Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 12.117
Filtrar
1.
Adv Exp Med Biol ; 1131: 93-129, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646508

RESUMO

Plasma membrane Ca2+ transport ATPases (PMCA1-4, ATP2B1-4) are responsible for removing excess Ca2+ from the cell in order to keep the cytosolic Ca2+ ion concentration at the low level essential for normal cell function. While these pumps take care of cellular Ca2+ homeostasis they also change the duration and amplitude of the Ca2+ signal and can create Ca2+ gradients across the cell. This is accomplished by generating more than twenty PMCA variants each having the character - fast or slow response, long or short memory, distinct interaction partners and localization signals - that meets the specific needs of the particular cell-type in which they are expressed. It has become apparent that these pumps are essential to normal tissue development and their malfunctioning can be linked to different pathological conditions such as certain types of neurodegenerative and heart diseases, hearing loss and cancer. In this chapter we summarize the complexity of PMCA regulation and function under normal and pathological conditions with particular attention to recent developments of the field.


Assuntos
Membrana Celular , ATPases Transportadoras de Cálcio da Membrana Plasmática , Animais , Membrana Celular/enzimologia , Membrana Celular/patologia , Citosol/metabolismo , Homeostase/fisiologia , Humanos , ATPases Transportadoras de Cálcio da Membrana Plasmática/genética , ATPases Transportadoras de Cálcio da Membrana Plasmática/metabolismo
2.
Adv Exp Med Biol ; 1178: 57-76, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31493222

RESUMO

Aging is a natural process defined by the gradual, time-dependent decline of biological and behavioural functions, for which individuals of the same chronological age show variability. The capacity of biological systems to continuously adjust for optimal functioning despite ever changing environments is essential for healthy aging, and variability in these adaptive homeostatic mechanisms may reflect such heterogeneity in the aging process. With an ever-increasing aging population, interest in biomarkers of aging is growing. Although no universally accepted definition of biomarkers of healthy aging exists, mediators of homeostasis are consistently used as measures of the aging process. As important sex differences are known to underlie many of these systems, it is imperative to consider that this may reflect, to some extent, the sex differences observed in aging and age-related disease states. This chapter aims to outline sex differences in key homeostatic domains thought to be associated with the pathophysiology of aging, often proposed as biomarkers of aging and age-related disease states. This includes considering sex-based differences and hormonal status with regards to the gonadal and adrenal endocrine systems and immune function.


Assuntos
Envelhecimento , Biomarcadores , Homeostase , Biomarcadores/metabolismo , Homeostase/fisiologia , Humanos , Fatores Sexuais
3.
Br J Anaesth ; 123(5): 610-617, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31542162

RESUMO

BACKGROUND: Traumatic brain injury (TBI) is associated with reduced cerebral blood flow and impaired autoregulation after TBI, which may lead to poor outcome. Clinical evidence has implicated neurological injuries and associated neuroinflammation as causes of cardiac dysfunction. Studies on newborn pigs show an association of elevated catecholamines with a sex-dependent impairment of cerebral autoregulation after TBI. One strategy to decrease sympathetic hyperactivity is pharmacological intervention with beta blockade. We tested the hypothesis that propranolol would prevent the impairment of cerebral autoregulation and tissue changes after TBI via inhibition of interleukin-6 (IL-6) upregulation. METHODS: Using newborn pigs of both sexes equipped with a closed cranial window, TBI was induced via lateral fluid percussion injury. Propranolol was administered at 1 h post-TBI. Analyses included cerebral autoregulation (pial artery reactivity) before and 4 h post-TBI, CSF IL-6 analysed (enzyme-linked immunosorbent assay), and histopathology at 4 h post-TBI. RESULTS: Propranolol administration prevented impairment of hypotensive dilation in both male and female newborn pigs after fluid percussion injury, which was paralleled by reduced upregulation of IL-6 in the CSF. Moreover, propranolol prevented neuronal cell death in cornu amonis (CA)1 and CA3 hippocampus equivalently in male and female pigs after TBI. Papaverine-induced dilation was unchanged by TBI and propranolol. CONCLUSIONS: These data indicate that sympathetic hyperactivity noted after TBI can be limited by propranolol administration to result in improved brain outcome post-injury via block of IL-6 upregulation, and this effect is irrespective of sex.


Assuntos
Lesões Encefálicas Traumáticas/tratamento farmacológico , Morte Celular/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Interleucina-6/antagonistas & inibidores , Propranolol/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Animais Recém-Nascidos , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/fisiopatologia , Modelos Animais de Doenças , Feminino , Hipocampo/fisiologia , Homeostase/fisiologia , Masculino , Neurônios/efeitos dos fármacos , Suínos , Regulação para Cima/efeitos dos fármacos
4.
Prensa méd. argent ; 105(8): 469-476, sept 2019. tab
Artigo em Inglês | LILACS, BINACIS | ID: biblio-1023268

RESUMO

In rats with experimentally formed arterial hypertension, lipid perxidation in the plasma, amplification of blood chotting mechanisms with a decrease in anticoagulation and fibrinolysis was noted. Regular forced jogging provided the experimental rats with a positive dynamic of all the indicators considered. Thus, with increased muscular activity, the level of acyl hydro-peroxides of plasma decreased in rats with arterial hypertension formed due to the enhancement of its antioxidant activity. In addition, with the increase in muscle activity in experimental rats, normalization of clotting factor activity, indices of general coagulation tests, antithrobin III activity and protein C was achieved. This was accompanied by a normalization of the level of plasminogen, a2-antiplasmin and spontaneous euglobulin lysis time. In rats with formed arterial hipertension with stgandard physical activity, the initial violations of the measured parameters were completely preserved (AU)


Assuntos
Ratos , Coagulação Sanguínea , Experimentação Animal , Hemostasia , Homeostase/fisiologia , Hipertensão , Atividade Motora
5.
Braz J Cardiovasc Surg ; 34(4): 436-443, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31454197

RESUMO

OBJECTIVE: To investigate the effect of continuous lung ventilation with low tidal volume on oxidation parameters, such as thiol/disulphide homeostasis and albumin-adjusted ischemia-modified albumin (AAIMA), during cardiopulmonary bypass (CBP) in coronary artery bypass grafting (CABG). METHODS: Seventy-four patients who underwent elective CABG with CPB were included in the study. Blood samples were taken in the preoperative period, 10 minutes after CPB, and six and 24 hours postoperatively. Patients were assigned to the continuous ventilation group (Group 1, n=37) and the non-ventilated group (Group 2, n=37). The clinical characteristics, thiol/disulphide homeostasis, ischemia-modified albumin (IMA), and AAIMA levels of the patients were compared. RESULTS: A significant difference was found between the groups regarding native thiol, total thiol, and IMA levels at the postoperative 24th hour (P=0.030, P=0.031, and P=0.004, respectively). There was no difference between the groups in terms of AAIMA. AAIMA levels returned to preoperative levels in Groups 1 and 2, at the 6th and 24th postoperative hours, respectively. Length of hospital stay was significantly shorter in Group 1 (P<0.001) than in Group 2. CONCLUSION: Continuous ventilation during CPB caused an increase in native and total thiol levels, an earlier return of AAIMA levels, and shorter hospital stay. Continuous ventilation may reduce the negative effects of CPB on myocardium (Table 2, Figure 1, and Reference 31).


Assuntos
Ponte Cardiopulmonar/efeitos adversos , Dissulfetos/sangue , Respiração Artificial , Albumina Sérica/análise , Compostos de Sulfidrila/sangue , Idoso , Antioxidantes , Biomarcadores/sangue , Ponte Cardiopulmonar/métodos , Ponte de Artéria Coronária , Método Duplo-Cego , Feminino , Homeostase/fisiologia , Humanos , Lesão Pulmonar/etiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Albumina Sérica Humana
6.
An Acad Bras Cienc ; 91(2): e20180452, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31269107

RESUMO

The aim of this study was investigate the effects of a low-protein, high-carbohydrate (LPHC) diet introduced to rats soon after weaning. The animals were distributed in the following groups: LPHC45: fed an LPHC diet (6%-protein, 74%-carbohydrate) for 45 days; C45: fed a control (C) diet (17%-protein, 63%-carbohydrate) for 45 days; R (Reverse): fed with LPHC for 15 days followed by C diet for 30 days. The LPHC45 group showed alterations in the energetic balance with an increase in brown adipose tissue, and in glucose tolerance, and lower final body weight, muscle mass and total protein in blood when compared with C45 group. The HOMA-IR index was similar between LPHC45 and C45 groups, but this parameter was lower in LPHC45 compared with R groups. Serum adiponectin was higher in LPHC45 group than C45 and R groups. The R group presented higher fed insulin than C45 and LPHC45 and higher T4 compared with C45 group. Total cholesterol in R group was higher when compared with LPHC45 group. Thus, the data show that the change of the diet LPHC for a balanced diet led to different metabolic evolution and suggest that the different response can be due to different levels of adiponectin.


Assuntos
Adiponectina/sangue , Glicemia/metabolismo , Dieta com Restrição de Proteínas , Carboidratos da Dieta/metabolismo , Homeostase/fisiologia , Animais , Masculino , Ratos , Ratos Wistar
7.
Nat Commun ; 10(1): 2988, 2019 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-31278345

RESUMO

Precise control of stem cell (SC) proliferation ensures tissue homeostasis. In the Drosophila intestine, injury-induced regeneration involves initial activation of intestinal SC (ISC) proliferation and subsequent return to quiescence. These two phases of the regenerative response are controlled by differential availability of the BMP type I receptor Thickveins (Tkv), yet how its expression is dynamically regulated remains unclear. Here we show that during homeostasis, the E3 ubiquitin ligase Highwire and the ubiquitin-proteasome system maintain low Tkv protein expression. After ISC activation, Tkv is stabilized by proteasome inhibition and undergoes endocytosis due to the induction of the nucleoside diphosphate kinase Abnormal Wing Disc (AWD). Tkv internalization is required for the activation of the Smad protein Mad, and for the return to quiescence after a regenerative episode. Our data provide insight into the mechanisms ensuring tissue homeostasis by dynamic control of somatic stem cell activity.


Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Proteínas de Drosophila/metabolismo , Núcleosídeo-Difosfato Quinase/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Receptores de Superfície Celular/metabolismo , Transdução de Sinais/fisiologia , Células-Tronco/metabolismo , Animais , Proteínas de Ligação a DNA/metabolismo , Drosophila melanogaster , Feminino , Homeostase/fisiologia , Intestinos/citologia , Modelos Animais , Proteínas do Tecido Nervoso/metabolismo , Regeneração , Fatores de Transcrição/metabolismo
8.
Nat Commun ; 10(1): 2998, 2019 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-31278365

RESUMO

At the Drosophila neuromuscular junction, inhibition of postsynaptic glutamate receptors activates retrograde signaling that precisely increases presynaptic neurotransmitter release to restore baseline synaptic strength. However, the nature of the underlying postsynaptic induction process remains enigmatic. Here, we design a forward genetic screen to discover factors in the postsynaptic compartment necessary to generate retrograde homeostatic signaling. This approach identified insomniac (inc), a putative adaptor for the Cullin-3 (Cul3) ubiquitin ligase complex, which together with Cul3 is essential for normal sleep regulation. Interestingly, we find that Inc and Cul3 rapidly accumulate at postsynaptic compartments following acute receptor inhibition and are required for a local increase in mono-ubiquitination. Finally, we show that Peflin, a Ca2+-regulated Cul3 co-adaptor, is necessary for homeostatic communication, suggesting a relationship between Ca2+ signaling and control of Cul3/Inc activity in the postsynaptic compartment. Our study suggests that Cul3/Inc-dependent mono-ubiquitination, compartmentalized at postsynaptic densities, gates retrograde signaling and provides an intriguing molecular link between the control of sleep and homeostatic plasticity at synapses.


Assuntos
Proteínas Culina/metabolismo , Proteínas de Drosophila/metabolismo , Somação de Potenciais Pós-Sinápticos/fisiologia , Terminações Pré-Sinápticas/metabolismo , Sono/fisiologia , Animais , Drosophila melanogaster , Feminino , Homeostase/fisiologia , Masculino , Modelos Animais , Junção Neuromuscular/metabolismo , Neurotransmissores/metabolismo , Ubiquitinação/fisiologia
9.
Emerg Med Clin North Am ; 37(3): 395-408, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31262411

RESUMO

Patients in shock present frequently to the emergency department. The emergency physician must be skilled in the resuscitation of both differentiated and undifferentiated shock. Early, aggressive resuscitation of patients in shock is essential, using macrocirculatory, microcirculatory, and clinical end points to guide interventions. Therapy should focus on the restoration of oxygen delivery to match tissue demand. This article reviews the evidence supporting common end points of resuscitation for common etiologies of shock and limitations to their use.


Assuntos
Ressuscitação , Choque/terapia , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/prevenção & controle , Pressão Arterial/fisiologia , Biomarcadores , Circulação Sanguínea/fisiologia , Dióxido de Carbono/sangue , Débito Cardíaco/fisiologia , Medicina de Emergência , Homeostase/fisiologia , Humanos , Hipotensão/prevenção & controle , Ácido Láctico/sangue , Oxigênio/sangue , Sepse/fisiopatologia , Choque/sangue , Urina
10.
Nat Commun ; 10(1): 2576, 2019 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-31189900

RESUMO

Mitochondrial quality control is essential in highly structured cells such as neurons and muscles. In skeletal muscle the mitochondrial fission proteins are reduced in different physiopathological conditions including ageing sarcopenia, cancer cachexia and chemotherapy-induced muscle wasting. However, whether mitochondrial fission is essential for muscle homeostasis is still unclear. Here we show that muscle-specific loss of the pro-fission dynamin related protein (DRP) 1 induces muscle wasting and weakness. Constitutive Drp1 ablation in muscles reduces growth and causes animal death while inducible deletion results in atrophy and degeneration. Drp1 deficient mitochondria are morphologically bigger and functionally abnormal. The dysfunctional mitochondria signals to the nucleus to induce the ubiquitin-proteasome system and an Unfolded Protein Response while the change of mitochondrial volume results in an increase of mitochondrial Ca2+ uptake and myofiber death. Our findings reveal that morphology of mitochondrial network is critical for several biological processes that control nuclear programs and Ca2+ handling.


Assuntos
Dinaminas/metabolismo , Mitocôndrias Musculares/patologia , Dinâmica Mitocondrial/fisiologia , Miopatias Mitocondriais/patologia , Músculo Esquelético/patologia , Animais , Cálcio/metabolismo , Núcleo Celular/metabolismo , Modelos Animais de Doenças , Dinaminas/genética , Homeostase/fisiologia , Humanos , Camundongos , Camundongos Knockout , Miopatias Mitocondriais/genética , Miopatias Mitocondriais/mortalidade , Músculo Esquelético/citologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Ubiquitinas/metabolismo , Resposta a Proteínas não Dobradas/fisiologia
11.
Arch Endocrinol Metab ; 63(3): 222-227, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31066759

RESUMO

OBJECTIVE: Type 2 diabetes (T2DM) is characterized by the progressive deterioration of pancreatic islet ß-cell function over time and insulin resistance. Knowing more about the differences in pancreatic islet function in T2DM patients who have had diabetes for different lengths of time can help improve therapy for T2DM. SUBJECTS AND METHODS: We conducted a cross-sectional study to compare islet ß-cell function and insulin resistance in T2DM patients (n = 3,254) who had had diabetes for different lengths of time and those in normal controls (n = 794) using ANOVA and LSD analysis. RESULTS: We found that compared with that in normal controls, HOMA-ß in T2DM patients with a history of diabetes of less than 1 year was lower (approximately 52% of that of normal controls, p = 0.003), while HOMA-IR in these patients was higher (approximately 50% of that of normal controls, p = 0.007). Compared with that in other diabetic patients, HOMA-ß in patients with a history of diabetes of more than 30 years was the lowest. HOMA-IR in patients with a history of diabetes of between 20 and 30 years was lower than that in other diabetic patients (p < 0.05). CONCLUSIONS: There were obvious decreases in HOMA-ß and increases in HOMA-IR in T2DM patients with a history of diabetes of less than 1 year compared with those in normal controls. Therefore, early screening and intervention for T2DM might help improve islet function and delay the progression of diabetes.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Homeostase/fisiologia , Resistência à Insulina , Células Secretoras de Insulina/metabolismo , Adulto , Idoso , Glicemia/análise , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/fisiopatologia , Teste de Tolerância a Glucose , Humanos , Ilhotas Pancreáticas/metabolismo , Pessoa de Meia-Idade , Modelos Biológicos , Fatores de Tempo
12.
Arq Gastroenterol ; 56(1): 28-33, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31141077

RESUMO

BACKGROUND: Insulin resistance, especially that induced by obesity, plays a central role in the development of non-alcoholic fatty liver disease. Although the evaluation of overweight patients is important, the nutritional assessment tools used in clinical practice have limitations. Neck circumference (NC), from this, becomes a viable and low-cost alternative, which seems to be related to the accumulation of fat in the hepatic tissue. OBJECTIVE: To evaluate the association between NC and metabolic alterations in patients with non- alcoholic fatty liver disease. METHODS: A cross-sectional study performed in 82 patients, of whom 76 underwent liver biopsy. We performed weight, height, abdominal circumference and NC measures. Values of NC ≥42 cm and ≥36 cm were considered as altered for men and women, respectively. Laboratory tests and liver biopsy result were collected in the participants' charts. We evaluated fasting blood glucose levels, insulin, glycosylated hemoglobin, triglycerides, total cholesterol, high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), ferritin, alkaline phosphatase, gamma glutamyltransferase, albumin, total bilirubin, direct bilirubin, glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase and the HOMA-IR index. RESULTS: We evaluated eighty-two patients. Patients with altered NC had increased body mass index (P=0.043), abdominal circumference (P=0.007), insulin (P=0.003) and HOMA-IR (P=0.029) when compared to those with adequate NC. NC was significantly correlated with reduced levels of high-density cholesterol (HDL-C) in men (r= -042, P<0.05), increased insulin levels in men and female (rs=0.47; P<0.05 and rs=0.51; P<0.01, respectively), as well as higher HOMA-IR index both males (rs=0.49; P<0.01) and female (rs=0.30; P<0.05). There was no significant association between NC and liver outcomes (r=0.145; P=0.36). CONCLUSION: NC is associated with the HOMA-IR index in patients with non-alcoholic fatty liver disease. NC can be used in the screening of insulin resistance in these patients, considering that insulin resistance plays a key role in the progression of the disease.


Assuntos
Resistência à Insulina/fisiologia , Pescoço/anatomia & histologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Adulto , Biópsia , Glicemia/análise , Índice de Massa Corporal , HDL-Colesterol/sangue , Estudos Transversais , Feminino , Ferritinas/sangue , Homeostase/fisiologia , Humanos , Insulina/sangue , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Fatores Sexuais , Circunferência da Cintura
13.
An Acad Bras Cienc ; 91(2): e20180547, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31038539

RESUMO

Dynamic thiol-disulfide homeostasis is considered to have critical roles in maintenance of physiological functioning. We aimed to reveal whether there is any specific aberration in thiol-disulfide homeostasis in three distinct categories of individuals, including those who 1) exercise regularly (fitness group), 2) have a sedentary lifestyle (sedentary group) and 3) are overweight or obese (overweight/obese group). 72 male individuals were included in the study, 21 of whom were in fitness group, 28 of whom were overweight or obese and 23 of whom had a sedentary lifestyle. Plasma native thiol (-SH) and total thiol [(-SH) + (-S-S-)] levels were quantitatively determined. Total thiol levels in sedentary group were significantly lower than those in overweight/obese (p<0.05) and fitness groups (p<0.001). Also, disulfide values in fitness group were significantly higher than those in sedentary and overweight/obese groups (p<0.005, p<0.05). On the other hand, disulfide level, reduced and oxidized thiol ratios and oxidation/reduction ratio in fitness group differed significantly from the other groups (p<0.05). Thiol-disulfide homeostasis varies depending on lifestyle. The results of our study indicate that higher total thiol and disulfide levels are conspicuously distinctive features of thiol-disulfide homeostasis in individuals exercising regularly.


Assuntos
Dissulfetos/sangue , Exercício/fisiologia , Obesidade/sangue , Sobrepeso/sangue , Comportamento Sedentário , Compostos de Sulfidrila/sangue , Adulto , Análise de Variância , Antioxidantes/fisiologia , Índice de Massa Corporal , Homeostase/fisiologia , Humanos , Masculino , Estresse Oxidativo/fisiologia , Curva ROC , Valores de Referência , Estatísticas não Paramétricas
14.
Nutrients ; 11(4)2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30979078

RESUMO

: Autophagy plays a role in several physiological and pathological processes as it controls the turnover rate of cellular components and influences cellular homeostasis. The liver plays a central role in controlling organisms' metabolism, regulating glucose storage, plasma proteins and bile synthesis and the removal of toxic substances. Liver functions are particularly sensitive to autophagy modulation. In this review we summarize studies investigating how autophagy influences the hepatic metabolism, focusing on fat accumulation and lipids turnover. We also describe how autophagy affects bile production and the scavenger function within the complex homeostasis of the liver. We underline the role of hepatic autophagy in counteracting the metabolic syndrome and the associated cardiovascular risk. Finally, we highlight recent reports demonstrating how the autophagy occurring within the liver may affect skeletal muscle homeostasis as well as different extrahepatic solid tumors, such as melanoma.


Assuntos
Autofagia/fisiologia , Células Epiteliais/fisiologia , Homeostase/fisiologia , Fígado/citologia , Ductos Biliares/citologia , Morte Celular , Dieta , Dislipidemias , Células Endoteliais/fisiologia , Ingestão de Energia , Hepatócitos/fisiologia , Humanos , Macrófagos do Fígado/fisiologia , Metabolismo dos Lipídeos/fisiologia , Lipólise , Melanoma , Músculo Esquelético/metabolismo , Neoplasias , Estresse Oxidativo
15.
Mediators Inflamm ; 2019: 5764061, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30936776

RESUMO

Purpose: Hepcidin is an acute-phase protein involved also in regulation of iron homeostasis. The aim of the study was to prospectively assess for the first time the hepcidinEL concentration in patients with subacute thyroiditis (SAT), to identify biochemical determinants of hepcidinEL concentration and evaluate the potential role of hepcidin in SAT diagnosis and monitoring. Methods: Out of 40 patients with SAT initially recruited, restrictive inclusion criteria fulfilled 21 subjects aged 45 ± 10 years and 21 healthy control subjects (CS). HepcidinEL concentration, thyroid status, and iron homeostasis were evaluated at SAT diagnosis and following therapy and compared with CS. Results: The median hepcidinEL concentration at SAT diagnosis is higher than that in CS (48.8 (15.9-74.5) ng/mL vs. 18.2 (10.2-23.3) ng/mL, p = 0.009) and is significantly lower after treatment (4.0 (1.2-10.0) ng/mL, p = 0.007) compared with CS. The ROC analysis for hepcidinEL at SAT diagnosis revealed that area under the curve (AUC) is 0.735 (p = 0.009), and the cut-off for hepcidinEL concentration is 48.8 ng/mL (sensitivity 0.52 and specificity 0.95). HepcidinEL in SAT patients correlated with CRP (r = 0.614, p = 0.003), ferritin (r = 0.815, p < 0.001), and aTPO (r = -0.491, p = 0.024). On multiple regression, the correlation between hepcidinEL and ferritin was confirmed (p < 0.001). Conclusions: SAT is accompanied by a significant increase in hepcidin, which reflects an acute-phase inflammatory process. Parameters of iron homeostasis improved significantly while inflammatory indices got lower following recovery. The potential role of hepcidin as a predictive factor of the risk of SAT relapse needs to be assessed in studies on larger groups of SAT patients.


Assuntos
Hepcidinas/metabolismo , Ferro/metabolismo , Tireoidite Subaguda/metabolismo , Adulto , Feminino , Homeostase/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
16.
Eur J Radiol ; 113: 158-164, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30927942

RESUMO

BACKGROUND: Marrow fat accumulates in diabetic conditions but remains elusive. The published works on the relationships between marrow fat phenotypes and glucose homeostasis are controversial. PURPOSE: To detect the association of insulin resistance with marrow adiposity in postmenopausal women with newly diagnosed type 2 diabetes (T2D) using chemical shift-encoded water-fat MRI. METHODS: We measured vertebral proton density fat fraction (PDFF) by 3T-MRI in 75 newly diagnosed T2D and 20 nondiabetic postmenopausal women. Bone mineral density (BMD), whole body fat mass and lean mass were determined by dual-energy X-ray absorptiometry. Insulin sensitivity was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Lumbar spine PDFF was higher in women with T2D (65.9 ± 6.8%) than those without diabetes (59.5 ± 6.1%, P = 0.009). There was a consistent inverse association between the vertebral PDFF and BMD. PDFF had a positive association with glycated hemoglobin and HOMA-IR but not with fasting plasma glucose and insulin. PDFF was significantly increased, and BMD was decreased in a linear trend from the lowest (<1.90) to highest (≥2.77) HOMA-IR quartile. Multivariate linear regression analyses revealed a positive association between log-transformed HOMA-IR and PDFF after adjustment for multiple covariates (ß = 0.382, P < 0.001). The positive association of HOMA-IR with PDFF remained robust when total body lean mass and fat mass, BMD was entered into the multivariate regression model, respectively (ß = 0.293 and ß = 0.251, respectively; all P <0.05). CONCLUSIONS: Elevated HOMA-IR was linked to higher marrow fat fraction in postmenopausal women with newly diagnosed T2D independently of body compositions.


Assuntos
Adiposidade/fisiologia , Doenças da Medula Óssea/patologia , Diabetes Mellitus Tipo 2/patologia , Resistência à Insulina/fisiologia , Absorciometria de Fóton/métodos , Tecido Adiposo/patologia , Composição Corporal/fisiologia , Água Corporal/fisiologia , Medula Óssea/patologia , Estudos Transversais , Feminino , Homeostase/fisiologia , Humanos , Vértebras Lombares , Imagem por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Pós-Menopausa/fisiologia
17.
Thorac Surg Clin ; 29(2): 123-131, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30927993

RESUMO

The thymus is a primary lymphoid organ essential for the development of T lymphocytes, which orchestrate adaptive immune responses. T-cell development in the thymus is spatially regulated; key checkpoints in T-cell maturation and selection occur in cortical and medullary regions to eliminate self-reactive T cells, establish central tolerance, and export naïve T cells to the periphery with the potential to recognize diverse pathogens. Thymic output is also temporally regulated due to age-related involution of the thymus accompanied by loss of epithelial cells. This review discusses the structural and age-related control of thymus function in humans.


Assuntos
Timo/imunologia , Timo/fisiologia , Envelhecimento/imunologia , Envelhecimento/fisiologia , Homeostase/fisiologia , Humanos , Sistema Imunitário/fisiologia , Linfócitos T/fisiologia , Timo/embriologia
18.
Yale J Biol Med ; 92(1): 93-101, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30923476

RESUMO

Sleep is an essential physiological behavior that promotes cognitive development and function. Although the switch between sleep/wake cycles is controlled by specific neural circuits, sleep need and the restorative benefits of sleep are likely controlled by cellular mechanisms localized in critical areas of the brain involved in learning and memory including the cortex and hippocampus. However, the molecular basis for the restorative function(s) of sleep that support cognition, or for the homeostatic build-up of sleep need are poorly understood. Synapses undergo local and global changes in strength to support learning and memory and are likely a point of restoration during sleep. Homer1a and mGluR1/5, recently implicated in sleep function, are molecules involved in the scaling down process that weakens synapses during sleep to restore synapse homeostasis. During wake, long-form Homer proteins tether mGluR1/5 to IP3R and to the post-synaptic density (PSD). During sleep, short-form Homer1a uncouples mGluR1/5 from IP3R leaving mGluR1/5 open to interact with other effectors, switching mGluR1/5 signaling from "awake-type" to "sleep-type" signaling modes. Importantly, mGluR1/5 have been implicated in several neurological and neurodevelopmental disorders such as Alzheimer's disease (AD) and autism spectrum disorder (ASD), all of which show abnormal sleep phenotypes, linking sleep, disease, and mGluR1/5 signaling. Further investigation into the downstream effectors of mGluR1/5 and sleep/wake signaling will lead to more targeted therapeutic interventions.


Assuntos
Homeostase/fisiologia , Proteínas de Arcabouço Homer/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Transdução de Sinais , Sono/fisiologia , Animais , Humanos , Plasticidade Neuronal
19.
Arch Pharm Res ; 42(5): 383-392, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30835074

RESUMO

Obesity is one of the worldwide prevalent disease caused by the imbalance between food intake and energy expenditure. Over a 100 years of research demonstrate that hypothalamus is the critical brain region regulating energy homeostasis, and evidences suggest the participation of non-neuronal populations such as astrocytes and microglia in the regulation of energy homeostasis. Recently, fat-rich diet induced hypothalamic inflammation has been found to deregulate the energy homeostasis, leading to the insulin resistance, glucose intolerance, and obesity. Several underlying mechanisms have been proposed, yet compelling evidences require further elucidations. This review discusses the up to date proposed mechanisms by which fat-rich diet induces hypothalamic inflammation and obesity.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Ingestão de Alimentos/fisiologia , Metabolismo Energético/fisiologia , Hipotálamo/patologia , Inflamação/fisiopatologia , Obesidade/etiologia , Animais , Astrócitos/metabolismo , Modelos Animais de Doenças , Homeostase/fisiologia , Humanos , Hipotálamo/citologia , Hipotálamo/fisiopatologia , Inflamação/etiologia , Inflamação/patologia , Microglia/metabolismo , Obesidade/patologia , Obesidade/fisiopatologia
20.
Dev Cell ; 48(5): 697-709.e5, 2019 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-30861376

RESUMO

Calcium signals act as universal second messengers that trigger many cellular processes in animals and plants, but how specific calcium signals are generated is not well understood. In this study, we determined that AtANN4, a putative calcium-permeable transporter, and its interacting proteins, SCaBP8 and SOS2, generate a calcium signal under salt stress, which initially activates the SOS pathway, a conserved mechanism that modulates ion homeostasis in plants under salt stress. After activation, SCaBP8 promotes the interaction of protein kinase SOS2 with AtANN4, which enhances its phosphorylation by SOS2. This phosphorylation of AtANN4 further increases its interaction with SCaBP8. Both the interaction with and phosphorylation of AtANN4 repress its activity and alter calcium transients and signatures in HEK cells and plants. Our results reveal how downstream targets are required to create a specific calcium signal via a negative feedback regulatory loop, thereby enhancing our understanding of the regulation of calcium signaling.


Assuntos
Proteínas de Arabidopsis/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Cálcio/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Estresse Salino/fisiologia , Arabidopsis/metabolismo , Homeostase/fisiologia , Fosforilação , Transdução de Sinais/fisiologia , Fatores de Transcrição/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA