• 동의신경정신과학회지
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• 제28권3호
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• pp.183-194
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• 2017

Objectives: Chijasitang (CJST) has been prescribed for patients with anxiety disorder, and is believed to treat insomnia. The present study was carried out to investigate whether Fructus Gardeniae, Fermented Semen Sojae Preparatum and CJST have beneficial effects on treating anti-stress. Methods: The mice were divided into the following groups: normal, control, positive control, and experimental. Then, the experimental groups were further divided into the Fructus Gardeniae group (FG), the Fermented Semen Sojae Preparatum group (FS), the Chijasitang water extract group (CJSTW), and the Chijasitang 30% ethanol extract group (CJSTE). In the positive control group, a single dose of imipramine ($500{\mu}g/g$) was applied to the mice. In the experimental groups, each single dose of FG, FS, CJSTW and CJSTE ($50{\mu}g/g$) was applied to the mice. After one hour, the mice in all groups except the normal group were exposed to immobilization stress. Their body weights, phagocytosis, nitric oxide in macrophage, corticosterone, and adrenocorticotropic hormone (ACTH) were observed. Results: Fructus Gardeniae, Fermented Semen Sojae Preparatum and Chijasitang prevented weight loss and suppressed the decrease of phagocytosis in the mice after their exposure to immobilization-stress. Although they did not influence the amount of NO, they suppressed the increment of ACTH and corticosterone in the immobilization-stressed mice. Conclusions: According to the results of this study, they suggest that Fructus Gardeniae, Fermented Semen Sojae Preparatum and Chi-Ja-Si-Tang all have some anti-stress effects.

• Journal of Chest Surgery
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• 제51권2호
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• pp.109-113
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• 2018

Background: Low cardiac output syndrome (LCOS) after cardiac surgery usually requires inotropes. In this setting, critical illness-related corticosteroid insufficiency (CIRCI) may develop. We aimed to investigate the clinical features of CIRCI in the presence of LCOS and to assess the efficacy of steroid treatment. Methods: We reviewed 28 patients who underwent a rapid adrenocorticotropic hormone (ACTH) test due to the suspicion of CIRCI between February 2010 and September 2014. CIRCI was diagnosed by a change in serum cortisol of <$9{\mu}g/dL$ after the ACTH test or a random cortisol level of <$10{\mu}g/dL$. Results: Twenty of the 28 patients met the diagnostic criteria. The patients with CIRCI showed higher Sequential Organ Failure Assessment (SOFA) scores than those without CIRCI ($16.1{\pm}2.3$ vs. $11.4{\pm}3.5$, p=0.001). Six of the patients with CIRCI (30%) received glucocorticoids. With an average elevation of the mean blood pressure by $22.2{\pm}8.7mm\;Hg$ after steroid therapy, the duration of inotropic support was shorter in the steroid group than in the non-steroid group ($14.1{\pm}2.3days$ versus $30{\pm}22.8days$, p=0.001). Three infections (15%) developed in the non-steroid group, but this was not a significant between-group difference. Conclusion: CIRCI should be suspected in patients with LCOS after cardiac surgery, especially in patients with a high SOFA score. Glucocorticoid replacement therapy may be considered to reduce the use of inotropes without posing an additional risk of infection.

• Journal of Yeungnam Medical Science
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• 제33권2호
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• pp.155-158
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• 2016

Sorafenib (Nexavar) has been regarded as a treatment for unresectable hepatocellular carcinoma (HCC), with side effects that include hand-foot skin reaction, diarrhea, rash, fatigue, hypertension, nausea, anorexia, weight loss, and alopecia. Thyroid disorder, such as endocrine side effect, has also been reported. However no case involving adrenal insufficiency has been reported. Here, we report a case of adrenal insufficiency which occurred after taking sorafenib in a patient with HCC. A 56-year-old man visited our hospital due to right upper quadrant abdominal pain and he was diagnosed as multiple disseminated and unresectable HCCs with portal vein invasion; therefore transarterial chemoembolization was performed and sorafenib administration was started. Two months later, he was admitted to the hospital complaining of severe fatigue. The laboratory results showed cortisol of <$0.2{\mu}g/dL$ and adrenocorticotropic hormone of <1.00 pg/mL. The patient had no history of taking steroids or herbal medications. Secondary adrenal insufficiency was diagnosed and prednisolone 10 mg per day was started immediately; as a result, fatigue remarkably improved. This may be the first report indicating a possible association between sorafenib and adrenal insufficiency and it implies that the possibility of adrenal insufficiency should be considered in patients taking sorafenib who complain of severe fatigue.

• The Korean Journal of Physiology and Pharmacology
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• 제22권1호
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• pp.23-33
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• 2018

Cushing's syndrome (CS) is a collection of symptoms caused by prolonged exposure to excess cortisol. Chronically elevated glucocorticoid (GC) levels contribute to hepatic steatosis. We hypothesized that histone deacetylase inhibitors (HDACi) could attenuate hepatic steatosis through glucocorticoid receptor (GR) acetylation in experimental CS. To induce CS, we administered adrenocorticotropic hormone (ACTH; 40 ng/kg/day) to Sprague-Dawley rats by subcutaneous infusion with osmotic mini-pumps. We administered the HDACi, sodium valproate (VPA; 0.71% w/v), in the drinking water. Treatment with the HDACi decreased steatosis and the expression of lipogenic genes in the livers of CS rats. The enrichment of GR at the promoters of the lipogenic genes, such as acetyl-CoA carboxylase (Acc), fatty acid synthase (Fasn), and sterol regulatory element binding protein 1c (Srebp1c), was markedly decreased by VPA. Pan-HDACi and an HDAC class I-specific inhibitor, but not an HDAC class II a-specific inhibitor, attenuated dexamethasone (DEX)-induced lipogenesis in HepG2 cells. The transcriptional activity of Fasn was decreased by pretreatment with VPA. In addition, pretreatment with VPA decreased DEX-induced binding of GR to the glucocorticoid response element (GRE). Treatment with VPA increased the acetylation of GR in ACTH-infused rats and DEX-induced HepG2 cells. Taken together, these results indicate that HDAC inhibition attenuates hepatic steatosis through GR acetylation in experimental CS.

• 대한수의학회지
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• 제38권3호
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• pp.614-628
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• 1998

The effects of electroacupuncture(EA) on blood concentration of endocrine substances were investigated in 6 horses. Three acupuncture points ; Guan Yuan Shu(BL-26), Wei Shu(BL-21) and Da Chang Shu(BL-25) were stimulated for 20 minutes by EA at separate occasions under varying condition ; 2V-1Hz, 2V-5Hz, 2V-30Hz, 4V-1Hz, 4V-5Hz and 4V-30Hz. Plasma levels of adrenocorticotropic hormone(ACTH), ${\beta}$-endorphin, epinephrine, norepinephrine and serum levels of gastrin were analysed. Blood samplings were carried out before, 0, 20 and 40 minutes after the EA stimulation. The serum gastrin levels were increased by 2V-5Hz stimulation on the Wei Shu. Plasma ACTH levels were decreased by 2V-1Hz stimulation on the Wei Shu, but largely increased by 4V-30Hz stimulation on the Guan Yuan Shu. Plasma ${\beta}$-endorphin levels were slightly increased or decreased by 2V-1Hz stimulation, but largely increased by 4V-30Hz stimulation on the Guan Yuan Shu. Plasma levels of epinephrine and norepinephrine were not so much changed by 2V-1Hz or 5Hz stimulation, but tended to increase by 4V-30Hz stimulation on Guan Yuan Shu. These results suggest that the low voltage-low frequence EA stimulation increased blood concentration of gastrin, but decreased ACTH, ${\beta}$-endorphin, epinephrine and norepinephrine, whereas high voltage-high frequence EA stimulation induced opposite results. Accordingly, there appears to be a close relationship between the changes of gastrointestinal motility and the changes of blood concentration of endocrine substances by EA stimulation.

• Clinical and Experimental Pediatrics
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• 제57권9호
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• pp.416-419
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• 2014

X-linked adrenoleukodystrophy (X-ALD) is a rare peroxisomal disorder, that is rapidly progressive, neurodegenerative, and recessive, and characteristically primary affects the central nervous system white matter and the adrenal cortex. X-ALD is diagnosed basaed on clinical, radiological, and serological parameters, including elevated plasma levels of very long chain fatty acids (VLCFA), such as C24:0 and C26:0, and high C24:0/C22:0 and C26:0/C22:0 ratios. These tests are complemented with genetic analyses. A 7.5-year-old boy was admitted to Department of Pediatrics, Chungnam National University Hospital with progressive weakness of the bilateral lower extremities. Brain magnetic resonance imaging confirmed clinically suspected ALD. A low dose adrenocorticotropic hormone stimulation test revealed parital adrenal insufficiency. His fasting plasma levels of VLCFA showed that his C24:0/C22:0 and C26:0/C22:0 ratios were significantly elevated to 1.609 (normal, 0-1.390) and 0.075 (normal, 0-0.023), respectively. Genomic DNA was extracted from peripheral whole blood samples collected from the patient and his family. All exons of ABCD1 gene were amplified by polymerase chain reaction (PCR) using specific primers. Amplified PCR products were sequenced using the same primer pairs according to the manufacturer's instructions. We identified a missense mutation (p.Arg163Leu) in the ABCD1 gene of the proband caused by the nucleotide change 488G>T in exon 1. His asymptomatic mother carried the same mutation. We have reported an unpublished mutation in the ABCD1 gene in a patient with X-ALD, who showed increased ratio of C24:0/C22:0 and C26:0/C22:0, despite a normal VLCFA concentrations.

• 한국임상수의학회지
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• 제26권5호
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• pp.472-475
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• 2009

A 3-year old, female Cocker Spaniel dog was referred to Seoul National University Hospital for Animals with depression and vomiting. The dog was diagnosed as hypoadrenocorticism based on the typical electrolyte alteration and the result of adrenocorticotropic hormone (ACTH) stimulation test. Initial treatment with oral fludrocortisone at a dose rate of 0.02 mg/kg/q24h for 6 weeks period was ineffective at maintaining serum electrolyte concentrations within normal limits. Although a dose rate of oral fludrocortisone was significantly increased up to 0.06 mg/kg/q24h during 24 weeks period, the treatment was still ineffective. Moreover, the patient showed side effects related to the glucocorticoid excess including PU/PD, weight gain and lipemia. After alternation with desoxycorticosterone pivalate (DOCP, 2.2 mg/kg, IM) every 25 day, the clinical signs was disappeared and the electrolyte balance was maintain with no side effect. Therefore, DOCP may be suggested as an effective drug in canine hypoadrenocorticism uncontrolled with oral fludrocortisone.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 제4회 추계심포지움
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• pp.153-159
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• 1996

${\alpha}$-Melanotropin (Ac-Ser-Tyr- Ser-Met-Glu$\^$5/-His-Phe-Arg-Trp-Gly$\^$10/-Lys-Pro-Val-NH$_2$) is one of the first peptide hormones to be isolated and have its structure determined. It was early recognized to have essentially the same N-terminal tridecapeptide sequence as adrenocorticotropic hormone (ACTH) except that the N-terminal was acetylated in the case of ${\alpha}$-MSH but not in the case of ACTH, indicating that their biosyntheses were different (Figure 1). Subsequently it was discovered that ${\alpha}$-MSH and ACTH were derived from the same gene, currently referred to as proopiomelanocortin (POMC). Its original bioactivity was pigmentation, but it also was recognized that it may have activity in the central nervous system, though the precise nature of these central activities have been controversial. The recent cloning and expression of five melanocortin receptors, with the MC3 and MC4 receptors found primarily in the brain and the MC5 receptor (MC5-R) found throughout the body, has provided new impetus to understand the structure-activity relationships of ${\alpha}$-MSH at these receptors. The effects of ${\alpha}$-MSH on pigmentation are mediated by the MC1-R expressed specifically on the surface of melanocytes. Similarly the MC2-R is involved in the regulation of adrenal steroidogenesis by ACTH. However, given the complexity of expression of the MC3, MC4, and MC5 receptors, it has not been possible to identify any simple correlations between these receptors and the reported biological activities of the melanocortin peptides. Consequently, potent and receptor specific agonists and especially antagonists would be extremely valuable tools for the determination of the physiological roles of the MC3, MC4, and MC5 receptors. Though the extensive structure-activity relationships have provided much information on agonist activity related to pigmentary effects, only recently has it been possible to begin to systematically develop potent and selective antagonists.

• Journal of Genetic Medicine
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• 제13권1호
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• pp.31-35
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• 2016

Antley-Bixler syndrome (ABS) is a rare form of syndromic craniosynostosis with additional systemic synostosis, including radiohumeral or radioulnar synostosis. Another characteristic feature of ABS is mid-facial hypoplasia that leads to airway narrowing after birth. ABS is associated with mutations in the FGFR2 and POR genes. Patients with POR mutations present with either skeletal manifestations or congenital adrenal hyperplasia with ambiguous genitalia. We report here two cases of ABS caused by mutations in FGFR2 and POR. Although the patients had craniosynostosis and radiohumeral synostosis in common and cranioplasty was performed in both cases, the male with POR mutations showed an elevated level of $17{\alpha}$-hydroxyprogesterone during newborn screening and was diagnosed with congenital adrenal hyperplasia by adrenocorticotropic hormone stimulation. This patient has been treated with hydrocortisone and fludrocortisone. He had no ambiguous genitalia but had bilateral cryptorchidism. On the other hand, the female with the FGFR2 mutation showed severe clinical manifestations: upper airway narrowing leading to tracheostomy, kyphosis of the cervical spine, and coccyx deformity. ABS shows locus heterogeneity, and mutations in two different genes can cause similar craniofacial and skeletal phenotypes. Because the long-term outcomes and inheritance patterns of the disease differ markedly, depending on the causative mutation, early molecular genetic testing is helpful.

• 한국임상수의학회지
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• 제22권2호
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• pp.130-135
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• 2005

A retrospective study was performed with 9 cases of spontaneous canine hypoadrenocorticism presented to the Veterinary Medical Teaching Hospital of Seoul National University. The disease occurred mostly in young to middle­aged dogs. Most dogs had chronic nonspecific signs such as episodic anorexia, lethargy and vomiting, but 3 dogs were brought to the hospital with an acute adrenal crisis. Serum biochemical analysis revealed azotemia, abnormal concentration of sodium, potassium, and chloride in almost all the patients. Diagnoses were made based on lack of adrenocortical response to exogenous adrenocorticotropic hormone(ACTH). Most dogs have been responded well with mineralocorticoid and glucocorticoid replacement except for a dog which died during treatment for adrenal crisis. Three dogs treated with fludrocortisone acetate(final median dosage, $31.0{\mu}g/kg/day$) for mineralocorticoid supplementation showed some adverse effects, such as excessive appetite and polyuria/polydipsia. In this study, it was suggested that clinicians should also consider hypoadrenocorticism when they diagnose a patient showing nonspecific gastrointestinal signs with unknown cause or laboratory findings which mimic primary renal diseases.