The pharmacokinetics and dosage regimen of norfloxacin-glycine acetate (NFLXGA) was investigated in pigs after a single intravenous (i.v.) or oral (p.o.) administration at a dosage of 7.2 mg/kg body weight. After both i.v. and p.o. administration, plasma drug concentrations were best fitted to an open two-compartment model with a rapid distribution phase. After i.v. administration of NFLXGA, the distribution (t1/2alpha) and elimination half-life (t1/2beta) were 0.36 +/- 0.07 h and 7.42 +/- 3.55 h, respectively. The volume of distribution of NFLXGA at steady state (Vdss) was 4.66 +/- 1.39 l/kg. After p.o. administration of NFLXGA, the maximal absorption concentration (Cmax) was 0.43 +/- 0.06 microgram/ ml at 1.36 +/- 0.39 h (Tmax). The mean absorption (t1/2ka) and elimination half-life (t1/2beta) of NFLXGA were 0.78 +/- 0.27 h and 7.13 +/- 1.41 h, respectively. The mean systemic bioavailability (F) after p.o. administration was 31.10 +/- 15.16%. We suggest that the optimal dosage calculated from the pharmacokinetic parameters is 5.01 mg/kg per day i.v. or 16.12 mg/kg per day p.o.
Administration, Oral ; Animals ; Anti-Bacterial Agents/administration & dosage/blood/*pharmacokinetics ; Biological Availability ; Cross-Over Studies ; Glycine/administration & dosage/*analogs & derivatives/blood/pharmacokinetics ; Half-Life ; Injections, Intravenous/veterinary ; Male ; Norfloxacin/administration & dosage/*analogs & derivatives/blood/pharmacokinetics ; Swine/*metabolism ; Time Factors

Aggregatibacter actinomycetemcomitans is the most important etiologic agent of aggressive periodontitis and can interact with endothelial cells. Monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) are chemokines, playing important roles in periodontal pathogenesis. In our current study, the effects of A. actinomycetemcomitans on the production of MCP-1 and IL-8 by human umbilical vein endothelial cells (HUVEC) were investigated. A. actinomycetemcomitans strongly induced the gene expression and protein release of both MCP-1 and IL-8 in a dose- and time-dependent manner. Dead A. actinomycetemcomitans cells were as effective as live bacteria in this induction. Treatment of HUVEC with cytochalasin D, an inhibitor of endocytosis, did not affect the mRNA up-regulation of MCP-1 and IL-8 by A. actinomycetemcomitans. However, genistein, an inhibitor of protein tyrosine kinases, substantially inhibited the MCP-1 and IL-8 production by A. actinomycetemcomitans, whereas pharmacological inhibition of each of three members of mitogen-activated protein (MAP) kinase family had little effect. Furthermore, gel shift assays showed that A. actinomycetemcomitans induces a biphasic activation (early at 1-2 h and late at 8-16 h) of nuclear factor-kappaB (NF-kappaB) and an early brief activation (0.5-2 h) of activator protein-1 (AP-1). Activation of canonical NF-kappaB pathway (IkappaB kinase activation and IkappaB-alpha degradation) was also demonstrated in these experiments. Although lipopolysaccharide from A. actinomycetemcomitans also induced NF-kappaB activation, this activation profile over time differed from that of live A. actinomycetemcomitans. These results suggest that the expression of MCP-1 and IL-8 is potently increased by A. actinomycetemcomitans in endothelial cells, and that the viability of A. actinomycetemcomitans and bacterial internalization are not required for this effect, whereas the activation of protein tyrosine kinase(s), NF-kappaB, and AP-1 appears to play important roles. The secretion of high levels of MCP-1 and IL-8 resulting from interactions of A. actinomycetemcomitans with endothelial cells may thus contribute to the pathogenesis of aggressive periodontitis.
Aggressive Periodontitis ; Bacteria ; Chemokine CCL2 ; Chemokines ; Cytochalasin D ; Endocytosis ; Endothelial Cells ; Gene Expression ; Genistein ; Human Umbilical Vein Endothelial Cells ; Humans ; I-kappa B Proteins ; Interleukin-8 ; Monocytes ; NF-kappa B ; Phosphotransferases ; Protein-Tyrosine Kinases ; RNA, Messenger ; Transcription Factor AP-1 ; Tyrosine ; Up-Regulation

Diffuse pulmonary nodular lesions have many causes. When they are caused by infection, the likely organisms are M. tuberculosis and various fungi. Silicosis, eosinophilic granuloma and pulmonary metastasis should be considered for differential diagnosis. Differential diagnosis needs detailed clinical history, physical examination and various laboratory tests. A case of persistent diffuse pulmonary nodular lesions which had persisted 5 years is reported. The patient was a 25 years old man with minimal pulmonary symptoms. Detailed past history and physical examination suggested thyroid tumor. Chest radiography showed numerous evenly sized well-defined nodules scattered in entire lung fields. Previous chest X-rays showed similar nodular lesions, which had lasted for 5 years. The number of nodules was slightly increased. Neck CT showed heterogenous mass in left lobe of thyroid gland and multiple lymphadenopathies along both internal jugular chains. Total thyroidectomy was performed. A case of lung metastasis which progressed slowly in papillary thyroid cancer is reported.
Diagnosis, Differential ; Eosinophilic Granuloma ; Fungi ; Humans ; Lung ; Neck ; Neoplasm Metastasis ; Physical Examination ; Radiography ; Silicosis ; Thorax ; Thyroid Gland ; Thyroid Neoplasms ; Thyroidectomy ; Tuberculosis

BACKGROUND: The tuberculin skin test (TST) is the standard tool to diagnose latent tuberculosis infection (LTBI) in mass screening. The aim of this study is to find an optimal cut-off point of the TST+ rate within tuberculosis (TB) contacts to predict the active TB development among adolescents in school TB outbreaks. METHODS: The Korean National Health Insurance Review and Assessment database was used to identify active TB development in relation to the initial TST (cut-off, 10 mm). The 7,475 contacts in 89 schools were divided into two groups: Incident TB group (43 schools) and no incident TB group (46 schools). LTBI treatment was initiated in 607 of the 1,761 TST+ contacts. The association with active TB progression was examined at different cut-off points of the TST+ rate. RESULTS: The mean duration of follow-up was 3.9+/-0.9 years. Thirty-three contacts developed active TB during the 4,504 person-years among the TST+ contacts without LTBI treatment (n=1,154). The average TST+ rate for the incident TB group (n=43) and no incident TB group (n=46) were 31.0% and 15.5%, respectively. The TST+ rate per group was related with TB progression (odds ratio [OR], 1.025; 95% confidence interval [CI], 1.001-1.050; p=0.037). Based on the TST+ rate per group, active TB was best predicted at TST+ > or = 16% (OR, 3.11; 95% CI, 1.29-7.51; area under curve, 0.64). CONCLUSION: Sixteen percent of the TST+ rate per group within the same grade students can be suggested as an optimal cut-off to predict active TB development in middle and high schools TB outbreaks.
Adolescent ; Area Under Curve ; Disease Outbreaks* ; Follow-Up Studies ; Humans ; Latent Tuberculosis ; Mass Screening ; National Health Programs ; Prevalence* ; Skin Tests* ; Skin* ; Tuberculin Test ; Tuberculin* ; Tuberculosis*

BACKGROUND: In hypertrophic cardiomyopathy(HCM), which is known as genetic disease, severity and location of left ventricular hypertrophy(LVH) is variable. So we investigated additional modify role of angintensin-I converting enzyme(ACE) gene, which is known to be implicated in cardiac hypertrophy. ACE genotypes and degree of hypertrophy were determined in each subject. METHOD: 172 patients(37 HCM, 26 normotenisve LVH, 19 hypertenisve LVH, 79 normal control) were included in this study. Left ventricular mass index(LVMI) was calculated from electrocardiogram by Rautaharju equation, and LVH was defined as LVMI is above 131g/m2 in male or above 110g/m2 in female. In HCM group, extent of left ventricular hypertrophy was also assessed by Wigle's method. DNA was extracted from peripheral blood and ACE I/D polymorphism was confirmed by PCR method. RESULTS: Frequency of D/D genotype is significantly higher in normotensive LVH group(0.231) and in HCM group(0.243) than normal control group(0.076)(Fisher's exact test, p<0.05). There was no significant difference in genotype frequency between other groups. The mean LVMI(g/m2) and Wigle's LVH score was significantly higher in DD than II and ID(259.8+/-156.4g/m2 vs 176.6+/-56.2g/m2, p<0.05, t-test, 7.82+/-2.4 vs 5.35+/-1.9, p<0.05, Mann-Whitney test). LVMI and LVH score also exhibited increasing tendency toward II, ID DD genotypes. CONCLUSION: D allele of ACE gene contribute to the development of cardiac hypertrophy in HCM as well as normotensive LVH.
Alleles ; Cardiomegaly ; DNA ; Electrocardiography ; Female ; Genotype ; Humans ; Hypertrophy ; Hypertrophy, Left Ventricular ; Male ; Polymerase Chain Reaction

BACKGROUND: Cough is a frequent side effect of angiotensin converting enzyme(ACE) inhibitors and the mechanism of cough is postulated to be associated with accumulation of bronchial irritants which are substrates of ACE. Based on this pathophysiologic mechanism, baseline ACE activity could potentially play the key role in the development of ACE inhibitor-induced cough and ACE gene polymorphism, which account for part of the ACE activity, and to compare the clinical characteristics between subjects who developed cough and those who did not with ACE inhibitor use. METHOD: The cough group(N=84) consisted of subjects who developed troublesome cough with ACE inhibiors and who ceased coughing in 4 weeks after cessation of ACE inhibitor treatment. Patients with evidence of acute respiratioy illness were excluded. The non-cough group(N=116) consisted of subjects who did not develop cough with over 12 months of ACE inhibitor treatment. Clinical characteristics were collected by personal contact and chart review. ACE genotyping was done by PCR amplification of DNA from peripheral blood using previously published primers and agarose gel electrophoresis. RESULTS: Underlying diseases of the cough group were hypertension(47), valvular heart disease(23), ischemic heart disease(4), dilated cardiomyopathy(7) and others (3), whereas Underlying diseases of the non-cough group were hypertension(48), valvular heart disease(33), ischemic heart disease(12), dilated cardiomyopathy(20) and others(3). There was no significant difference in the distribution of underlying diseases between the two groups. Cough induced by ACE inhibitors occurred in an average of 8 weeks after treatment initiation and subsided in an average of 3.8 weeks after discontinuation of ACE inhibitors. There was a preponderance of females in the cough group(F : M=73 : 27) compared to the non-cough group(F : M=40 : 60, p<0.01). There was no significant difference in mean age, total cholesterol, and the frequency of hypertension and diabetes between the two groups. Genotypic frequencies of ACE gene were I/I : I/D : D/D=38 : 42 : 30 for the cough group and 45 : 36 : 19 for the non-cough group which showed no significant difference between the two groups. Allelic frequencies were I : D=54 : 46 and 62 : 38 in the cough and non-cough group respectively and the difference was not statistically significant. CONCLUSION: Women are more susceptible to ACE inhibitor-induced cough, and ACE inhibitor induced cough is not associated with ACE gene polymorphism.
Angiotensin-Converting Enzyme Inhibitors ; Angiotensins* ; Cholesterol ; Cough* ; DNA ; Electrophoresis, Agar Gel ; Female ; Heart ; Humans ; Hypertension ; Irritants ; Peptidyl-Dipeptidase A* ; Polymerase Chain Reaction

BACKGROUND: In hypertrophic cardiomyopathy(HCM), which is known as genetic disease, severity and location of left ventricular hypertrophy(LVH) is variable. So we investigated additional modify role of angintensin-I converting enzyme(ACE) gene, which is known to be implicated in cardiac hypertrophy. ACE genotypes and degree of hypertrophy were determined in each subject. METHOD: 172 patients(37 HCM, 26 normotenisve LVH, 19 hypertenisve LVH, 79 normal control) were included in this study. Left ventricular mass index(LVMI) was calculated from electrocardiogram by Rautaharju equation, and LVH was defined as LVMI is above 131g/m2 in male or above 110g/m2 in female. In HCM group, extent of left ventricular hypertrophy was also assessed by Wigle's method. DNA was extracted from peripheral blood and ACE I/D polymorphism was confirmed by PCR method. RESULTS: Frequency of D/D genotype is significantly higher in normotensive LVH group(0.231) and in HCM group(0.243) than normal control group(0.076)(Fisher's exact test, p<0.05). There was no significant difference in genotype frequency between other groups. The mean LVMI(g/m2) and Wigle's LVH score was significantly higher in DD than II and ID(259.8+/-156.4g/m2 vs 176.6+/-56.2g/m2, p<0.05, t-test, 7.82+/-2.4 vs 5.35+/-1.9, p<0.05, Mann-Whitney test). LVMI and LVH score also exhibited increasing tendency toward II, ID DD genotypes. CONCLUSION: D allele of ACE gene contribute to the development of cardiac hypertrophy in HCM as well as normotensive LVH.
Alleles ; Cardiomegaly ; DNA ; Electrocardiography ; Female ; Genotype ; Humans ; Hypertrophy ; Hypertrophy, Left Ventricular ; Male ; Polymerase Chain Reaction

BACKGROUND: Cough is a frequent side effect of angiotensin converting enzyme(ACE) inhibitors and the mechanism of cough is postulated to be associated with accumulation of bronchial irritants which are substrates of ACE. Based on this pathophysiologic mechanism, baseline ACE activity could potentially play the key role in the development of ACE inhibitor-induced cough and ACE gene polymorphism, which account for part of the ACE activity, and to compare the clinical characteristics between subjects who developed cough and those who did not with ACE inhibitor use. METHOD: The cough group(N=84) consisted of subjects who developed troublesome cough with ACE inhibiors and who ceased coughing in 4 weeks after cessation of ACE inhibitor treatment. Patients with evidence of acute respiratioy illness were excluded. The non-cough group(N=116) consisted of subjects who did not develop cough with over 12 months of ACE inhibitor treatment. Clinical characteristics were collected by personal contact and chart review. ACE genotyping was done by PCR amplification of DNA from peripheral blood using previously published primers and agarose gel electrophoresis. RESULTS: Underlying diseases of the cough group were hypertension(47), valvular heart disease(23), ischemic heart disease(4), dilated cardiomyopathy(7) and others (3), whereas Underlying diseases of the non-cough group were hypertension(48), valvular heart disease(33), ischemic heart disease(12), dilated cardiomyopathy(20) and others(3). There was no significant difference in the distribution of underlying diseases between the two groups. Cough induced by ACE inhibitors occurred in an average of 8 weeks after treatment initiation and subsided in an average of 3.8 weeks after discontinuation of ACE inhibitors. There was a preponderance of females in the cough group(F : M=73 : 27) compared to the non-cough group(F : M=40 : 60, p<0.01). There was no significant difference in mean age, total cholesterol, and the frequency of hypertension and diabetes between the two groups. Genotypic frequencies of ACE gene were I/I : I/D : D/D=38 : 42 : 30 for the cough group and 45 : 36 : 19 for the non-cough group which showed no significant difference between the two groups. Allelic frequencies were I : D=54 : 46 and 62 : 38 in the cough and non-cough group respectively and the difference was not statistically significant. CONCLUSION: Women are more susceptible to ACE inhibitor-induced cough, and ACE inhibitor induced cough is not associated with ACE gene polymorphism.
Angiotensin-Converting Enzyme Inhibitors ; Angiotensins* ; Cholesterol ; Cough* ; DNA ; Electrophoresis, Agar Gel ; Female ; Heart ; Humans ; Hypertension ; Irritants ; Peptidyl-Dipeptidase A* ; Polymerase Chain Reaction

BACKGROUND AND OBJECTIVES: Climacteric women often suffer from vasomotor symptoms. These symptoms are thought to be related to an imbalance of autonomic control of the cardiovascular system and are effectively controlled with hormonal replacement therapy. Heart rate variability (HRV) reflects the autonomic integration of the cardiovascular system. In this study, we attempted to compare the HRV indices of postmenopausal women before and after hormonal replacement therapy. SUBJECTS AND METHODS: Eighteen patients with postmenopausal syndrome (mean age:53+/-4 years) received estrogen and/or progesterone replacement therapy. They underwent 24-hour ambulatory electrocardiographic monitoring at baseline and after the early period of therapy (mean:112+/-19 days) and eleven patients underwent the examination after the later period of therapy (mean 213+/-23 days). HRV was analyzed over a full 24-hour period, using time and frequency domain parameters. RESULTS: No statistically significant HRV change was observed during the early period of therapy. However, during the later therpy period , HRV indices such as rMSSD[from 27.6 to 31.3 (msec)], HF[from 4.8 to 5.05 ln (ms2)], LF/HF ratio (from 1.17 to 1.12) were significantly changed (p value<0.05). CONCLUSION: HRV was significantly changed in postmenopausal women during the later period of hormonal replacement therapy.
Cardiovascular System ; Climacteric ; Electrocardiography, Ambulatory ; Estrogens ; Female ; Heart Rate* ; Heart* ; Hormone Replacement Therapy ; Humans ; Menopause ; Progesterone

BACKGROUND AND PURPOSE: The quality of anticoagulation is critical for ensuring the benefit of warfarin, but this has been less well studied in Korean ischemic stroke patients with atrial fibrillation (AF). METHODS: This study retrospectively analyzed the data of patients who had an AF-related ischemic stroke and were treated with long-term warfarin therapy in 16 Korean centers. The quality of warfarin therapy was primarily assessed by the time in therapeutic range [TTR; international normalized ratio (INR), 2.0–3.0] and additionally by the proportion of INR values within the therapeutic range. RESULTS: The long-term warfarin-treated cohort comprised 1,230 patients. They were aged 70.1±9.7 years (mean±SD), 42.5% were female, and their CHA₂DS₂-VASc score was 4.75±1.41. The TTR analysis included 33,941 INR measurements for 27,487 months: per patients, 27.6 (SD, 22.4) INR measurements for 22.4 (SD, 12.9) months. The mean TTR of individual patients was 49.1% (95% confidence interval, 47.9–50.3%), and the TTR quartiles were <34.5, 34.5–49.1, 49.1–64.5%, and >64.5%. None of the 16 centers achieved a mean TTR of >60%. Of all INR measurements, 44.6% were within the therapeutic range, 41.7% were <2.0, and 13.7% were >3.0. CONCLUSIONS: In Korean ischemic stroke patients who had AF, the quality of warfarin therapy was low and might be inadequate to effectively prevent recurrent stroke or systemic embolism.
Atrial Fibrillation* ; Cohort Studies ; Embolism ; Female ; Humans ; International Normalized Ratio ; Observational Study* ; Retrospective Studies* ; Stroke* ; Warfarin*