Biomedical subjects

M K Lee

Publications and source records attributed to M K Lee.

At least 19 recordsLinked to original sources

PubMed2000

Cutting edge: a role for CD1 in the pathogenesis of lupus in NZB/NZW mice.

Since anti-CD1 TCR transgenic T cells can activate syngeneic B cells via CD1 to secrete IgM and IgG and induce lupus in BALB/c mice, we studied the role of CD1 in the pathogenesis of lupus in NZB/NZW mice. Approximately 20% of B cells from the spleens of NZB/NZW mice expressed high levels of CD1 (CD1high B cells). The latter subset spontaneously produced large amounts of IgM anti-dsDNA Abs in vitro that was up to 25-fold higher than that of residual CD1int/low B cells. T cells in the NZB/NZW spleen proliferated vigorously to the CD1-transfected A20 B cell line, but not to the parent line. Treatment of NZB/NZW mice with anti-CD1 mAbs ameliorated the development of lupus. These results suggest that the CD1high B cells and their progeny are a major source of autoantibody production, and activation of B cells via CD1 may play an important role in the pathogenesis of lupus.

Animals↗

PubMed2000

Bivalent sequential binding model of a Bacillus thuringiensis toxin to gypsy moth aminopeptidase N receptor.

Specificity for target insects of Bacillus thuringiensis insecticidal Cry toxins is largely determined by toxin affinity for insect midgut receptors. The mode of binding for one such toxin-receptor complex was investigated by extensive toxin mutagenesis, followed by real-time receptor binding analysis using an optical biosensor (BIAcore). Wild-type Cry1Ac, a three-domain, lepidopteran-specific toxin, bound purified gypsy moth (Lymantria dispar) aminopeptidase N (APN) biphasically. Site 1 displayed fast association and dissociation kinetics, while site 2 possessed slower kinetics, yet tighter affinity. We empirically determined that two Cry1Ac surface regions are involved in in vivo toxicity and APN binding. Mutations within domain III affected binding rates to APN site 1, whereas mutations in domain II affected binding rates to APN site 2. Furthermore, domain III contact is completely inhibited in the presence of N-acetylgalactosamine, indicating loss of domain III binding eliminates all APN binding. Based upon these observations, the following model is proposed. A cavity in lectin-like domain III initiates docking through recognition of an N-acetylgalactosamine moiety on L. dispar APN. Following primary docking, a higher affinity domain II binding mechanism occurs, which is critical for insecticidal activity.

Animals↗

PubMed2000

Identification of a novel human member of the DEAD box protein family.

The cDNA library of human pancreatic islets was screened with sera from patients with insulin-dependent diabetes mellitus (IDDM). From the library screening, we isolated a novel cDNA, RNA helicase-like protein (RHELP), which exhibited strong sequence homology to p68 RNA helicase, a prototypic member of the DEAD (Asp-Glu-Ala-Asp) box protein family. Sequence analysis of the cDNA revealed that RHELP contained DEAD sequence motif and other conserved motifs of the DEAD box protein family, indicating that RHELP is a new member of this family. DEAD box-containing proteins are involved in the RNA processing, ribosome assembly, spermatogenesis, embryogenesis, and cell growth and division. RHELP showed 42% and 44% amino acid sequence identity to human p68 RNA helicase and yeast DBP2 RNA helicase, respectively, among the DEAD box protein family. Northern blot analysis revealed that RHELP is expressed in most tissues including the liver, lung, tonsil, thymus, and muscle in addition to the pancreatic islets. In vivo or in vitro functions of RHELP as a putative RNA helicase and its potential role as a diabetic autoantigen need to be further investigated.

Amino Acid Sequence↗

PubMed2000

Prognostic significance of cytogenetic abnormalities of chromosome arm 12p in childhood acute lymphoblastic leukemia: a report from the Children's Cancer Group.

BACKGROUND: The authors have determined the prognostic significance of cytogenetically detectable 12p abnormalities, which are frequent in children with acute lymphoblastic leukemia (ALL), in a large cohort of patients treated on risk-adjusted protocols of the Children's Cancer Group (CCG). METHODS: The presence of an abnormal 12p was identified among 1880 children with newly diagnosed ALL; outcome was assessed by standard life table methods. RESULTS: A total of 174 cases (9%) had cytogenetically detectable 12p abnormalities; the majority of cases had a balanced translocation, a del(12p), or an add(12p). In the overall cohort, event free survival (EFS) at 6 years was similar for patients with or without a 12p abnormality (76%, SD = 6%, vs. 75%, SD = 2%, respectively; P = 0.60). Among patients with pseudodiploidy, an abnormal 12p conferred improved outcome (P = 0.008; relative risk = 0.51; 95% confidence interval [CI], 0.31-0.85). There was a trend for improved EFS for those with abnormalities in both chromosome 12 homologues (P = 0.16; relative risk = 0.39; 95% CI, 0.10-1.55) and those with low hyperdiploidy (P = 0.07; relative risk = 0.44; 95% CI, 0.18-1.09). Among T-lineage ALL patients, there was a trend for worse outcome for abnormal versus normal 12p (P = 0.14; relative risk = 1.97; 95% CI, 0.78-4.93). There was no difference in EFS for the 12 patients with a dic(9;12) compared with patients lacking an abnormal 12p. CONCLUSIONS: These data suggest that although a cytogenetically detectable 12p aberration is a favorable risk factor for children with ALL and pseudodiploidy, it is not prognostic for the overall group of pediatric ALL patients treated with contemporary therapies of the CCG.

Adolescent↗

PubMed2000

Cynandione A from Cynanchum wilfordii protects cultured cortical neurons from toxicity induced by H2O2, L-glutamate, and kainate.

Oxidative stress has been implicated as a primary cause of neuronal death in certain neurodegenerative disorders and in aging brains. Natural products have been used in Asian societies for centuries for treating such neurodegenerative disorders as senile dementia. In an effort to identify active neuroprotective compounds from these products, we have employed cultures of rat cortical neurons as our screening system. A methanolic extract from dried roots of Cynanchum wilfordii Hemsley (Asclepiadaceae) significantly mitigated the neurotoxicity induced by H2O2 in this screening system. Activity-guided fractionation using several chromatographic techniques resulted in the isolation of the neuroprotective compound, cynandione A, a biacetophenone. At a concentration of 50 microM, cynandione A significantly reduced neurotoxicity induced by H2O2. Cynandione A significantly attenuated decreases in levels of glutathione, superoxide dismutase, and other enzymes that participate in the cellular defense against oxidative stress. Furthermore, cynandione A alleviated neurotoxicity induced by the excitotoxic neurotransmitter, L-glutamate, the neurotoxicity induced by kainate, but not that mediated by N-methyl-D-aspartate. Cynandione A was demonstrated to be a natural antioxidant as it facilitated the breakdown of hydrogen peroxide in vitro; however, no mechanism was uncovered to explain its neuroprotectant effects against glutamate and kainate. Therefore, cynandione A may be efficacious in protecting neurons from oxidative stress mediated via activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate/kainate receptors since it exerted significant neuroprotective effects on cultured cortical neurons.

Animals↗

PubMed2000

Enhanced synaptic potentiation in transgenic mice expressing presenilin 1 familial Alzheimer's disease mutation is normalized with a benzodiazepine.

Mutations in presenilin 1 (PS1) are the most common causes of familial Alzheimer's disease (FAD). We examined synaptic physiology in hippocampal brain slices of transgenic mice expressing the FAD-linked PS1 deletion of exon 9 variant. Basal excitatory transmission and paired-pulse facilitation in PS1 mutant mice were unchanged. Short- and long-term potentiation of excitatory transmission following high-frequency stimulation were greater in transgenic mice expressing mutant PS1. Mutants had enhanced synaptic inhibition, which may be a compensatory change offsetting an abnormally sensitized plasticity of excitatory transmission. Increasing inhibitory transmission in mutant animals even more with a benzodiazepine reverted synaptic potentiation to the levels of controls. These results support the potential use of benzodiazepines in the treatment of familial Alzheimer's disease.

Alzheimer Disease↗

PubMed2000

Inhibition of dopamine biosynthesis by protoberberine alkaloids in PC12 cells.

Berberine and palmatine exhibit a mild and competitive inhibition on bovine adrenal tyrosine hydroxylase (EC 1.14.16.2; TH). In this study, the inhibitory effects of protoberberine alkaloids (such as berberine, palmatine and coptisine) on dopamine biosynthesis in PC12 cells were investigated. Treatment with berberine and palmatine showed 53.7% and 61.0% inhibition of dopamine content in PC12 cells at a concentration of 20 microM for 24 hr, respectively. However, coptisine did not reduce dopamine content. The IC50 values of berberine and palmatine were 18.6 microM and 7.9 microM. Dopamine content was lowered at 6 hr and reached the minimal level at 24 hr after exposure to berberine and palmatine at 20 microM. The decreased dopamine level was maintained up to 48 hr, and then recovered to the control level at about 72 hr. TH activity was inhibited at 6 hr following treatment with berberine and palmatine, and was maintained at a reduced level up to 36 hr in PC12 cells (21-27% inhibition at 20 microM), whereas TH mRNA level was not found to alter for 24 hr. However, the intracellular Ca2+ concentration decreased by treatment with berberine and palmatine at 20 microM by 22-26% inhibition relative to the control level in PC12 cells. These results give evidence that berberine and palmatine lead to decreased dopamine content by inhibition of TH activity but not by regulation of TH gene expression in PC12 cells.

Animals↗

PubMed2000

Protection of rat hepatocytes exposed to CCl4 in-vitro by cynandione A, a biacetophenone from Cynanchum wilfordii.

To identify hepatoprotective agents from plant sources we use primary cultures of rat hepatocytes injured by CCl4. The hepatoprotective agents are the compounds that mitigate the injury caused by CCl4. Using this system we have investigated the biochemical mechanisms involved in the hepatoprotective activity of cynandione A, a biacetopherone, isolated from the roots of Cynanchum wilfordii Hemsley (Asclepiadaceae). Cynandione A (50 microM) significantly reduced (approximately 50%) the release into the culture medium of glutamic pyruvic transaminase and sorbitol dehydrogenase from the primary cultures of rat hepatocytes exposed to CCl4. Glutathione, superoxide dismutase, catalase and glutathione reductase play important roles in the cellular defence against oxidative stress. Cynandione A appeared to protect primary cultured rat hepatocytes exposed to CCl4 from significant drops in the levels of each of these four specific markers. Cynandione A also ameliorated lipid peroxidation by up to 50% as demonstrated by a reduction in the production of malondialdehyde. These results suggest that cynandione A protected the hepatocytes from CCl4-injury by maintaining the level of glutathione and by inhibiting the production of malondialdehyde, due to its radical scavenging properties.

Alanine Transaminase↗

PubMed2000

Clinical significance of deletions of chromosome arm 6q in childhood acute lymphoblastic leukemia: a report from the Children's Cancer Group.

We have compared outcome for 167 (9.0%) children with a del(6q) and 1713 (91%) children without a del(6q) treated on Children's Cancer Group (CCG) risk-adjusted treatment protocols for acute lymphoblastic leukemia (ALL). Thirty-three patients had a del(6q) as the sole aberration; 22 patients had a del(6q) only as a secondary abnormality. Thirty-six cases had a del(6q) and high hyperdiploidy (>50 chromosomes). Six patients with a del(6q) also had +16 and 8 patients had loss of a sex chromosome. Frequent recurring breakpoints were q13, q15, q21, q23, and q25. Patients with a del(6q) were more likely to have T-lineage ALL (p < 0.001), a mediastinal mass (p = 0.01), and higher WBC counts (p = 0.04), although only half of these patients were classified as poor risk. Event-free survival at 6 years was similar for patients with or without a del(6q), with estimates of 77% (SD = 5%) and 74% (SD = 2%), respectively (p = 0.44). This finding was also observed within NCI poor and standard risk groups. Thus, cytogenetically detectable del(6q) is not associated with adverse risk in pediatric ALL.

Antineoplastic Agents↗

PubMed1999

Hypodiploidy with less than 45 chromosomes confers adverse risk in childhood acute lymphoblastic leukemia: a report from the children's cancer group.

We have determined the prognostic significance of hypodiploidy (<46 chromosomes) in a large cohort of children with acute lymphoblastic leukemia (ALL) treated by the Children's Cancer Group. Among 1,880 patients, 110 (5.8%) had hypodiploid karyotypes: 87 had 45 chromosomes, 15 had 33 to 44 chromosomes, none had 29 to 32 chromosomes, and 8 had 24 to 28 chromosomes (near-haploidy). Six-year event-free survival (EFS) estimates for patients with 45 chromosomes, 33 to 44 chromosomes, or 24 to 28 chromosomes were 65% (standard deviation [SD], 8%), 40% (SD, 18%), and 25% (SD, 22%), respectively (log rank, P =.002; test for trend, P =.0009). The combined hypodiploid group had worse outcome than nonhypodiploid patients, with 6-year EFS of 58% (SD, 7%) and 76% (SD, 2%), respectively (P <.0001). EFS for the subgroup with 45 chromosomes was similar to that of patients with pseudodiploidy (P =.43) or 47 to 50 chromosomes (P =.76). None of the patients with 24 to 28 chromosomes had a t(4;11), a t(9;22), or a t(1;19), and most received highly intensive therapy. The adverse risk associated with 33 to 44 and 24 to 28 chromosomes remained significant in multivariate analyses adjusted for important risk factors including age, white blood cell count, and Philadelphia chromosome status. Thus, hypodiploidy with less than 45 chromosomes, particularly 24 to 28 chromosomes, is a significant adverse risk factor despite treatment with contemporary intensive therapies.

Child↗

PubMed1999

Binding of Bacillus thuringiensis Cry1Ac toxin to Manduca sexta aminopeptidase-N receptor is not directly related to toxicity.

Bacillus thuringiensis Cry1Ac delta-endotoxin specifically binds a 115-kDa aminopeptidase-N purified from Manduca sexta midgut. Cry1Ac domain III mutations were constructed around a putative sugar-binding pocket and binding to purified aminopeptidase-N and brush border membrane vesicles (BBMV) was compared to toxicity. Q509A, R511A, Y513A, and 509-511 (QNR-AAA) eliminated aminopeptidase-N binding and reduced binding to BBMV. However, toxicity decreased no more than two-fold, indicating activity is not directly correlated with aminopeptidase-N binding. Analysis of toxin binding to aminopeptidase-N in M. sexta is therefore insufficient for predicting toxicity. Mutants retained binding, however, to another BBMV site, suggesting alternative receptors may compensate in vivo.

Acetylgalactosamine↗

PubMed1999

Pharmacokinetics and organ distribution of cyclosporin A incorporated in liposomes and mixed micelles.

The commercially available intravenous dosage form of cyclosporin A (C-CsA) contains a solubilizing agent, polyoxyethylated castor oil, which has been reported to be toxic. To replace the toxic solubilizing agent present in C-CsA, liposomal and mixed micellar preparations were made to solubilize CsA by the proliposome method and characterized. Furthermore, pharmacokinetics and organ distributions of these preparations were evaluated in comparison to C-CsA, which is micellar. The mean size of liposomal preparation (L-CsA) composed of DPPC/PA (molar ratio 3/1) and CsA was 43.6 nm and that of mixed micellar preparation (M-CsA) composed of DMPC/DSPE-PEG (molar ratio 95/5) and CsA was 6.5 nm. The solubilization of CsA was 2-fold greater in mixed micellar solution than in liposomes (0.06 vs 0.03 mg of CsA/mg of lipid). L-CsA, M-CsA and C-CsA were intravenously administered into rats via the femoral vein to analyze pharmacokinetics and organ distribution of CsA. M-CsA was not significantly different from C-CsA in every pharmacokinetic parameter studied. However, L-CsA resulted in 30% decrease in AUC and 55% increase in Cl(t) compared with C-CsA (P<0. 05), without any significant differences in MRT, V(dss) and t(1/2). In addition, the distributions of M-CsA and L-CsA in different organs were not significantly different from those of C-CsA (0.05), except for a 51% decrease of M-CsA in the spleen at 4 h and a 33% increase of L-CsA in the liver at 4 h (P<0.05). These findings demonstrate that the liposomal preparation composed of DPPC/PA and CsA shows slightly different pharmacokinetics and organ distribution patterns from C-CsA, whereas the mixed micellar preparation composed of DMPC/DSPE-PEG and CsA exhibits similar patterns to C-CsA, as expected. Furthermore, these results suggest that those mixed micellar and liposomal preparations can replace C-CsA containing the toxic solubilizing agent, thus providing useful alternative dosage forms for intravenous administration of CsA.

Animals↗

PubMed1999

Mortality in North Korean migrant households: a retrospective study.

BACKGROUND: A deteriorating economy, coupled with a series of natural disasters in 1995-97, led to a severe food crisis in North Korea. Although the country has received substantial international aid since 1996, demographic assessments of crisis impact have been limited. We assessed mortality trends in North Korea since 1995. METHODS: At 15 randomly selected sites in China, 440 North Korean adult migrants were interviewed during July-September, 1998. Respondents were asked about births, deaths, and migration patterns in their households between mid-1994 and mid-1998, and about household food sources. The respondents also provided basic demographic information about the households of their relatives. We compared mortality rates from migrant households with data from the 1993 census and with data about households of non-migrant relatives. FINDINGS: Households that included a recent migrant to China showed increasing mortality: crude death rates rose from 28.9 per 1000 in 1995, to 45.6 per 1000 in 1996, and to 56.0 per 1000 in 1997 (p=0.0001), with a 3-year average rate of 42.8 per 1000. The crude 3-year birth rate was 11.0 per 1000. Average household size declined from 4.0 at the beginning of 1995 to 3.4 at the end of 1997 (p=0.0002). Among 259 households of non-migrant relatives, the crude death rate was 43.2 per 1000 and the crude birth rate was 8.8 per 1000. In these households, the 3-year trend of increasing mortality was significant (p=0.001), as was the decline in average household size from 4.3 at the beginning of 1995 to 3.7 at the end of 1997 (p=0.0001). INTERPRETATION: Among North Korean households that include a recent migrant to China, mortality has increased and household size has declined since 1995. This trend raises concern about the state of the general population, at least in the province of North Hamkyong, from where most of the migrants originated.

Adolescent↗

PubMed1999

Phospholipid-based microemulsions of flurbiprofen by the spontaneous emulsification process.

The purpose of this study was to investigate the possibility for parenteral delivery of flurbiprofen without chemical modification using a phospholipid-based microemulsion system. Microemulsions composed of ethyl oleate, lecithin and distearoylphosphatidyl-ethanolamine-N-poly(ethyleneglycol) 2000 (DSPE-PEG) were prepared using ethanol as a cosolvent. The effect of formulation variables on the particle size of the microemulsion was investigated. Flurbiprofen concentrations in plasma and various organs after the intravenous administration of flurbiprofen-loaded microemulsion were measured and compared with those after the intravenous administration of flurbiprofen axetil-entrapped emulsion (Lipfen(R), 50 mg/5 ml as flurbiprofen axetil) and flurbiprofen solution. Phospholipid-based microemulsions could solubilize more than 10 mg ml-1 of flurbiprofen at the ratio of vehicle to drug at least 10:1, if the oil contents (10 or 20%) of common parenteral emulsions were used. The half-life, AUC and MRT of flurbiprofen loaded in microemulsion (ethyl oleate:lecithin:DSPE-PEG:flurbiprofen=8:3:1:1.2) increased significantly. The biodistribution of flurbiprofen loaded in this microemulsion was quite different from others. Reticuloendothelial uptake of flurbiprofen loaded in microemulsion decreased compared with that in solution or Lipfen(R). It is concluded that the current microemulsion system might be applicable to formulate the parenteral dosage form of poorly water-soluble flurbiprofen without chemical modification.

Animals↗

PubMed1999

Development of dried liposomes containing beta-galactosidase for the digestion of lactose in milk.

The hydrolyzed-lactose milk for lactase-deficient subjects has a sweeter taste than whole milk, and some subjects dislike its taste. In order to cope with this shortcoming, we examined whether beta-galactosidase, which hydrolyzes lactose, added to the whole milk in the form of dried liposomes, would be able to digest lactose in milk following the lysis of liposomes in the presence of bile salts. Dried liposomes containing beta-galactosidase were prepared in the presence of trehalose by the dehydration-rehydration vesicle method to overcome the instability of the conventional liposome suspension. The stability of liposomal membranes was evaluated by measuring the activity of entrapped beta-galactosidase under various storage conditions. By treating liposomes with trehalose, which was found to prevent the fusion of liposomes and the leakage of entrapped drug, the entrapping efficiency increased up to fourfold. Over 95% of dried liposomes which had been stored at 17 degrees C for 60 days were reconstituted to liposomes upon rehydration process. From the stability study, dried liposomes were found to retain 87% of beta-galactosidase activity at 17 degrees C after 60 days and to be more stable than the multilamellar vesicle suspension prepared without trehalose. The lysis study showed that dried liposomes were hardly lyzed in the simulated gastric fluid with pepsin, but lyzed immediately more than 90% in 0.01 M deoxycholic acid. Lactose hydrolysis in the presence of deoxycholic acid after the addition of dried liposome-entrapped beta-galactosidase to whole milk was proportional to the quantity of entrapped beta-galactosidase and the amount of dried liposomes added. These results demonstrate that beta-galactosidase entrapped in liposome is stable and reconstituted mostly upon rehydration, and can digest lactose in milk after the efficient lysis of liposomes in the presence of bile salts. This study implies that beta-galactosidase entrapped in liposome may be applied to whole milk for lactase-deficient subjects.

Animals↗

PubMed1999

Identification of determinants of interaction between CXCR4 and gp120 of a dual-tropic HIV-1DH12 isolate.

Using a panel of chimeric viruses and their chimeric envelope glycoproteins, we have previously reported that the V1/V2 or the V3 regions of a dual-tropic primary human immunodeficiency virus type 1 (HIV-1) isolate (HIV-1DH12) could individually confer CXCR4 usage when introduced into the backbone of a macrophage-tropic (M-tropic) virus isolate (HIV-1AD8). In this study, chimeric CXCR4-CXCR2 chemokine receptors were employed to identify the determinants involved in the interaction between CXCR4 and the dual-tropic HIV-1DH12 gp120. Our results indicate that (i) HIV-1DH12 gp120 interacts primarily with the extracellular domains 1 (E1) and 2 (E2) of CXCR4, (ii) the V1/V2 and the V3 regions interact with different domains of CXCR4, and (iii) the V1/V2 region plays a more critical role in the interaction between CXCR4 and HIV-1DH12 gp120. Combining our data and those of others suggests that the pattern of CXCR4 usage is highly dependent on HIV-1 isolates. In addition, an M-tropic virus may evolve to become dual-tropic by first acquiring the ability to interact with CXCR4 through the V1/V2 region of gp120.

HIV Envelope Protein gp120↗

PubMed1999

Application of dynamic computed tomography for measurements of local aortic elastic modulus.

A novel computed tomographic (CT) technique used for the instantaneous measurement of the dynamic elastic modulus of intact excised porcine aortic vessels subjected to physiological pressure waveforms is described. This system was comprised of a high resolution X-ray image intensifier based computed tomographic system with limiting spatial resolution of 3.2 mm-1 (for a 40 mm field of view) and a computer-controlled flow simulator. Utilising cardiac gating and computer control, a time-resolved sequence of 1 mm thick axial tomographic slices was obtained for porcine aortic specimens during one simulated cardiac cycle. With an image acquisition sampling interval of 16.5 ms, the time sequences of CT slices were able to quantify the expansion and contraction of the aortic wall during each phase of the cardiac cycle. Through superficial tagging of the adventitial surface of the specimens with wire markers, measurement of wall strain in specific circumferential sectors and subsequent calculations of localised dynamic elastic modulus were possible. The precision of circumferential measurements made from the CT images utilising a cluster-growing segmentation technique was approximately +/- 0.25 mm and allowed determination of the dynamic elastic modulus E(dyn) with a precision of +/- 8 kPa. Dynamic elastic modulus was resolved as a function of the harmonics of the physiological pressure waveform and as a function of the angular position around the vessel circumference. Application of this dynamic CT (DCT) technique to seven porcine thoracic aortic specimens produced a circumferential average (over all frequency components) E(dyn) of 373 +/- 29 kPa. This value was not statistically different (p < 0.05) from the values of 430 +/- 77 and 390 +/- 47 kPa obtained by uniaxial tensile testing and volumetric measurements respectively.

Animals↗

PubMed1999

Inhibitory activity of monoamine oxidase by coumarins from Peucedanum japonicum.

Four coumarins were isolated from chloroform extract of the root of Peucedanum japonicum and identified as praeruptorin A(1), xanthotoxin (2), psoralen (3) and bergapten (4) on the basis of spectroscopic methods. The inhibitory activities of these coumarins on monoamine oxidase prepared by mouse brain were tested. The IC50 values of them were shown to be 27.4 microM (1), 40.7 microM (2), 35.8 microM (3), and 13.8 microM (4), in vitro.

Animals↗