 3-OH kinase (PI3-K), respectively. Cell motility in HGF/SF treated cultures was inhibited by LY294002 but not by PD98059, suggesting that PI3-K plays a key role in mediating the HGF/SF-induced dissociation of ST14A cells. Previous evidence of HGF stimulation of motility in nervous system has been obtained on postmitotic neurons, which have already acquired their specificity. Data reported here of a motogenic response of ST14A cell line, which displays properties of neuronal progenitors, seem of interest because they suggest that HGF could play a role in very early steps of neurogenesis.
Assuntos
Movimento Celular/efeitos dos fármacos , Fator de Crescimento de Hepatócito/farmacologia , Neurônios/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-met/fisiologia , Células-Tronco/efeitos dos fármacos , Animais , Western Blotting , Comunicação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Corpo Estriado/citologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/embriologia , Embrião de Mamíferos , Genes Precoces/efeitos dos fármacos , Imuno-Histoquímica , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Neurônios/fisiologia , Fosfatidilinositol 3-Quinases/metabolismo , Testes de Precipitina , Ratos , Células-Tronco/fisiologiaRESUMO
Present transfusional regimen protocols increase the life expectancy of patients with beta-thalassemia major, but cause a progressive iron overload that can be prevented or limited only by appropriate iron chelation. Siderosis is responsible for the clinical complications of the disease. Short stature and hypogonadism are extremely frequent in patients with thalassemia. Many factors are responsible for short stature in patients with thalassemia, the most important of which are dysfunction of the GH-IGF-I axis and desferoxamine (DFX)-induced bone dysplasia. Hypogonadism is the most frequent endocrine complication, mostly due to gonadotrophins deficiency secondary to iron overload. Sex steroid treatment for induction of puberty and/or maintenance of sexual characteristics is necessary. Both short stature and hypogonadism are present in a significant percentage of bone marrow transplanted patients with thalassemia. Factors responsible for short stature are previous iron overload, liver impairment, DFX treatment, and toxicity of chemotherapeutic agents. In some patients absence of pubertal development is due to gonadotropin insufficiency, probably secondary to previous iron overload; other patients exhibit hypergonadotrophic hypogonadism due to the toxic effect of chemotherapeutic agents on the gonads. Both groups need hormonal replacement therapy. These data support the need for vigilant follow-up of patients with thalassemia before and after transplantation, in order to treat endocrine dysfunctions at the appropriate age.
Assuntos
Puberdade , Talassemia beta/fisiopatologia , Estatura , Transplante de Medula Óssea , Terapia por Quelação , Crescimento , Humanos , Hipogonadismo/etiologia , Talassemia beta/complicações , Talassemia beta/patologia , Talassemia beta/terapiaRESUMO
As a rule, hepatocyte growth factor/scatter factor (HGF/SF) is produced by mesenchymal cells, while its receptor, the tyrosine kinase encoded by the met proto-oncogene, is expressed by the neighboring epithelial cells in a canonical paracrine fashion. In the present work we show that both HGF/SF and met are coexpressed by undifferentiated C2 mouse myoblasts. In growing cells, the autocrine loop is active as the receptor exhibits a constitutive phosphorylation on tyrosine that can be abrogated by exogenously added anti-HGF/SF neutralizing antibodies. The transcription of HGF/SF and met genes is downregulated when myoblasts stop proliferating and differentiate. The coexpression of HGF/SF and met genes is not exclusive to C2 cells since it has been assessed also in other myogenic cell lines and in mouse primary satellite cells, suggesting that HGF/SF could play a role in muscle development through an autocrine way. To analyze the biological effects of HGF/SF receptor activation, we stably expressed the constitutively activated receptor catalytic domain (p65(tpr-met)) in C2 cells. This active kinase determined profound changes in cell shape and inhibited myogenesis at both morphological and biochemical levels. Notably, a complete absence of muscle regulatory markers such as MyoD and myogenin was observed in p65(tpr-met) highly expressing C2 clones. We also studied the effects of the ectopic expression of human isoforms of met receptor (h-met) and of HGF/SF (h-HGF/SF) in stable transfected C2 cells. Single constitutive expression of h-met or h-HGF/SF does not alter substantially the growth and differentiation properties of the myoblast cells, probably because of a species-specific ligand-receptor interaction. A C2 clone expressing simultaneously both h-met and h-HGF/SF is able to grow in soft agar and shows a decrease in myogenic potential comparable to that promoted by p65(tpr-met) kinase. These data indicate that a met kinase signal released from differentiation-dependent control provides a negative stimulus for the onset of myogenic differentiation.
Assuntos
Fator de Crescimento de Hepatócito/farmacologia , Músculos/citologia , Fosfotransferases/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Animais , Diferenciação Celular/fisiologia , Cães , Regulação para Baixo/fisiologia , Ativação Enzimática , Expressão Gênica/fisiologia , Gliceraldeído-3-Fosfato Desidrogenases/genética , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Humanos , Túbulos Renais Distais/citologia , Fígado/citologia , Camundongos , Camundongos Endogâmicos C3H , Músculos/química , Músculos/enzimologia , Proteína MyoD/genética , Proteína MyoD/metabolismo , Miogenina/genética , Miogenina/metabolismo , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-met , RNA Mensageiro/metabolismo , Receptores Proteína Tirosina Quinases/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Especificidade da Espécie , Teratocarcinoma , Transfecção , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/enzimologiaRESUMO
Based on a review of the literature and personal observation, the authors discuss the most frequent endocrine complication that occur in patients with thalassemia major given blood transfusion and chelating therapy. All the complication are attributed to iron overload in the endocrine glands. The authors conclude that an adequate chelating therapy protects against hemosiderosis and thus against endocrine pathologies.
Assuntos
Doenças do Sistema Endócrino/etiologia , Talassemia/complicações , Adolescente , Transfusão de Sangue , Criança , Terapia Combinada , Doenças do Sistema Endócrino/fisiopatologia , Doenças do Sistema Endócrino/terapia , Transfusão de Eritrócitos , Feminino , Humanos , Quelantes de Ferro/uso terapêutico , Masculino , Talassemia/fisiopatologia , Talassemia/terapiaRESUMO
Transcobalamin 2 is the only vitamin B12-binding protein found in mouse serum. Two allelic forms of mouse transcobalamin 2 are described. The two forms differ in their mobilities on polyacrylamide gel electrophoresis. The slowly migrating form has been found in serum from 25 inbred mouse strains. The more rapidly migrating form was detected in 3 inbred mouse strains (NZB, ST/bJ, and CPB-WV). Both parental variants were expressed in F1 progeny of appropriate interstrain crosses, showing codominant expression of the transcobalamin 2 alleles. In backcrosses between F1 and parental individuals, the two electrophoretic variants were inherited as single Mendelian traits. The strain distribution pattern of the two variants in recombinant inbred lines likewise suggested a single-gene mode of inheritance and indicated a lack of close linkage with a number of genetic loci on chromosomes 1, 2, 4, 5, 6, 7, 9, 12, 14, 15, and 17. We propose the symbol Tcn-2 for the polymorphic gene locus coding for transcobalamin 2 in the mouse and Tcn-2s and Tcn-2f for the two alleles.