Chemical analysis of the volatiles released by sexual females (oviparae) of the peach aphid, Tube... more Chemical analysis of the volatiles released by sexual females (oviparae) of the peach aphid, Tuberocephalus momonis, identified two ubiquitous aphid sex pheromone components, (4aS,7S,7aR)-nepetalactone and (4aS,7S,7aR)-nepetalactol, in a ratio of 4 : 1. In field trials in Korea, employing traps releasing the two compounds in differing ratios, the most effective sex pheromone blend for trapping male T. momonis was found to be 85 : 15 nepetalactone-nepetalactol. Surprisingly, large numbers of presexual females (gynoparae) of this species were also collected when the catching rates were highest. In addition to T. momonis, over 20 other species of aphids were caught, particularly Myzus lythri, M. dycei, Lachnus tropicalis and M. persicae, in descending order of abundance.
Because bioequivalence studies are performed using a crossover design, information on the intrasu... more Because bioequivalence studies are performed using a crossover design, information on the intrasubject coefficient of variation (intra-CV) for pharmacokinetic measures is needed when determining the sample size. However, calculated intra-CVs based on bioequivalence results of identical generic drugs produce different estimates. In this study, we collected bioequivalence results using public resources from the Ministry of Food and Drug Safety (MFDS) and calculated the intra-CVs of various generics. For the generics with multiple bioequivalence results, pooled intra-CVs were calculated. The estimated intra-CVs of 142 bioequivalence studies were 14.7±8.2% for AUC and 21.7±8.8% for C max. Intra-CVs of C max were larger than those of area under the concentrationtime curve (AUC) in 129 studies (90.8%). For the 26 generics with multiple bioequivalence results, the coefficients of variation of intra-CVs between identical generics (mean±sd (min ~ max)) were 38.0±24.4% (1.9 ~ 105.3%) for AUC and 27.9±18.2% (4.0 ~ 70.1%) for C max. These results suggest that substantial variation exists among the bioequivalence results of identical generics. In this study, we presented the intra-CVs of various generics with their pooled intra-CVs. The estimated intra-CVs calculated in this study will provide useful information for planning future bioequivalence studies. (This is republication of the article 'Transl Clin Pharmacol 2017;25:179-182' retracted from critical typographic errors. See the 'Retraction and Republication section of this issue for further information)
Levofloxacin is a bactericidal broad spectrum antibiotic against Gram-positive and Gram-negative ... more Levofloxacin is a bactericidal broad spectrum antibiotic against Gram-positive and Gram-negative pathogens. A randomized, two-treatment, two-period, two-way crossover study was conducted to evaluate the bioequivalence of Lectacin 250 mg tablet, a generic levofloxacin, to its reference drug, Cravit 250 mg tablet. Each period was separated by a 7-day washout. Serial blood samples were collected until 24 h after dosing and plasma levofloxacin concentrations were determined using a high performance liquid chromatography. Pharmacokinetic parameters were analyzed using K-BE Test 2007 and BA calc 2007 (Ministry of Food and Drug Safety, Cheongju-si, South Korea). The peak concentration (C max) and the area under the plasma concentration versus time curve from 0 to the last measurable concentration (AUC 0-t) for the generic and reference levofloxacin were 4.48±0.89 mg/L and 4.46± 0.95 mg/L, and 25.33±4.12 mg*h/L and 25.77±4.01 mg*h/L, respectively, leading to a geometric mean ratio (90% confidence interval) of the generic to the reference levofloxacin of 1.0060 (0.9339-1.0842) and 0.9810 (0.9476-1.0159), respectively, for C max and AUC 0-t. Lectacin 250 mg tablet is bioequivalent to Cravit 250 mg tablet.
To study the elastic properties of the medial gastrocnemius (GCM) in children with spastic cerebr... more To study the elastic properties of the medial gastrocnemius (GCM) in children with spastic cerebral palsy.
Voltage-gated sodium channels are integral transmembrane proteins responsible for the rapidly-ris... more Voltage-gated sodium channels are integral transmembrane proteins responsible for the rapidly-rising phase of action potentials in most excitable cells. In mammals, the functional diversity and wide distribution of sodium channel proteins in various tissues and cell types are achieved mainly by selective expression of many distinct sodium channel genes. In the model insect, Drosophila melanogaster, however, only one confirmed sodium channel gene, para, and one putative sodium channel gene, DSC1, are known. We cloned and sequenced a DSC1 ortholog, BSC1, from the German cockroach, Blattella germanica. We found that the BSC1 transcript was present in a wide range of tissues, including nerve cord, muscle, gut, fat body and ovary, whereas the para transcript was detected only in nerve cord and muscle. Moreover, different tissues contained distinct alternatively spliced variants of BSC1, and two muscle-specific spliced variants are predicted to encode truncated proteins with only the first two of the four homologous domains. Therefore, alternative splicing and expression of distinct splicing variants in functionally different tissues may be a major mechanism by which insects increase BSC1 channel diversity in neuronal and non-neuronal tissues.
As inhibitors of organic cation transporters (OCTs), proton pump inhibitors (PPIs) may affect the... more As inhibitors of organic cation transporters (OCTs), proton pump inhibitors (PPIs) may affect the plasma levels of metformin, an OCT substrate. We investigated the effects of two PPIs, pantoprazole and rabeprazole, on metformin pharmacokinetics and glucose levels in healthy subjects. In this open, randomized, 6 × 3 cross-over study, 24 participants were administered metformin, either alone or in combination with pantoprazole or rabeprazole. The plasma concentrations of metformin and serum concentrations of glucose after a 75 g oral glucose tolerance test (OGTT) were determined. The area under the concentration-time curve (AUC) for metformin was 15% and 16% greater following co-administration with pantoprazole and rabeprazole, respectively. The maximum plasma metformin concentrations (C max) also increased by 15% and 22%, respectively, compared to when it was administered without the PPIs. The percentage change in the AUC for glucose concentration versus time for metformin plus rabeprazole was significantly lower than that for metformin plus pantoprazole (geometric mean ratio: 0.96 [90% CI: 0.92-0.99] and 0.77 [0.63-0.93], respectively). There was no significant difference in the maximum glucose concentration. In conclusion, concomitant administration of PPIs with metformin significantly increased plasma metformin exposure, but the effects on glucose disposition were minor and varied depending on the PPI administered.
BSC1, which was originally identified by its sequence similarity to voltage-gated Na + channels, ... more BSC1, which was originally identified by its sequence similarity to voltage-gated Na + channels, encodes a functional voltage-gated cation channel whose properties differ significantly from Na + channels. BSC1 has slower kinetics of activation and inactivation than Na + channels, it is more selective for Ba 2+ than for Na + , it is blocked by Cd 2+ , and Na + currents through BSC1 are blocked by low concentrations of Ca 2+. All of these properties are more similar to voltage-gated Ca 2+ channels than to voltage-gated Na + channels. The selectivity for Ba 2+ is partially due to the presence of a glutamate in the pore-forming region of domain III, since replacing that residue with lysine (normally present in voltage-gated Na + channels) makes the channel more selective for Na +. BSC1 appears to be the prototype of a novel family of invertebrate voltage-dependent cation channels with a close structural and evolutionary relationship to voltage-gated Na + and Ca 2+ channels.
Chemical analysis of the volatiles released by sexual females (oviparae) of the peach aphid, Tube... more Chemical analysis of the volatiles released by sexual females (oviparae) of the peach aphid, Tuberocephalus momonis, identified two ubiquitous aphid sex pheromone components, (4aS,7S,7aR)-nepetalactone and (4aS,7S,7aR)-nepetalactol, in a ratio of 4 : 1. In field trials in Korea, employing traps releasing the two compounds in differing ratios, the most effective sex pheromone blend for trapping male T. momonis was found to be 85 : 15 nepetalactone-nepetalactol. Surprisingly, large numbers of presexual females (gynoparae) of this species were also collected when the catching rates were highest. In addition to T. momonis, over 20 other species of aphids were caught, particularly Myzus lythri, M. dycei, Lachnus tropicalis and M. persicae, in descending order of abundance.
Because bioequivalence studies are performed using a crossover design, information on the intrasu... more Because bioequivalence studies are performed using a crossover design, information on the intrasubject coefficient of variation (intra-CV) for pharmacokinetic measures is needed when determining the sample size. However, calculated intra-CVs based on bioequivalence results of identical generic drugs produce different estimates. In this study, we collected bioequivalence results using public resources from the Ministry of Food and Drug Safety (MFDS) and calculated the intra-CVs of various generics. For the generics with multiple bioequivalence results, pooled intra-CVs were calculated. The estimated intra-CVs of 142 bioequivalence studies were 14.7±8.2% for AUC and 21.7±8.8% for C max. Intra-CVs of C max were larger than those of area under the concentrationtime curve (AUC) in 129 studies (90.8%). For the 26 generics with multiple bioequivalence results, the coefficients of variation of intra-CVs between identical generics (mean±sd (min ~ max)) were 38.0±24.4% (1.9 ~ 105.3%) for AUC and 27.9±18.2% (4.0 ~ 70.1%) for C max. These results suggest that substantial variation exists among the bioequivalence results of identical generics. In this study, we presented the intra-CVs of various generics with their pooled intra-CVs. The estimated intra-CVs calculated in this study will provide useful information for planning future bioequivalence studies. (This is republication of the article 'Transl Clin Pharmacol 2017;25:179-182' retracted from critical typographic errors. See the 'Retraction and Republication section of this issue for further information)
Levofloxacin is a bactericidal broad spectrum antibiotic against Gram-positive and Gram-negative ... more Levofloxacin is a bactericidal broad spectrum antibiotic against Gram-positive and Gram-negative pathogens. A randomized, two-treatment, two-period, two-way crossover study was conducted to evaluate the bioequivalence of Lectacin 250 mg tablet, a generic levofloxacin, to its reference drug, Cravit 250 mg tablet. Each period was separated by a 7-day washout. Serial blood samples were collected until 24 h after dosing and plasma levofloxacin concentrations were determined using a high performance liquid chromatography. Pharmacokinetic parameters were analyzed using K-BE Test 2007 and BA calc 2007 (Ministry of Food and Drug Safety, Cheongju-si, South Korea). The peak concentration (C max) and the area under the plasma concentration versus time curve from 0 to the last measurable concentration (AUC 0-t) for the generic and reference levofloxacin were 4.48±0.89 mg/L and 4.46± 0.95 mg/L, and 25.33±4.12 mg*h/L and 25.77±4.01 mg*h/L, respectively, leading to a geometric mean ratio (90% confidence interval) of the generic to the reference levofloxacin of 1.0060 (0.9339-1.0842) and 0.9810 (0.9476-1.0159), respectively, for C max and AUC 0-t. Lectacin 250 mg tablet is bioequivalent to Cravit 250 mg tablet.
To study the elastic properties of the medial gastrocnemius (GCM) in children with spastic cerebr... more To study the elastic properties of the medial gastrocnemius (GCM) in children with spastic cerebral palsy.
Voltage-gated sodium channels are integral transmembrane proteins responsible for the rapidly-ris... more Voltage-gated sodium channels are integral transmembrane proteins responsible for the rapidly-rising phase of action potentials in most excitable cells. In mammals, the functional diversity and wide distribution of sodium channel proteins in various tissues and cell types are achieved mainly by selective expression of many distinct sodium channel genes. In the model insect, Drosophila melanogaster, however, only one confirmed sodium channel gene, para, and one putative sodium channel gene, DSC1, are known. We cloned and sequenced a DSC1 ortholog, BSC1, from the German cockroach, Blattella germanica. We found that the BSC1 transcript was present in a wide range of tissues, including nerve cord, muscle, gut, fat body and ovary, whereas the para transcript was detected only in nerve cord and muscle. Moreover, different tissues contained distinct alternatively spliced variants of BSC1, and two muscle-specific spliced variants are predicted to encode truncated proteins with only the first two of the four homologous domains. Therefore, alternative splicing and expression of distinct splicing variants in functionally different tissues may be a major mechanism by which insects increase BSC1 channel diversity in neuronal and non-neuronal tissues.
As inhibitors of organic cation transporters (OCTs), proton pump inhibitors (PPIs) may affect the... more As inhibitors of organic cation transporters (OCTs), proton pump inhibitors (PPIs) may affect the plasma levels of metformin, an OCT substrate. We investigated the effects of two PPIs, pantoprazole and rabeprazole, on metformin pharmacokinetics and glucose levels in healthy subjects. In this open, randomized, 6 × 3 cross-over study, 24 participants were administered metformin, either alone or in combination with pantoprazole or rabeprazole. The plasma concentrations of metformin and serum concentrations of glucose after a 75 g oral glucose tolerance test (OGTT) were determined. The area under the concentration-time curve (AUC) for metformin was 15% and 16% greater following co-administration with pantoprazole and rabeprazole, respectively. The maximum plasma metformin concentrations (C max) also increased by 15% and 22%, respectively, compared to when it was administered without the PPIs. The percentage change in the AUC for glucose concentration versus time for metformin plus rabeprazole was significantly lower than that for metformin plus pantoprazole (geometric mean ratio: 0.96 [90% CI: 0.92-0.99] and 0.77 [0.63-0.93], respectively). There was no significant difference in the maximum glucose concentration. In conclusion, concomitant administration of PPIs with metformin significantly increased plasma metformin exposure, but the effects on glucose disposition were minor and varied depending on the PPI administered.
BSC1, which was originally identified by its sequence similarity to voltage-gated Na + channels, ... more BSC1, which was originally identified by its sequence similarity to voltage-gated Na + channels, encodes a functional voltage-gated cation channel whose properties differ significantly from Na + channels. BSC1 has slower kinetics of activation and inactivation than Na + channels, it is more selective for Ba 2+ than for Na + , it is blocked by Cd 2+ , and Na + currents through BSC1 are blocked by low concentrations of Ca 2+. All of these properties are more similar to voltage-gated Ca 2+ channels than to voltage-gated Na + channels. The selectivity for Ba 2+ is partially due to the presence of a glutamate in the pore-forming region of domain III, since replacing that residue with lysine (normally present in voltage-gated Na + channels) makes the channel more selective for Na +. BSC1 appears to be the prototype of a novel family of invertebrate voltage-dependent cation channels with a close structural and evolutionary relationship to voltage-gated Na + and Ca 2+ channels.
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