BACKGROUND: Glucagon-like peptide-1 (GLP-1) is an incretin hormone produced by cleavage of proglucagon in intestinal L-cells. In the pancreas, GLP-1 stimulates post-prandial insulin secretion, promotes insulin biosynthesis, and improves insulin sensitivity. Because of its insulinotropic activity, GLP-1 has been considered a good candidate drug for treatment of diabetes mellitus. However, clinical use of GLP-1 has been limited by its short half-life, as a result of rapid degradation by dipeptidyl peptidase-IV (DPP-IV). METHODS: We designed a novel GLP-1 analog, Xenopus GLP-1 (xGLP)-E4. The Ala residue in the second position of xGLP was replaced with a Ser residue to increase the half-life in the body. The C-terminal tail of exendin-4 was added to enhance the binding affinity for the GLP-1 receptor (GLP1R). The potency of GLP-1 and its analogs was determined by luciferase assay. The stability of GLP1R agonists was evaluated by determining the activity of agonists that had been preincubated in the presence of fetal bovine serum, which contains innate DPP-IV activity. The effects of xGLP-E4 on insulin secretion and beta-cell growth were investigated using insulin enzyme-linked immunosorbent assay and cell counting. RESULTS: xGLP-E4 exhibited improved stability against DPP-IV activity and increased potency to GLP1R, compared with GLP-1. An increase in glucose-dependent insulin secretion was observed in xGLP-E4-treated pancreatic beta-cells. The effect of xGLP-E4 on beta-cell growth was greater than that of GLP-1. CONCLUSION: We developed a novel GLP-1 analog, xGLP-E4, that shows prolonged longevity and improved efficacy. This analog is a potential candidate for treatment of type 2 diabetes.
Cell Count ; Diabetes Mellitus ; Enzyme-Linked Immunosorbent Assay ; Glucagon-Like Peptide 1* ; Half-Life ; Incretins ; Insulin Resistance ; Insulin* ; Longevity ; Luciferases ; Pancreas ; Proglucagon ; Xenopus ; Glucagon-Like Peptide-1 Receptor

OBJECTIVE: This study is intended to identify predictive factors of delirium, including risk factors and prodromal symptoms. METHODS: This study included sixty-five patients aged 65 years or older who had undergone hip surgery. Baseline assessments included age; gender; admission type (acute/elective); reason for surgery (fracture/replacement); C-reactive protein (CRP); Acute Physiology, Age, Chronic Health Evaluation (APACHE III); and the Mini-Mental State Examination (MMSE). The Korean version of the Delirium Rating Scale-Revised-98 (K-DRS-98) was used to assess prodromal symptoms daily before the onset of delirium. RESULTS: Almost 28% (n=18) of the 65 patients developed delirium after surgery. Delirium in elderly patients after hip surgery was observed more often in older patients and those with acute admission, hip fracture, higher APACHE III score, lower MMSE score, and higher CRP levels within early days after the operation. Sleep-wake cycle disturbances, thought process abnormalities, orientation, and long-term memory in symptom items of K-DRS-98 were showed significant difference on 4 days before delirium, lability of affect on 3 days before, perceptual disturbances and hallucination, and visuo-spatial ability on 2 days before, and delusion, motor agitation, and short-term memory on the day before the occurrence of delirium. CRP levels within 24 hours and 72 hours after hospitalization were significantly higher in the delirium group. CONCLUSION: Medical professionals must pay attention to behavioral, cognitive changes and risk factors in elderly patients undergoing hip surgery and to the prodromal phase of delirium. K-DRS-98 may help in identifying the prodromal symptoms of delirium in elderly patients after hip surgery.
Aged ; APACHE ; C-Reactive Protein ; Delirium ; Delusions ; Dihydroergotamine ; Hallucinations ; Hip ; Hospitalization ; Humans ; Memory, Long-Term ; Memory, Short-Term ; Orientation ; Prodromal Symptoms ; Risk Factors

BACKGROUND: Inflammation in the brain has known to be associated with the development of a various neurological diseases. The hallmark of neuro-inflammation is the activation of microglia, brain macrophage. Pro-inflammatory compounds including nitric oxide (NO) are the main cause of neuro-degenerative disease such as Alzheimer's disease (AD) which is resulted in cell death. Among those pro-inflammatory compounds, NO contributes to the cell death by directly or indirectly. METHODS: In the study, we examined whether ursodeoxycholic acid (UDCA), a non-toxic hydrophilic bile acid, inhibits the NO production by a direct method using Griess reagent and by RT-PCR in the gene expression of inducible nitric oxide synthase (iNOS). In signal transduction, we also examined the NF-kappa B (p65/p50), IKK, and Ikappa B, which are associated with the expression of iNOS gene using western blots. RESULTS: In the present study, we found that UDCA effectively inhibited NO production in BV-2 microglial cell, and NF-kappa B activation was reduced by suppressing IKK gene expression and by increasing the Ikappa B in cytosol comparing those to the positive control LPS. CONCLUSION: Taken together, these data suggested that UDCA may play a crucial role in inhibiting the NO production and the results imply that UDCA suppresses a cue signal of the microglial activation via stimulators, such as beta-amyloid peptides which are known to stimulate microglia in AD pathogenesis.
Alzheimer Disease ; Bile ; Blotting, Western ; Brain ; Cell Death ; Cell Line* ; Cues ; Cytosol ; Gene Expression ; Inflammation ; Macrophages ; Microglia ; NF-kappa B ; Nitric Oxide ; Nitric Oxide Synthase Type II ; Peptides ; Signal Transduction ; Ursodeoxycholic Acid*

OBJECT: It is reported that the effect of antipsychotics on the extracellular dopamine levels in the prefrontal cortex is related to the their effect on the negative symptoms. Therefore, we investigated the acute and chronic effects of olanzapine and risperidone on the extracellular dopamine concentrations in the prefrontal cortex of rat. Samples were obtained using in vivo brain microdialysis. METHOD: Dopamine levels in the samples were measured by high pressure liquid chromatography with electrochemical detection. RESULTS: 1) Both the acute treatment of olanzapine and risperidone increased the extracellular dopamine concentrations in the prefrontal cortex, dose-dependently. 2) There was a no significant difference in the maximal change of the extracellular dopamine concentrations in the prefrontal cortex induced by the acute treatment of olanzapine and risperidone. 3) Both the chronic treatment of olanzapine and risperidone also increased the extracellular dopamine concentrations in the prefrontal cortex, but they showed the tolerance effect that the degree of increase was smaller than that of the acute treatment. 4) As for the maximal changes of the extracellular dopamine concentrations in the prefrontal cortex induced by the chronic treatment of olanzapine and risperidone, the effect of the former was greater than that of the latter. CONCLUSION: These results suggest that the effects of olanzapine and risperidone on the negative symptoms are related to the increased extracellular dopamine concentrations in the prefrontal cortex induced by these drugs.
Animals ; Antipsychotic Agents ; Brain ; Chromatography, Liquid ; Dopamine* ; Microdialysis ; Prefrontal Cortex* ; Rats* ; Risperidone*

PURPOSE: To evaluate the efficacy of physical examination and dynamic arthroscopy in the diagnosis and treatment of medial patellar plica syndrome which is likely to be overlooked. SUBJECTS AND METHODS: 23 cases diagnosed as medial patellar plica syndrome from August 1998 through December 1999 were evaluated. Diagnosis was made by a symptom of a pain and a click sound during knee flexion, a physical examination of mass palpation and dynamic arthroscopy. RESULT: A dynamic rotation test was an useful physical examination having 96% rate of sensitivity. The results of excellent and good cases were in 19 cases (83%) and there was no worsened case symptomatically after arthroscopic resection. Postoperative complications were 3 cases including incomplete excision (1 case), postoperative hemarthrosis (1 case) and medial meniscus instability due to incorrect arthroscopic technique (1 case). In patients younger than 30 year old, the result of arthroscopic excision was better than that in older ones. CONCLUSION: Careful physical examination with dynamic arthroscopy is a useful method to diagnose the medial patellar plica syndrome which is likely to be overlooked, and arthroscopic complete excision result in excellent results which is of benefit to fast rehabilitation.
Adult ; Arthroscopy ; Diagnosis* ; Hemarthrosis ; Humans ; Knee* ; Menisci, Tibial ; Palpation ; Physical Examination ; Postoperative Complications ; Rehabilitation

Hepatoid adenocarcinoma is a rare variant of adenocarcinoma that can occur in the stomach. This neoplasm has a poor prognosis and it frequently presents at an advanced stage of disease; it is clinically characterized by increased serum levels of alpha-fetoprotein (AFP) in most cases. We experienced a case of hepatoid adenocarcinoma of the stomach with multiple liver metastases that mimicked germ cell tumor in a 43-year-old man. He had incidentally detected gastric adenocarcinoma via gastrofibroscopy and he underwent subtotal gastrectomy. The postoperative pathologic stage was II (T2N1M0). He complained of epigastric pain. The serum AFP was markedly increased (227,325 IU/mL) and abdominal CT revealed multiple liver masses. We considered these as extragonadal germ cell tumors that occurred in the liver because of the markedly elevated AFP, the short duration of follow-up and early stage of stomach cancer at the that time. To confirm the diagnosis, biopsy of liver mass was done and he was diagnosed with hepatoid adenocarcinoma.
Adenocarcinoma* ; Adult ; alpha-Fetoproteins ; Biopsy ; Diagnosis ; Follow-Up Studies ; Gastrectomy ; Germ Cells* ; Humans ; Liver ; Neoplasm Metastasis ; Neoplasms, Germ Cell and Embryonal* ; Prognosis ; Stomach ; Stomach Neoplasms ; Tomography, X-Ray Computed

BACKGROUND/AIMS: Various techniques of hepatocyte transplantation were actively studied as an alternative to liver transplantation, because of the difficulty of obtaining donor organ, technical difficulties, and high cost. Isolated hepatocytes could be appropriately banked and distributed on demand. We tried to investigate the effect of intrasplenic transplantation of allogenic cryopreserved hepatocytes, into spleen prior to 90% partial hepatectomy in rats, on the survival rate. METHODS: Cryopreserved hepatocytes, isolated by collagenase perfusion of the liver via the portal vein, were thawed and transplanted into the spleen of rats prior to induction of acute hepatic failure by resection of all lobes except caudate lobe (2.0x107 hepatocytes/rat). RESULTS: 1. The viability of freshly isolated hepatocyte was 70-5%, but cell viability after cryopreservation 30-0%. 2. Difference of survival in control and transplant group is not statistically significant. but the survival rate, 48 hours after 90% partial hepatectomy, for control (7) and transplanted group (11) were 0% and 18%, respectively. 3. Although the glucose reduction gradient was not significantly different between two groups, it was more prominent in the control group than in the transplanted group. 4. Engraftment and survival of transplanted hepatocytes were noted in the spleen 2 days after transplantation. CONCLUSIONS: We could not observe statistically significant improvement of survival with intrasplenic transplantation of cryopreserved hepatocytes in rats with 90% partial hepatectomy-nduced acute liver failure. However, 18% survival after 90% partial hepatectomy was noted in the transplanted group, compared to no survival in the control group. This suggests that intrasplenic transplantation of cryopreserved hepatocytes might be effective in the treatment of acute liver failure.
Animals ; Cell Survival ; Collagenases ; Cryopreservation ; Glucose ; Hepatectomy ; Hepatocytes* ; Humans ; Liver ; Liver Failure, Acute ; Liver Transplantation ; Perfusion ; Portal Vein ; Rats* ; Spleen ; Survival Rate ; Tissue Donors

PURPOSE: To evaluate the plain radiographic findings of bone and joint changes following electrical burn. MATERIALS AND METHODS: This study involved 19 patients with 27 bone and joints regions which had sufferedelectrical injury. The most common input and output sites were, respectively, the hand(7/14) and foot (6/10).Three other sites were involved. Four cases involved osteomyelitis, and in four, amputation was performed. Weobserved bone and joint changes, changes following osteomyelitis and changes in the amputation stump. We analyzedthe difference between input and output changes, and when this was interesting, the average time of onset wasassessed. RESULTS: In bone and joint changes following electrical burn, the most frequent radiographic findingwas joint contracture (n=16). Other findings included osteolysis (n=8), articular abnormalites (n=6), periostitis(n=5), fracture (n=5), acro-osteolysis (n=2), and heterotopic bone formation (n=2). In cases involvingosteomyelitis(n=4), aggravation of underlying bone changes was noted. CONCLUSION: In electrical burn, variouschanges were noted in bone and joints, and input injury was more severe than that of output.
Acro-Osteolysis ; Amputation ; Amputation Stumps ; Burns* ; Contracture ; Foot ; Humans ; Joints* ; Osteogenesis ; Osteolysis ; Osteomyelitis

PURPOSE: The purpose of this study was to describe the clinical and MR imaging features of acute gouty arthritis and to define the characteristic findings that would be helpful for differentiating acute gouty arthritis from septic arthritis. MATERIALS AND METHODS: The authors retrospectively studied seven patients who suffered from acute gouty arthritis. The MR imaging findings were analyzed by two musculoskeletal radiologists who focused on joint effusion, subchondral bone erosion, bone marrow edema, synovial thickening (regular and even, or irregular and nodular), and the soft tissue changes (edema or abscess). The clinical records of the patients were reviewed with regard to age and gender, the clinical presentation and the laboratory findings (serum uric acid, WBC, erythrocyte sedimentation rate, C-reactive protein and synovial fluid culture). RESULTS: The patients consisted of six men and one woman whose mean age was 41 years (age range: 24-65 years). The joints involved were the knee (n=6), and ankle (n=1). Two patients had medical histories of gouty attacks that involved the first metatarsophalangeal joint. In six cases, the serum uric acid level during acute attacks was elevated. In all the patients, the affected joint became swollen, hot, erythematous and extremely tender, and this was accompanied by a high ESR and a high C-reactive protein level at the time of presentation. The results of Gram stain and culture of the synovial fluid were negative. In all patients, the MR images showed large amounts of joint effusion, thick irregular and nodular synovial thickening and soft tissue edema without subchondral bone erosions and soft tissue abscess. In one case, subchondral bone marrow edema of the medial femoral condyle was present. In five cases, there were multiple low signal foci in the joint on the spin-echo T2-weighted MR image. CONCLUSION: Even though the MR imaging findings of acute gouty arthritis are nonspecific, it should be considered as a possible diagnosis when a large amount of joint effusion, irregular and nodular synovial thickening and soft tissue edema without subchondral bone erosion, bone marrow edema or soft tissue abscess are seen in the knee or ankle joint, and especially if this is accompanied by the clinical and laboratory features of infection.
Abscess ; Ankle ; Ankle Joint ; Arthritis ; Arthritis, Gouty* ; Arthritis, Infectious ; Blood Sedimentation ; Bone Marrow ; C-Reactive Protein ; Diagnosis ; Edema ; Female ; Gout ; Humans ; Joints ; Knee ; Magnetic Resonance Imaging* ; Male ; Metatarsophalangeal Joint ; Retrospective Studies ; Synovial Fluid ; Uric Acid

OBJECTIVE: We analyzed the gene status of p16INK4A, p18INK4C, the expression of cell cycle associated proteins (p16INK4A, p18INK4C, cyclin D1, CDK4, pRb, and p53), and human papillomavirus (HPV) infection to investigate whether the inactivation of these genes participated in carcinogenesis, and to evaluated the expression of cell cycle associated proteins and HPV infections. METHODS: We examined forty-one primary cervical carcinomas (17 adenocarcinomas, 13 keratinizing squamous cell carcinomas, and 11 nonkeratinizing squamous cell carcinomas) using PCR, comparative multiplex PCR, PCR-SSCP, methylation-specific PCR, and immunohistochemistry. RESULTS: Ninety percent of cervical carcinomas showed HPV infection. HPV type 16 was detected in 41% and HPV type 18 was found in 44%. Homozygous deletions at p16INK4A gene were observed in 2 cases, but the mutation of p16INK4A and alterations of p18INK4C gene were not detected. The promoter hypermethylation for p16INK4A in nine cases (31%) of 29 cervical carcinomas was found. Expression of p16INK4A protein was observed in 93% and p18INK4C protein expression was noted in 78%. Positive immunostaining for cyclin D1 was only identified in 5%, whereas positive immunostaining for CDK4 was observed in 95%. Expression of pRb protein was found in 93% and p53 protein in 24% of cervical carcinomas. CONCLUSION: These results suggest that high risk HPV infections and methylation of the p16INK4A promoter region seem to play an important role in the pathogenesis of cervical carcinomas. Alterations of p18INK4C gene and cyclin D1-CDK4 pathway does not contribute significantly in the cervical carcinogenesis.
Adenocarcinoma ; Carcinogenesis ; Carcinoma, Squamous Cell ; Cell Cycle* ; Cyclin D1 ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p18 ; Cyclins ; Genes, p16 ; Humans* ; Immunohistochemistry ; Methylation ; Multiplex Polymerase Chain Reaction ; Papillomavirus Infections* ; Polymerase Chain Reaction ; Promoter Regions, Genetic