OBJECTIVETo study the effects of glucocorticoid on skeletal muscle protein metabolism in burn sepsis and its possible mechanism.

METHODSThe rats were randomly divided into four groups with 15 rats in each group. Group B, 30% TBSA full-thickness burn was produced on the back and endotoxin (6 mg/kg bw) was given intraperitoneally after the injury to simulate burn sepsis. Groups C and D, glucocorticoid receptor antagonist RU38486 (10 mg/kg bw) was given by gavage 2 hours before or 2 hours after burn with endotoxin, respectively. Group A, the rats received only normal saline in same volume as endotoxin. Plasma levels of cortisol were determined with standard procedure. Extensor digitorium longus muscles (EDL) were procured from both legs 12 hours after the injury. After weighing, the proteolytic rate was determined in vitro in an incubation system with oxygen rich environment by high performance liquid chromatography. The gene expressions of ubiquitin, E(2)-14kDa and C2 in the muscles were determined by Northern blot analysis.

RESULTSThe weight of EDL was significantly lower in group B than in group A (t = 9.03, P < 0.01). Although the weight of EDL muscles was also lower in groups C and D than in group A, it was significantly higher than in group B (t = 2.26, 6.42, P < 0.05 or P < 0.01). The concentrations of plasma cortisol were markedly higher in groups B, C and D than in group A (t = 9.03 - 22.94, P < 0.01). A 58.8% (210/357) of the total and 335.5% (4.16/1.24) of myofibrillar proteolytic rate in group B was higher than in group A (t = 36.99 and t = 46.19, P < 0.01), respectively. The total and myofibrillar proteolytic rate in group D was 28.3% (161/567) and 49.6% (2.68/5.40) and in group C 18.9% (108/567) and 23.2% (1.25/5.40), which were lower than those in group B (t = 5.34 approximately 34.68, P < 0.01), respectively. Although the expressions of ubiquitin mRNA (2.4 kb), E(2)-14 kDa mRNA (1.2 kb) and C2 mRNA in groups C and D were significantly higher than in group A, all the values were lower than those in group B (t = 3.22, 11.32, P < 0.01), especially in group C.

CONCLUSIONSThe proteolytic rate of skeletal muscle, especially the myofibrillar proteolytic rate, was enhanced during burn with sepsis. Hypersecretion of glucocorticoid could upgrade the gene expression of ubiquitin system, resulting in hyperdegradation of skeletal muscle protein during burn with sepsis. Glucocorticoid receptor antagonist RU38486 could decrease the hyperdegradation of skeletal muscle during burn with sepsis.

Animals ; Burns ; metabolism ; Gene Expression Regulation ; Glucocorticoids ; physiology ; Hydrocortisone ; blood ; Male ; Mifepristone ; pharmacology ; Muscle Proteins ; metabolism ; Muscle, Skeletal ; metabolism ; Rats ; Rats, Wistar ; Sepsis ; metabolism ; Ubiquitin ; metabolism

PURPOSE: The primary objective of this study was to examine the changes of basal cortisol and DHEA levels present in saliva and serum with age, and to determine the correlation coefficients of steroid concentrations between saliva and serum. The secondary objective was to obtain a standard diurnal rhythm of salivary cortisol and DHEA in the Korean population. MATERIALS AND METHODS: For the first objective, saliva and blood samples were collected between 10 and 11 AM from 359 volunteers ranging from 21 to 69 years old (167 men and 192 women). For the second objective, four saliva samples (post-awakening, 11AM, 4PM, and bedtime) were collected throughout a day from 78 volunteers (42 women and 36 men) ranging from 20 to 40 years old. Cortisol and DHEA levels were measured using a radioimmunoassay (RIA). RESULTS: The morning cortisol and DHEA levels, and the age-related steroid decline patterns were similar in both genders. Serum cortisol levels significantly decreased around forty years of age (p < 0.001, when compared with people in their 20s), and linear regression analysis with age showed a significant declining pattern (slope= -2.29, t= -4.297, p < 0.001). However, salivary cortisol levels did not change significantly with age, but showed a tendency towards decline (slope= -0.0078, t= -0.389, p=0.697). The relative cortisol ratio of serum to saliva was 3.4 - 4.5% and the ratio increased with age (slope=0.051, t=3.61, p < 0.001). DHEA levels also declined with age in saliva (slope= -0.007, t= -3.76, p < 0.001) and serum (slope= -0.197 t= -4.88, p < 0.001). In particular, DHEA levels in saliva and serum did not start to significantly decrease until ages in the 40s, but then decreased significantly further at ages in the 50s (p < 0.001, when compared with the 40s age group) and 60s (p < 0.001, when compared with the 50 age group). The relative DHEA ratio of serum to saliva was similar throughout the ages examined (slop = 0.0016, t = 0.344, p = 0.73). On the other hand, cortisol and DHEA levels in saliva reflected well those in serum (r = 0.59 and 0.86, respectively, p < 0.001). The highest salivary cortisol levels appeared just after awakening (about two fold higher than the 11 AM level), decreased throughout the day, and reached the lowest levels at bedtime (p < 0.001, when compared with PM cortisol levels). The highest salivary DHEA levels also appeared after awakening (about 1.5 fold higher than the 11 AM level) and decreased by 11AM (p < 0.001). DHEA levels did not decrease further until bedtime (p=0.11, when compared with PM DHEA levels). CONCLUSION: This study showed that cortisol and DHEA levels change with age and that the negative slope of DHEA was steeper than that of cortisol in saliva and serum. As the cortisol and DHEA levels in saliva reflected those in serum, the measurement of steroid levels in saliva provide a useful and practical tool to evaluate adrenal functions, which are essential for clinical diagnosis.
Adult ; Age Factors ; Aged ; Analysis of Variance ; *Circadian Rhythm ; Dehydroepiandrosterone/blood/*metabolism ; Female ; Humans ; Hydrocortisone/blood/*metabolism ; Male ; Middle Aged ; Saliva/*metabolism

PURPOSE: The primary objective of this study was to examine the changes of basal cortisol and DHEA levels present in saliva and serum with age, and to determine the correlation coefficients of steroid concentrations between saliva and serum. The secondary objective was to obtain a standard diurnal rhythm of salivary cortisol and DHEA in the Korean population. MATERIALS AND METHODS: For the first objective, saliva and blood samples were collected between 10 and 11 AM from 359 volunteers ranging from 21 to 69 years old (167 men and 192 women). For the second objective, four saliva samples (post-awakening, 11AM, 4PM, and bedtime) were collected throughout a day from 78 volunteers (42 women and 36 men) ranging from 20 to 40 years old. Cortisol and DHEA levels were measured using a radioimmunoassay (RIA). RESULTS: The morning cortisol and DHEA levels, and the age-related steroid decline patterns were similar in both genders. Serum cortisol levels significantly decreased around forty years of age (p < 0.001, when compared with people in their 20s), and linear regression analysis with age showed a significant declining pattern (slope= -2.29, t= -4.297, p < 0.001). However, salivary cortisol levels did not change significantly with age, but showed a tendency towards decline (slope= -0.0078, t= -0.389, p=0.697). The relative cortisol ratio of serum to saliva was 3.4 - 4.5% and the ratio increased with age (slope=0.051, t=3.61, p < 0.001). DHEA levels also declined with age in saliva (slope= -0.007, t= -3.76, p < 0.001) and serum (slope= -0.197 t= -4.88, p < 0.001). In particular, DHEA levels in saliva and serum did not start to significantly decrease until ages in the 40s, but then decreased significantly further at ages in the 50s (p < 0.001, when compared with the 40s age group) and 60s (p < 0.001, when compared with the 50 age group). The relative DHEA ratio of serum to saliva was similar throughout the ages examined (slop = 0.0016, t = 0.344, p = 0.73). On the other hand, cortisol and DHEA levels in saliva reflected well those in serum (r = 0.59 and 0.86, respectively, p < 0.001). The highest salivary cortisol levels appeared just after awakening (about two fold higher than the 11 AM level), decreased throughout the day, and reached the lowest levels at bedtime (p < 0.001, when compared with PM cortisol levels). The highest salivary DHEA levels also appeared after awakening (about 1.5 fold higher than the 11 AM level) and decreased by 11AM (p < 0.001). DHEA levels did not decrease further until bedtime (p=0.11, when compared with PM DHEA levels). CONCLUSION: This study showed that cortisol and DHEA levels change with age and that the negative slope of DHEA was steeper than that of cortisol in saliva and serum. As the cortisol and DHEA levels in saliva reflected those in serum, the measurement of steroid levels in saliva provide a useful and practical tool to evaluate adrenal functions, which are essential for clinical diagnosis.
Adult ; Age Factors ; Aged ; Analysis of Variance ; *Circadian Rhythm ; Dehydroepiandrosterone/blood/*metabolism ; Female ; Humans ; Hydrocortisone/blood/*metabolism ; Male ; Middle Aged ; Saliva/*metabolism

Depression is an important post-stroke sequela with negative impact on mortality, functional outcome and quality of life. Changes in cytokines have been hypothesized to be associated with the etiology of post-stroke depression (PSD). The altere dhypothalamic-pituitary-adrenal (HPA) functioning is associated with the onset of depression. The activity of HPA could induce the fluctuations of cortisol levels. In this study, we prospectively checked interleukin 6 (IL-6) and cortisol levels in patients with early ischemic stroke. It was hypothesized that early serum IL-6 and cortisol fluctuations in stroke patients were the predictions of PSD. Totally, 100 participants were selected from stroke inpatients consecutively admitted to the Department of Neurology, Tongji Hospital from July 2014 to December 2015. Fifty health people served as the controls. The serum of all the patients was collected at 8:00 am and 4:00 pm respectively one week after stroke. The serum of controls was collected only at 8:00 am. The levels of IL-6 were analyzed by enzyme-linked immunosorbent assay kit, and those of cortisol were detected by chemiluminescence immunoassay. On the 3rd week after stroke, the patients were enrolled to the PSD group and non-PSD group based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and The Hamilton Depression Rating Scale (HAMD-21, score>7). The IL-6 level (13.24±2.89 ng/L) was elevated significantly in PSD groups as compared with that in non-PSD group and control group respectively (P<0.05 for both), but there was no significant difference in the IL-6 level between non-PSD group and control group. The patients in both PSD group and non-PSD group had significantly elevated morning cortisol levels in comparison with those in the control group (P<0.05; for PSD, non-PSD and control: 508.86±119.51, 420.83±70.04 and 340.40±76.30 nmol/L respectively). Moreover, afternoon cortisol levels in PSD group were significantly higher than those in non-PSD group, and the morning baseline cortisol levels in these two groups were similar (P>0.05). It was suggested that PSD generally runs a chronic course and is related to a variety of adverse health outcomes including increased disability, morbidity and mortality. This study will help the screening of potential PSD in the early stage.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Depression ; blood ; etiology ; physiopathology ; Female ; Humans ; Hydrocortisone ; blood ; Hypothalamo-Hypophyseal System ; metabolism ; Interleukin-6 ; blood ; Male ; Middle Aged ; Stroke ; blood ; complications ; physiopathology

OBJECTIVETo explore the association between plasma fat and glucose, cortisol and adrenocorticotropic hormone (ACTH) levels and genotypes of GR and ACTHR genes in healthy Chinese Han subjects.

METHODSTwo hundred healthy subjects were analyzed for GR and ACTHR gene polymorphisms using PCR-restriction fragment length polymorphism method. Plasma lipid, glucose, cortisol, ACTH levels were determined and correlated with the genotypes.

RESULTSNo significant difference was found between plasma lipid and glucose levels and various GR and ACTHR genotypes. Subjects with AG genotype of GR 5556A/G polymorphism had lower plasma cortisol levels than AA genotype. Compared with subjects with GG genotype of GR 4534-4536GAG/AAA [GAGAGG (GluArg)>GAAAAG(GluLys)] polymorphism, those with AG genotype had significantly lower plasma cortisol levels. Subjects with CC and CG genotypes of GR 6294C/G polymorphism also had significantly lower plasma cortisol levels compared with those with GG genotype. With regard to plasma ACTH levels, those with TT genotype of ACTHR 2T/C polymorphism were significantly lower than CC and CT genotypes, and those with AG genotype for GR 5556 A/G polymorphism were also significantly lower than AA genotype.

CONCLUSIONThere was no difference in plasma cortisol and glucose levels between subjects with GR and ACTHR gene variants. GR gene variants (5556A/G, 4534-4536GAG/AAA and 6294C/G polymorphisms) may influence plasma cortisol level, and ACTHR 2T/C, GR 5556A/G polymorphisms may decrease plasma ACTH level.

Adrenocorticotropic Hormone ; blood ; genetics ; Adult ; Blood Glucose ; genetics ; metabolism ; Female ; Genotype ; Humans ; Hydrocortisone ; blood ; genetics ; Lipids ; blood ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Receptors, Glucocorticoid ; genetics

OBJECTIVETo investigate the influence of Yiqi Huatan Decoction (, YHD) on a model of depression in rats under different pathological conditions.

METHODSThirty-two male SD rats were randomly divided into 4 groups of 8: normal, model, YHD, and maprotiline. The model group, YHD group and maprotiline group used separate feeding and rats were exposed to chronic and unpredictable stress to build the depression model. From day 2, the YHD group and maprotiline group were respectively given YHD (7 g/kg) and maprotiline (10 mg/kg) by gastrogavage once daily. The normal and model groups were given the same volume of drinking water. The medication duration were 21 days. At the end of the experiment, the serum levels of copper and zinc were determined by atomic absorption spectroscopy, plasma concentrations of adrenocorticotropic hormone (ACTH) and cortisol (COR) were detected by radioimmunoassay, and levels of norepinephrine (NE), dopamine (DA), and 5-hydroxytryptamine (5-HT) in the hypothalamus were analysed by high performance liquid chromatography-eletricochemistry.

RESULTSCompared with the content of copper and zinc in the serum of rats in the normal group, serum copper levels in model rats were significantly increased and zinc content was significantly reduced (both P<0.05). Plasma concentrations of ACTH and COR in the model group were significantly increased compared with those in the normal group (P<0.05, P<0.01). The contents of NE, DA, and 5-HT in the hypothalamus of rats in the model group were significantly reduced compared with those of the normal group (P<0.05 or P<0.01). Compared with those in the model group, the serum copper content and plasma concentrations of ACTH and COR were significantly decreased (all P<0.05); meanwhile, serum zinc content and hypothalamic contents of NE, DA, and 5-HT were significantly increased in rats of the YHD group (all P<0.05). The same effects were also shown in the maprotiline group except for 5-HT (all P<0.05)

CONCLUSIONThe pharmacological actions of YHD for depression might be related to improving trace-element anomalies, reversing endocrine dysfunction, and modulating the disorders of monoaminergic neurotransmitters.

Adrenocorticotropic Hormone ; blood ; Animals ; Behavior, Animal ; drug effects ; Copper ; blood ; Depression ; blood ; drug therapy ; Dopamine ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hydrocortisone ; blood ; Hypothalamus ; drug effects ; metabolism ; Male ; Norepinephrine ; metabolism ; Rats ; Rats, Sprague-Dawley ; Serotonin ; metabolism ; Zinc ; blood

PURPOSE: We wanted to evaluate the effect of body composition and age on the metabolic responses before and after elective colorectal resection. METHODS: We studied 20 active, healthy patients who underwent elective colorectal surgery. Their body composition was measured by using a Bioelectrical Impedance Analyzer. The O2 and CO2 consumption (VO2 and VCO2), respiratory quotient (RQ) and resting energy expenditure (REE) were measured by Indirect Calorimetry with using a Ventilated Hood System. RESULTS: The median age was 55 year (range: 35~70 year). The serum glucose, cortisol, insulin, C-reactive protein, cathecholamine and total body water (TBW), postoperative mean VO2, VCO2 and REE were all independent of patient age. The REE increased 9+/-4.3% after operation, but this increase was not related to age. The TBW was strongly related with the preoperative VO2 and VCO2, and the preoperative REE (r2=0.42~0.57, P<0.001). The postoperative VO2, VCO2 and REE were dependent on the TBW. The preoperative REE was dependent on the age, gender, preoperative TBW and body muscle mass (r2=0.526, P<0.000). The postoperative REE was dependent on the TBW and it was strongly related with the preoperative value (r2=0.796, P< 0.000). The postoperative day change of the REE was dependent on the postoperative day change of the TBW (r2=0.700, P=0.04). CONCLUSION: The TBW was not related to age. The TBW was the most valuable index to predict the change of the postoperative REE. Therefore, the preoperative TBW may be considered as the meaningful indicator to predict the change of the postoperative REE.
Blood Glucose ; Body Composition* ; Body Water ; C-Reactive Protein ; Calorimetry, Indirect ; Colorectal Surgery* ; Electric Impedance ; Energy Metabolism ; Humans ; Hydrocortisone ; Insulin

OBJECTIVEMyasthenia gravis is an autoimmunity disease and its pathogenesis has not been fully identified. Heat shock protein 90 (HSP90) shows an abnormal expression in other autoimmunity diseases. This study examined the mRNA expression of two isoforms of HSP90 in peripheral blood mononuclear cells (PBMC) and serum cortisol content in children with myasthenia gravis.

METHODSThirty-six children with myasthenia gravis and 19 healthy children were enrolled. Serum cortisol content was measured by the chemiluminescence assay. The expression of HSP90alpha and HSP90beta mRNA in PBMC was detected by the RT-PCR technique.

RESULTSThe mRNA expression of HSP90alpha (0.7329+/- 0.2120) and HSP90beta (0.7193+/- 0.2869) in children with myasthenia gravis was significantly higher than that in healthy controls (0.5574+/- 0.2084 and 0.4892+/- 0.2104 respectively) (P<0.01). Serum cortisol content (285.04+/- 146.39 nmol/L) in children with myasthenia gravis was also higher than that in the healthy controls (196.25+/- 64.52 nmol/L) (P<0.01).

CONCLUSIONSThe high mRNA expression of HSP90alpha and HSP90beta in PBMC might be associated with the development of myasthenia gravis. The high serum cortisol level indicates a high stress state or might be correlated to the glucocorticoid receptor abnormality in children with myasthenia gravis.

Child ; Child, Preschool ; Female ; HSP90 Heat-Shock Proteins ; genetics ; Humans ; Hydrocortisone ; blood ; Leukocytes, Mononuclear ; metabolism ; Male ; Myasthenia Gravis ; etiology ; metabolism ; RNA, Messenger ; blood

OBJECTIVETo study the changes in serum cortisol levels in adolescents with type 1 diabetes (T1DM) and elevated depressive symptoms.

METHODSTwenty-eight adolescents with T1DM and 31 healthy peers were assessed for depressive symptoms using a depression self-rating scale developed by the Epidemiological Survey Center. Selected subjects were classified into four groups: T1DM with elevated depressive symptoms group (n=15), T1DM without elevated depressive symptoms group (n=13), elevated depressive symptoms without T1DM group (n=15), and normal control group (n=16). Fasting blood samples were collected in the morning, and the levels of serum cortisol were compared among the four groups. The correlations of serum levels of cortisol and glycosylated hemoglobin A1c (HbA1c) with the score of depression self-rating scale were evaluated by Pearson correlation analysis.

RESULTSThe fasting serum cortisol levels in the 28 T1DM patients were significantly higher than in the 31 healthy peers (P<0.01). The fasting cortisol levels in the T1DM with elevated depressive symptoms group were significantly higher compared with those in the elevated depressive symptoms without T1DM group and normal control group (P<0.01). In adolescents with T1DM, serum HbA1c level was positively correlated with the score of depression self-rating scale (r=0.481, P=0.010).

CONCLUSIONSThe fasting serum cortisol levels in adolescents with T1DM and elevated depressive symptoms are significantly increased, suggesting that the patients with comorbidity of T1DM and depression develop dysfunction of the corticotropin-releasing hormone-adrenocorticotropic hormone-cortisol axis. The elevated depressive symptoms may be associated with a poor control of glucose metabolism.

Adolescent ; Adrenocorticotropic Hormone ; physiology ; Child ; Corticotropin-Releasing Hormone ; physiology ; Depression ; blood ; etiology ; Diabetes Mellitus, Type 1 ; blood ; Female ; Glucose ; metabolism ; Glycated Hemoglobin A ; analysis ; Humans ; Hydrocortisone ; blood ; Male

OBJECTIVETo investigate the nutritional status in acute stage ischemic stroke and its relation to disease severity and prognosis of patients.

METHODSFifty patients with ischemic stroke were admitted in hospital within 48 h after onset. National Institute of Health stroke scale (NIHSS) was used to assess the severity of stroke. Physical index and laboratory index were measured on d1, d7 and d14 after admission. Physical index included body weight, body mass index, triceps skin folds, upper arm circumference and arm muscle circumference. Laboratory index included prealbumin, high sensitivity C-reactive protein (hs-CRP), complement C3 and cortisol. The severity of metabolic disturbance was expressed as the difference of biochemical indexes between the d7 and d1. All cases were followed up for 6 months. The prognosis of stroke was evaluated with modified Rankin (mRankin) scores.

RESULTSNo significant changes of physical indexes were found between d7 and d1. The levels of prealbumin and complement C3 on d7 after admission were significantly decreased compared to d1 (198.8 mg/L±20.3 mg/L vs 286.7 mg/L±23.8 mg/L and 0.6 g/L±0.1 g/L vs 1.0 g/L±0.1 g/L, respectively, both P<0.05). The levels of hs-CRP and cortisol at d7 were significantly increased compared to d1 (495.2 nmol/L±39.5 nmol/L vs 24.1 mg/L±5.2 mg/L and 396.4 nmol/L±41.3 nmol/L vs 5.1 mg/L±1.2 mg/L, respectively, both P<0.05). On d14 after admission hs-CRP (13.2 mg/L±4.5 mg/L) and cortisol levels (463.4 nmol/L±32.1 nmol/L) were still significantly higher than d1 (both P<0.05). However, there were no difference in prealbumin (259.2 mg/L±22.8 mg/L) and complement C3 (0.8 g/L±0.2 g/L) levels between d1 and d14 after admission. Correlation analysis revealed that the NIHSS scores and mRankin scores were correlated with nutrition metabolism disturbances (P<0.05).

CONCLUSIONNutrition metabolism disturbances in patients with acute ischemic stroke are related to the disease duration, the severity and prognosis of stroke.

C-Reactive Protein ; metabolism ; Complement C3 ; metabolism ; Humans ; Hydrocortisone ; blood ; Nutritional Status ; Prealbumin ; metabolism ; Prognosis ; Severity of Illness Index ; Stroke ; diagnosis ; physiopathology