RESUMO
Aging involves numerous changes in body composition that include a decrease in skeletal muscle mass. The gradual reduction in muscle mass is associated with a simultaneous decrease in muscle strength, which leads to reduced mobility, fragility and loss of independence. This process called sarcopenia is secondary to several factors such as sedentary lifestyle, inadequate nutrition, chronic inflammatory state and neurological alterations. However, the endocrine changes associated with aging seem to be of special importance in the development of sarcopenia. On one hand, advancing age is associated with a decreased secretion of the main hormones that stimulate skeletal muscle mass and function (growth hormone, insulin-like growth factor 1 (IGFI), testosterone and estradiol). On the other hand, the alteration of the IGF-I signaling along with decreased insulin sensitivity also have an important impact on myogenesis. Other hormones that decline with aging such as the adrenal-derived dehydroepiandrosterone, thyroid hormones and vitamin D seem to also be involved in sarcopenia. Adipokines released by adipose tissue show important changes during aging and can affect muscle physiology and metabolism. In addition, catabolic hormones such as cortisol and angiotensin II can accelerate aged-induced muscle atrophy, as they are involved in muscle wasting and their levels increase with age. The role played by all of these hormones and the possible use of some of them as therapeutic tools for treating sarcopenia will be discussed.
Assuntos
Sarcopenia , Idoso , Envelhecimento/fisiologia , Sistema Endócrino/metabolismo , Hormônios , Humanos , Músculo Esquelético/metabolismo , Sarcopenia/metabolismo , Sarcopenia/terapia , TestosteronaRESUMO
INTRODUCTION: Quality improvement in health care entails the design of reliable processes which prevent and mitigate medical errors. Checklists are cognitive tools which reduce such errors. The primary objective of this study was to design an anesthetic checklist in Pediatrics to be implemented in our hospital. METHODS: Delphi technique was used, with 3 rounds of questionnaire surveys: a generic questionnaire to obtain dimensions and items; and 2 specific ones to score individual items and obtain an overall rating for the checklist (median), and to measure the level of consensus (relative interquartile range) and internal reliability (Wilcoxon signed-rank test). RESULTS: Final version of the checklist obtained a high overall score (Med 9) with a very high consensus (RIR 5%). Internal consensus was reached on all items (RIR ≤ 30%). Wilcoxon signed-rank test found no statistically significant differences, demonstrating reliability or consistency of responses between consecutive rounds. CONCLUSION: The Anesthetic checklist in Pediatrics has been methodically designed for implementation and use in our hospital.
Assuntos
Anestesia/normas , Lista de Checagem/normas , Erros Médicos/prevenção & controle , Pediatria/normas , Melhoria de Qualidade , Lista de Checagem/métodos , Consenso , Técnica Delphi , Retroalimentação , Pesquisas sobre Atenção à Saúde/normas , Humanos , Segurança do Paciente , Qualidade da Assistência à Saúde , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Inquéritos e Questionários/normasRESUMO
Adjuvant-induced arthritis in rats decreases body weight and muscle mass. Melanocyte stimulating hormone administration to arthritic rats decreases inflammation and skeletal muscle wasting. In this study, we investigate whether activation of melanocortin-4 receptor by RO27-3225 administration is able to prevent the effect of arthritis on the expression of muscle-specific E3 ubiquitin ligases and MyoD in two different muscles, gastrocnemius (a mainly fast type muscle) and soleus (slow type). Arthritis was induced in male Wistar rats by intradermal injection of Freund's adjuvant. Control and arthritic rats were injected with RO27-3225 (180 µg/kg i.p. twice a day) or saline, for 8 days. Body weight change, food intake and arthritis index were assessed daily. After sacrifice, serum insulin-like growth factor -1 (IGF-1) and corticosterone, as well as nuclear factor-κB(p65), cyclooxygenase-2 (COX-2), atrogene and MyoD in gastrocnemius and soleus were analysed. Administration of RO27-3225 to arthritic rats decreased arthritis scores, hind paw volume as well as nuclear factor-κB(p65) phosphorylation in gastrocnemius and soleus. However, RO27-3225 was not able to modify the effects of arthritis on serum IGF-1 and corticosterone. RO27-3225 ameliorates arthritis-induced decrease in food intake, body weight gain, epidydimal white adipose tissue and soleus weight, but not in gastrocnemius weight. Arthritis increased COX-2, atrogin-1 and MuRF1 expression in gastrocnemius and soleus, whereas RO27-3225 prevented this increase in soleus but not in gastrocnemius. Arthritis also increased MyoD expression in gastrocnemius and soleus (P < 0.01). RO27-3225 decreased MyoD expression in gastrocnemius but not in soleus of arthritic rats. In control rats RO27-3225 did not modify MyoD expression in gastrocnemius or soleus. In conclusion, our data suggest that in arthritic rats, RO27-3225 treatment decreases inflammation and muscle atrophy, preventing atrogene upregulation in slow type muscle but not in gastrocnemius. The lack of effect in the gastrocnemius can be related to the inability of RO27-3225 to prevent arthritis-induced corticosterone upregulation as well as IGF-1 downregulation.
Assuntos
Anti-Inflamatórios/uso terapêutico , Artrite/tratamento farmacológico , Músculo Esquelético/efeitos dos fármacos , Atrofia Muscular/tratamento farmacológico , Peptídeos/uso terapêutico , Receptor Tipo 4 de Melanocortina/agonistas , Hormônio Adrenocorticotrópico/sangue , Animais , Anti-Inflamatórios/farmacologia , Artrite/sangue , Artrite/metabolismo , Artrite/patologia , Corticosterona/sangue , Ciclo-Oxigenase 2/metabolismo , Fator de Crescimento Insulin-Like I/análise , Masculino , Proteínas Musculares/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular/sangue , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Proteína MyoD/metabolismo , Peptídeos/farmacologia , Ratos Wistar , Proteínas Ligases SKP Culina F-Box/metabolismo , Fator de Transcrição RelA/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/metabolismoRESUMO
In autumn 2014, enterovirus D68 (EV-D68) cases presenting with severe respiratory or neurological disease were described in countries worldwide. To describe the epidemiology and virological characteristics of EV-D68 in England, we collected clinical information on laboratory-confirmed EV-D68 cases detected in secondary care (hospitals), between September 2014 and January 2015. In primary care (general practitioners), respiratory swabs collected (September 2013-January 2015) from patients presenting with influenza-like illness were tested for EV-D68. In secondary care 55 EV-D68 cases were detected. Among those, 45 cases had clinical information available and 89% (40/45) presented with severe respiratory symptoms. Detection of EV-D68 among patients in primary care increased from 0.4% (4/1074; 95% CI 0.1-1.0) (September 2013-January 2014) to 0.8% (11/1359; 95% CI 0.4-1.5) (September 2014-January 2015). Characterization of EV-D68 strains circulating in England since 2012 and up to winter 2014/2015 indicated that those strains were genetically similar to those detected in 2014 in USA. We recommend reinforcing enterovirus surveillance through screening respiratory samples of suspected cases.
Assuntos
Enterovirus Humano D/isolamento & purificação , Infecções por Enterovirus/epidemiologia , Infecções Respiratórias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Inglaterra/epidemiologia , Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/virologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Filogenia , Prevalência , Atenção Primária à Saúde , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/virologia , Estações do Ano , Atenção Secundária à Saúde , Proteínas Virais de Fusão/genética , Adulto JovemRESUMO
INTRODUCTION: The 2013 Kidney Disease Outcomes Quality Initiative Clinical Practice Guideline suggests measuring cystatin C (sCys) in adults with glomerular filtration rate (GFR) based on creatinine (sCr) between 45 and 59 mL/min/1.73 m2 if confirmation of chronic kidney disease (CKD) is required. There is not enough evidence to recommend the use of sCys or sCr to estimate GFR in kidney transplant recipients. OBJECTIVES: Our aims were to describe the evolution of sCr, sCys, and GFR in a group of kidney transplant patients and to determine their association with some markers of morbidity at 1 year. METHODS: A total of 54 patients were included. Analytical and clinical data were recorded. Renal function was analyzed using the CKD Epidemiology Collaboration (EPI) sCr equation and CKD-EPI sCys equation. RESULTS: sCys-estimated GFR was higher than estimated from sCr by CKD-EPI. The values of sCys have more variability than those of sCr. The agreement between the stages of CKD by sCr or sCys-estimated GFR measured by Cohen's kappa coefficient was only fair. One-year CKD-associated variables correlated differently with sCr and sCys-estimated GFR. Hemoglobin, uric acid, calcium, and phosphorus related to sCr-estimated GFR, whereas serum albumin was associated with sCys-estimated GFR. CONCLUSIONS: sCys values have a higher variability than sCr in kidney transplant recipients. sCys- or sCr-based GFRs have a nonsimilar behavior in these patients with weak agreement to stratify CKD stages and a different relationship to CKD-related comorbid conditions.
Assuntos
Creatinina/metabolismo , Cistatina C/metabolismo , Transplante de Rim , Transplantes/fisiologia , Biomarcadores/metabolismo , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Rim/fisiologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/cirurgiaAssuntos
Neoplasias Brônquicas/patologia , Tumor Carcinoide/secundário , Neoplasias da Coroide/secundário , Lutécio/administração & dosagem , Octreotida/administração & dosagem , Radioisótopos , Biópsia por Agulha Fina , Neoplasias Brônquicas/diagnóstico por imagem , Neoplasias Brônquicas/tratamento farmacológico , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/tratamento farmacológico , Neoplasias da Coroide/diagnóstico , Neoplasias da Coroide/tratamento farmacológico , Relação Dose-Resposta a Droga , Feminino , Humanos , Octreotida/uso terapêutico , Somatostatina/análogos & derivados , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
Cyclooxygenase-2-induction by inflammatory stimuli has been proposed as a mediator of inflammatory cachexia. We analyse whether cyclooxygenase-2 inhibition by meloxicam administration is able to modify the response of skeletal muscle to inflammation induced by lipopolysaccharide endotoxin (LPS). Male rats were injected with 1 mg kg(-1) LPS at 17:00 h and at 10:00 h the following day, and euthanized 4, 24 or 72 hours later. Atrogin-1, MuRF1, myogenic regulatory factors and cyclooxygenase-2 in the gastrocnemius were determined by real time-PCR (mRNA) and Western blot (protein). In a second experiment the effect of meloxicam administration (1 mg kg⻹) was analyzed. Meloxicam was administered either in a preventive manner, 1 hour before each endotoxin injection, or in a therapeutic manner, starting 2 hours after the second LPS injection and at 24 and 48 hours afterwards. There was a marked increase in MuRF1 mRNA (P<0.01) 4 hours after LPS, and in atrogin-1 mRNA 4 hours (P<0.01) and 24 hours (P<0.01) after LPS. Cyclooxygenase-2 was increased, whereas MyoD was decreased at 4, 24 and 72 h. Both types of meloxicam treatment blocked LPS-induced increase in atrogin-1. Preventive, but not therapeutic, meloxicam decreased myostatin (P<0.01) and increased Pax7 (P<0.01) and MyoD (P<0.05). Therapeutic meloxicam treatment decreased gastrocnemius myogenin. These data suggest that cyclooxygenase-2 inhibition by meloxicam administration can prevent the increase in atrogin-1 and the decrease in MyoD induced by LPS administration. However, prolonged therapeutic meloxicam treatment seems to be less effective, since it can inhibit myogenic regulatory factors.
Assuntos
Inibidores de Ciclo-Oxigenase 2/farmacologia , Ciclo-Oxigenase 2/metabolismo , Lipopolissacarídeos/administração & dosagem , Proteínas Musculares/metabolismo , Músculo Esquelético/efeitos dos fármacos , Fatores de Regulação Miogênica/metabolismo , Proteínas Ligases SKP Culina F-Box/metabolismo , Tiazinas/farmacologia , Tiazóis/farmacologia , Animais , Western Blotting , Injeções Intraperitoneais , Masculino , Meloxicam , Proteínas Musculares/genética , Músculo Esquelético/metabolismo , Proteína MyoD/genética , Proteína MyoD/metabolismo , Fatores de Regulação Miogênica/genética , Fatores de Transcrição Box Pareados/genética , Fatores de Transcrição Box Pareados/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Ligases SKP Culina F-Box/genética , Fatores de Tempo , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
The aim of this work was to analyse the role of cyclooxygenase-2 (Ptgs2) in endotoxin-induced decrease in Igf1 and Igf binding protein-3 (Igfbp3). For this purpose, male Wistar rats were injected with lipolysaccharide (LPS) and/or the Ptgs2 inhibitor meloxicam. LPS induced a significant decrease (P<0.01) in serum concentrations of Igf1 and Igfbp3 and their mRNAs in the liver. Meloxicam administration prevented the inhibitory effect of LPS injection on serum Igf1 and its liver mRNA. By contrast, meloxicam administration was unable to modify the inhibitory effect of LPS on Igfbp3. LPS injection also induced a decrease in GH receptor (Ghr) mRNA in the liver, and meloxicam attenuated this effect. In order to elucidate a direct action of the Ptgs2 inhibitor on the liver cells, the effect of LPS and/or meloxicam was studied in primary cultures of hepatocytes with non-parenchymal cells. LPS decreased Igf1 and Ghr but not Igfbp3 gene expression in liver cells in culture. Meloxicam administration attenuated the inhibitory effect of LPS on Igf1 mRNA, whereas it did not modify the decrease in Ghr mRNA after LPS. The effect of meloxicam on the LPS response does not seem to be mediated by changes in nitric oxide or tumour necrosis factor (Tnf) production, since meloxicam did not modify the stimulatory effect of LPS on nitric oxide or Tnfalpha gene expression both in vivo and in vitro. All these data suggest that LPS-induced Ptgs2 activation decreases Igf1 gene expression in liver cells.
Assuntos
Ciclo-Oxigenase 2/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Lipopolissacarídeos/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Animais , Western Blotting , Células Cultivadas , Inibidores de Ciclo-Oxigenase/farmacologia , Ativação Enzimática/efeitos dos fármacos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Fator de Crescimento Insulin-Like I/genética , Masculino , Meloxicam , Nitratos/metabolismo , Nitritos/metabolismo , Reação em Cadeia da Polimerase , Distribuição Aleatória , Ratos , Ratos Wistar , Tiazinas/farmacologia , Tiazóis/farmacologia , Fator de Necrose Tumoral alfa/genéticaRESUMO
Adjuvant-induced arthritis is a model of rheumatoid arthritis that induces cachexia. In other cachectic situations, there is an increase in lipolysis resulting in a loss of adipose tissue mass. The aim of this work was to analyse the effect of chronic arthritis, induced by adjuvant injection, on white adipose tissue (WAT). For this purpose, rats were killed 10 days after adjuvant injection, when the first external symptoms appeared, on days 15 and 22 when the external signs of the illness reach their severest level. As arthritis decreases food intake, a pair-fed group was also included. Serum concentrations of insulin, leptin, adiponectin, glycerol and nitrites, as well as gene expression of leptin, adiponectin, hormone-sensitive lipase (HSL), fatty acid synthase (FAS), tumour necrosis factor alpha and zinc-alpha(2)-glycoprotein (ZAG) were determined. Arthritis decreased food intake between days 5 and 16, but not during the last 5 days of the experiment. There was a marked decrease in relative adipose tissue weight and in serum leptin and adiponectin as well as in their gene expression in WAT in arthritic rats. Arthritis decreased the gene expression of FAS in the WAT. However, none of these effects was found in pair-fed rats. Arthritis did not increase lipolysis, since arthritic rats have lower serum concentrations of glycerol, HSL mRNA in WAT, as well as liver ZAG mRNA than the pair-fed or control rats. These data suggest that in chronic arthritis the decrease in white adipose mass is secondary to a reduced adipose lipogenesis, and this effect is not mainly due to the decrease in food intake.
Assuntos
Tecido Adiposo Branco/metabolismo , Artrite Experimental/metabolismo , Lipogênese , Lipólise , Animais , Peso Corporal , Ácido Graxo Sintases/genética , Insulina/sangue , Lipase/genética , Masculino , Tamanho do Órgão , RNA Mensageiro/análise , Ratos , Ratos Wistar , Proteínas de Plasma Seminal/genética , Esterol Esterase/sangue , Esterol Esterase/genética , Fator de Necrose Tumoral alfa/fisiologia , Glicoproteína Zn-alfa-2RESUMO
This work describes the evaluation of a glass ceramic (55S41C4P-1300) as a potential substrate for bone tissue engineering. For that purpose, the capacity of mesenchymal stem cells (MSCs), isolated from rabbit bone marrow, to adhere, proliferate and differentiate into osteoblast (OBs) with or without 55S41C4P-1300 was investigated. Two types of culture medium, i.e. growth medium (GM) and osteogenic medium (OM), were evaluated. The bioactive 55S41C4P-1300, containing pseudowollastonite, wollastonite, tricalcium phosphate and crystoballite as crystalline phases, was obtained by heat treatment of a sol-gel glass (55SiO(2), 41CaO, 4P(2)O(5) (mol.%)) at 1300 degrees C. The results showed that the MSCs adhered, spread, proliferated and produced mineralized extracellular matrix on 55S41C4P-1300 regardless of the culture medium used. As the same time, they showed an osteoblastic phenotype, and this phenomenon was accompanied by the gradual diminution of the marker CD90 expression. The 55S41C4P-1300 was able to induce the differentiation of MSCs into OBs in the same way as OM without glass ceramic. This effect increased with the combination of 55S41C4P-1300 with OM. The glass ceramic evaluated in this work is bioactive, cytocompatible and capable of promoting the differentiation of MSCs into OBs. For that reason, it could be regarded as a suitable matrix in tissue engineering for bone tissue regeneration.
Assuntos
Cerâmica/farmacologia , Vidro/química , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Animais , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Meios de Cultura , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Fluorescência , Células-Tronco Mesenquimais/ultraestrutura , Microscopia Eletrônica de Varredura , Osteocalcina/metabolismo , Coelhos , Análise Espectral , Antígenos Thy-1/metabolismoRESUMO
Chronic inflammation is associated with a decrease in body weight and cachexia, which is characterized by anorexia and skeletal muscle wasting. The expression of atrogens muscle RING finger-1 (MuRF-1) and muscle atrophy F-box (MAFbx) are increased in muscle atrophy and it is known that tumour necrosis factor (TNF) regulates skeletal muscle loss through TNF receptor p55 (TNFRI). The aim of this study was to examine the effect of polyethylene glycol linked to soluble TNFRI (PEG-sTNFRI) on gene expression of the atrogens MuRF-1 and MAFbx in skeletal muscle of arthritic rats. Rats were injected with Freund's adjuvant and, 15 days later, arthritic and control rats were injected daily with PEG-sTNFRI (1 mg/kg, s.c.) or saline for 8 days. Arthritis decreased body weight gain, the weight of skeletal muscle and adipose mass. PEG-sTNFRI administration increased body weight gain and adipose mass of arthritic rats; however, it did not modify the skeletal muscle weight. The gene expression of TNF-alpha, MuRF1 and MAFbx, IGF-I and IGFBP-5 were increased in the skeletal muscle of arthritic rats, and the administration of PEG-sTNFRI did not modify these parameters. These data suggest that the anti-TNF agent PEG-sTNFRI did not prevent the increase in E3 ubiquitin-ligating enzymes, MuRF1 and MAFbx, gene expression in the skeletal muscle of arthritic rats.
Assuntos
Artrite Experimental/metabolismo , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/farmacologia , Proteínas Ligases SKP Culina F-Box/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Ubiquitina-Proteína Ligases/metabolismo , Animais , Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Fator de Crescimento Insulin-Like I/análise , Masculino , RNA Mensageiro/análise , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas com Motivo Tripartido , Fator de Necrose Tumoral alfa/análiseRESUMO
Gram-negative bacterial infection or treatment of animals with bacterial lipopolysaccharide (LPS) induces a catabolic state with proteolysis, liver injury and an inhibition of the insulin-like growth factor-I (IGF-I) system. The purpose of this work was to elucidate the role of Kupffer cells in LPS-induced inhibition of the IGF-I/IGF-binding protein-3 (IGFBP-3) system. Adult male Wistar rats were either pretreated with the Kupffer cell inhibitor gadolinium chloride (10 mg/kg, i.v., 24 h prior to LPS exposure) or saline vehicle. Rats received two i.p. injections of 1 mg/kg LPS (at 17:30 and 08:30 h the following day) and were killed 4 h after the second injection. LPS administration induced a significant decrease in body weight and in serum concentrations of IGF-I and IGFBP-3 (P < 0.01), as well as in their gene expression in the liver. LPS-injected rats had increased serum concentrations of ACTH, corticosterone (P < 0.05), tumour necrosis factor-alpha (TNF-alpha) and nitrites (P < 0.01). Pretreatment of the animals with gadolinium chloride blocked the inhibitory effect of LPS on body weight, and on serum concentrations of IGF-I, IGFBP-3 and nitrites, as well as growth hormone receptor (GHR), IGF-I and IGFBP-3 gene expression in the liver. In contrast, gadolinium chloride administration did not modify the stimulatory effect of LPS on serum concentrations of ACTH, corticosterone and TNF-alpha. These results suggest that Kupffer cells are important mediators in the inhibitory effect of LPS on GHR, IGF-I and IGFBP-3 gene expression in the liver, leading to a decrease in serum concentrations of IGF-I and IGFBP-3.
Assuntos
Gadolínio/farmacologia , Hepatite/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Fator de Crescimento Insulin-Like I/genética , Células de Kupffer/microbiologia , Hormônio Adrenocorticotrópico/sangue , Animais , Northern Blotting/métodos , Western Blotting/métodos , Peso Corporal/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Hepatite/patologia , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Fator de Crescimento Insulin-Like I/análise , Células de Kupffer/efeitos dos fármacos , Células de Kupffer/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Nitratos/sangue , Nitritos/sangue , RNA Mensageiro/análise , Ratos , Ratos Wistar , Receptores da Somatotropina/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/análiseRESUMO
While it is well known that sepsis inhibits serum IGF-I and its gene expression in the liver, the effect on pituitary GH and IGF-binding protein-3 (IGFBP-3) is poorly understood. The GH-IGF-I-IGFBP-3 response to different doses of lipopolysaccharide (LPS) administration has been investigated in adult male rats. Two experiments were performed, administration of low doses of LPS (5, 10, 50 and 100 microg/kg) and high doses of LPS (100, 250, 500 and 1000 microg/kg). Rats received two i.p. injections of LPS (at 1730 h and 0830 h the following day) and were killed 4 h after the second injection. LPS administration induced a biphasic response in serum concentrations of GH, with an increase at the 10 microg/kg dose, followed by a decrease at higher doses (100 microg/kg on up). Pituitary GH mRNA was also increased by the administration of 10 and 50 microg/kg LPS, whereas at higher doses LPS did not modify pituitary GH mRNA. We also analyzed the GH response to LPS in primary pituitary cell cultures. When exposed to LPS, in the culture medium, there was an increase in GH release at the concentration of 0.1 and 10 ng/ml, whereas more concentrated LPS did not modify GH release. Serum concentrations of IGF-I declined in a dose-dependent fashion after LPS administration in the rats injected with 10 microg/kg LPS on up. This decrease is secondary to modifications in its synthesis in the liver, since endotoxin injection decreased both IGF-I and its mRNA in the liver. The liver GH receptor mRNA was also decreased by LPS administration, but only in the animals injected with high LPS doses. There was a decrease in both the IGFBP-3 serum levels and its gene expression in the liver with all LPS doses studied. These data suggest a biphasic LPS effect on pituitary GH, a stimulatory effect at low doses and an inhibitory effect at higher doses, whereas it has a clear inhibitory effect on IGF-I and IGFBP-3 synthesis in the liver. The decrease in liver IGFBP-3 mRNA and in serum concentrations of IGFBP-3 in the rats injected with LPS may contribute to the decrease in serum concentrations of IGF-I.
Assuntos
Hormônio do Crescimento/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Lipopolissacarídeos/farmacologia , Adeno-Hipófise/efeitos dos fármacos , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônio do Crescimento/sangue , Hormônio do Crescimento/genética , Fígado/metabolismo , Masculino , Adeno-Hipófise/citologia , Adeno-Hipófise/metabolismo , RNA Mensageiro/genética , Ratos , Ratos WistarRESUMO
A 56 year-old patient, with a history of surgically removed breast cancer three years earlier, presented with incoordination of hand movements while playing piano. Neurological examination disclosed mild position sensory loss and limb-kinetic apraxia of the distal part of the right upper extremity. The most conspicuous neurological sign was a dystonic posturing of the right hand, which was only elicited when the patient outstretched her arms with the eyes closed. MRI revealed a metastatic lesion involving the left parietal cortex. The association of focal dystonic postures with lesions of the parietal association cortex indicates that dystonia may feature damage of brain cortical areas far from the basal ganglia. In addition, this provides support to the hypothesis that impairment of sensory pathways may play a role in the origin of some hyperkinetic movement disorders, such as dystonia and athetosis.
Assuntos
Apraxias/etiologia , Neoplasias Encefálicas/secundário , Distúrbios Distônicos/etiologia , Mãos/fisiopatologia , Lobo Parietal/patologia , Postura , Distúrbios Somatossensoriais/etiologia , Apraxias/fisiopatologia , Neoplasias Encefálicas/fisiopatologia , Neoplasias da Mama/patologia , Diagnóstico Diferencial , Distúrbios Distônicos/diagnóstico , Evolução Fatal , Feminino , Lateralidade Funcional , Humanos , Pessoa de Meia-Idade , Música , Lobo Parietal/fisiopatologia , Distúrbios Somatossensoriais/fisiopatologiaRESUMO
The aim of this work was to examine the effect of different periods of restraint on the humoral and cellular immune functions in adult male rats. Short restraint stress (2 h over 2 consecutive days) enhanced the primary serum antibody response to sheep red blood cells. The enhancement of this humoral response was dependent on the restraint period, since long restraint stress (6 h over 4 days) failed to modify this response. Short and long restraint decreased both the number of lymphocytes and the T-lymphocyte response to Con A stimulation in the peripheral blood. Neither 2 h over 2 days nor 6 h over 4 days modified the splenic lymphoproliferative response to Con A stimulation, but restraint stress progressively decreased the number of mononuclear splenic cells. Both periods of restraint significantly increased plasma concentration of corticosterone, however plasma prolactin levels were significantly lower after 4 days of restraint but not after short restraint (2 h over 2 days). These results indicate that although some immune functions can be increased after acute or short stress, long stress has an immunosuppressive effect, above all on the cellular immunity which is more susceptible to this effect than the humoral response.
Assuntos
Formação de Anticorpos/fisiologia , Imunidade Celular/fisiologia , Estresse Psicológico/imunologia , Animais , Peso Corporal , Corticosterona/sangue , Contagem de Leucócitos , Masculino , Tamanho do Órgão , Prolactina/sangue , Ratos , Ratos Wistar , Baço/patologia , Estresse Psicológico/sangue , Estresse Psicológico/patologiaRESUMO
From about 10 to 36 h after superior cervical ganglionectomy (SCGx), peripheral sympathetic nerve terminals in the median eminence degenerate, nerve ending content is released, and a transient period of increased postsynaptic activity ensues. After this time, an irreversible, paralytic phase is established in the denervated territory. The present experiment was undertaken to examine, at single points during the wallerian degeneration phase (24 h after SCGx) and during the paralytic phase (10 days after denervation), the participation of peripheral sympathetic nerves in restraint-stress-induced changes of circulating luteinizing hormone (LH), prolactin (PRL), growth hormone (GH) and corticosterone levels. During the wallerian degeneration phase, serum LH did not augment after stress, as it did in sham-operated controls. In the paralytic phase, the poststress increases in LH attained similar values in sham-operated and SCGx rats. Immobilization stress augmented PRL levels to a similar extent in sham-operated and SCGx rats either 24 h or 10 days after surgery. During the wallerian degeneration phase, a decrease in serum GH levels was found in unrestrained rats. Immobilization stress decreased GH levels to 5-12% of unrestrained values in sham-operated and SCGx rats at both examination time points after surgery. Rats studied 24 h after SCGx exhibited significantly augmented serum corticosterone levels and failed to show restraint-stress-induced stimulation of corticosterone release. In rats subjected to SCGx 10 days earlier, both basal and poststress levels of corticosterone did not differ from sham-operated controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Corticosterona/sangue , Hormônio do Crescimento/sangue , Hormônio Luteinizante/sangue , Prolactina/sangue , Gânglio Cervical Superior/fisiologia , Animais , Ganglionectomia , Masculino , Ratos , Ratos Wistar , Restrição FísicaRESUMO
There is considerable evidence suggesting that endogenous opioids may play an important role in acute stress-induced decreases in luteinizing hormone (LH) release. Studies were undertaken to analyze the role of endogenous opioids in chronic stress-induced decrease in circulating LH and follicle-stimulating hormone (FSH). Chronic restraint (6 h daily over 4 days) evoked a decrease in circulating LH and FSH. Naltrexone treatment, (2 mg/kg three times daily) during the 4 days of restraint, caused an increase in plasma concentrations of LH and FSH, and antagonized the LH suppressory effect of morphine (10 mg/kg) administration. Despite this, naltrexone treatment was ineffective in preventing the inhibitory effect of chronic restraint stress on circulating LH and FSH. Chronic restraint also induced a decrease in hypothalamic LH-releasing hormone (LHRH) content in saline-treated rats. On the contrary, in naltrexone-treated rats, chronic restraint evoked an increase in hypothalamic LHRH content. Thus endogenous opioids and chronic stress seem to act by different mechanisms on the hypothalamic LHRH neuron. In unstressed orchidectomized rats, naltrexone administration did not modify circulating LH, but increased plasma concentrations of LH in acutely restrained rats. These data suggest that endogenous opioids may mediate gonadotropin secretion during acute stress, but not during chronic stress.