Adrenal insufficiency is caused by either primary adrenal failure or by hypothalamic-pituitary impairment of the corticotropic axis which is predominantly due to long-term glucocorticoid treatment or by pituitary disease. Primary adrenal failure is a rare disease that is life-threatening when overlooked whle adrenal failure secondary to hypothalamo-pituitary disease is a common clinical problem that has serious impact on the quality of life. Recent data suggests that the health-related quality of life in many patients with adrenal insufficiency is more severely impaired than previously thought and that current hormone replacement strategies are insufficient to prevent increased morbidity and mortality due to the disease. Therefore, the optimization and careful monitoring of glucocorticoid and mineralocorticoid replacement therapy remains one of the most challenging tasks in endocrinology. Leaving treatment aside, diagnosis of adrenal insufficiency is also challenging, because the main presenting symptoms such as fatigue, anorexia, and weight loss are non-specifically associated with many other common ailments, delaying a correct diagnosis. Some pitfalls in diagnostic work-up, particularly in the identification of secondary adrenal insufficiency, make the diagnosis even more difficult. Despite the difficulties, the complications associated with adrenal insufficiency make the rapid diagnosis and proper management of adrenal failure are important tasks for all physicians. We review here current standards for clinical assessment, diagnosis and treatment of adrenal insufficiency in light of recent research findings.
Addison Disease ; Adrenal Cortex Function Tests ; Adrenal Insufficiency ; Anorexia ; Endocrinology ; Fatigue ; Glucocorticoids ; Humans ; Light ; Pituitary Diseases ; Quality of Life ; Rare Diseases ; Weight Loss ; Axis, Cervical Vertebra

Stress induces degeneration of brain structures and functions. Particularly, hippocampus is sensitive to stressful stimulations. In the present study, the change of synaptic related molecules in the mouse dentate gyrus was examined with immunohistochemistry after restraint stress. We subjected mice to restraint stress for 6 h per day for 4 days. As a result, the number of Ki-67, a marker for proliferation, and doublecortin (DCX), a marker for neurogenesis, immunoreactive cells was decreased in the stress group. On the other hand, the intensity of calbindinD-28k, a marker of pre-existing granule cells, immunoreactivity was increased in the granule cell layer after 4 days restraint stress. As well as, the immunoreactivity of synaptic related molecules, postsynaptic density-95 (PSD-95), growth association protein-43 (GAP-43) and beta-NADPH-d reactivity were increased in the inner molecular layer of dentate gyrus after 4 days restraint stress. In conclusion, this study shows that repeated restraint stress suppresses neurogenesis in dentate gyrus and strengthens synaptic plasticity of existing granule cells.
Animals ; Brain ; Dentate Gyrus* ; Hand ; Hippocampus ; Immunohistochemistry ; Mice* ; Neurogenesis ; Plastics*

Voluntary running is known to dramatically increase the cell proliferation and neurogenesis in the dentate gyrus of the adult mouse hippocampus. However, it is crucial to realize that adding excitatory neurons could result in serious maladaptive outcomes for hippocampal circuit function. To investigate the response of mature granule cells on the increase of cell proliferation during voluntary running, we investigated the temporal change of calbindin-D28k (a marker for mature granule cells) using immunohistochemistry during voluntary running with upregulated neurogenesis. By using immunohistochemsitry for Ki-67 and doublecortin (DCX), we observed that the cell proliferation and differentiation of granule cells increased at 1 week of voluntary running. We found that, at 6 weeks of voluntary running, the cell proliferation and differentiation of granule cells returned to sedentary control levels. On the other hand, calbindin-D28k immunoreactivity decreased in the granular cell layer of the dentate gyrus and CA3 region of hippocampus after 1 week of voluntary running. At 6 weeks of voluntary running, the density of the calbindin-D28k in the granular cell layer and CA3 region was returned to the sedentary control level. These results demonstrate that the cell proliferation and differentiation are increased at early point of voluntary running, and the granule cell activity in the dentate gyrus is temporally changed for response to the increase of cell proliferation and differentiation during voluntary running.
Adult ; Animals ; Calbindin 1* ; Cell Proliferation ; Dentate Gyrus* ; Hand ; Hippocampus ; Humans ; Immunohistochemistry ; Mice* ; Neurogenesis ; Neurons ; Running*

OBJECTIVES: To compare the clinical effectiveness of the virtual reality (VR) programs in assessing psychosocial problems, improving symptoms, and reducing suicide risk in depressive patients with those of pharmacotherapy. METHODS: Thirty-six patients were recruited with depression in the treatment group and 22 participants in the healthy control group through internet advertisements between November 2018 and March 2019. Participants in the treatment group were allocated randomly at a 1:1 ratio to either the VR group or pharmacotherapy group. At the baseline, all participants were assessed with a comprehensive battery for their psychological characteristics by structured scales using VR technologies. Assessments of patients in the treatment group were repeated four weeks after therapeutic intervention. The primary outcome measures were the Korean Version of Quick Inventory of Depressive Symptomatology-Self-Report and suicidality scales of the Korean Mini International Neuropsychiatric interview. The borderline personality (Personality Assessment Inventory-Borderline Features Scale) and resilience (Korean Resilience Questionnaire) were also evaluated. RESULTS: Twenty-four depressive patients completed the treatment, and the final assessment was conducted after four weeks of treatment. In the initial assessment, the patient group showed significantly higher depressive symptoms, suicidality, borderline personality trait, and lower resilience than healthy control group. After the four-week therapeutic interventions, the VR group showed significant improvement in depression, suicidality, borderline personality trait, and resilience. In addition, there was no significant difference in the treatment efficacy between the VR group and the pharmacotherapy group. CONCLUSION In this study, the VR treatment program has clear benefits for emotional distress and reducing suicidality in depressive patients. Evidence-based VR treatments may show new clinical potential for depressive disorder.

Salivary function in mammals may be defective for various reasons, such as aging, Sjogren's syndrome or radiation therapy in head and neck cancer patients. Recently, tissue-specific stem cell therapy has attracted public attention as a next-generation therapeutic reagent. In the present study, we isolated tissue-specific stem cells from the human submandibular salivary gland (hSGSCs). To efficiently isolate and amplify hSGSCs in large amounts, we developed a culture system (lasting 4-5 weeks) without any selection. After five passages, we obtained adherent cells that expressed mesenchymal stem cell surface antigen markers, such as CD44, CD49f, CD90 and CD105, but not the hematopoietic stem cell markers, CD34 and CD45, and that were able to undergo adipogenic, osteogenic and chondrogenic differentiation. In addition, hSGSCs were differentiated into amylase-expressing cells by using a two-step differentiation method. Transplantation of hSGSCs to radiation-damaged rat salivary glands rescued hyposalivation and body weight loss, restored acinar and duct cell structure, and decreased the amount of apoptotic cells. These data suggest that the isolated hSGSCs, which may have characteristics of mesenchymal-like stem cells, could be used as a cell therapy agent for the damaged salivary gland.
Amylases/genetics/metabolism ; Animals ; Antigens, CD/genetics/metabolism ; Apoptosis ; Cell Differentiation ; Humans ; Male ; Mesenchymal Stromal Cells/*cytology/metabolism ; Radiation Injuries, Experimental ; Rats ; Rats, Wistar ; *Regeneration ; Salivary Glands/cytology/injuries/physiology/*surgery ; *Salivation ; *Stem Cell Transplantation

BACKGROUND: Recently, the rate of infections with non-tuberculous mycobacteria (NTM) has been increasing in Korea. Precise identification of NTM is critical to determination of the pathogen and to target treatment of NTM patients. METHODS: Sixty-eight unclassified mycobacteria isolates by rpoB PCR-RFLP assay (PRA) collected in 2008 were analyzed by National Center for Biotechnology Information (NCBI) Basic Local Alignment Search Tool (BLAST) search after sequencing of 16S rRNA, hsp65, rpoB genes. RESULTS: Nineteen strains of 68 isolates were specified as species after sequencing analysis of 3 gene types. We found 3 M. lentifulavum, 5 M. arupense, 4 M. triviale, 4 M. parascrofulaceum, and one M. obuense. One M. tuberculosis and another M. peregrinum were mutated at the Msp I recognition site needed for rpoB PRA. The remaining 49 isolates did not coincide with identical species at the 3 kinds genes. CONCLUSION: Sequencing analysis of 16S rRNA, hsp65, rpoB was useful for identification of NTM unclassified by rpoB PRA.
Biotechnology ; Korea ; Nontuberculous Mycobacteria ; RNA, Ribosomal, 16S ; Tuberculosis

Objective: With trends in population aging an increasing number of older patients are visiting the emergency department (ED). This study aimed to identify the characteristics of ED utilization and risk factors for in-hospital mortality in older patients who visited EDs. Methods: This nationwide observational study used National Emergency Department Information System data collected during a 2-year period from January 2016 to December 2017. The characteristics of older patients aged 70 years or older were compared with those of younger patients aged 20 to 69 years. Risk factors associated with in-hospital mortality were analyzed by multivariable logistic regression. Results: A total of 6,596,423 younger patients and 1,737,799 older patients were included. In the medical and nonmedical older patient groups, significantly higher proportions of patients were transferred from another hospital, utilized emergency medical services, had Korean Triage and Acuity Scale scores of 1 and 2, required hospitalization, and required intensive care unit admission in the older patient group than in the younger patient group. ED and post-hospitalization mortality rates increased with age; in particular, older medical patients aged 90 or older had an in-hospital mortality rate of 9%. Older age, male sex, transfer from another hospital, emergency medical service utilization, a high Korean Triage and Acuity Scale score, systolic blood pressure <100 mmHg, respiratory rate >20/min, heart rate >100/min, body temperature <36°C, and altered mental status were associated with in-hospital mortality. Conclusion Development of appropriate decision-making algorithms and treatment protocols for high risk older patients visiting the ED might facilitate appropriate allocation of medical resources to optimize outcomes.

Objective: With trends in population aging an increasing number of older patients are visiting the emergency department (ED). This study aimed to identify the characteristics of ED utilization and risk factors for in-hospital mortality in older patients who visited EDs. Methods: This nationwide observational study used National Emergency Department Information System data collected during a 2-year period from January 2016 to December 2017. The characteristics of older patients aged 70 years or older were compared with those of younger patients aged 20 to 69 years. Risk factors associated with in-hospital mortality were analyzed by multivariable logistic regression. Results: A total of 6,596,423 younger patients and 1,737,799 older patients were included. In the medical and nonmedical older patient groups, significantly higher proportions of patients were transferred from another hospital, utilized emergency medical services, had Korean Triage and Acuity Scale scores of 1 and 2, required hospitalization, and required intensive care unit admission in the older patient group than in the younger patient group. ED and post-hospitalization mortality rates increased with age; in particular, older medical patients aged 90 or older had an in-hospital mortality rate of 9%. Older age, male sex, transfer from another hospital, emergency medical service utilization, a high Korean Triage and Acuity Scale score, systolic blood pressure <100 mmHg, respiratory rate >20/min, heart rate >100/min, body temperature <36°C, and altered mental status were associated with in-hospital mortality. Conclusion Development of appropriate decision-making algorithms and treatment protocols for high risk older patients visiting the ED might facilitate appropriate allocation of medical resources to optimize outcomes.

Allergic reaction to insulin is uncommon since the introduction of human recombinant insulin preparations and is more rare in pregnant than non-pregnant females due to altered immune reaction during pregnancy. Herein, we report two cases of allergic reaction to insulin in gestational diabetes that were successfully managed. One case was a 33-year-old female using isophane-neutral protamine Hagedorn human insulin and insulin lispro. She experienced dyspnea, cough, urticaria and itching sensation at the sites of insulin injection immediately after insulin administration. We discontinued insulin therapy and started oral hypoglycemic agents with metformin and glibenclamide. The other case was a 32-year-old female using insulin lispro and insulin detemer. She experienced pruritus and burning sensation and multiple nodules at the sites of insulin injection. We changed the insulin from insulin lispro to insulin aspart. Assessments including immunoglobulin E (IgE), IgG, eosinophil, insulin antibody level and skin biopsy were performed. In the two cases, the symptoms were resolved after changing the insulin to oral agents or other insulin preparations. We report two cases of allergic reaction to human insulin in gestational diabetes due to its rarity.
Adult ; Biopsy ; Burns ; Cough ; Diabetes, Gestational* ; Dyspnea ; Eosinophils ; Female ; Glyburide ; Humans ; Hypersensitivity* ; Hypersensitivity, Immediate ; Hypoglycemic Agents ; Immunoglobulin E ; Immunoglobulin G ; Immunoglobulins ; Insulin Aspart ; Insulin Lispro ; Insulin* ; Metformin ; Pregnancy ; Pruritus ; Sensation ; Skin ; Urticaria