CDK5-dependent inhibitory phosphorylation of Drp1 during neuronal maturation

Mitochondrial functions are essential for the survival and function of neurons. Recently, it has been demonstrated that mitochondrial functions are highly associated with mitochondrial morphology, which is dynamically changed by the balance between fusion and fission. Mitochondrial morphology is primarily controlled by the activation of dynamin-related proteins including dynamin-related protein 1 (Drp1), which promotes mitochondrial fission. Drp1 activity is regulated by several post-translational modifications, thereby modifying mitochondrial morphology. Here, we found that phosphorylation of Drp1 at serine 616 (S616) is mediated by cyclin-dependent kinase 5 (CDK5) in post-mitotic rat neurons. Perturbation of CDK5 activity modified the level of Drp1S616 phosphorylation and mitochondrial morphology in neurons. In addition, phosphorylated Drp1S616 preferentially localized as a cytosolic monomer compared with total Drp1. Furthermore, roscovitine, a chemical inhibitor of CDKs, increased oligomerization and mitochondrial translocation of Drp1, suggesting that CDK5-dependent phosphorylation of Drp1 serves to reduce Drp1's fission-promoting activity. Taken together, we propose that CDK5 has a significant role in the regulation of mitochondrial morphology via inhibitory phosphorylation of Drp1S616 in post-mitotic neurons.

Use of Behavioral Analysis in Animal Models for Schizophrenia Research / 대한정신분열병학회지

Animal models are useful tools to study the molecular basis of schizophrenia pathophysiology and efficacy of potential therapeutic agents. Schizophrenia animal models can be subdivided into three classes ; drug-induced models, genetic models, and environmental models and each model is designed based on specific traits corresponding to the characteristic symptoms of human schizophrenia patients. Psychomotor agitation and sensitivity to psychotomimetic drugs are often thought to reflect positive symptoms. Social interaction deficits and affective impairments are known to correspond to negative symptoms. Also, cognitive symptoms have been linked to the working memory impairments, attention deficits and related cognitive deficits in animals. To analyze such components in quantifiable manners, various behavioral paradigms have been developed and utilized. Here, we overview these animal models, focusing on underlying rationales for their use in the context of schizophrenia research.

Modulation of lipid metabolism by mixtures of protamine and chitooligosaccharide through pancreatic lipase inhibitory activity in a rat model / 한국실험동물학회지

Overweight and obesity are usually related with high fat and calorie intake, and seriously causative of lifestyle-related diseases such as cardiovascular disorders, arteriosclerosis, and colon cancer. In this study, we propose a novel dietary therapy against overweight and obesity using mixtures of protamine and chitooligosaccharide (COS), which are known to interrupt the lipid metabolism in the body. Protamine is a dietary protein originated from salmon reproductive organ, and COS is an oligosaccharide made from chitin or chitosan by chemical or enzymatic hydrolysis. In the enzyme activity analysis in vitro, protamine and COS strongly suppressed the activity of pancreatic lipase, which is the primary enzyme for the digestion and absorption of lipids in the intestine. In in vivo animal test, the mixtures of protamine and COS significantly reduced the serum levels of triglyceride (TG), total cholesterol (T-CHO), and low density lipoprotein-cholesterol (LDLC) and inhibited the accumulation of lipids in liver tissue of Sprague Dawley (SD) rats fed high fat diets. On the other hand, they increased fecal TG and T-CHO contents. From these alterations in lipid metabolism, we verified that protamine and COS mixtures could effectively interrupt the digestion and absorption of dietary lipids in the body by inhibiting pancreatic lipase activity. In addition, protamine and COS mixtures increased the serum level of high density lipoprotein-cholesterol (HDLC), responsible for removing cholesterol from cells and protecting atherosclerosis, and therefore decreased the potential risks of cardiovascular diseases by lowering values of the atherogenic index (AI) and cardiac risk factor (CRF). Taken together, we suggest protamine and COS mixtures as a prominent dietary therapy for the prevention of overweight, obesity, and further cardiovascular diseases related with hyperlipidemia.

Anxiolytic Effect of a Combination of Green Tea Extract and L-theanine / 한국실험동물학회지

The purpose of this study is to investigate whether the combination of green tea extract (GTE) and L-theanine has an anxiolytic effect by oral administration through behavioral tests and neurtransmitters (or hormone) anaylses. Four week oral administration of GTE (24 mg/kg), L-theanine (4 mg/kg) or their combination showed anxiety-reducing effects determined by increasing numbers of head-dips in a hole board test and reducing retention time in a rota-rod test without changing spontaneous locomotor activity. Biochemical analyses indicated that the test materials decreased dopamine (DA), noradrenaline (NA), corticosterone (CS) and increased serotonin (5-HT) levels in brain cortex, hippocampus, and striatum, which suggests a possible mechanism of previous behavioral tests. Although the synergistic effects of GTE and L-theanine combination were not observed on the behavioral test, its effects on neurotransmitters (NA, CS) were synergistic and comparable to diazepam (2 mg/kg i.p.) with much less muscle relaxation side effect. Therefore, a combination of GTE and L-theanine may be useful as a functional food ingredient having an anxiolytic effect.

Effects of the Mixture of Vitamin C, Vitamin E, Pycnogenol and Evening Primrose Oil on the UV-Induced Pigmentation and Wrinkle Reductions in Human Skin

In this study, the effects of a mixture consisting of vitamin E, vitamin C, pycnogenol and evening primrose oil (mixture LGNC-5) on ultraviolet light (UV) induced pigmentation and wrinkle reductions of normal healthy volunteers were studied. In a double-blind placebo-controlled study, each of 54 subjects took daily either 4 capsules of the mixture LGNC-5 (Group ABC; 282.5 mg/capsule) or placebo (Group Ganada). We irradiated 2.5 MED UV on the upper arms and measured the whitening effect by colorimeter-based L value. The level of wrinkle reduction was determined by image analysis using skin replica around the crow' feet, and the level of serum vitamin E was determined at baseline and 12 weeks. After 12-week oral administration, the treated group showed a significant reduction in skin pigmentation and wrinkles compared with the placebo group (p = 0.011 and p = 0.000005 , respectively). Also, the level of serum vitamin E was significantly increased in the treated group after 12-week oral adminstration of the mixture compared with that in the placebo group (p = 0.0001). In conclusion, 12-week oral administration of LGNC-5 as a dietary supplement could be effective to reduce both UV induced pigmentation and skin wrinkle without side effects.

An Obstetric aspects of RDS of Preterm Infants in Kwang-Ju and Chon-nam / 대한산부인과학회잡지

OBJECTIVES: This study was performed to evaluate obstetric aspects and epidemiologic data of respiratory distress syndrome(RDS) in premature baby(under 37 gestational weeks). We compared the mortality and incidence of RDS in premature baby according to gestational age, birth weight, infant sex, mode of delivery. In addition, this study was searched for demonstrating the influence of hypertensive mother, and effectiveness of surfactant and corticosteoid administration. METHODS: A study was conducted for 2,360 premature baby under 37gestatinal weeks, who were born at four main hospitals in Kwangju and Chonnam from January 1, 1995 to December 31, 1997. Data were collected from hospital records and was analyzed by SPSS computer program. RESULTS: 1. The total incidence of RDS among all the preterm infants under 37gestational weeks, who were admitted in NICU of four hospitals was 22.7%. 2. Neonatal mortality was decreased as the gestational age and or birth weight advanced. (p0.005) 4. The mortality of RDS infants in this study was 28.1%. 5. There was no statistical correlation between neonatal mortality and use of surfactant. 6. Corticosteroids administration to preterm mother did not decrease the incidence of RDS, but, there was no statistical significance due to insufficient study group. 7. The incidence of RDS among the babies of hypertensive mother was 21.0%. CONCLUSION: Still the RDS in premature baby is the most common cause of perinatal death in this country. In our study, the incidence and mortality of RDS in prematue baby was mainly depends on gestational age of infants. Therefore, we suggested that prevention of preterm labor is the important to decrease the incidence and mortality of RDS.

Epidemiologic Study of Preterm Birth in Kwangju and Chonnam(I) / 대한주산의학회잡지

No abstract available.

A Study of Preterm Infants Care in Kwang-Ju and Chon-nam(I) / 대한산부인과학회잡지

OBJECTIVE: To investigate the preterm labor & preterm infants care in Kwangju and Chonam. METHODS: A study was conducted for 2,360 newborns who were born at four main hospitals in Kwangju and chonam from January 1, 1995 to December 31, 1997. Data were collected by review of hospital records. RESULTS: 1. The survival rate was 6.90% at 23~34 weeks, 38.60% at 27~28weeks and 90.67% after 31wks. 2. The survival rate divided according to birth weight were 8.89% below 1,000gm, 57.14% in 1,001~1,500gm, 86.75% in 1,501~2,000gm and 93.37% over 2,000gm respectively. 3. Clinical causes of neonatal death were RDS(48.84%) hyperbilirubinemia (20.74%), sepsis(11.95%) and pneumonia(9.67%). 4. Incidence of RDS was 23.22% and it's neonatal mortality was 36.28%. CONCLUSION: The survival rate of preterm birth in Kwang-Ju and Chon-nam was still lower than data from advancing countries, and main cause of neonatal death was respiratory distress syndrome.

A Clinical Study on Tuberculous Cervical Lymphadenitis / 대한내과학회지

OBJECTIVES: Tuberculous cervical lymphadenitis is one of the common cause of cervical mass in young adult in Korea. Sometimes it appears to be difficult in defining the role of surgery and duration of antituberculous treatment. To clarify the duration of medical treatment and to define the cause of prolonged treatment duration METHODS: we analyzed the clinical data of 62 patients with tuberculous cervical lymphadenitis diagnosed at the Chungnam National University Hospital from Jan. 1994 to July 1996 and all patients were divided into two groups (standard and prolonged) by treatment duration. RESULTS: The most prevalent age group was 20 to 39 years old (67%) and male to female ratio was 1:2.6. The most common physical finding was painless swelling on neck, standard group was 52%, prolonged group was 42%. The average size of lymph node was 2.7cm and 3.2cm, respectively (p<0.05). In prolonged group, incidence of associated pulmonary tuberculosis and previous antituberculous treatment history were higher than that in standard group (27%, 35% respectively). The most common affected site was right side of neck , whereas 19% of prolonged regimen group were involved in both side of neck. Bacteriological study from node aspirates showed relatively higher positivity in prolonged group (27%) than in standarded group (5%). The causes of prolonged treatment were increased mass(27%) or remnant mass(23%) and the develoment of new node formation and existing nodes after completion of treatment were found in both groups(10% of standard group , 19% of prolonged group). CONCLUSION: A new, prospective trial for proper regimens or duration of antituberculosis treatment is strongly needed.

The Study of Combined Treatment in Locally Advanced Non - Small Cell Lung Cancer / 대한내과학회지

BACKGROUND: The majority of patients with locally advanced, unresectable, non-small cell lung cancer(NSCLC) were treated with conventional thoracic radiation therapy Throcic radiation therapy produces tumor regression in most patients but few cures and dismal 5-year survival rate. Several randomized studies have demonstrated that systemic chemotherapy controls micrometastasis and improve survival ratNes for patients who have locally advanced NSCI.C. Hut the optimal frequency of chemotherapy and sequence for chemotherapy and radiotherapy are yet to be determined. In this study, we analyzed response rate, median survival time, side effects and prognostic variables according to the frequency of chemotheray in locally advanced NSCLC patients. METHODS: We separated locally advanced, unresectable, NSCLC patients into two groups according to given number of chemotherapy cycles. Among 28 patients evaluated, eleven patients were classified to group A, receiving above 3 cycled chemotherapy and seventeen patients, classified to group B, receiving 3 cycled chemotherapy. In both groups, thoracic irradiation of 5940 cGy was given to all patients after chemotherapy. RESULTS: 1) Median survival time was 12.9 months for group A, 12.8 months for group B but there was no statistically significant difference(P>0.05), 2) Overall response rates were not significantly different between two groups(P>0.05). 3) Frequency rate of local failure and distant metastasis were not significantly different between two groups (P>0.05). 4) The grade and frequency of toxicities during treatment were not significantly different between two groups (P>0.05). 5) Clinical stage was the only major prognostic factor for overall survival (P<0.05). CONCLUSION: Median survival time, response rate, toxicities and frequency of local failure and distant metastasis were not significantly different between two groups. So, when we treat locally advanced, unresectable, NSCLC patients in sequential combined treatement, we should consider planned therapy(limiting chemotherapy cycles given), because planned therapy reduces many troubles of patients, that is, economic loss and time consuming, psychiatric anxiety etc, during treatment period. The optimal frequency of chemotherapy is remained to be validated in large scale study in the future in the setting of combined treatment.

The effects according to the timing of thoracic radiotherapyin limited stage small cell lung cancer / 결핵

Background: Combination chemotherapy is now considered to be the cornerstone of small cell lung cancer (SCLC). management but the optimal management of limited SCLC is not well defined. The role of thoracic radiotherapy (TRT) is less well established. Recent meta-analyses reports revealed that TRT combined with chemotherapy produce "good" local control and prolonged survival. But other reports that survival was not changed. The timing, dose, volume and fractionation for TRT with the combined chemotherapy of SCLC remains unsettled. In this study, we analyzed the effects according to the timing of thoracic radiotherapy in limited SCLC. Method: All fifty one patients received cytoxan, adriamycin and vincristine(CAV) alternating with etoposide and cisplatin(VPP) every 3 weeks for 6 cycles were randomized prospectively into two groups: concurrent and sequential. 27 patients received 4500cGy in 30 fractions(twice daily 150cGy fractional dose) over 3 weeks to the primary site concurrent with the first cycle of VPP(concurrent gorup). 24 patients received 4000 to 5000cGy over 5 or 6 weeks after completion of sixth cycles of chemotherapy(sequential group). Results: 1. Response rates and response duration: Response rates were not significantly different between two groups(p=0.13). But response duration was superior in the concurrent group(p=0.03). 2. Survival duration was not different between two groups(p=0.33). 3. Local control rate was superior in the concurrent group(p=0.00). 4. Side effects and toxicities: Hematologic toxicides, especially leukopenia, infection and frequency of radiation esophagitis were higher in the concurrent group(p=0.00, 0.03, 0.03). Conclusion: The concurrent use of TRT with chemotherapy failed to improve the survival of limited stage SCLC patients compared with the sequential use of TRT but response duration and local control rate were superior in the concurrent group. Frequency of radiation esophagitis, life threatening hematologic toxicities and infection were more frequent in the concurrent group than sequential group. So, the selection of an optimal schedule of chemotherapy combined with TRT that would lead to a major increase in survival with minimal toxicity is remained to be validated in large scale study in the future.

A Case of EIEE (Early Infantile Epileptic Encephalopathy)

The EIEE is defined by very early onest, within the first few months of life. Frequent tonic spasms, and suppression burst of EEG pattern in both waking and sleeping state. Its etiology and underlying pathology are obscure. The prognosis is usually grave with severe psychomotor retardation and intractable seizures. Occassionaly it may evolve into the West syndrome. We report a case of 3-month-old female delivered by Casesarean section, who showed typical features of EIEE disorder, with the review of literatures.