Nocodazole is an anticancer agent that acts on microtubules or filaments. HeLa, Hep G2, A549, L929 and NIH/3T3 cell lines were cultivated in alpha-MEM with 3micrometer or 30micrometer nocodazole. To elucidate the associations between nocodazole`s antitumor actions and these effects, the influences of nocodazole on the cellular morphology and the organelles involving synthesis, secretion and destruction of proteins were investigated under light and electron microscopes. The changes of intermediate filaments such as pancytokeratins and vimentins that maybe suggest antimetastatic action of nocodazole were observed using immunocytochemical technique, PAP at light microscopic level. Rounded or micronucleate cells were induced by treatment with 3micrometer and 30micrometer nocodazole for 2 hours to 4 days. Multimicronucleate cells appeared in experimental groups of all cell lines. Nuclear foldings occurred in cells of experimental groups treated with nocodazole for 2-3 days. The numerical increases of rough endoplasmic reticulum were observed in HeLa cells treated with nocodazole for 3 days and the dilatation or numerical increases in L929 cells treated with nofodazole for 1-3 days. The fragmentations or dispersion of Golgi complex were observed in cells treated with nocodazole for 1-3 days. The amount of filaments increased in cells treated with nocodazole for 1-3 days. The number of lysosomes increased in cells treated with nocodazole for 1-3 days. The number of liposomes also increased in Hep G2 cells treated with 30micrometer nocodazole for 3 days and in 3micrometer & 30micrometer, 3 days group of 3T3 cells. The amount of pancytokeratins and vimentins increased in cells treated with nocodazole for 1-3 days. Taken together, depolymerization of microlubules was induced by nocodazole, and then the organization of cells was disintegrated. As a result, the rounded cells, the cells having multimicronuclei, and the changes of golgi complexes occurred. But there were relatively no great changes of rough endoplasmic reticulum. The amount of intermediate filaments that maintain the differentiated states of cells increased by nocodazole treatment. It was suggested that morphological changes of cells could be used in evaluation of actions of nocodazole. Especially, the increase of amount of intermediate filaments by nocodazole changed cells of each cell line from undifferentiated state to differentiated, and therefore the author hope that the changes in amount of intermediate filaments provide an important clue in anticancer and antimetastatic actions of nocodazole.
3T3 Cells ; Animals ; Cell Line ; Dilatation ; Endoplasmic Reticulum, Rough ; Golgi Apparatus ; HeLa Cells ; Hep G2 Cells ; Hope ; Humans ; Intermediate Filaments ; Liposomes ; Lysosomes ; Mice ; Microtubules ; Nocodazole* ; Organelles ; Vimentin

This study was designed to examine the effects of two antidepressant drugs on the expression of c-fos mRNA in cultured embryonic rat hippocampal neurons. The drugs used were imipramine and amitriptyline. On the fourth day of culture, hippocampal neurons were treated with variable concentrations of each drug. Competitive RT-PCR(Reverse Transcriptase-PCR) analysis was used to quantify the c-fos mRNA expression induced by each drug. Experimental results showed that acute and direct treatment with imipramine and amitriptyline with relatively low concentrations(imipramine < or =10micrometer, amitriptyline < or =10micrometer) had no inductive effect on the expression of c-fos mRNA in the rat hippocampal neurons. However, after treatment with relatively high concentrations(imipramine > or =100micrometer, amitriptyline > or =100micrometer) c-fos mRNA was not detected. These findings suggest the followings. Firstly, the action mechanisms of these drugs on the hippocampal neurons might not be mediated by c-fos but by other immediate-early genes(IEGs). Secondly, their actions may be mediated indirectly via other areas of the brain. Thirdly, the expression of c-fos might be inhibited by high concentrations of these drugs, or the high concentrations could induce cell death. Finally, though cell death remains to be confirmed, the inhibition of c-fos induction or cell death could play a role in the cognitive impairments known to be adverse effects of some antidepressants. This study is believed to be a first step toward understanding the mechanisms of learning and memory. Further studies are needed to investigate the expression of various IEGs and changes in the hippocampal neurons of rat resulting from chronic treatment with antidepressant drugs.
Amitriptyline ; Animals ; Antidepressive Agents* ; Brain ; Cell Death ; Imipramine ; Learning ; Memory ; Neurons* ; Rats* ; RNA, Messenger*

PURPOSE: Most recently developed anti-adhesive membranes are not suitable for laparoscopic surgery due to weak mechanical properties or adhesive characteristics. To overcome these problems, we prepared electrospun bioabsorbable nanofibrous poly (lactic-co-glycolic acid)-based membranes as an adhesion barrier. We evaluated the efficacy and safety of this material for laparoscopic surgery in a rabbit model. METHODS: A standardized laparoscopic surgical trauma was made on the rabbit's uterine horn and adjacent abdominal wall to induce adhesion formation. The injured uterus was covered by a nanofibrous barrier or it was left untreated (the negative control group) (each group: n=14). To evaluate acute toxicity of this material, blood sampling was made 3 and 7 days after laparoscopic surgery to check liver and renal function. Three weeks after laparoscopy, a second look laparoscopy was performed and the adhesions were scored according to Blauer's scoring system. Tissue between abdominal wall and uterus was obtained to examine microscopically. Liver, kidney and uterus were harvested to examine chronic toxicity. RESULTS: 36.4% of the nanofiber treatment group and 70% of the untreated control group showed severe adhesions (grade>3) after laparoscopic surgery but failed to get a statistical significance (P=0.198). Acute and chronic toxicity induced by this material were not noted in the blood and tissue exam. CONCLUSION: This study showed that nanofiber barrier seems to be a novel resorbable biomaterial for the reduction of postoperative adhesions. Easy placement and handling of this material make these membranes potentially successful candidates for laparoscopic surgery. But further study is needed to get a statistical significance.
Abdominal Wall ; Adhesives ; Animals ; Handling (Psychology) ; Horns ; Kidney ; Laparoscopy ; Liver ; Membranes ; Nanofibers ; Uterus

PURPOSE: Guardix-sol(TM) is solution type of anti-adhesion barrier, and it is composed of a mixture of hyaluronate (HA) and carboxymethylcellulose (CMC). The anti-adhesive effect was proved through several clinical trials with using this material, but the most efficient viscosity for this solution has not been shown by the previous research. The objective of this study was to evaluate the efficacy and safety of HA/CMC mixture solutions, with varying viscosities, in a rat model. METHODS: Three different viscosities (low=LV, mid=MV and high=HV) of the HA/CMC mixture solutions were prepared to evaluate their potential as a tissue adhesion barrier. The viscosity was measured by a Brookfield viscometer. To evaluate the anti-adhesion effect, a cecal-abdominal wall abrasion model was adopted. The denuded cecum was coated by a HA/CMC mixture of different viscosity or it was left uncoated (the negative control group) and then the denuded cecum was apposed to the abdominal wall (each group: n=10). All the rats underwent a second celiotomy after 14 days to evaluate the extent of their abdominal adhesions and tissue reactions (inflammatory response, granulation tissue formation and toxicity in organs). RESULTS: The viscosities of the HA/CMC mixture solutions were 248.+/-24.4 cps in the LV, 1,353.8+/-4.4 cps in the MV and 3,556.7+/-38.8 cps in the HV. The grade of adhesion and the adhesion area were significantly lower in the all HA/CMC mixture solution groups compared to the control regardless of their viscosity. The inflammatory responses were not remarkable at the application site and the major solid organs did not show histological change in the experimental groups. CONCLUSION: The difference of viscosity of HA/CMC mixture solutions did not affect the efficacy of the adhesion barrier. All the HA/CMC mixture solutions with varying viscosities showed a low inflammatory response and non-toxicity.
Abdominal Wall ; Animals ; Carboxymethylcellulose Sodium ; Cecum ; Granulation Tissue ; Rats ; Tissue Adhesions ; Viscosity

PURPOSE: Guardix-sol(TM) is solution type of anti-adhesion barrier, and it is composed of a mixture of hyaluronate (HA) and carboxymethylcellulose (CMC). The anti-adhesive effect was proved through several clinical trials with using this material, but the most efficient viscosity for this solution has not been shown by the previous research. The objective of this study was to evaluate the efficacy and safety of HA/CMC mixture solutions, with varying viscosities, in a rat model. METHODS: Three different viscosities (low=LV, mid=MV and high=HV) of the HA/CMC mixture solutions were prepared to evaluate their potential as a tissue adhesion barrier. The viscosity was measured by a Brookfield viscometer. To evaluate the anti-adhesion effect, a cecal-abdominal wall abrasion model was adopted. The denuded cecum was coated by a HA/CMC mixture of different viscosity or it was left uncoated (the negative control group) and then the denuded cecum was apposed to the abdominal wall (each group: n=10). All the rats underwent a second celiotomy after 14 days to evaluate the extent of their abdominal adhesions and tissue reactions (inflammatory response, granulation tissue formation and toxicity in organs). RESULTS: The viscosities of the HA/CMC mixture solutions were 248.+/-24.4 cps in the LV, 1,353.8+/-4.4 cps in the MV and 3,556.7+/-38.8 cps in the HV. The grade of adhesion and the adhesion area were significantly lower in the all HA/CMC mixture solution groups compared to the control regardless of their viscosity. The inflammatory responses were not remarkable at the application site and the major solid organs did not show histological change in the experimental groups. CONCLUSION: The difference of viscosity of HA/CMC mixture solutions did not affect the efficacy of the adhesion barrier. All the HA/CMC mixture solutions with varying viscosities showed a low inflammatory response and non-toxicity.
Abdominal Wall ; Animals ; Carboxymethylcellulose Sodium ; Cecum ; Granulation Tissue ; Rats ; Tissue Adhesions ; Viscosity

BACKGROUND: Serum lactate is a potentially useful biomarker to risk-stratify patients with severe sepsis and septic shock. However, there are only a few studies on the association of serum lactate levels and prognosis in septic shock patients with initial low lactate levels. METHODS: To evaluate whether initial and follow-up lactate levels associated with mortality in septic shock patients with low lactate level, we conducted a retrospective observational study of patients with septic shock, who were hospitalized through the emergency department in February-July 2008. Initial lactate level was stratified as low (<4 mmol/L) or high (> or =4 mmol/L). The primary outcome was 28-day mortality and multiple logistic regression analysis was used to adjust for potential confounders in the association between lactate clearance and mortality. RESULTS: Of 90 patients hospitalized with septic shock during the study period, 68 (76%) patients had low initial lactate. Mortality at 28 days was 18% in patients with low lactate level. In these patients, initial lactate level was not associated with mortality (p = 0.590). However, increased lactate at follow-up and lactate clearance were associated with mortality (p = 0.006, p = 0.002, respectively). In a multiple logistic regression analysis, increased mortality rate independently associated with age (OR 1.162, 95% CI 1.041-1.298) and lactate clearance (OR 0.654, 95% CI 0.498-0.859). CONCLUSIONS: In septic shock patients with a low lactate level, lactate clearance independently associated with a decreased mortality rate. Therefore, lactate clearance could be useful for predicting the outcome in these patients.
Emergencies ; Follow-Up Studies ; Humans ; Lactic Acid ; Logistic Models ; Prognosis ; Retrospective Studies ; Sepsis ; Shock, Septic

PURPOSE: The occurrence of post-surgical adhesion is still a major cause of postoperative morbidity due to the lack of satisfactory treatment or prophylaxis. Several adhesion barriers have been developed in the form of solutions or membrane in an attempt to solve these problems. However both types of tissue barriers have some limitations in their practical applications. In order to overcome these problems, a temperature-sensitive Poloxamer/Alginate/CaCl2 mixture was prepared as an adhesion barrier. With this material, toxicity, inflammation and the adhesion prevention effect was evaluated in an animal model. METHODS: The sol-gel transition behavior was measured using a viscometer. An in vitro gel stability test and an in vivo degradation test was performed. The anti-adhesion effect was evaluated using a cecal-abdominal wall abrasion model. The denuded cecum was coated with Poloxamer/ Alginate/CaCl2 mixture, GUARDIX-SL (positive control group) or neither (negative control group) and apposed to the abdominal wall (each n=14). One week after surgery, the level of adhesion was graded from zero to three using a whole-number system. RESULTS: The LCST of the poloxamer/sodium alginate mixture was 25 degrees C. The gel stability of Poloxamer was improved by adding mild cross-linked sodium Alginate/CaCl2 mixture. The adhesion grade and area were significantly lower in the experimental group than in the control. CONCLUSION: The anti-adhesive effect of the Poloxamer/Alginate/CaCl2 mixture was comparable to the previously- developed solution type barrier and all the materials had degraded within 21 days. From these results, Poloxamer/ Alginate/CaCl2 mixture is a good candidate for use as a coatable or injectable tissue adhesion barrier.
Abdominal Wall ; Animals ; Cecum ; Inflammation ; Membranes ; Models, Animal* ; Poloxamer ; Rats* ; Sodium ; Tissue Adhesions

PURPOSE: The optimal treatment regimen for Mycobacterium avium complex (MAC) lung disease has not yet been fully established. We evaluated the efficacy of standardized combination antibiotic therapy and the factors that might affect unfavorable microbiologic responses in patients with MAC pulmonary disease. MATERIALS AND METHODS: This retrospective study reviewed data from 96 patients (56 females; median age 59 years) treated with newly diagnosed MAC lung disease between January 2003 and December 2006. RESULTS: All patients received standardized combination antibiotic therapy, consisting of clarithromycin, rifampicin, and ethambutol. Streptomycin was additionally given in 72 patients (75%) for a median duration of 4.5 months. The overall favorable microbiologic response rate was 79% (76/96); 20 patients (21%) had unfavorable microbiologic responses, including failure to sputum conversion (n = 13), relapse (n = 3), and MAC-related death (n = 4). A positive sputum acid-fast bacillus smear at the start of treatment was an independent predictor of an unfavorable microbiologic response. CONCLUSION: Standardized combination antibiotic therapy consisting of clarithromycin, rifampicin, and ethambutol with or without initial use of streptomycin is effective in treating patients with newly diagnosed MAC lung disease.
Aged ; Anti-Bacterial Agents/*therapeutic use ; Clarithromycin/therapeutic use ; Drug Therapy, Combination/*methods ; Ethambutol/therapeutic use ; Female ; Humans ; Lung Diseases/*drug therapy/*microbiology ; Male ; Middle Aged ; Mycobacterium Infections/*drug therapy ; Mycobacterium avium/*metabolism ; Retrospective Studies ; Rifampin/therapeutic use ; Streptomycin/therapeutic use ; Treatment Outcome

Many neoplasms, including lung cancer, breast cancer, melanoma, and gastrointestinal tract malignancy, possess potential for skin metastasis. Skin metastases can represent the first presentation of such malignancies and may be observed incidentally during routine exam. Skin metastases from gastric adenocarcinoma are uncommon, with a prevalence rate of 0.04-0.8%. Cutaneous metastases from gastric cancer are generally observed as the initial symptom of advanced gastric cancer. Early detection and treatment can increase patient survival. A 42-year-old woman visited our department with nodule about 1 cm in size on the right frontal scalp noticed incidentally after laparoscopy-assisted distal gastrectomy and adjuvant systemic chemotherapy for early gastric cancer about 16 months prior. The patient was diagnosed with skin metastasis from gastric adenocarcinoma. Complete excision of the skin lesion and additional chemotherapy were performed. Herein, we report a case of nodular tumor-like scalp metastasis from early gastric cancer with a brief review of the literature.
Adenocarcinoma ; Adult ; Breast Neoplasms ; Drug Therapy ; Female ; Gastrectomy ; Gastrointestinal Tract ; Humans ; Lung Neoplasms ; Melanoma ; Neoplasm Metastasis* ; Prevalence ; Scalp* ; Skin ; Stomach Neoplasms*

The proliferation of residual lens epithelial cells following cataract surgery is assumed to be a major cause of posterior capsular opacification. To assess the efficacy of mitomycin-C in preventing posterior capsular opacification, we determined the effective concentration and exposure time of mitomycin-C in inhibiting rabbit lens epithelial cell proliferation. The fourth-passaged rabbit lens epithelial cells were maintained for one day and then exposed to mitomycin-C for 1, 2, 3, and 5 minutes, respectively. There were 9 different plating concentrations of mitomycin-C with two-fold serial dilution. The maintenance of the phenotypic properties of lens epithelial cells was confirmed by continuous transcription of lambda-crystalline mRNA determined by reverse transcription-polymerase chain reaction and the polymorphism of the restriction fragment. Cell proliferation was assayed with 3H-thymidine incorporation into DNA. The fourth-passaged cells maintained the expression of lambda-crystalline mRNA, suggesting that they are phenotypically authentic lens epithelial cells. The effective concentrations and exposure time of mitomycin-C were 0.1 mg/ml for 1 minute and 2 minutes, and 0.025 mg/ml for 2 minutes. By these results, we postulated that mitomycin-C at relatively short incubation times could be clinically used for prevention of posterior capsular opacification after cataract surgery.
Animal ; Antibiotics, Antineoplastic/pharmacology* ; Cell Division/drug effects ; Cells, Cultured ; DNA/biosynthesis ; Dose-Response Relationship, Drug ; Epithelial Cells/drug effects ; Epithelial Cells/cytology ; Lens, Crystalline/drug effects* ; Lens, Crystalline/cytology ; Mitomycin/pharmacology* ; Rabbits ; Time Factors