Biomedical subjects

C K Kim

Publications and source records attributed to C K Kim.

321 records · Page 18Linked to original sources

PubMedDate not supplied

Early handling can attenuate adverse effects of fetal ethanol exposure.

The effects of early handling on physiological and hormonal responses of rats exposed to ethanol prenatally were studied. Male and female Sprague-Dawley rats from prenatal ethanol (E), pair-fed (PF), and ad lib-fed control (C) prenatal treatment groups were either handled (H) or nonhandled (NH) during the preweaning period and tested in adulthood. Early handling eliminated the deficit in preweaning weight gain observed in E compared to PF and C offspring. In adulthood, early handling eliminated the increased hypothermia observed in E and PF compared to C males following an ethanol challenge (2.0 g/kg, IP). In addition, H males displayed marginally less hypothermia overall than NH males. In contrast, handling accelerated the return to preinjection temperature in PF and C females but had no effect on E females. There were no significant differences among E, PF, and C rats in corticosterone (CORT) responses to ethanol challenge (1.5 g/kg, IP), but both males (marginally) and females in the H condition displayed higher CORT levels overall than NH rats. Early handling also eliminated the increased peak CORT response to restraint stress in E compared to C females, but did not affect the more prolonged elevation of CORT in E compared to PF and C females. There were no differences among E, PF, and C females in hippocampal type I and type II glucocorticoid receptor density or affinity. However, binding affinity of type II receptors was slightly but significantly increased in H compared to NH females. Together, these data indicate that early handling may modulate or attenuate some, but not all, of the adverse effects of fetal ethanol exposure on offspring growth and physiological responsiveness.

Animals↗

PubMedDate not supplied

Acute hemiplegia associated with HIV infection.

An acute hemiplegia secondary to a large cerebral infarct is described in a 16-month-old infant with congenitally-acquired human immunodeficiency virus infection. Serial imaging studies during the next year documented improvement in his hemiplegia and a static underlying human immunodeficiency virus encephalopathy. Acquired immunodeficiency syndrome should be included in the differential diagnosis of children with acute hemiplegia.

AIDS Dementia Complex↗

PubMedDate not supplied

Comparison of in vivo fate and immunogenicity of hepatitis B surface antigen incorporated in cationic and neutral liposomes.

To compare cationic liposomes (CatL) and neutral liposomes (NeuL), as a vaccine carrier, the in vivo fate and immunogenicity of hepatitis B surface antigen (HBsAg), incorporated in CatL and NeuL, were investigated. CatL, composed of phosphatidyl choline (PC) and stearyl amine (SA) with a molar ratio of 9:1, showed a 2.5-fold higher incorporating efficiency of HBsAg than NeuL composed of PC alone. Most of HBsAg incorporated in both liposomes existed in an antibody-available form on the outer surface of liposomes. After intramuscular injection to rats, HBsAg in CatL resided at the injection site for a longer period than that in NeuL with terminal half lives of 52.5 and 42.9 h, respectively. However, HBsAg in NeuL was more efficiently taken up by the lymphatic organs and spleen than that in CatL. Furthermore, the group treated with HBsAg in NeuL showed earlier sero-conversion with higher anti-HBsAg titre than the group treated with HBsAg in CatL. Sero-conversion rates (SCRs) in both CatL- and NeuL-treated animals were 100% after every injection carried out, except the primary injection of CatL. These results demonstrate that CatL can enhance the retention of incorporated antigen at the injection site, compared with NeuL. However, the production of antibody by HBsAg in NeuL is more effective than that by HBsAg in CatL, probably due to the higher lymphatic targeting ability of NeuL. Thus, NeuL appears to be a better carrier for HBsAg than CatL.

Adjuvants, Immunologic↗

PubMedDate not supplied

Altered pharmacokinetics and liver targetability of methotrexate by conjugation with lactosylated albumins.

To enhance the liver targetability, methotrexate (MTX) was conjugated with albumin previously substituted with varying content of lactose (L0, L5, and L24). The uptake of MTX by rat hepatocytes in vitro increased according to the increase in the lactose content on the albumin conjugates. The MTX level in the plasma and various organs was determined by counting the radioactivity of [3H]MTX and by HPLC assay, separately, to monitor the in vivo fate of MTX not only as total, regardless of forms of MTX, but also as free/intact MTX level. Conjugation of MTX with albumin alone provided the enhanced delivery of MTX to the liver, accompanied by decreased accumulation in the kidney, but by increased accumulation in other nontarget organs such lung, heart, and spleen. Lactosylation of albumin conjugates further enhanced the delivery of MTX to the liver in a lactose content-dependent manner, accompanied by decreased accumulation of MTX in the lung and heart as well as kidney. The total MTX level accumulated in the liver was 2.9-, 4.1-, and 11.0-fold higher at 1 h and 5.4-, 7.0-, and 16.5-fold higher at 4 h after injection of MTX-L0, L5, L24 albumin conjugates compared with MTX alone. MTX conjugates with lactosylated albumin provided low but prolonged level of free/intact MTX in the liver. Taken together, the pharmacokinetics and liver targetability of MTX could be favorably modulated by controlling the lactose content on the albumin conjugates. Lactosylated albumin conjugation might also provide prolonged and targeted delivery of other drugs for the treatment of liver diseases.

Animals↗

PubMedDate not supplied

Prolonged blood circulation of methotrexate by modulation of liposomal composition.

Prolonged circulation by liposomal incorporation has been shown to enhance the therapeutic efficacy of drugs in many cases. The purpose of this study was to investigate whether the prolonged circulation of methotrexate (MTX) can be achieved by modulating the liposomal compositions. Various compositions of liposomes were prepared with 2:1 of phosphatidylcholine (PC) and cholesterol (CH) with or without distearoylphosphatidyl-ethanolamine-N-poly(ethyleneglycol) 2000 (DSPE-PEG). The MTX encapsulation efficiency depended on the type of PC used. It also appeared to increase by inclusion of DSPE-PEG. The size of liposomes decreased by the inclusion of DSPE-PEG. The inclusion of DSPE-PEG lowered the plasma-induced release of MTX from EggPC/CH and DPPC/CH liposomes, suggesting its enhancement effect on the liposomal stability. After intravenous injection to rats, the pharmacokinetics and biodistribution of MTX were significantly changed by liposomal incorporation and also by the composition of liposomes. The total body clearance of MTX incorporated in EggPC/CH, DPPC/CH, EggPC/CH/DSPE-PEG, and DPPC/CH/DSPE-PEG liposomes decreased 4.4-, 14.9-, 24.5-, and 53.1-fold, compared with that of free MTX. The ratio of MTX concentration in blood to liver and spleen after injection of DPPC/CH, EggPC/CH/DSPE-PEG, and DPPC/CH/DSPE-PEG liposomes was 5.4-, 8.5-, and 13.5-fold higher than that of EggPC/CH liposomes. Furthermore, the accumulation of MTX in the kidney, one of the organs in which MTX exhibits its toxicity, was significantly lowered by liposomal incorporation, especially by DSPE-PEG-containing liposomes. Taken together, DPPC/CH/DSPE-PEG liposomes most effectively prolonged the blood circulation, and reduced hepatosplenic and kidney uptake of MTX. DPPC/CH/DSPE-PEG liposomes may have potential as an efficient delivery system for MTX.

Animals↗

PubMedDate not supplied

Dorsal defect of the patella: MR features.

Dorsal defect of the patella (DDP) is a benign lesion with characteristic radiologic features. We describe the MR appearance of a typical DDP and a healed DDP as seen in two patients. The classic CT appearance is also described.

Adult↗

PubMedDate not supplied

Anti-cancer effect of adenovirus p53 on human cervical cancer cell growth in vitro and in vivo.

To evaluate anti-tumor effects of recombinant adenovirus p53, time-course p53, E6 expression, and cell growth inhibition were investigated in vitro and in vivo using cervical cancer cell lines such as CaSki, SiHa, HeLa, HeLaS3, C33A, and HT3. The cell growth inhibition was studied via cell count assay, MTT assay and neutral red assay. After transfecting AdCMVp53 into SiHa cells-xenografted nude mice, the transduction efficiency and anti-tumor effect were investigated for a month. The results showed that adenoviral p53 expression induced significant growth suppression on the cancer cells, in which E6 transcript was strongly repressed, and that the expression of p53 and E6 were remarkably dependent on each cell type. The transduction efficiency was highly maintained in vivo as well as in vitro, and the size of tumor was remarkably decreased in comparison with AdCMVLacZ control. The results suggest that the adenovirus-mediated p53 gene transfection was done very effectively in vitro and in vivo experiment, and the cell growth was suppressed via p53-dependent apoptotic cell death, and that the anti-tumor effect could be related to E6 and p53 expression pattern.

Adenoviruses, Human↗

PubMedDate not supplied

Necrosis-like death with plasma membrane damage against cervical cancer cells by photodynamic therapy.

In order to elucidate the antitumor effect of photodynamic therapy (PDT) using the photosensitizing agent hematoporphyrin derivative (Photogem) and a diode laser, we evaluated the cell death of uterine cancer cell lines (CaSki, HT3, HeLa, and SKOV-3) and mice transplanted with TC-1 lung cancer cells. Morphological changes, MTT assay, flow cytometry, cytotoxicity, and tumor growth-inhibition study were evaluated at various time intervals after PDT. The results showed that the survival rates of each cell line decreased with time and dose-response after performing PDT. Also, PDT-induced damage of cancer cells was almost entirely confined to necrosis of the tumor cells in the early time courses. The irradiation of CaSki cells in the presence of Photogem induced plasma membrane disruption and cell shrinkage, indicating the plasma membrane as the main target for Photogem. In the experiment in vivo, the time courses of Photogem with irradiation showed significantly longer survival and a significantly smaller tumor size compared to those in the untreated control groups, and resorption of the tumor after PDT treatment was observed. Collectively, our results indicated that Photogem possesses tumor-specific affinity, and necrosis-like death with plasma membrane damage was postulated to be the principal mechanism of the antitumor effect of PDT using Photogem.

Adenocarcinoma↗

PubMedDate not supplied

Cellular process classification of human papillomavirus-16-positive SiHa cervical carcinoma cell using Gene Ontology.

This study utilized mRNA differential display and the Gene Ontology (GO) analysis to characterize the multiple interactions of a number of genes involved in human papillomavirus (HPV)-16-induced cervical carcinogenesis. We used HPV-16-positive cervical cancer cell line (SiHa) and normal human keratinocyte cell line (HaCaT) as a control. Each gene has several biological functions in the GO, and hence, we chosen the several functions for each gene. and then, the specific functions were correlated with gene expression patterns. The results showed that 157 genes were up- or down-regulated above two-fold and organized into mutually dependent subfunction sets depending on the cervical cancer pathway, suggesting the potentially significant genes of unknown function. The GO analysis suggested that cervical cancer cells underwent repression of cancer-specific cell-adhesive properties. Also, genes belonging to DNA metabolism such as DNA repair and replication were strongly down-regulated, whereas significant increases were shown in protein degradation and in protein synthesis. The GO analysis can overcome the complexity of the gene expression profile of the HPV-16-associated pathway and identify several cancer-specific cellular processes as well as genes of unknown function. Also, it can become a major competing platform for the genome-wide characterization of carcinogenesis.

Carcinoma, Squamous Cell↗

PubMedDate not supplied

Development of anticancer gene vaccine interact with human papillomavirus oncoprotein inhibition.

Adeno-associated virus (AAV) Rep 78 protein is known to inhibit the promoter site of several oncogenes and viral genes, including the human papillomavirus (HPV) type 16 E6 transforming genes. The biochemical studies of Rep 78 have been reported, but the effects of Rep 78 gene-mediated inhibition of HPV 16 E6 promoter activity on the various human cervical carcinoma cells have not been characterized. pEGFP-N1 vector, cloned by AAV-mediated Rep 78, is transfected into cervical carcinoma cells. Transfection efficiency of Rep 78 was approximately 30-60% different. Messenger RNA (mRNA) and protein expression of Rep 78 gene was significantly higher on day 1 of the transfection of Rep 78 DNA in CaSki cells, and DNA level of HPV 16 E6 was decreased on day 1 of the transfection. The growth of CaSki cervical cancer cells was only 10-15% inhibited by Rep 78, and the other cervical cells, HeLa, HeLaS3, HT3, and QGU, were unaffected by Rep 78 transfection. In spite of the high efficiency of Rep 78 gene transformation and expression rate, we could not show the significant growth inhibition in various cervical cancer cell lines. Taken together, long-term expression of Rep 78 strategy might be needed for cervical carcinoma gene therapy using AAV vector.

Base Sequence↗

PubMedDate not supplied

Rapid prenatal diagnosis of trisomy 21 by polymerase chain reaction- associated analysis of small tandem repeats and S100B in chromosome 21.

OBJECTIVES: The incidence of Down syndrome increases with maternal age and a rapid and accurate method for prenatal diagnosis is a necessity. This study was devised to evaluate and compare the methods for detecting trisomy 21 by polymerase chain reaction (PCR)-associated analysis of small tandem repeats (STR) of D21S11 and semiquantitative analysis of S100B of chromosome 21. METHODS: PCR was performed with DNA template obtained from 20 normal samples (10 blood, 10 amniotic fluid) and 12 Down syndrome samples (10 blood, 2 amniotic fluid). 32P-labelled primers for D21S11 and S100B were used. PCR products for D21S11 were subjected to polyacrylamide urea gel (6%) electrophoresis, followed by exposure to X-ray film, and then the densities of signals were recorded by densitometer. PCR products for S100B and insulin-like growth factor-I (IGF-I) as an internal control were subjected to agarose gel (2%) electrophoresis and the relative amounts of radioactivity in their products were measured to assess the quantitation of template DNA. RESULTS: Analysis of D21S11 STR showed equivalent triplets in 4 cases and unequivalent doublets (1:2) in 8 Down syndrome samples. The normal control group showed singlets in 5 cases and equivalent doublets in 15 cases. In the analysis of S100B, the ratios of S100B to IGF-I was 1.4-1.6 in 7 of 12 Down syndrome samples, while the ratios of S100B in all normal samples were close to 1.0. All the results were obtained within 24 h. The D21S11 STR analysis managed to distinguish more clearly between normal and trisomy 21, while semiquantitative PCR analysis of S100B was less able to assess trisomy 21. CONCLUSION: Prenatal diagnosis of trisomy 21 by PCR-associated STR analysis of D21S11 and semiquantitative analysis of S100B are useful, innovative, accurate and rapid diagnostic methods, while D21S11 STR analysis is more discriminating in detecting trisomy 21 and also may be employed in preimplantation diagnosis of Down syndrome.

Calcium-Binding Proteins↗

PubMedDate not supplied

Development of digoxin dry elixir as a novel dosage form using a spray-drying technique.

A rapidly absorbed new novel oral dosage form for digoxin termed 'digoxin dry elixir' was developed by the spray-drying technique. Digoxin, dextrin and sodium lauryl sulphate were dissolved in a ethanol-water mixture (20:25 w/w) and therefore spray-dried to form the digoxin dry elixir. According to scanning electron micrographs, digoxin dry elixir is spherical in shape with a smooth surface. The geometric mean diameter of dry elixir determined by laser particle size analysis was about 13 microns. The appearance and flow properties were almost unchanged and about 10% of ethanol contents in the dry elixir decreased during 180 days in a sealed bottle at room temperature. Comparative studies on the in vitro dissolution and in vivo absorption of digoxin in the form of digoxin dry elixir, digoxin elixir and digoxin powder were carried out. Digoxin in the dry elixirs was completely dissolved within 2 min. On the other hand, only about 87% of digoxin powder dissolved in 60 min. The initial dissolution rates of digoxin in the dry elixirs markedly increased in distilled water at 37 degrees C, which were over 100 fold higher than that of digoxin powder alone. The maximal plasma concentration of digoxin (Cmax) and area under the digoxin concentration-time curve from zero to 6 h (AUC0-6h) after the oral administration of digoxin dry elixir were almost 3.8 and 5.5 fold increased compared to digoxin powder alone. No significant difference of AUC0-6 h between dry elixir and elixir was observed, but the Cmax of digoxin in the form of dry elixir was significantly reduced compared to the digoxin elixir (0.57 versus 0.83). Digoxin dry elixir might be a useful solid dosage form to improve the dissolution rate and bioavailability of poorly water-soluble digoxin compared to digoxin powder alone. It also indicates that dry elixir might reduce the side effects in oral digitalis glycoside therapy compared to the digoxin elixir due to the reduction of Cmax.

Animals↗

PubMedDate not supplied

Lymphatic delivery and pharmacokinetics of methotrexate after intramuscular injection of differently charged liposome-entrapped methotrexate to rats.

The lymph node targeting ability and pharmacokinetics of methotrexate (MTX) after intramuscular (i.m.) injection of differently charged liposome-entrapped [3H]MTX to rats were evaluated using [3H]MTX as a tracer. Neutral liposomes were prepared with a mixture of phosphatidylcholine, cholesterol and alpha-tocopherol (8:4:0.1, molar ratio). Positively and negatively charged liposomes were also prepared by incorporation of stearylamine (8:4:0.1, molar ratio) and dicetylphosphate (8:4:0.1:1, molar ratio) into neutral liposomes respectively. The encapsulation efficiency (as expressed in terms of radioactivity) in liposomes was increased as alpha-tocopherol was incorporated into the lipid bilayer. The disappearance of [3H]MTX from the i.m. injection site was rapid and essentially complete after 30 min. On the other hand, the disappearance of radioactivity of liposome-entrapped [3H]MTX was much slower when compared to free drug. The area under the drug concentration-time curve (AUC) of liposome-entrapped [3H]MTX in lymph nodes was significantly increased when compared to free [3H]MTX. It suggested that liposomes injected by the i.m. route entered into the lymphatics and only drug released from liposomes diffused directly into the systematic circulation. The liposome-entrapped [3H]MTX by i.m. route was markedly localized in the lymph nodes. The concentration of MTX-equivalents in regional lymph node after i.m. injection of liposome-entrapped [3H]MTX was > 100-350 fold higher when compared to the plasma concentration. These values are more than 10-20 fold higher compared to the i.m. injection of free [3H]MTX. The positively charged liposomes were more localized in lymph nodes compared to neutral and negatively charged ones. While liposomes injected by i.v. route were localized in liver, spleen and lung compared to free [3H]MTX, it was evident that i.m. administration of liposomes resulted in enhanced localization of MTX in the lymphatic system but decreased deposition in kidney, liver and other non-targeting tissues compared to free [3H]MTX. The targeting ability and carrier properties of liposome-entrapped anticancer drugs with varying surface charge, lipid compositions and route of administration are of significant importance to alter biodistribution in chemotherapy.

Animals↗

PubMedDate not supplied

Preparation and characterization of sustained-release microspheres of chlorpromazine.

Sustained release microspheres of chlorpromazine were prepared from Eudragit RS 100 by an emulsion-solvent evaporation method using a six-baffled vessel. The morphology of microspheres was characterized by scanning electron microscopy (SEM). In the presence of aluminium tristearate (5%), microspheres were spherical in shape and uniform. The release of chlorpromazine from microspheres was pH-independent. With increasing amount of aluminium tristearate and increasing ratio of Eudragit RS 100/drug from 1:1 to 9:1, the particle size of chlorpromazine microspheres was reduced and the release rate decreased. The microspheres prepared with the polymer/drug ratio of 9:1 produced a 12-h sustained release pattern.

Antipsychotic Agents↗

PubMedDate not supplied

Preparation and characterization of melatonin-loaded stearyl alcohol microspheres.

A sustained release dosage form which delivers melatonin (MT), a pineal hormone, is of clinical value because of the short half-life of MT, for those who have a disordered circadian rhythm. The purpose of this study was to prepare MT-loaded microspheres by the emulsion melting/cooling method using stearyl alcohol (SA) and also dual walled chitosan and sodium alginate beads, and to evaluate the release characteristics in simulated gastric and intestinal fluid. The MT-loaded microspheres were spherical, ranging in diameter from about 250-750 microm. When polyethylene glycol 4000 (PEG), as a water-soluble or aluminium tristearate (AT), as a water-insoluble additive, was incorporated, the surface roughness was further reduced resulting in a smooth matrix structure. The dual walled chitosan and sodium alginate beads entrapping small MT-loaded microspheres were not spherical in structure. As the additives incorporated into SA microspheres increased, the drug content decreased. The release profiles of the MT-loaded microspheres were independent of pH. When the melted SA solution was cooled rapidly in 10 min to 25 degrees C, the drug content increased but the release rate of MT-loaded microspheres decreased. The release rate of drug decreased as the amount of SA increased but an increase of agitation speed and amount of AT and PEG resulted in increased release rates. The release rate of drug from dual walled chitosan beads increased slightly but was retarded in the case of dual walled alginate beads when compared to MT-loaded microspheres. The emulsion melting/cooling method used to prepare MT-loaded microspheres using SA is simple and inexpensive, and may provide an alternative for the preparation of an oral sustained release dosage form of MT without using harmful organic solvents. The dual walled chitosan and sodium alginate beads may also provide a convenient way to control the release of drugs.

Alginates↗