Altered Metabolic Phenotypes and Hypothalamic Neuronal Activity Triggered by Sodium-Glucose Cotransporter 2 Inhibition

Background@#Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are currently used to treat patients with diabetes. Previous studies have demonstrated that treatment with SGLT-2 inhibitors is accompanied by altered metabolic phenotypes. However, it has not been investigated whether the hypothalamic circuit participates in the development of the compensatory metabolic phenotypes triggered by the treatment with SGLT-2 inhibitors. @*Methods@#Mice were fed a standard diet or high-fat diet and treated with dapagliflozin, an SGLT-2 inhibitor. Food intake and energy expenditure were observed using indirect calorimetry system. The activity of hypothalamic neurons in response to dapagliflozin treatment was evaluated by immunohistochemistry with c-Fos antibody. Quantitative real-time polymerase chain reaction was performed to determine gene expression patterns in the hypothalamus of dapagliflozin-treated mice. @*Results@#Dapagliflozin-treated mice displayed enhanced food intake and reduced energy expenditure. Altered neuronal activities were observed in multiple hypothalamic nuclei in association with appetite regulation. Additionally, we found elevated immunosignals of agouti-related peptide neurons in the paraventricular nucleus of the hypothalamus. @*Conclusion@#This study suggests the functional involvement of the hypothalamus in the development of the compensatory metabolic phenotypes induced by SGLT-2 inhibitor treatment.

The role of lysophosphatidic acid receptor 1 in inflammatory response induced by lipopolysaccharide from Porphyromonas gingivalis in human periodontal ligament stem cells

Lysophosphatidic acid (LPA) is a lipid messenger mediated by G protein-coupled receptors (LPAR1-6). It is involved in the pathogenesis of certain chronic inflammatory and autoimmune diseases. In addition, it controls the self-renewal and differentiation of stem cells. Recent research has demonstrated the close relationship between periodontitis and various diseases in the human body. However, the precise role of LPA in the development of periodontitis has not been studied. We identified that LPAR1 was highly expressed in human periodontal ligament stem cells (PDLSCs). In periodontitis-mimicking conditions with Porphyromonas gingivalis -derived lipopolysaccharide (Pg-LPS) treatment, PDLSCs exhibited a considerable reduction in the cellular viability and osteogenic differentiation potential, in addition to an increase in the inflammatory responses including tumor necrosis factor-α and interleukin-1β expression and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. Of the various LPAR antagonists, pre-treatment with AM095, an LPAR1 inhibitor, showed a positive effect on the restoration of cellular viability and osteogenic differentiation, accompanied by a decrease in NF-κB signaling, and action against Pg-LPS. These findings suggest that the modulation of LPAR1 activity will assist in checking the progression of periodontitis and in its treatment.

Cystic Neck Mass in an Adult: Unusual Manifestation of a Mediastinal Mature Teratoma

Anterior mediastinal teratomas are congenital tumors containing derivatives of all three germ layers. They usually grow slowly and are often detected incidentally by imaging studies. We describe the case of a 38-year-old man with an anterior mediastinal teratoma extending to the anterior neck, which resulted in a cystic neck mass.

Herpes Virus Entry Mediator Signaling in the Brain Is Imperative in Acute Inflammation-Induced Anorexia and Body Weight Loss

BACKGROUND: Reduced appetite and body weight loss are typical symptoms of inflammatory diseases. A number of inflammatory stimuli are responsible for the imbalance in energy homeostasis, leading to metabolic disorders. The herpes virus entry mediator (HVEM) protein plays an important role in the development of various inflammatory diseases, such as intestinal inflammation and diet-induced obesity. However, the role of HVEM in the brain is largely unknown. This study aims to investigate whether HVEM signaling in the brain is involved in inflammation-induced anorexia and body weight loss. METHODS: Food intake and body weight were measured at 24 hours after intraperitoneal injection of lipopolysaccharide (LPS) or intracerebroventricular injection of recombinant mouse LIGHT (also called tumor necrosis factor receptor superfamily 14, TNFSF14), an HVEM ligand, into 8- to 10-week-old male C57BL/6 mice and mice lacking HVEM expression (HVEM-/-). We also assessed LPS-induced change in hypothalamic expression of HVEM using immunohistochemistry. RESULTS: Administration of LPS significantly reduced food intake and body weight, and moreover, increased expression of HVEM in the hypothalamic arcuate nucleus. However, LPS induced only minor decreases in food intake and body weight in HVEM-/- mice. Administration of LIGHT into the brain was very effective at decreasing food intake and body weight in wild-type mice, but was less effective in HVEM-/- mice. CONCLUSION: Activation of brain HVEM signaling is responsible for inflammation-induced anorexia and body weight loss.

The Role of Hypothalamic FoxO1 on Hyperphagia in Streptozotocin-Induced Diabetic Mice / 당뇨병

BACKGROUND: Streptozotocin-induced diabetic animals are characterized by hyperphagia due to deficiencies of insulin and leptin. Forkhead box-containing protein of the O subfamily-1 (FoxO1) regulates energy homeostasis by regulating energy expenditure and food intake as well as mediating insulin and leptin signals in the hypothalamus. To identify the mediator of diabetic hyperphagia, we examined the effects of insulin or leptin on hypothalamic FoxO1 expression in a diabetic animal model. METHODS: Diabetes was induced in mice (C57BL/6) by intraperitoneal administration of streptozotocin (200 mg/kg). Stainless steel cannula was implanted into the lateral ventricle of the brain in each mouse. After three weeks, the mice were administered saline, insulin or leptin via intracerebroventricular (ICV) route. The medial hypothalamus was isolated to evaluate the mRNA expressions of FoxO1 and neuropeptides. RESULTS: Streptozotocin-induced diabetic mice exhibited significant elevations of blood glucose and food intake and significantly low levels of serum insulin and leptin. The levels of hypothalamic FoxO1 mRNA were significantly increased in diabetic mice. The hypothalamic expression of neuropeptide Y (NPY) mRNA was increased, but the expression of preproopiomelanocortin (POMC) mRNA was decreased in diabetic mice. ICV administration of insulin or leptin attenuated the upregulation of hypothalamic FoxO1 mRNA, and resulted in downregulation of NPY mRNA and upregulation of POMC mRNA in diabetic mice. CONCLUSION: We observed that the expression of hypothalamic FoxO1 mRNA was increased in streptozotocin-induced diabetic mice, and that it was significantly attenuated by central administration of insulin or leptin. These results suggest that hypothalamic FoxO1 is the direct mediator of diabetic hyperphagia.

The Results of Postoperative Radiotherapy for Hypopharyngeal Carcinoma / 대한방사선종양학회지

PURPOSE: This study was carried out to confirm clinical values and limitations of postoperative radiotherapy for hypopharyngeal carcinoma, to evaluate various prognostic factors which may affect to the treatment results and to use these results as fundamental data for making a new treatment strategy. METHODS AND MATERIALS: A retrospective analysis was performed on 64 previously untreated patients with squamous cell carcinoma of the hypopharynx, seen between 1988 and 1999 at Pusan National University Hospital. Most of patients were treated by laryngopharyngectomy and neck dissection followed by conventional fractionated postoperative radiotherapy on surgical bed and cervical nodal areas. RESULTS: The five-year overall survival rate and cause-specific survival rate were 42.2 percent and 51.6 percent, respectively. Univariate analysis of various clinical and pathologic factors confirmed the overall stage, TN-stage, secondary primary cancers, surgical positive margin, nodal extracapsular extension, total radiation doses as significant prognostic factors of hypopharyngeal carcinomas. But in multivariate analysis, TN-stage, surgical positive margin and extracapsular extesion were only statistically significant. CONCLUSION: In resectable cases of hypopharyngeal carcinoma, combined surgery and postoperative radiotherapy obtained good treatement results, even though sacrificing the function of larynx and pharynx. But in advanced and unresectable cases, with respect to survivals and quality of life issues, we were able to confirm some limitations of combined therapy. So we recommend that comparative studies of recent various chemo-radiotherapy methods and advanced radiotherapy techniques with these data should be needed.

The Effectiveness of Biofeedback Therapy for Children Patients with Chronic Constipation

PURPOSE: Chronic constipation is not uncommon even in children. Recently biofeedback treatment (BT) is considered as a useful modality in the treatment of various types of constipation. The aim of this study was to evaulate the effectiveness of BT in children with chronic constipation. METHODS: We reviewed 24 cases of childhood constipation (17 boys, 7 girls) who visited the Jinju Hakmoon colorectal surgery clinic and GNUH1 between April, 2001 and September, 2002. Balloon-mediated anorectal manometry system was used for BT. The effects of therapy was assessed by bowel movement, defecation time, fecal soiling and balloon evacuation test in the early course of therapy. The long term follow up survey was done by telephone interview at January 2003 and the effects of therapy was assessed by bowel movement, defecation time, fecal soiling and parents' satisfaction. RESULTS: Patients received the BT for the three times on average, and as the result of the therapy, 20 patients experienced disappearance of symptoms (87%) or at least improvement of symptoms. In terms of manometric values, the mean resting pressure was 113.4 mmHg before the BT, but decreased to 86.3 mmHg after the BT (P=0.0012). Mean pushing pressure dropped to 85.98 mmHg from 130.45 mmHg (P=<0.0001). Mean sensitivity decreased from 55 ml to 35 ml (P=0.0053). Mean compliance decreased from 20.28 H2O/cm to 4.21 H2O/cm (P=0.0015). 13 patients (76%) showed disappearance or improvement of symptoms in the long term follow up. CONCLUSIONS: The Balloon mediated biofeedback therapy is effective in children with chronic constipation. It is safe, easy to administer and also improve symptoms and objective parameters of anorectal function. Balloon mediated biofeedback therapy could be the first-line therapy in child patient with chronic constipation who failed conservative management.

Docetaxel and Cisplatin Combination Chemotherapy in Patients with Squamous Cell Carcinomas of the Head and Neck / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The objective of this phase II study was to assess the clinical antitumor activity and toxicities of docetaxel and cisplatin chemotherapy, in patients with locally advanced and metastatic, recurrent squamous cell carcinomas of the head and neck (SCCHN). MATERIALS AND METHODS: All eligible patients with locally advanced and metastatic, recurrent SCCHN had received two courses of chemotherapy followed by repeated head and neck examinations and computed tomography. Patients who had received prior chemotherapy with taxanes were ineligible. If the patients achieved a response (either CR or PR), they received one more course of chemotherapy prior to undergoing definitive local treatment. The combination chemotherapy consisted of docetaxel, 70 mg/m2, and cisplatin, 75 mg/m2, on day 1, with the cycles repeated every 3~4 weeks. RESULTS: All 32 patients were assessable for response and toxicity analyses. The most common grade 3/4 adverse event was neutropenia, which occurred in 11% of cases. No febrile neutropenia was noticed. The other grade 3/4 adverse events included: anemia (2%) and stomatitis (3%). The response rate in patients with locally advanced cancer was 19/21 (90%). Fifteen patients (71%) achieved a CR and 4 (19%) a PR. Out of the 4 patients presenting with a distant metastatic disease, 1 each achieved CR and PR, with 2 stable disease (SD). Out of the 7 patients with a recurrence at a distant site, 1 each achieved PR and SD, and 5 (71%) had a progression of the disease (PD). The overall response rate was 22/32 (69%). CONCLUSION: Docetaxel plus cisplatin is an effective regimen with an acceptable toxicity profile. This regimen may offer high antitumor activity on short outpatient administration, with a low incidence of severe toxicity.

A Case of Kennedy Syndrome Mimicking Myasthenia Gravis

Patients with Kennedy syndrome, which progresses more slowly than amyotrophic lateral sclerosis show a mild degree of motor fluctuation but rarely show significant decremental responses to repetitive nerve stimulations. Even in a patient with decremental responses to repetitive nerve stimulations, there is usually no significant improvements in motor symptoms to anticholinesterases. We experienced a patient with Kennedy syndrome, who showed significant decremental responses to repetitive nerve stimulations and a marked degree of motor fluctuation. His motor fluctuation responded dramatically to anticholinesterase. (J Korean Neurol Assoc 19(5):544~546, 2001)

Body image perceptions and its related problems of local high school students

BACKGROUND: Recently, the trend pursuing slimness is significantly increasing in adolescents. Because of distorted body image, excessive body weight control can cause problems of health. The goal of this study is to investigate the factors of distorted body image and its problems. METHODS: The survey was performed in a high school of Jindo island on May, 2000. All of 258 students in 1st and 2nd grade participated in this study by questionnaires. Thirteen truthless questionnaires were excluded in this study. Therefore 245 student were selected. RESULTS: Only 20% of 245 repliers were satisfied with their body figure. In male, 24.1% wanted weight loss, and 39.8% wanted weight gain. In female, 73% wanted weight loss. In a populations(BMI<20), 70 males wanted weight loss, whereas 35(52.2%) among 67 females want weight loss. According to these result, female stuedents wanted strongly weight loss than male. The factors which most influenced body figure were sports star in males(36.1%), and movie stars in female.(43.8%) A group of 58.4% of repliers has experienced body weight control. A group of 37% in male and 39.6% in female suffered from side effects. 77% of total hoped to be educated about adequate body weight control method. CONCLUSION: Almost of adolescents dissatisfied with their body figure, Many adolescent who is not obese attempt weight loss, and are sufferd from side effects. Therefore, it is required for effective education about body weight control and social attitude permitting adequate body image.

The relationship between serum cholesterol level and violent behavior in suicidal patients

BACKGROUND: There are epidemiological clinical studies that describe the relationship of decreased serum cholesterol levels or their treatment with suicides, offensive actions and depression. METHODS: We studied 140 patients who were hospitalized at Asan Foundation Jeongup Hospital (in Korea) via emergency room after suicide attempts and whose serum cholesterol levels were acquired during 53 months (from Jan. 1. 1995 to May 31. 1999). They were evaluated with the use of t-test. The serum cholesterol levels were compared between the control group of 140 persons who underwent health check ups and 140 patients who were of similar age and sex ratios. RESULTS: Subjects showed significant decrease in serum cholesterol levels in comparison with the control group. Low serum cholesterol levels were related with the severity of suicidal attempts. 1) The subjects showed lower serum cholesterol levels than the control group(150.51+/-56.69mg/dl vs 185.61+/-31.94mg/dl; t= 6.382, df=278, P<0.001) (Table 3). 2) Those who killed themselves showed statistically significant decrease in serum cholesterol levels than those who survived after their suicidal attempts(169.13+/-49.29mg/dl vs 135.89+/-34.14; t=2.005, P<0.05) (Table 4). CONCLUSION: This study was carried out in farming and fishing villages of Korea. The result showed that the decrease in serum cholesterol levels increased the risk of suicide trials. This fact is similar to the results of the previous studies performed at other farming and fishing communities. In addition, those who killed themselves had lower serum cholesterol levels compared to those who survived suicide attempts. This relationship was associated with depression.

A Case of Vigabatrin Induced Symptomatic Visual Field Defect

Vigabatrin (VGB) is one of the most frequently prescribed new anti-epileptic drugs in the world since 1989. It has minimal side effects and fewer drug interactions with other anti-epileptic drugs. Recently, concern of the prevalence and pathophysiology of visual impairment with VGB has been increased since the reports of visual field constriction in patients treated with VGB. We report a 46-year-old man with a visual field defect who has been suffering from complex partial seizures for 29 years. Brain magnetic resonance image (MRI) and electroencephalogram (EEG) were non-specific. The frequency of seizures was about 5 times a month for the past 5 years. VGB, in a dose of 1500 mg/day, was prescribed as an add on drug in addition to carbamazepine. 19 months after VGB treatment, the patient complained of visual dimness especially in the lower half of the visual field. He expressed it as "waving". He had no metabolic derangement. Fundus examination, visual evoked potential, and electroretinogram showed normal findings. A visual field analysis showed a bilateral field defect in the lower half. A follow up visual field analysis, 6 months after the withdrawal of VGB, revealed a slight improvement of visual field defects which were noted without significant clinical improvement. This case implicates that visual field defects due to VGB may be partially reversible.

Molecular Regulation of Hypothalamic Development and Differentiation in Mammals / 대한내분비학회지

No Abstract Available.

Ontogeny of tryosine hydroxylase in rat fetus by immunohistochemistry / 대한해부학회지

No abstract available.