This study aimed to investigate the in vivo relevance of P-glycoprotein (P-gp) in the pharmacokinetics and adverse effect of phenformin. To investigate the involvement of P-gp in the transport of phenformin, a bi-directional transport of phenformin was carried out in LLC-PK1 cells overexpressing P-gp, LLC-PK1-Pgp. Basal to apical transport of phenformin was 3.9-fold greater than apical to basal transport and became saturated with increasing phenformin concentration (2-75 µM) in LLC-PK1-Pgp, suggesting the involvement of P-gp in phenformin transport. Intrinsic clearance mediated by P-gp was 1.9 µL/min while passive diffusion clearance was 0.31 µL/min. Thus, P-gp contributed more to phenformin transport than passive diffusion. To investigate the contribution of P-gp on the pharmacokinetics and adverse effect of phenformin, the effects of verapamil, a P-gp inhibitor, on the pharmacokinetics of phenformin were also examined in rats. The plasma concentrations of phenformin were increased following oral administration of phenformin and intravenous verapamil infusion compared with those administerd phenformin alone. Pharmacokinetic parameters such as Cmax and AUC of phenformin increased and CL/F and Vss/F decreased as a consequence of verapamil treatment. These results suggested that P-gp blockade by verapamil may decrease the phenformin disposition and increase plasma phenformin concentrations. P-gp inhibition by verapamil treatment also increased plasma lactate concentration, which is a crucial adverse event of phenformin. In conclusion, P-gp may play an important role in phenformin transport process and, therefore, contribute to the modulation of pharmacokinetics of phenformin and onset of plasma lactate level.
Administration, Oral ; Animals ; Area Under Curve ; Diffusion ; Intestinal Absorption ; Lactic Acid* ; LLC-PK1 Cells ; P-Glycoprotein* ; Pharmacokinetics ; Phenformin* ; Plasma* ; Rats ; Swine ; Verapamil

No abstract available.
Gastrectomy* ; Stomach Neoplasms*

No abstract available.
Colorectal Neoplasms* ; Follow-Up Studies*

No abstract available.
Colorectal Neoplasms* ; Follow-Up Studies*

Operations on the inner aspect of the pelvis are often necessary for irreducible fracture of the ilium, irreducible fracture of superior and medial portion of the acetabulum, tumors and infections involving iliac fossa, and fracture-dislocation and infection of the sacro-iliac joint. Until now Letournel and Judet's ilioinguinal and iliofemoral approaches provided access to anterior column of the pelvis by elevating muscle layer on inner aspect of the pelvis. We used modified iliofemoral approach using ASIS(anterior superior iliac spine) osteotomy to gain better access to anterior column, the pelvlc brim, and in some occasions as far as anterior sacroiliac joint while avoiding injury to the structures in the inguinal ligament and lateral femoral cutaneous nerve and reported six cases treated with this approach. In conclusion, a modified iliofemoral approach using ASIS osteotomy is a useful approach which can obtain an excellent exposure in the inner pelvis.
Acetabulum ; Ilium ; Joints ; Ligaments ; Osteotomy ; Pelvis ; Sacroiliac Joint

No abstract available.
Colon* ; Colonic Neoplasms*

BACKGROUND: Sex steroid hormones are believed to play an important role in the genesis and growth of uterine myoma. Several studies suggest a possible role of insulin-like growth factor(IGF) as a mediator of estradiol in uterine myama. We have recently demonstrated that some IGF binding proteins(IGFRPs) messenger ribonucleic acid(mRNA) expressions in myoma are dependent on the in vivo esttogen status. The purposes of this study are to evaluate the in vitro effects of sex steroid hormones including estrogen on the IGFBPs gene expression in tissues from uterine myoma and adjacent normal myometrium. METHODS: Tissues from myoma and adjacent normal myometrium of patients with uterine myoma during early proliferative phase of menstrual cycle were cultured in the absence(control) and presence of 17b-estradiol(10M/L) or/and progesterone(10M/L) for 3 days. The IGFBPs mRNA expressions in these explants were analyzed by Nothern blot using specific human complementary deoxyribonucleic acid(cDNA) probes. RESULTS: The addition of 17b-estradiol, progesterone alone and in combination to conditioned media of explants from myoma and adjacent normal myornetrium did not result in any changes in the expression of IGFBP-2, IGFBP-4, IGFBP-5, and IGFBP-6 mRNA. With progesterone addtion, lGFBP-3 rnRNA expression was significantly reduced in myoma explant but not in adjacent ncemal myometrium explant. There was no significant change in the IGFBP-3 mRNA expression with 17b-estradiol and with the combination of both 17b-estradiol and progesterone. CONCLUSION: 17b-estradiol does not affect IGFBPs gene expression in the myoma and adjacent normal myometrium explant regardless of the presence of progesterone in vitro. However progesterone alone induces a decrease in IGFBP-3 synthesis in myoma explant.
Animals ; Culture Media, Conditioned ; Estradiol ; Estrogens ; Female ; Gene Expression ; Gonadal Steroid Hormones ; Humans* ; Insulin-Like Growth Factor Binding Protein 2 ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Protein 4 ; Insulin-Like Growth Factor Binding Protein 5 ; Insulin-Like Growth Factor Binding Protein 6 ; Insulin-Like Growth Factor Binding Proteins ; Leiomyoma* ; Menstrual Cycle ; Mice ; Myoma ; Myometrium* ; Progesterone ; RNA, Messenger*

No abstract available.
Child* ; Hepatitis, Chronic* ; Humans ; Interferon-alpha*

OBJECTIVES: Very early-onset schizophrenia (VEOS) is a type of psychosis having a low frequency, insidious onset, and devastating clinical outcome. In this study, the demographic features, information on medication, clinical outcomes, and intellectual capability of patients diagnosed with VEOS in a hospital were analyzed to provide therapeutic strategies for this type of schizophrenia. METHODS: Using the electronic medical records of the National Center for Mental Health, 69 patients with VEOS were identified based on the DSM-5 criteria of schizophrenia. The data were summarized and analyzed according to the demographic characteristics, medications used, intellectual strength measured by the full intelligence quotient (FIQ) score, and current clinical status measured by the Clinical Global Impression-Severity (CGI-S) and various combinations of these parameters. RESULTS: The screened study group contained similar numbers of males and females. The younger the onset of psychosis, the lower the frequency. The study population included a significantly higher proportion of births in the winter season than that of the general population. The 3 most frequently used antipsychotic medications were risperidone and its derivatives, clozapine and olanzapine. Valproic acid and divalproex sodium were the most commonly added drugs for outcome augmentation. 53.5% of the study population had received benzodiazepines and/or hypnotics. The average FIQ of the study population was 69.4, which is quite low compared to previous Korean studies with similar populations. There was a weak negative correlation between FIQ and CGI-S, but it was not statistically significant. The average CGI-S score was 4.2, which meant that the patients were moderately ill. CONCLUSION: This study demonstrated that patients with VEOS showed more frequent intellectual deficits at baseline and poorer outcomes than the control group. Risperidone, clozapine, valproic acid and their combinations were the most preferred medications for the treatment of psychosis. Benzodiazepines were quite commonly added for various reasons.
Antipsychotic Agents ; Benzodiazepines ; Clozapine ; Electronic Health Records ; Female ; Humans ; Hypnotics and Sedatives ; Intelligence ; Male ; Mental Health ; Parturition ; Psychotic Disorders ; Risperidone ; Schizophrenia* ; Seasons ; Treatment Outcome* ; Valproic Acid

OBJECTIVE: To determine whether the follicle stimulating hormone(FSH) receptor gene mutation (C566T point mutation) is present in Korean women with premature ovarian failure and normal karyotype. METHODS: Genomic deoxyribonucleic acid(DNA) obtained from 40 patients with chromosomally competent premature ovarian failure and from 30 normal fertile women(control group) was amplified by polymerase chain reaction(PCR). PCR products were digested by the enzyme BsmI and polyacrylamide gel(PAG) elctrophoretic patterns of these enzyme-digested products were analyzed. The direct sequencing of PCR products was also performed. RESULTS: All patients with premature ovarian failure and 30 normal control women demonstrated homozygous, normal alleles with 51- and 27- base pairs fragments in PAG elctrophoresis. The absence of C566T point mutation in both group was confirmed by direct DNA sequencing. CONCLUSIONS: A C566T mutation in FSH receptor gene is rare in Korean women with premature ovarian failure and normal karyotype.
Alleles ; Base Pairing ; Female ; Follicle Stimulating Hormone* ; Humans ; Karyotype* ; Point Mutation ; Polymerase Chain Reaction ; Primary Ovarian Insufficiency* ; Receptors, FSH* ; Sequence Analysis, DNA