Histopathological Evaluation of Heart Toxicity of a Novel Selective PPAR-gamma Agonists CKD-501 in db/db Mice

High risk of cardiovascular diseases caused by existing PPAR-gamma agonists such as rosiglitazone and pioglitazone has been recently reported. CKD-501 is a novel selective PPAR-gamma agonist as a potential target to reduce cardiovascular risk in non-insulin dependent diabetes mellitus (NIDDM). In this study, We investigated potential cardiotoxicity of CKD-501 and compared its toxicity with that of rosiglitazone or pioglitazone using db/db mice. After 12-week repeated administration of CKD-501 at doses of 3, 10 and 30 mg/kg/day or rosiglitazone at doses of 10 and 30 mg/kg/day or pioglitazone at doses of 200 and 540 mg/kg/day, animals were sacrificed for investigation of potential toxicities. Diameters of left ventricles and areas of cardiomyocytes were measured. And lipid accumulation and apoptosis in heart muscle were examined by oil red O staining and TUNEL staining, respectively. Diameters of left ventricles were significantly increased in high dose treatment group of pioglitazone compared to control (p CKD-501 > or = rosiglitazone. However, lipid accumulation and apoptotic changes in heart were not observed in all dosing groups. Taken together, the myocardial cell hypertrophy of CKD-501 are relatively lower than that of pioglitazone and similar to rosiglitazone. And it is suggested that the myocardial cell hypertrophy of CKD-501 are less adverse in clinical use for the management of the NIDDM.

CKD-712, (S)-1-(alpha-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, Inhibits the NF-kappaB Activation and Augments Akt Activation during TLR4 Signaling

Since CKD-712 has been developed as an anti-inflammatory agent, we examined the effect of CKD-712 during TLR4 signaling. Using HEK293 cells expressing TLR4, CKD-712 was pre-treated 1 hr before LPS stimulation. Activation of NF-kappaB was assessed by promoter assay. The activation of ERK, JNK, p38, IRF3 and Akt was measured by western blotting. CKD-712 inhibited the NF-kappaB signaling triggered by LPS. The activation of ERK, JNK, p38 or IRF3 was not inhibited by CKD-712. On the contrary the activation of these molecules was augmented slightly. The activation of Akt with stimulation of LPS was also enhanced with CKD-712 pre-treatment at lower concentration, but was inhibited at higher concentration. We suggest that during TLR4 signaling CKD-712 inhibits NF-kappaB activation. However, CKD-712 augmented the activation of Akt as well as Map kinases. Therefore, we suggest that CKD-712 might have a role as an immunomodulator.

Health status of children in low socioeconomic conditions / 소아과

PURPOSE: The purpose of this study was to investigate the health status and nutritional condition of children living in a low-income community through anthropometric, laboratory evaluation. METHODS: A community-based survey identified children below 15 years living in a low-income community. Their weight, height, visual acuity, hearing level and dental status were measured. Blood sample were obtained on June and July, 2004. Hemoglobin, serum cholesterol, Hepatitis B antigen/antibody, AST and ALT were measured. RESULTS: A total of 285 students(M:F=141:144) aged 6 to 14 years were included in this study. The heights and weights in some grades were smaller than controls. The prevalence of obesity was 10.6 percent in males and 10.7 percent in females. The prevalence of abnormal visual acuity, hearing impairments and dental carries were 20.5 percent, 0.3 percent and 69.4 percent. The prevalence of anemia was 10.1 percent. Serum total cholesterol was over 200 mg/dL in 7 percent. They complained of abdominal pain(22.1 percent) and headache(17.1 percent). Hyperthyroidism, cataract, neurofibromatosis, severe atopic dermatitis, ventricular septal defect, strabismus and inguinal hernia were newly diagnosed. CONCLUSION: Mean heights and weights of children in the low-income community were smaller than controls. The prevalence of abnormal visual acuity, hearing impairment and dental carries were higher than in the 2003 national health survey. Additional research is needed to evaluate the health status of the low-income community.

A Case of Krabbe Disease with Infantile Spasm

Krabbe disease is a rare autosomal recessive disorder clinically characterized by retardation in motor development, prominent spasticity, seizures, and optic atrophy. Pathologically, there are many globoid cells in the white matter, in addition to the lack of myelin and the presence of severe gliosis. Hence Krabbe disease is known as globoid cell leukodystrophy. Biochemically, the primary enzymatic deficiency in Krabbe disease is galactocerebroside beta-galactosidase. Patients with Krabbe disease can be subdivided into the early-onset type and late-onset type, according to the onset of clinical manifestations. Most patients with early-onset type die before their second birthday. We describe a girl with Krabbe disease associated with uncontrolled seizures, which was confirmed with biochemical study and MRI. The clinical findings of this patient included hyperirritability, scissoring of the legs, flexion of arm, and clenching of the fists, and generalized tonic seizures. EEG showed hypsarrhythmia, and MRI demonstrated degenerative white matter changes in bilateral periventricular white matter, posterior rim of internal capsule, basal ganglia and brain stem on T2W1 and FLAIR image. The diagnosis was based on clinical features of progressive neurologic deterioration in conjunction with low galactocerebroside beta-galactosidase activity.

Effective Screening Test for Obesity in Obese Adolescents and the Correlation Among Obesity Index, Body Mass Index and Serum Lipid Profile

PURPOSE: Every year, there is a remarkable increase in the prevalence of children with excess body fat. The aim of this study is to find a useful screening method in assessing adolescent, obesity and to specify the predictable risk factors that are related to adult cardiovascular disease according to BMI and obesity index. METHODS: From July to November in 2001, a total of 2,814(male : female=2,011 : 803) mid to high school students who were in the obesity range according to obesity index(>20%) were evaluated according to height, weight, body mass index(BMI), obesity index, and serum lipid levels. RESULTS: Among the obese students over 20% by obesity index, 86.6% were over the range of 95 percentile by BMI. Among students defined as obese by BMI, 21.0% of males and 21.4% of females students had hypercholesterolemia; by obesity index, the ratio was 20.7% male and 19.0% female. The frequency of hypertriglyceremia in male students was 15.0% in group I(overweight group, 85P 97p); in female students 11.8%, 20.7% and 28.2% respectively. CONCLUSION: In this study, using BMI alone to test the serum lipid level in adolescent obesity had a limit of 10.0-17.0% omission. Therefore using obesity index as a screening method to find the adult cardiovascular disease would rather reduce the omission rate. The risk factor of cardiovascular disease according to BMI was the increasing level of triglyceride in both male and female students. We think that using the obesity index has more rationale rather than BMI in assessing lipid profiles.

Relationship between Body Fat Distribution and Metabolic Risk Factors in Adolescents

PURPOSE: The objectives of this study were to estimate the prevalence of obesity in adolescents; to study the association between obesity, blood pressure, and dyslipidemia; and to evaluate the superiority of waist circumference to waist/hip ratio(WHR) in central obesity. METHODS: We selected 1382 adolescents(M : F=690 : 692) aged from 11 to 18 years(mean age; boys15.0, girls 15.4) in Incheon. We measured weight, height, waist, waist/hip ratio, and blood pressure, with blood sampling to evaluate the dyslipidemia. RESULTS: The prevalence of obesity was 6.7% in boys and 6.9% in girls by body mass index(BMI). The prevalence of systolic hypertension was 15.7% in normal group, 32.4% in the overweight group, and 35.4% in the obese group by BMI. The prevalence of diastolic hypertension was 4.9% in the normal group, 6.9% in the overweight group, and 14.6% the in obese group. In boys and girls, BMI, waist circumference, and WHR were positively correlated with systolic and diastolic blood pressure. respectively. In boys, triglyceride was positively correlated with waist circumference(r=0.34, P<0.05). In boys and girls, BMI was highly correlated with obesity index(r=0.98, each), with waist circumference(r=0.89, r=0.82, respectively), and with body fat(r=0.85, r=0.89) respectively. CONCLUSION: These data suggest the importance of the screening of blood pressure in obese adolescents, with prevention and intervention of obesity since it may be the most cost-effective way of reducing the complications related with obesity.

A Case of Rhizomelic Chondrodysplasia Punctata Type I

Rhizomelic chondrodysplasia punctata(RCDP) is a rare autosomal recessive disorder clinically characterized by symmetrical shortening of the proximal limbs, contractures of joints, a typical dysmorphic face, cataracts, and itchyosis. Patients with RCDP can be subdivided into three subgroups based on biochemical analysis and complementation studies. RCDP type I results from mutations in the PEX7 gene encoding the peroxisomal targeting signal type II(PST2) receptors and presents with both a defect in plasmalogen biosynthesis and phytanic acid oxidation. RCDP type II is deficient in the activity of dihydroxyacetonephosphate acyltransferase(DHAP-AT). RCDP type III is deficient in alkyl-dihydroxyacetonephosphate synthase(alkyl-DHAP). We report a case of RCDP type I which was confirmed with biochemical study, fibroblast culture, and gene study.

A Case of Immotile Cilia Syndrome Diagnosed by Lack of Dynein Inner Arms on Electron Microscopy / 소아알레르기및호흡기학회지

Immotile cilia syndrome is an inherited disorder characterized by specific ultrastructural defects of cilia and associated impairment of ciliary motion and mucociliary clearance. Disorders of ciliary structure or function result in chronic sinopulmonary diseases manifested as chronic sinusitis, bronchitis, otitis media, nasal polyposis, and ultimately bronchiectasis. In addition, situs inversus, dextrocardia, and infertility can be associated with dysfunctional ciliary activity. We experienced a case of immotile cilia syndrome presenting with recurrent bronchitis, pneumonia, chronic sinusitis, otitis media, and bronchiectasis. She was diagnosed by lack of dynein inner arm on electron microscopy. Treatment included chest percussion, bronchodilators, antibiotics, and surgical intervention. She has been followed up at regular intervals. We report this case with related literatures.