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Biomedical subjects

Y Chen

Publications and source records attributed to Y Chen.

At least 487 records · Page 27Linked to original sources

Pattern and component motion selectivity in cortical area PMLS of the cat.

Visual motion perception is one of the most prominent functions performed by the mammalian cerebral cortex. The moving images are commonly considered to be processed in two stages. The first-stage neurons are sensitive to the motion of one-dimensional orientated components, and their outputs are combined at the second stage to perceive the global motion of the whole pattern. Alternatively, the pattern motion may be signalled by monitoring a distinctive feature of the image, such as a line-end or a corner. In the present study, a series of 'random-line' patterns were used to measure the direction-tuning responses of 138 neurons in the posteromedial lateral suprasylvian area of the cat. The novel stimuli comprised identical thin line segments, with a length : width ratio no less than 10 : 1, which were moved perpendicularly or obliquely to their common orientation during the recordings. When the component lines were much shorter than the size of receptive field, the majority of cells were selective to the direction of pattern motion while only a small subset was sensitive to the direction of component motion. However, the response profiles of most cells became more component-motion selective with the increment of orientation element in stimulus by elongating the component lines in the patterns. These findings imply that the two-stage theory might be incomplete for modelling the visual motion analysis. Even at relatively low levels of the visual system, some kind of nonorientation-based processing may coexist with the orientation-sensitive processing in a dynamic competition, where one rises as the other falls depending upon the strength of the orientation element in the stimulus, so that under some circumstances it becomes possible to signal the veridical direction of pattern motion.

Action Potentials↗

Role of vicinal cysteine pairs in metalloid sensing by the ArsD As(III)-responsive repressor.

ArsD is a 120-residue repressor that regulates expression of the arsRDABC arsenical resistance operon of plasmid R773 in Escherichia coli. ArsD is released from arsRDABC promoter DNA by binding of the compounds with the metalloids As(III) or Sb(III). ArsD has three vicinal cysteine pairs, Cys-12 and Cys-13, Cys-112 and Cys-113 and Cys-119 and Cys-120. In this study, the role of these three cysteine pairs was investigated. Mutation or deletion of Cys-119-Cys-120 had no effect on repression or metalloid responsiveness in vivo or in vitro. Mutagenesis of either the Cys-12-Cys-13 pair or the Cys-112-Cys-113 pair had no effect on repression but produced loss of inducibility, suggesting that both Cys-12-Cys-13 and Cys-112-Cys-113 may be required for As(III) or Sb(III) responsiveness. Assays of binding of wild-type and mutant ArsDs by As(III) affinity chromatography showed that each of the three vicinal cysteine pairs is capable of binding As(III) independently. The effect of As(III) or Sb(III) on intrinsic protein fluorescence was used to examine the properties of individual cysteine pairs. The fluorescence of Trp-97 was shown to be quenched by the addition of Sb(III) or As(III). The vicinal Cys-112-Cys-113 pair was required for the majority of the metalloid-dependent quenching of Trp-97 fluorescence. The data are consistent with a model in which Cys-12-Cys-13 and Cys-112-Cys-113 form independent As(III) binding sites, both of which are required for in vivo ArsD function.

Amino Acid Sequence↗

The Schistosoma mansoni egg-derived r38 peptide-induced Th1 response affects the synchronous pulmonary but not the asynchronous hepatic granuloma growth.

The p38 peptide derived from Schistosoma mansoni egg-antigens (SEA) is a preferential inducer of the Th1 response. In the present study, we investigated whether induction of a p38-specific Th1 or Th2 response can influence granuloma development in infected or sensitized mice. Mice sensitized with SEA/IL-12 3 weeks after infection but before worm oviposition commenced developed Th1 cytokine responses and had significantly reduced hepatic granuloma size. Similar immunization with p38/IL-12 induced a strong peptide-specific Th1, mixed SEA-specific Th1/Th2 responses without effect on hepatic granuloma development. Presentation of p38 with alum or alum/IL-12 mixture enhanced Th2 cytokine responses and hepatic granuloma sizes. In the synchronized pulmonary model, sensitization of naïve mice with p38/IL-12 induced a strong Th1 cytokine production to p38 and SEA, led to a moderate increase in granuloma growth at days 4 and 8 following egg injection and actually promoted the resolution of the lesion by day 16. Sensitization with p38 in alum induced Th2 cytokine production and generated the largest granulomas whereas the p38/alum/IL-12 sensitized group showed intermediate results in cytokine production and granuloma growth. Thus, in infected mice, the p38 induced strong Th1 response was insufficient to cross-regulate the evolving Th2 environment that generated large granulomas.

Animals↗

In vitro evaluation of an enhanced human serum amyloid A (SAA2) promoter-regulated soluble TNF receptor fusion protein for anti-inflammatory gene therapy.

Tumour necrosis factor (TNF)-alpha contributes to the pathogenesis of many inflammatory diseases. Recombinant soluble TNF receptor fusion proteins (sTNFR:Ig) are potent TNF antagonists, both in vitro and in vivo. The concentration of serum amyloid A (SAA) increases by up to 1000-fold during inflammation, largely owing to cytokine-driven transcriptional upregulation. A reporter plasmid, comprising the proximal 0.7 kb of the human SAA2 promoter fused to a luciferase gene, was used in transient transfection experiments in human HepG2 hepatoma cells to assess the quantitative and qualitative TNF antagonist properties of a construct in which sTNFR:Ig synthesis is under the control of a chimera of the SAA2 promoter and a tat/HIV element. The SAA2-tat/HIV-sTNFR:Ig construct retained the fine-tuned cytokine responsiveness of the SAA2 promoter, while exhibiting the quantitatively enhanced level of protein expression conferred by the tat/HIV element. It produced a biologically significant TNF inhibition that was at least as strong as that achieved using a CMV promoter-driven sTNFR:Ig construct. There was a dose- and time-dependent relationship between the pro-inflammatory cytokine used, and the generation of TNF antagonist activity by SAA2-tat/HIV-sTNFR:Ig. Although sTNFR:Ig protein can be induced by either TNF-alpha or interleukin (IL)-1beta, its antagonist activity is limited to the former cytokine. The SAA2-tat/HIV-sTNFR:Ig construct, and derivatives thereof, may therefore be ideally suited to gene therapy applications that require the local production of potent and specific immune modifiers only when there is active pathology. It may consequently be of particular use in the future treatment of diseases such as rheumatoid arthritis.

Arthritis, Rheumatoid↗

Catalytic selenols couple the redox cycles of metallothionein and glutathione.

Co-ordination of zinc to the thiol group of cysteine allows mobilization of zinc through oxidation of its ligand. This molecular property links the binding and release of zinc in metallothionein (MT) to the cellular redox state [Maret W. & Vallee B.L. (1998) Proc. Natl Acad. Sci. USA 95, 3483-3488]. Biological disulfides such as glutathione disulfide (GSSG) oxidize MT with concomitant release of zinc, while glutathione (GSH) reduces the oxidized protein to thionein, which then binds to available zinc. Neither of these two redox processes is very efficient, even at high concentrations of GSSG or GSH. However, the GSH/GSSG redox pair can efficiently couple with the MT/thionein system in the presence of a selenium compound that has the capacity to form a catalytic selenol(ate). This coupling provides a very effective means of modulating oxidation and reduction. Remarkably, selenium compounds catalyze the oxidation of MT even under overall reducing conditions such as those prevailing in the cytosol. In this manner, the binding and release of zinc from zinc-thiolate co-ordination sites is linked to redox catalysis by selenium compounds, changes in the glutathione redox state, and the availability of either a zinc donor or a zinc acceptor. The results also suggest that the pharmacological actions of selenium compounds in cancer prevention and other antiviral and anti-inflammatory therapeutic applications, as well as unknown functions of selenium-containing proteins, may relate to coupling between the thiol redox state and the zinc state.

Catalysis↗

Actions of activins, inhibins and follistatins: implications in anterior pituitary function.

1. The anterior pituitary is well documented to be under the control of central and peripheral factors that dynamically interact to affect cell-specific modulation of pituitary functions. However, it is becoming increasingly evident that these extrinsic factors work in concert with a variety of local products that exert autocrine/paracrine control on pituitary cells. 2. These factors modulate the activity of their target pituitary cells by altering the synthesis and secretion of cell-specific hormones and by exerting control on the growth and differentiation of cells of this tissue. Included in the list of growth factors and bioactive peptides known to be products of pituitary cells are the activins, possibly inhibins and follistatins. 3. These protein factors play an important role in the local modulation of several pituitary cell types and are crucial for the maintenance of normal follicle-stimulating hormone production and, thus, reproductive function and fertility.

Activins↗

The cAMP responsive element and CREB partially mediate the response of the tyrosine hydroxylase gene to phorbol ester.

Tyrosine hydroxylase (TH) gene promoter activity is increased in PC12 cells that are treated with the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA). Mutagenesis of either the cAMP responsive element (CRE) or the activator protein-1 element (AP1) within the TH gene proximal promoter leads to a dramatic inhibition of the TPA response. The TH CRE and TH AP1 sites are also independently responsive to TPA in minimal promoter constructs. TPA treatment results in phosphorylation of cAMP responsive element binding protein (CREB) and activation of cAMP-dependent protein kinase (PKA) in PC12 cells; hence, we tested whether CREB and/or PKA are essential for the TPA response. In CREB-deficient cells, the response of the full TH gene proximal promoter or the independent response of the TH CRE by itself to TPA is inhibited. The TPA-inducibility of TH mRNA is also blocked in CREB-deficient cells. Expression of the PKA inhibitor protein, PKI, also inhibits the independent response of the TH CRE to TPA. Our results support the hypothesis that TPA stimulates the TH gene promoter via signaling pathways that activate either the TH AP1 or TH CRE sites. Both signaling pathways are dependent on CREB and the TH CRE-mediated pathway is dependent on PKA.

Animals↗

Astrocytes protect neurons from nitric oxide toxicity by a glutathione-dependent mechanism.

Nitric oxide (NO) contributes to neuronal death in cerebral ischemia and other conditions. Astrocytes are anatomically well positioned to shield neurons from NO because astrocyte processes surround most neurons. In this study, the capacity of astrocytes to limit NO neurotoxicity was examined using a cortical co-culture system. Astrocyte-coated dialysis membranes were placed directly on top of neuronal cultures to provide a removable astrocyte layer between the neurons and the culture medium. The utility of this system was tested by comparing neuronal death produced by glutamate, which is rapidly cleared by astrocytes, and N-methyl-D-aspartate (NMDA), which is not. The presence of an astrocyte layer increased the LD(50) for glutamate by approximately four-fold, but had no effect on NMDA toxicity. Astrocyte effects on neuronal death produced by the NO donors S-nitroso-N-acetyl penicillamine and spermine NONOate were examined by placing these compounds into the medium of co-cultures containing either a control astrocyte layer or an astrocyte layer depleted of glutathione by prior exposure to buthionine sulfoximine. Neurons in culture with the glutathione-depleted astrocytes exhibited a two-fold increase in cell death over a range of NO donor concentrations. These findings suggest that astrocytes protect neurons from NO toxicity by a glutathione-dependent mechanism.

Animals↗

Relationship between dopamine-stimulated phospholipid methylation and the single-carbon folate pathway.

In a previous study we demonstrated the ability of dopamine (DA) to stimulate phospholipid methylation (PLM) via a novel mechanism involving the D4 dopamine receptor (D4R) in which single-carbon folates appeared to be the primary source of methyl groups. To further understand the relationship between D4R-mediated PLM and folate metabolism, we examined the effect of several folate pathway interventions on the level of basal and DA-stimulated incorporation of [14C]-labeled formate into phospholipids in cultured SH-SY5Y neuroblastoma cells. These interventions included: (i) Overexpression of methenyltetrahydrofolate synthetase (MTHFS). (ii) Treatment with 5-formylTHF. (iii) Treatment with the MTHFS inhibitor 5-formyltetrahydrohomofolic acid (5-formylTHHF). (iv) Growth in nucleoside-free media. 31P-NMR was also used to follow DA-induced changes in cell phospholipid composition. MTHFS overexpression and 5-formylTHHF treatment, both of which lower 5-methylTHF levels, each reduced basal PLM and its stimulation by DA. In contrast, 5-formylTHF, which increases 5-methylTHF, caused a dose-dependent increase in both basal and DA-stimulated PLM. Growth in nucleoside-free media caused time-dependent changes in PLM, which were due to the absence of purine nucleosides. While basal PLM was maintained at a reduced level, DA-stimulated PLM was initially increased followed by a later decrease. Together, these findings indicate a close functional relationship between single-carbon folate metabolism and DA-stimulated PLM, consistent with a role for 5-methylTHF as the methyl donor for the D4R-mediated process.

Carbon Radioisotopes↗

Cytokines and vascular cell adhesion molecule-1 in the blood of patients undergoing HPC mobilization.

BACKGROUND: The mechanism of HPC mobilization in humans is unclear. In this study, the relationship between PBPC mobilization and blood levels of G-CSF, endogenous cytokines (IL-8, SCF, thrombopoietin [TPO]), and the vascular cell adhesion molecule-1 (VCAM-1) was analyzed in patients with malignancy who were undergoing a PBPC mobilization regimen. STUDY DESIGN AND METHODS: Fifty-four patients with multiple myeloma (MM) and 29 with breast cancer (BC) underwent a mobilization regimen combining conventional chemotherapy and G-CSF up to the last day of PBPC collection. The CD34+ cell count was determined on each day when leukapheresis was scheduled. Venous blood samples (n = 117) were drawn before apheresis for CD34+ cell count (flow cytometry) and cytokine (G-CSF, IL-8, SCF, TPO) and VCAM-1 measurements (ELISA). RESULTS: In multiple regression analysis, SCF was a significant determinant of CD34+ cell levels in BC patients (R = 0.50, p = 0.03) and of VCAM-1 levels in MM patients (R = 0.32, p = 0.02). SCF was negatively correlated with CD34+ cell count in patients with BC. SCF and VCAM-1 blood levels were correlated in MM and BC patients. CONCLUSION: SCF and VCAM-1 could play a role in PBPC mobilization in patients and could be useful measures by which to study patients undergoing a mobilization regimen.

Adult↗

Coccidioides immitis in the gallbladder and biliary tree.

Intraabdominal coccidioidomycosis is a very rare entity and usually responds to medical therapy. Operative intervention is reserved for diagnosis or drainage of localized collections. With biliary coccidioidomycosis, medical treatment appears to be ineffective, and biliary tract drainage is necessary for optimal management. A case of coccidioidomycosis in the gallbladder and biliary tree is described and the literature reviewed.

Bile Ducts, Extrahepatic↗

Leisure-time energy expenditure in asthmatics and non-asthmatics.

An association between obesity and asthma has been documented previously, but the nature of this relationship remains unknown. This study aimed to determine if asthma is associated with a sedentary lifestyle which may explain this association. The energy expenditure (EE) on leisure activities was examined in 16,813 subjects, of at least 12 years of age, who participated in the Canadian National Population Health Survey 1994-95. Energy expenditure was calculated by multiplying the duration of leisure-time physical activity by its estimated metabolic energy cost. Asthma was considered to be present if an affirmative response was given to the question, 'Do you have asthma diagnosed by a health professional?' The average EE (+/- standard error) in males was 2.47 (+/- 0.11) kcal kg(-1) day(-1) for asthmatics and 1.98 (+/- 0.03) kcal kg(-1) day(-1) for non-asthmatics. The corresponding average EEs in females were 1.77 (+/- 0.08) and 1.54 (+/- 0.02) kcal kg(-1) day(-1) for asthmatics and non-asthmatics, respectively. The mean EE values decreased with increasing age. A significant interaction between asthma and age was noted with respect to EE; asthmatics tended to have higher mean EE values than non-asthmatics among younger subjects, and lower mean EE values in older subjects. This effect was more pronounced in females than in males. It was concluded that asthmatics were not consistently inactive compared with non-asthmatics. Leisure-time physical activity cannot explain the positive association between obesity and asthma.

Adolescent↗

Induction of immune hyporesponsiveness after portal vein immunization with ovalbumin.

BACKGROUND: Previous work has demonstrated prolonged allograft survival after donor-specific portal vein immunization before the transplantation. The purpose of this study was to examine the potential mechanism of portal vein-induced hyporesponsiveness after portal vein immunization with the soluble protein ovalbumin. METHODS: Balb/c mice were immunized with a portal vein injection of ovalbumin. After the immunization, in vivo delayed-type hypersensitivity response and in vitro proliferative response of ovalbumin-specific T cells were assessed to determine host immune response. Type 1 (IL-2, IL-12, IFN-gamma) and type 2 (IL-4, TGF-beta) regulatory cytokines were assessed by semiquantitative reverse transcriptase polymerase chain reaction. Sera anti-ovalbumin IgG, IgG1, and IgG2a were measured by enzyme-linked immunosorbent assay, and the antigen-presenting ability of liver nonparenchymal cells (NPCs) was assessed by T-cell proliferation to ovalbumin in vitro. RESULTS: There was significant inhibition of ovalbumin-specific delayed-type hypersensitivity and T-cell proliferation in portal vein-immunized mice compared with intraperitoneal-immunized or control mice. Reverse transcriptase polymerase chain reaction analysis results showed that lymphocytes from portal vein-immunized mice exhibited decreased type 1 and increased type 2 cytokine messenger RNA expression compared with intraperitoneal-immunized or control animals. The type 2 cytokine response of lymphocytes from ovalbumin portal vein-immunized mice correlated with increased sera ovalbumin-IgG1 and decreased IgG2a. The results of an antigen-presenting assay revealed that liver NPCs were deficient antigen-presenting cells compared with adherent cells from heart or spleen. CONCLUSIONS: Processing of ovalbumin by hepatic NPCs results in hyporesponsiveness to ovalbumin by an impaired type 1 cytokine response and a preferential shift toward a type 2 cytokine response, possibly because of defective antigen presentation by hepatic NPCs. Intrahepatic processing of antigen may play an important role in the development of strategies to reduce host immunoreactivity against transplanted allografts.

Animals↗

Edge deepithelialization: a method to prevent leakage when tubed free skin flap is used for pharyngoesophageal reconstruction.

BACKGROUND: Anastomosis leakage remains a major source of morbidity and mortality in patients who receive pharyngoesophageal reconstruction, especially when a free skin flap is used as the substitute. This makes free skin flaps less favored than other substitutes in pharyngoesophageal reconstruction. However, a free skin flap provides many advantages for pharyngoesophageal reconstruction and, in some circumstances, may be the only choice. To reduce the incidence of postoperative leakage, we developed a technical modification called edge-deepithelialization for skin flap to ensure a more secure anastomosis. METHODS: Twenty-four patients who received tubed free skin flaps for cervical esophagus or hypopharynx reconstruction during a 7-year period were included in this study. Group 1 (n = 12) received flap edge-deepithelialization before undergoing the anastomosis, and Group 2 (n = 12) received the conventional anastomosis method. Preoperative nutritional status was evaluated by serum albumin level. All the patients were followed up for at least 1 year (1 approximately 14 years; mean, 7.3 years). Postoperative leakage was detected by clinical symptoms and signs or by routine esophagography. RESULTS: Postoperative anastomosis leakage developed in 1 patient in Group 1 (8.3%) and 5 patients in Group 2 (41.67%). The difference in the leakage rate between these groups was of statistical significance (P =.0001). There were no significant differences in the preoperative serum albumin level noted between these 2 groups (t test, P >.05). Older age was not associated with a higher leakage rate. Among the 6 leakage cases, 1 was treated conservatively, and the other 5 needed an additional 1 to 5 procedures for the management of leakage. All the leakages were cured during the follow-up period. CONCLUSIONS: With the flap edge deepithelialized, a more secure and reliable anastomosis can be obtained. This makes the free skin flap an easier and safer alternative in pharyngoesophageal reconstruction, especially when laparotomy and enteric flaps are contraindicated.

Adult↗

Nitric oxide mediates dendritic cell apoptosis by downregulating inhibitors of apoptosis proteins and upregulating effector caspase activity.

BACKGROUND: Dendritic cells (DCs) play a crucial role in the amplification of the immune response by promoting antigen presentation, T-lymphocyte proliferation, and proinflammatory cytokine and nitric oxide (NO) production. We have previously shown that the exogenous NO donor, s-nitroso-N-acetyl-penicillamine, promotes DC apoptosis by disrupting the mitochondrial membrane potential, which induces cytochrome-C release and activates caspase 3. To further elucidate the signaling pathway, we examined the expression of cellular inhibitors of apoptosis proteins (cIAPs) and poly (ADP-ribose) polymerase cleavage (PARP), a terminal event in the apoptotic cascade. METHODS: DC2.4 were exposed to 250 micromol/L s-nitroso-N-acetyl-penicillamine for various intervals. Apoptosis and necrosis were measured by terminal deoxynucleotidyl transferase nick-end labeling assay or flow cytometry with Annexin V and propidium iodide. DC2.4 were cultured with the pan-caspase inhibitor, ZVAD (100 micromol/L). cIAP, pro-caspases, and PARP expression or activation was measured by Western blot. Caspase enzyme activity was confirmed with the use of specific substrates. RESULTS: NO-induced DC apoptosis correlated with the downregulation of cIAP expression. Caspase 3 and 6 were upregulated by SNAP and significantly inhibited by ZVAD. Maximal PARP cleavage occurred at 8 hours and coincided with the downregulation of cIAP and peak caspase 3 and near maximal caspase 6 activity. CONCLUSIONS: NO-induced DC apoptosis is associated with the downregulation of cIAP expression, which facilitates caspase cascade activation and subsequent PARP cleavage.

Amino Acid Chloromethyl Ketones↗

Critical role of type IV collagens in the growth of bile duct carcinoma. In vivo and in vitro studies.

Most extrahepatic bile duct carcinomas (EBDC) are characterized by a striking stromal response (desmoplasia). Our previous studies showed deposition of type IV collagen in the desmoplastic stroma beyond the basement membrane. Although type IV collagen is expressed in EBDC, little is known about the pattern of deposition in tumor stroma and how this matrix component influences the behavior of tumor cells. With the progression of desmoplasia in EBDC, different changes occurred in the quantity and localization of type IV collagen from that of type I collagen. Type I collagen was diffusely distributed in the stroma and appeared to be concentrated in the center of the tumors. In contrast, type IV collagen was deposited in the interstitium alongside carcinoma cells at the tumors' periphery. Weak or no type IV collagen deposition was detected in the more central portion of the tumors containing sclerotic collagens. To investigate the role of stromal type IV collagen in tumor cell proliferation, EBDC cell lines were cultured in a three-dimensional matrix containing varying compositions of type I collagen and type IV collagen. They were also assayed for cell adhesion and migration using in vitro models. Type IV collagen more extensively stimulated tumor cell proliferation, adhesion and migration in a dose-dependent manner than did type I collagen. All of these results suggest that modified tumor stroma with the presence of type IV collagen in EBDC provides a better environment for tumor growth and invasion.

Adenocarcinoma↗

Origins of timing errors in human sensorimotor coordination.

The authors analyzed fluctuations in timing errors when 8 human participants attempted to coordinate movement with external rhythmic signals. The temporal dynamics of the errors is usually described in terms of simple, self-correcting models. Here the authors demonstrate that timing errors are characterized by a 1/f(alpha) type of long memory process. The value of the exponent alpha differentiates different types of coordination states: synchronization and syncopation. More interesting, evidence was found that alpha can be changed when participants use different coordination strategies. Together with the authors' understanding of the generation mechanism for long memory processes, these results suggest that 1/f(alpha) type of long-range correlated timing errors are of higher cortical origin and are likely the outcome of distributed neural processes acting on multiple time scales.

Brain↗

Pharmacokinetics and system linearity of tea catechins in rat.

1. The pharmacokinetics and dose proportionality of three tea catechins were assessed. 2. Male Sprague-Dawley rats (210-230 g) received intravenous (i.v.) doses (50, 100, 200 and 300 mg kg(-1)) of a decaffeinated tea fraction containing (-)-epicatechin (EC: 5%), (-)-epigallocatechin gallate (EGCG: 50%) and (-)-epicatechin gallate (ECG: 13%). 3. Catechins in plasma, urine and faeces were quantitated by HPLC. 4. A two-compartment model was utilized to describe the bi-exponential disposition exhibited by the three catechins. 5. Over this dose range, the central distribution volume (Vc) for these catechins increased significantly (p < 0.05) from 0.17-0.34 to 0.42-0.66 l kg(-1). 6. A concentration-dependent increase in the plasma free fraction of catechins that mirrored the increases in Vc was observed. 7. The estimates of steady-state volume of distribution (Vss) were between 0.68 and 2.08 l kg(-1) at the lowest dose, and tended to increase with dose. 8. Appreciable amount of catechins partitioned into red blood cells (range 9-43%) and was apparently independent of concentration. 9. The mean elimination half-life (t(1/2,beta)) for EC, EGCG and ECG across doses were 43, 124, and 222 min respectively, and were invariant with dose. 10. Parallel to Vc, a 2-3-fold dose-dependent increase (p < 0.05) in systemic clearance (CL) was observed for the three catechins. 11. Urinary recovery was highest (21-31%) for EC, while those for EGCG and ECG was only approximately 3-5%. 12. Faecal recoveries of the catechins were between 0.5 and 5%. 13. In conclusion, the pharmacokinetics of the catechins appeared to be non-linear; dose-dependent changes in xenobiotic distribution might contribute to this observation.

Animals↗