RESUMEN
BACKGROUND AND AIMS: Inflammation and calcification are major factors responsible for degeneration of bioprosthetic valve and other substitute heart valve implantations. The objective of this study was to evaluate the anti-inflammatory and anti-calcification effects of Entelon150® (consisting of grape-seed extract) in a beagle dog model of intravascular bovine pericardium implantation. METHODS: In total, 8 healthy male beagle dogs were implanted with a bovine pericardium bilaterally in the external jugular veins and divided into two groups. Animals in the Entelon150® group (n = 4) were treated with 150 mg of Entelon150® twice daily for six weeks after surgery. The negative control (NC) group (n = 4) was treated with 5 ml of saline using the same method. After six weeks, we measured the calcium content, performed histological examination, and performed molecular analysis. RESULTS: The calcium content of implanted tissue in the Entelon150® group (0.56±0.14 mg/g) was significantly lower than that in the NC group (1.48±0.57 mg/g) (p < 0.05). Histopathological examination showed that infiltration of chronic inflammatory cells, such as fibroblasts and macrophages, occurred around the graft in all groups; however, the inflammation level of the implanted tissue in the Entelon150® group was s lower than that in the NC group. Both immunohistochemical and western blot analyses revealed that bone morphogenetic protein 2 expression was significantly attenuated in the Entelon150® group. CONCLUSIONS: Our results indicate that Entelon150® significantly attenuates post-implantation inflammation and degenerative calcification of the bovine pericardium in dogs. Therefore, Entelon150® may increase the longevity of the bovine pericardium after intravascular implantation.
Asunto(s)
Antiinflamatorios/uso terapéutico , Calcinosis/tratamiento farmacológico , Extracto de Semillas de Uva/uso terapéutico , Complicaciones Posoperatorias/tratamiento farmacológico , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Bioprótesis , Calcinosis/etiología , Bovinos , Perros , Fibroblastos/efectos de los fármacos , Extracto de Semillas de Uva/administración & dosificación , Extracto de Semillas de Uva/farmacología , Prótesis Valvulares Cardíacas , Macrófagos/efectos de los fármacos , Masculino , Pericardio/trasplante , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversosRESUMEN
Neovascular age-related macular degeneration (nAMD) is a common cause of irreversible vision loss in the elderly. Anti-vascular endothelial growth factor has been effective in treating pathological ocular neovascularization, but it has limitations including the need for repeated intraocular injections for the maintenance of therapeutic effects in most patients and poor or non-response to this agent in some patients. in vitro cellular studies were conducted using retinal pigment epithelial cell lines (ARPE-19 and hTERT-RPE1), human umbilical vein endothelial cells (HUVECs), and human umbilical vein smooth muscle cells (HUVSMCs). in vivo efficacy of ilimaquinone (IQ) was tested in laser-induced choroidal neovascularization mouse and rabbit models. Tissue distribution study was performed in male C57BL6/J mice. IQ, 4,9-friedodrimane-type sesquiterpenoid isolated from the marine sponge, repressed the expression of angiogenic/inflammatory factors and restored the expression of E-cadherin in retinal pigment epithelial cells by inhibiting the Wnt/ß-catenin pathway. In addition, it selectively inhibited proliferation and tube formation of HUVECs by activating the p53 pathway. Topical and intraperitoneal administration of IQ significantly reduced choroidal neovascularization in rabbits and mice with laser-induced choroidal neovascularization. Notably, IQ by the oral route of exposure was highly permeable to the eyes and suppressed abnormal vascular leakage by downregulation of ß-catenin and stabilization of p53 in vivo. Our findings demonstrate that IQ functions through regulation of p53 and Wnt/ß-catenin pathways with conceivable advantages over existing cytokine-targeted anti-angiogenic therapies.
Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Neovascularización Coroidal/prevención & control , Degeneración Macular/prevención & control , Quinonas/farmacología , Neovascularización Retiniana/prevención & control , Vasos Retinianos/efectos de los fármacos , Sesquiterpenos/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Vía de Señalización Wnt/efectos de los fármacos , beta Catenina/metabolismo , Animales , Línea Celular , Neovascularización Coroidal/metabolismo , Neovascularización Coroidal/patología , Modelos Animales de Enfermedad , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Degeneración Macular/metabolismo , Degeneración Macular/patología , Masculino , Ratones Endogámicos C57BL , Conejos , Neovascularización Retiniana/metabolismo , Neovascularización Retiniana/patología , Vasos Retinianos/metabolismo , Vasos Retinianos/patologíaRESUMEN
HL235 is a new cathepsin K inhibitor designed and synthesized to treat osteoporosis. Since HL235 has poor aqueous solubility, a self-microemulsifying drug delivery system (SMEDDS) was formulated to enhance its oral bioavailability. A solubility study of HL235 was performed to select a suitable oil, surfactant and cosurfactant. Pseudoternary phase diagrams were plotted to identify the microemulsion region and to determine the range of components in the isotropic mixture. D-optimal mixture design and a desirability function were introduced to optimize the SMEDDS formulation for the desired physicochemical characteristics, i.e., high drug concentration at 15â¯min after dilution with simulated gastric fluid (SGF) and high solubilization capacity. The optimized HL235-loaded SMEDDS formulation consisted of 5.0% Capmul MCM EP (oil), 75.0% Tween 20 (surfactant) and 20.0% Carbitol (cosurfactant). The droplet size of the microemulsion formed by the optimized formulation was 10.7⯱â¯1.6â¯nm, and the droplets were spherical in shape. Pharmacokinetic studies in rats showed that the relative oral bioavailability of the SMEDDS formulation increased up to 3.22-fold compared to its solution in DMSO:PEG400 (8:92, v/v). Thus, the formulation of SMEDDS optimized by D-optimal mixture design could be a promising approach to improve the oral bioavailability of HL235.
Asunto(s)
Catepsina K/antagonistas & inhibidores , Sistemas de Liberación de Medicamentos , Pirimidinas/administración & dosificación , Administración Oral , Animales , Disponibilidad Biológica , Química Farmacéutica , Diglicéridos/química , Emulsiones , Glicoles de Etileno/química , Excipientes/química , Masculino , Monoglicéridos/química , Tamaño de la Partícula , Polisorbatos/química , Pirimidinas/química , Pirimidinas/farmacocinética , Ratas , Ratas Sprague-Dawley , SolubilidadRESUMEN
PURPOSE: A fixed-dose combination (FDC) pill of amlodipine (relatively old calcium channel blocker as dihydropyridine) and olmesartan (relatively new angiotensin II receptor blocker) is used for hypertension that is not adequately controlled with a single-formulation drug. Because the FDC is a one-pill formulation, and amlodipine and olmesartan have different mechanisms of action, it is expected to improve patients' medication compliance and have an increased blood pressure-lowering efficacy. The purpose of this study was to assess the safety profile and the bioequivalence of two different FDC formulations [amlodipine besylate/olmesartan medoxomil 10/40 mg (reference product) and S-amlodipine nicotinate/olmesartan medoxomil 5/40 mg (test product)]. METHODS: A randomized, open-label, single-dose, 2-treatment, 2-way, and 2-period crossover study, including a 3-week washout period, was performed in 32 healthy Korean male volunteers. To analyze the concentration of S-amlodipine or olmesartan, plasma samples were collected up to 144 hours after the dose for S-amlodipine and 48 hours after the dose for olmesartan. Pharmacokinetic parameters, including the Cmax and the area under the curve from time 0 to the last measurable concentration (AUC0-last) for the time versus concentration plot, were calculated. Analysis of variance for bioequivalence was conducted using Cmax and AUC0-last converted to log scale, and the mean ratios and 90% CIs were determined. Safety data included analysis of adverse events (AEs), vital signs, physical examinations, clinical laboratory test, and 12-lead ECGs. FINDINGS: Of the 32 enrolled participants, 29 healthy volunteers completed the study. For both S-amlodipine and olmesartan, the main pharmacokinetic parameters were all within the acceptable range for regulatory bioequivalence. The 90% CIs for the geometric mean ratios of Cmax and AUC0-last were 0.8766 to 0.9760 and 0.8288 to 0.9224, respectively, for S-amlodipine and 0.9097 to 1.1229 and 0.8904 to 1.0407, respectively, for olmesartan. Hypotension was the most frequent AE, and it was observed in 4 volunteers with the test product and 7 volunteers with the reference product. Both the test and reference formulations were well tolerated. IMPLICATIONS: The present study demonstrates that the newly developed FDC product (test drug) and the conventional FDC product (reference drug) have comparable pharmacokinetic characteristics in healthy adult male volunteers. Both the test and reference products indicated good tolerance in this population, and no serious AEs were observed.
Asunto(s)
Amlodipino/farmacocinética , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacocinética , Bloqueadores de los Canales de Calcio/farmacocinética , Niacina/farmacocinética , Olmesartán Medoxomilo/farmacocinética , Adulto , Amlodipino/administración & dosificación , Amlodipino/sangre , Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Bloqueadores del Receptor Tipo 1 de Angiotensina II/sangre , Pueblo Asiatico , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/sangre , Estudios Cruzados , Combinación de Medicamentos , Voluntarios Sanos , Humanos , Masculino , Niacina/administración & dosificación , Niacina/sangre , Olmesartán Medoxomilo/administración & dosificación , Olmesartán Medoxomilo/sangre , Comprimidos , Equivalencia Terapéutica , Adulto JovenRESUMEN
HL-217 is a new synthetic angiogenesis inhibitor. Platelet derived growth factor (PDGF) is a vasoactive factor and has been implicated in proliferative retinopathies. In this study, we examined the mechanism of action and efficacy of topical application of HL-217 on subretinal neovascularization in very low-density lipoprotein receptor knockout (Vldlr(-/-)) mice. In three-week-old male Vldlr(-/-) mice, HL-217 (1.5 or 3mg/ml) was administered twice per day for 4 weeks by topical eye drop instillation. Neovascular areas were then measured. We used a protein array to evaluate the expression levels of angiogenic factors. The inhibitory effect of HL-217 on the PDGF-BB/PDGFRß interaction was evaluated in vitro. The neovascular area in the Vldlr(-/-) mice was significantly reduced by HL-217. Additionally, HL-217 decreased the expression levels of PDGF-BB protein and VEGF mRNA. Moreover, HL-217 dose-dependently inhibited the PDGF-BB/PDGFRß interaction (IC50=38.9 ± 0.7 µM). These results suggest that HL-217 is a potent inhibitor of PDGF-BB. HL-217, when applied topically, is an effective inhibitor of subretinal neovascularization due to its ability to inhibit the pro-angiogenic effects of PDGF-BB.
Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Benzopiranos/farmacología , Imidazoles/farmacología , Retina/efectos de los fármacos , Neovascularización Retiniana/tratamiento farmacológico , Animales , Becaplermina , Proliferación Celular , Relación Dosis-Respuesta a Droga , Fluoresceína-5-Isotiocianato/química , Humanos , Concentración 50 Inhibidora , Lectinas/metabolismo , Ligandos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microscopía Fluorescente , Neovascularización Patológica , Proteínas Proto-Oncogénicas c-sis/metabolismo , ARN Mensajero/metabolismo , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Receptores de LDL/genética , Neovascularización Retiniana/genética , Transducción de SeñalRESUMEN
Poncirus trifoliata fruit (PTF) affects the digestive and cardiovascular systems, and kidney function. The authors studied the effects of ethyl acetate (EtOAc) extract of PTF on the activities of osteoblasts and in an animal model. The main compounds of the EtOAc extract, naringin and poncirin have been confi rmed by HPLC and NMR analysis. Effects of osteoblastic differentiation were mea-sured by alkaline phosphatase (ALP) activity, osteopontin (OPN) protein expression and osteoprotegerin (OPG) mRNA expression in MC3T3-E1 cells. Also, osteoclast differentiation was measured by multinucleated cells (MNCs) formation through tartrate resistance acid phosphatase (TRAP)-positive staining. Bone mineral density (BMD) was measured before and after treatment with EtOAc extract of PTF in prednisolone-induced osteoporotic mice. Dexamethasone (DEX) decreased OPN and OPG expression level in MC3T3-E1 cells and ALP activity was decreased by DEX dose-dependently. EtOAc extract of PTF recovered the levels of ALP activity, and the expression of OPN and OPG in MC3T3-E1 cells treated with DEX. In osteoclast differentiation, multinucleated TRAP-positive cell formation was significantly suppressed by the EtOAc extract of PTF. Total body BMD was restored by EtOAc extract of PTF in prednisolone-induced osteoporotic mice. In conclusion, EtOAc extract of PTF recovered DEX-mediated deteriorations in osteoblastic and osteoclastic functions, and increased BMD in glucocorticoid-induced osteoporosis.
RESUMEN
Imipenem-resistant Klebsiella pneumoniae (IRKP) were used to explore the synergistic anti-bacterial and proteomic effects of imipenem alone or in combination with epigallocatechin gallate (EGCg). The minimal inhibitory concentrations (MICs) of EGCG for 12 clinically isolated IRKP strains ranged from 300 to 650 µg/ml. Each of the 12 IRKP strains experienced a 4- to 64-fold reduction in the MIC of imipenem upon co-incubation with 0.25 × MIC level of EGCg. The time-kill method was used on the 12 IRKP clinical isolates to evaluate the bactericidal activities of imipenem alone or with EGCg. Compared to imipenem alone, EGCg with imipenem demonstrated enhanced bactericidal activity. Two-dimensional polyacrylamide gel electrophoresis identified eight down-regulated and four up-regulated proteins in the IRKP strain upon exposure to 1 × MIC of EGCg. Analysis of the outer membrane protein profiles of IRKP cultures treated with EGCg revealed unique changes in outer membrane proteins. In addition, scanning electron microscopic analysis demonstrated the presence of cells with wrinkled surfaces containing perforations and irregular rod-shaped forms after treatment with EGCg or imipenem. These studies demonstrate that EGCg can synergize the bacterial activity of imipenem and differentially stimulate the expression of various proteins in IRKP.
Asunto(s)
Catequina/análogos & derivados , Farmacorresistencia Bacteriana , Imipenem/farmacología , Klebsiella pneumoniae/efectos de los fármacos , Antibacterianos/farmacología , Proteínas de la Membrana Bacteriana Externa/efectos de los fármacos , Catequina/farmacología , Sinergismo Farmacológico , Electroforesis en Gel de Poliacrilamida , Klebsiella pneumoniae/ultraestructura , Pruebas de Sensibilidad Microbiana , Microscopía Electrónica de Rastreo , Proteómica , Té/químicaRESUMEN
In this study, the enhanced degradation of TNT using cultures of genome-shuffled Stenotrophomonas maltophilia OK-5 mt-3 has been examined and the proteome of shuffled strain was compared to the wild-type OK-5 strain. Genome shuffling of S. maltophilia OK-5 was used to achieve a rapid enhancement of TNT degradation. The initial mutant population was generated by NTG treatment and UV irradiation. The wild-type OK-5 strain was able to degrade 0.2 mM TNT within 6 days, yet barely tolerated 0.5 mM TNT while the shuffled OK-5 mt-3 was capable of completely degrading 0.5 mM TNT within 8 days, and 1.2 mM within 24 days. The proteomic analysis of the shuffled OK-5 mt-3 demonstrated the changes in the expression levels of certain proteins compared to wild-type OK-5. These results provide clues for understanding TNT tolerance and improved TNT degradation by shuffled S. maltophilia OK-5 mt-3 and have possible applications in the processing of industrial waste containing relatively high TNT concentrations.
Asunto(s)
Barajamiento de ADN , ADN Bacteriano/genética , Genoma Bacteriano , Stenotrophomonas maltophilia/genética , Stenotrophomonas maltophilia/metabolismo , Trinitrotolueno/metabolismo , Proteínas Bacterianas/análisis , Análisis por Conglomerados , ADN Bacteriano/química , ADN Ribosómico/química , ADN Ribosómico/genética , Electroforesis en Gel Bidimensional , Datos de Secuencia Molecular , Mutágenos/farmacología , Nitrosoguanidinas/farmacología , Filogenia , Proteoma/análisis , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Microbiología del Suelo , Stenotrophomonas maltophilia/química , Stenotrophomonas maltophilia/aislamiento & purificación , Rayos UltravioletaRESUMEN
TNT-induced cellular responses and proteomes in Pseudomonas sp. HK-6 were comparatively analyzed in two different media: basal salts (BS) and Luria broth (LB). HK-6 cells could not degrade more than 0.5 mM TNT with BS medium, while in LB medium, they exhibited the enhanced capability to degrade as much as 3.0 mM TNT. Analysis of total cellular fatty acids in HK-6 cells suggested that the relative abundance of several saturated or unsaturated fatty acids is altered under TNT-mediated stress conditions. Scanning electron microscopy showed the presence of perforations, irregular rod formations, and wrinkled extracellular surfaces in cells under TNT stress. Proteomic analysis of soluble protein fractions from HK-6 cultures grown with TNT as a substrate revealed 11 protein spots induced by TNT. Among these, seven proteins (including Alg8, AlgB, NirB, and the AhpC/Tsa family) were detected only in LB medium containing TNT. The proteins AspS, Tsf, and assimilatory nitrate reductase were increasingly expressed only in BS medium containing TNT. The protein dGTPase was found to be induced and expressed when cells were grown in either type of TNT-containing media. These results provide a better understanding of the cytotoxicity and survival mechanism used by Pseudomonas sp. HK-6 when placed under TNT stress conditions.
Asunto(s)
Medios de Cultivo/metabolismo , Proteoma/metabolismo , Pseudomonas/fisiología , Trinitrotolueno/metabolismo , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Biodegradación Ambiental , Electroforesis en Gel Bidimensional , Datos de Secuencia Molecular , Proteoma/química , Proteoma/genética , Pseudomonas/químicaRESUMEN
Scanning electron microscopy revealed pores and wrinkles on the surface of Pseudomonas sp. HK-6 cells grown in Luria Bertani (LB) medium containing 0.5 mM TNT (2,4,6-trinitrotoluene). Exopolymer connections were also observed on the wild-type HK-6 cells but not on the algA mutant cells. In addition, the amount of exopolymer from HK strain increased from 90 to 210 microg/mL under TNT stress, whereas the algA mutant produced approximately 30 microg/mL, and its exopolymer production was little increased by TNT stress. These results indicate that TNT stress induced exopolymer production with alginate as a major component. The algA mutant degraded TNT more slowly than the wild-type HK-6 strain. HK-6 was able to completely degrade 0.5 mM TNT within 8 days, whereas algA mutant only achieved approximately 40% within the same time period. Even after 20 days, no more than 80% of TNT was degraded. According to analyses of proteomes of HK-6 and algA mutant cells grown under TNT stress or no stress, several proteins (KinB, AlgB, Alg8, and AlgL) in alginate biosynthesis were only highly induced by both strains under TNT stress. Interestingly, two stress-shock proteins (SSPs), GroEL and RpoH, were more highly expressed in the algA mutant than the HK-6 strain. The algA mutant was rendered more vulnerable to environmental stress and had reduced ability to metabolize TNT in the absence of alginate synthesis.
Asunto(s)
Biopolímeros/biosíntesis , Proteoma/metabolismo , Pseudomonas/metabolismo , Microbiología del Suelo , Contaminantes del Suelo/metabolismo , Trinitrotolueno/metabolismo , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Biodegradación Ambiental , Biopolímeros/química , Electroforesis en Gel Bidimensional , Datos de Secuencia Molecular , Mutación , Proteoma/genética , Pseudomonas/química , Pseudomonas/genéticaRESUMEN
The antibacterial effects of tea polyphenols (TPP) extracted from Korean green tea (Camellia sinensis) against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) were evaluated. Characterization of the minimal inhibitory concentration (MIC) of oxacillin for 30 S. aureus strains isolated from patients treated with oxacillin identified 13 strains with an oxacillin MIC >or= 4 microg/mL as methicillin-resistant Staphylococcus aureus (MRSA) (range: 8 to 512 microg/mL), while 17 strains were methicillin-susceptible Staphylococcus aureus (MSSA) (range: 0.25-0.5 microg/mL). The MICs of TPP ranged from 50 to 180 microg/mL for both the MSSA and the MRSA strains. The MICs of oxacillin for each of the 13 MRSA strains were reduced between 8- and 128-fold when these strains were coincubated with sub-MIC (Asunto(s)
Antibacterianos/farmacología
, Camellia sinensis/química
, Flavonoides/farmacología
, Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos
, Fenoles/farmacología
, Antibacterianos/aislamiento & purificación
, Proteínas Bacterianas/análisis
, Recuento de Colonia Microbiana
, Electroforesis en Gel Bidimensional
, Flavonoides/aislamiento & purificación
, Perfilación de la Expresión Génica
, Humanos
, Staphylococcus aureus Resistente a Meticilina/química
, Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación
, Pruebas de Sensibilidad Microbiana
, Viabilidad Microbiana
, Oxacilina/farmacología
, Oxacilina/uso terapéutico
, Fenoles/aislamiento & purificación
, Polifenoles
, Proteoma/análisis
, Infecciones Estafilocócicas/tratamiento farmacológico
, Infecciones Estafilocócicas/microbiología
RESUMEN
Pseudomonas sp. HK-6 is able to utilize 2,4,6-trinitrotoluene (TNT) as a sole nitrogen source. The pnrB gene of the HK-6 strain was cloned using degenerate primers synthesized on the basis of the sequence information of the terminal amino acids of a previously purified native TNT nitroreductase. The nucleotide sequence of pnrB was 654 bp long, and its deduced polypeptide sequence was composed of 217 amino acid residues with a predicted molecular mass of 24 kDa. To facilitate the purification and characterization of this enzyme, an Escherichia expression plasmid harboring six histidine residues fused to a pnrB gene was constructed (His6-PnrB) and designated pPSC1. The His6-PnrB induced in E. coli BL21 was purified using a nickel affinity column to homogeneity. Its enzymatic activity was assayed by measuring absorbance changes at 340 nm due to NADH oxidation. The V (max) and K ( m ) values of the enzyme for TNT were 12.6 micromol/min/mg protein and 2.9 mM, respectively. In addition, the pnrB knockout mutant was constructed via a single-crossover homologous recombination with a partial pnrB DNA fragment that lacked both start and stop codons. Eight days was required for complete degradation of 0.5 mM TNT by the wild-type HK-6 strain, whereas the pnrB mutant degraded only 10% of the TNT in the same time period. Even after 20 days, only approximately 50% of the 0.5 mM TNT was degraded by the pnrB mutant. These results illustrate that pnrB may perform a crucial role in the TNT degradation pathway of the HK-6 strain.
Asunto(s)
Nitrorreductasas/genética , Nitrorreductasas/metabolismo , Pseudomonas/enzimología , Trinitrotolueno/metabolismo , Clonación Molecular , Escherichia coli/genética , Eliminación de Gen , Expresión Génica , Cinética , Peso Molecular , Mutagénesis Insercional , NAD/metabolismo , Nitrorreductasas/química , Nitrorreductasas/aislamiento & purificación , Oxidación-Reducción , Plásmidos , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/aislamiento & purificación , Proteínas Recombinantes de Fusión/metabolismoRESUMEN
Our previous research has demonstrated that novel 43-kDa DnaK and 41-kDa GroEL proteins are synthesized in Burkholderia sp. YK-2 in response to sublethal concentrations of 2,4-D stress [Cho et al. (2000) Curr Microbiol 41:33-38]. In this study, we have extended this work to examine the cellular responses of strain YK-2 to stresses induced in response to the phenoxyherbicides 2,4-D or 2,4,5-T. Strain YK-2 exhibited a more sensitive response to 2,4,5-T stress than to 2,4-D stress, as shown in physiological and morphological changes, suggesting a greater cytotoxic effect of 2,4,5-T. SEM analyses revealed the presence of perforations and irregular rod forms with wrinkled surfaces for cells treated with either herbicide. These irregularities were found more frequently for 2,4,5-T-treated cells than for 2,4-D-treated cells. Analysis of cellular fatty acids showed similar effects in the shifts of total cellular fatty acid composition in response to 2,4-D and 2,4,5-T. Strain YK-2 could degrade 2.25 m M 2,4-D completely during 28 h of incubation with transient production of 2,4-dichlorophenol as a metabolite; however, 2,4,5-T was not catabolized at any of the concentrations tested. BIOLOG and 16S rDNA analyses revealed that strain YK-2 was 98% similar to the Burkholderia cepacia species cluster; therefore, we have designated this strain as B. cepacia YK-2.