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Biomedical subjects

K K Kang

Publications and source records attributed to K K Kang.

9 recordsLinked to original sources
PubMed2003

Efficacy of DA-8159, a new PDE5 inhibitor, for inducing penile erection in rabbits with acute spinal cord injury.

DA-8159 is a pyrazolopyrimidinone derivative which exhibits potent and selective phosphodiesterase type 5 (PDE5) inhibition. The aim of this study was to investigate the effects of DA-8159 on inducing a penile erection in rabbits with an acute spinal cord injury (ASCI). DA-8159 was given either orally (1, 3, or 10 mg/kg) or intravenously (0.1 or 0.3 mg/kg) to conscious male albino rabbits with a surgical transection of the spinal cord at the L2-L4 lumbar vertebra or ischemic-reperfusion SCI rabbits. Erection was evaluated in a time-course manner by measuring the length of the uncovered penile mucosa. DA-8159 induced a dose-dependent erection in both transection and ischemic-reperfusion ASCI rabbits. The efficacy of DA-8159 was potentiated by an intravenous injection of sodium nitroprusside, a nitric oxide donor. Potentiation of the effect by nitric oxide donor implies that DA-8159 can enhance the erectile activity during sexual arousal. These results suggest that DA-8159 may be useful for treating erectile dysfunction in patients with an SCI.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2001

Identification of S-genotypes by PCR-RFLP in breeding lines of Brassica.

We developed a molecular method for the identification of the S-alleles of Brassicaceae, which belongs to the inbred line. This method is quicker and more precise than the existing methods. The genotype of the S-allele for 20 S-haplotypes of cabbage and 20 S-haplotypes of broccoli was determined by a pollination test. In order to identify the S-alleles, we performed PCR-RFLP with a mixture of the primers that are related to the S-locus glycoprotein (SLG) gene, which corresponds to the results of the pollination test. The selected primers amplified all of the single bands of about 1,150 bp in all 40 lines of cabbage and broccoli. Three out of 20 lines of cabbage were amplified by class I SLG specific primers, whereas all of the lines of the cabbage were amplified by class II SLG specific primers. Therefore, we could not classify class I and class II precisely by the class I and class II primers. However, 15 out of 20 lines of broccoli were amplified by the class I SLG specific primers. The remaining 5 lines were amplified with the class II SLG specific primers. We then digested the amplified PCR products with various restriction endonucleases and chose a restriction endonuclease, which accords exactly with the results of the diallel cross. The best one was HinfI. Its RFLP result was the same as that of the nucleotide sequence analysis. The 40 lines of cabbage and broccoli consisted of 16 different S-haplotypes. Therefore, the PCR-RFLP analysis was quicker and more precise in identifying the characteristics of S-haplotypes that are used in breeding. Also, we were able to check whether the lines could be mixed. The S-genotypes were difficult to determine due to the different flowering time.

Alleles↗
PubMed2000

Erectogenic effect of the selective phosphodiesterase type 5 inhibitor, DA-8159.

DA-8159, a new phosphodiesterase 5 inhibitor, was assessed for its erectogenic potential by a penile erection test in rats, the relaxation of isolated rabbit corpus cavernosum (CC), and estimation of the intracavernous pressure (ICP) in the anesthetized dog. Oral administration of DA-8159 (0.3 to 1 mg/kg) increased the number of erections in rats with increasing dosage, with the highest penile erection index at 10 mg/kg. DA-8159 induced the relaxation of phenylephrine (PHE)-induced contractions in the rabbit CC and decreased the IC50 of the nitric oxide donor sodium nitroprusside (SNP) in a dose-dependent fashion. In pentobarbital-anesthetized dogs, the intravenous administration of DA-8159 (1 approximately 300 g/kg) potentiated the increase in ICP induced by the intracavernosal SNP in a dose-related manner. These findings suggest that DA-8159 has significant therapeutic potential in the treatment of erectile dysfunction.

Animals↗
PubMed2000

One-month parenteral toxicity study of recombinant human basic fibroblast growth factor in dogs.

A 1-mo toxicity study followed by a 1-mo recovery period of recombinant human basic fibroblast growth factor (bFGF) was performed using Beagle dogs at doses of 30, 120 or 480 mg/kg/d to estimate the no observed adverse effect level (NOAEL). Subcutaneous thickening was seen and its incidence, as well as that of stiffness of the injection sites, increased with dose. There were neither dead animals nor significant changes of body weight during the experimental period. In addition, no significant bFGF-related changes were found in ophthalmologic and histopathological examination, urinalysis and hematological, biochemical and organ weight parameters. At necropsy, red-brownish spots and/or nodule formations were recognized in a dose-dependent manner. Splenomegaly was noted in the 480 mg/kg group, but these findings had a low incidence in all dose groups. The findings in the dosing period disappeared or were ameliorated during the recovery period. The above data suggests the NOAEL of bFGF in Beagle dogs is >480 mg/kg/d.

Animals↗
PubMed1997

The physical map of the chloroplast DNA from Korean ginseng (Panax ginseng C.A. Meyer).

To compare the gene order of the chloroplast genome among dicotyledonous plants, we constructed a physical map of chloroplast DNA (cpDNA) of Korean ginseng (Panax ginseng C.A. Meyer) with four restriction enzymes, BamHI, HindIII, EcoRI, and PstI. The restriction enzyme recognition sites of the physical map were also confirmed by Southern hybridization of total ginseng cpDNA with homologous and heterologous probes. The cpDNA of Korean ginseng was determined as a circular molecule with a total size of about 154 kb, which contain two inverted repeats of 23 kb each that disrupt the rest of the molecule into a large (90 kb) and a small single copy region (18 kb). The genome structure of Korean ginseng cpDNA was similar in size and gene order to that of tobacco cpDNA. The cpDNA of Korean and American ginseng (P. quinquefolius) showed very similar restriction patterns.

Chromosome Mapping↗
PubMedDate not supplied

The effect of PDE5 inhibition on the erectile function in streptozotocin-induced diabetic rats.

The aim of this study was to assess the effect of phosphodiesterase 5 inhibitor, DA-8159, on erectile function throughout the quantitative analysis of vascular endothelial cell, smooth muscle (SM), TGF-beta1 expression in rat corpus cavernosum and measurement of intracavernous pressure (ICP) in diabetic rats. DA-8159 (0, 5, 10, 20 mg/kg) was administered orally once a day to diabetic rats. After 8 weeks, immunohistochemistry and computerized image analysis were performed to quantify the percent area within the Corpora Cavernosa occupied by the endothelial cells, SM cells and fibrotic tissues. ICP/mean arterial pressure (MAP) was also measured by electrostimulation of the cavernous nerve. Diabetic rats showed a significant decrease in the SM and endothelial cell content, and an increase in the TGF-beta1 expression level within the cavernosa areas compared to the normal rats. The mean cavernous SM, endothelial cell content and TGF-beta1 expression level were 9.7+/-0.7, 4.5+/-0.7 and 17.9+/-2.1%, respectively. DA-8159 prevented reduction of SM (12.3+/-0.4% (5 mg/kg), 13.8+/-0.4% (20 mg/kg)) and endothelial cell content (5.6+/-0.5% (5 mg/kg), 6.3+/-0.6% (20 mg/kg)). Immunoreactivity of TGF-beta1 and intracorporal fibrosis were also significantly lower in DA-8159-treated groups (11.8+/-1.2% (5 mg/kg), 9.5+/-1.1% (20 mg/kg)). Electrostimulation of the cavernous nerve induced significant increase in maximum ICP (62.2+/-13.6 mmHg in 10 mg/kg vs 37.5+/-17.5 mmHg in diabetic group) and area under the curve of the ratio of ICP/MAP (8891.09+/-1957 in 10 mg/kg vs 6315.87+/-2272 in diabetic group). These results suggest that subchronic treatment of DA-8159 can prevent the development of erectile dysfunction (ED), and provides a rationale for the use of DA-8159 as treatment of diabetic ED.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMedDate not supplied

The effect of DA-8159, a novel PDE5 inhibitor, on erectile function in the rat model of hypercholesterolemic erectile dysfunction.

This study examined the effects of a new phosphodiesterase type 5 inhibitor, DA-8159, on erectile function associated with hypercholesterolemia. First of all, in order to investigate whether chronic administration of DA-8159 prevents the development of erectile dysfunction associated with hypercholesterolemia, male SD rats were divided into four groups (normal control, hypercholesterolemic control, DA-8159 5 or 20 mg/kg/day). Over a 5-month period, the animals were fed a 2% cholesterol diet and administered DA-8159 orally once a day. After 5 months, the electrostimulation-induced penile erection and the vascular function using acetylcholine-induced vasodilation with endothelium-intact aortic rings were examined. Furthermore, the plasma lipid profiles, endothelin and N(G),N(G)-dimethylarginine (asymmetrical dimethylarginine, ADMA) concentrations were measured. In order to investigate the acute treatment effect of DA-8159 on the erectile function in an established hypercholesterolemic model, additional animals were given a 2% cholesterol diet for 5 months without DA-8159. At the end of 5 months, the rats were divided into three groups (hypercholesterolemic control, DA-8159 0.3 or 1 mg/kg). DA-8159 was administered intravenously 1 min prior to the intracavernous pressure (ICP) measurement. In a chronic treatment study, while the hypercholesterolemic control showed a significantly lower erectile function, vascular reactivity, and increased plasma cholesterol, endothelin and ADMA concentration, the chronic DA-8159 treatment clearly restored the erectile responses by electric stimulation, preserved the potential of thoracic aortic relaxation in a dose-dependent manner, and significantly decreased the plasma endothelin and ADMA concentrations. In an acute treatment study, DA-8159 induced a dose- and frequency-dependent increase in ICP. The ICP/BP ratio and the corresponding AUC values, and the detumescence time were also significantly increased compared to the hypercholesterolemic control. These results suggest that DA-8159 is beneficial for erectile dysfunction in a rat hypercholesterolemic model and provided a rationale for the potential use of DA-8159 for treating erectile dysfunction secondary to hypercholesterolemia.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMedDate not supplied

DA-8159, a new PDE5 inhibitor, attenuates the development of compensatory right ventricular hypertrophy in a rat model of pulmonary hypertension.

This study evaluated the effect of DA-8159, a new phosphodiesterase 5 inhibitor, on the compensatory development of right ventricular hypertrophy in monocrotaline (MCT)-induced pulmonary hypertension (PH). Rats treated with subcutaneous MCT were divided into three groups, which received DA-8159 1 mg/kg, DA-8159 5 mg/kg or saline-vehicle orally, twice daily for 21 days. The vehicle group demonstrated increased right ventricular weight, pulmonary artery medial wall thickening, myocardial fibrosis, increased plasma cyclic guanosine monophosphate (cGMP) concentration and reduced body weight gains. DA-8159, however, markedly attenuated the compensatory development of right ventricular hypertrophy and pulmonary artery medial wall thickening, amplified the increase in plasma cGMP levels and increased lung cGMP concentrations. In addition, DA-8159 prevented myocardial fibrosis induced by MCT. These results demonstrate that DA-8159 attenuates the compensatory development of right ventricular hypertrophy in a rate model of PH. DA-8159 might, therefore, be a useful treatment option for PH, but its efficacy in humans needs evaluating.

3',5'-Cyclic-GMP Phosphodiesterases↗