Biomedical subjects

T Itoh

Publications and source records attributed to T Itoh.

At least 19 recordsLinked to original sources

PubMed1999

Microglia express CCR5, CXCR4, and CCR3, but of these, CCR5 is the principal coreceptor for human immunodeficiency virus type 1 dementia isolates.

Microglia are the main human immunodeficiency virus (HIV) reservoir in the central nervous system and most likely play a major role in the development of HIV dementia (HIVD). To characterize human adult microglial chemokine receptors, we analyzed the expression and calcium signaling of CCR5, CCR3, and CXCR4 and their roles in HIV entry. Microglia expressed higher levels of CCR5 than of either CCR3 or CXCR4. Of these three chemokine receptors, only CCR5 and CXCR4 were able to transduce a signal in microglia in response to their respective ligands, MIP-1beta and SDF-1alpha, as recorded by single-cell calcium flux experiments. We also found that CCR5 is the predominant coreceptor used for infection of human adult microglia by the HIV type 1 dementia isolates HIV-1DS-br, HIV-1RC-br, and HIV-1YU-2, since the anti-CCR5 antibody 2D7 was able to dramatically inhibit microglial infection by both wild-type and single-round luciferase pseudotype reporter viruses. Anti-CCR3 (7B11) and anti-CXCR4 (12G5) antibodies had little or no effect on infection. Last, we found that virus pseudotyped with the DS-br and RC-br envelopes can infect cells transfected with CD4 in conjunction with the G-protein-coupled receptors APJ, CCR8, and GPR15, which have been previously implicated in HIV entry.

AIDS Dementia Complex↗

PubMed1998

Activated endothelial cells induce apoptosis in leukemic cells by endothelial interleukin-8.

Tumor cells are eradicated by several systems, including Fas ligand-Fas and tumor necrosis factor (TNF)-tumor necrosis factor receptor (TNFR). In the previous study, we purified an apoptosis-inducing factor (AIF) to homogeneity from a medium conditioned by PDBu-treated HL-60 cells. N-terminal sequence analysis showed that AIF is identical to endothelial interleukin-8 (IL-8). A novel apoptosis system, in which endothelial cells participate via endothelial IL-8 release, is identified here. Human umbilical vein cells (VE cells) produce and secrete IL-8 by stimulation of IL-1alpha and TNF-alpha. Endothelial IL-8, which is secreted from VE cells by stimulation of IL-1alpha and TNF-alpha , induces apoptosis in myelogenous leukemia cell line K562 cells. Monocyte-derived IL-8 could not induce apoptosis in K562 cells. Moreover, interaction between VE cells and K562 cells induces the release of endothelial IL-8 from VE cells, and the attached K562 cells undergo apoptosis. Moreover, interactions between VE cell and other cell lines, such as HL-60, U937, Jurkat, and Daudi, induce the secretion of endothelial IL-8 and the induction of apoptosis in cell lines. Endothelial IL-8 significantly inhibits tumor growth of intraperitoneal and subcutaneous tumor mass of K562 cells and induces apoptosis in their cells in vivo. Endothelial IL-8 plays an important role in apoptosis involving endothelial cells, which may provide us with a new therapy for hematological malignancies.

Animals↗

PubMed1998

Combining volume-weighted mean nuclear volume with Gleason score and clinical stage to predict more reliably disease outcome of patients with prostate cancer.

BACKGROUND: Various criteria for patients with prostate cancer have been reported to be of prognostic value, and we have reported that estimates of volume-weighted mean nuclear volume (MNV), developed by Gundersen and Jensen based on a stereological technique, accurately predict the prognosis of prostate cancer. However, all of these studies were conducted on cases in a single institution, and it has remained unclear whether MNV calculations obtained at one institution apply to cases at another institution. In attempting to solve this problem, we made a prognostic index (P.I.) based on data from one hospital, and tested whether these data could be used to predict the prognosis of patients at another hospital. MATERIALS AND METHODS: A retrospective, multivariate prognostic study of 195 patients with prostate cancer, diagnosed at Kyoto University Hospital and treated conservatively, indicated that clinical stage, Gleason score, and MNV were all significantly correlated with the prognosis of patients with prostate cancer. From the relative strengths of these prognostic factors in a multivariate analysis, the following P.I. was constructed: P.I. = Clinical stage x 1.8040 + Gleason score x 1.5245 + MNV x 2.3162 (the constants correspond to the risk ratio estimated by Cox analysis). The P.I. was calculated for 104 patients with prostate cancer diagnosed at Shizuoka City Hospital and treated conservatively for analysis of disease-specific survival. RESULTS: The prognostic index ranged from 3.841-16.142. Using the median value of 12.5 as a cutoff point, a clear separation of cases with poor and favorable prognosis was achieved (P < 0.0001, observation period: 1-167 months). CONCLUSIONS: The results of this study suggest that estimates of MNV can be evaluated at multiple institutions with the use of P.I. calculation. Furthermore, combining estimates of MNV with Gleason score and clinical stage predicts most powerfully disease outcome of patients with prostate cancer.

Aged↗

PubMed1998

Phosphorylation of phospholipase Cgamma1 on tyrosine residue 783 by platelet-derived growth factor regulates reorganization of the cytoskeleton.

It is known that platelet-derived growth factor (PDGF) induces the phosphorylation of phospholipase C (PLC) gamma1 and that phosphorylation on tyrosine (Tyr) 783 of PLCgamma1 is essential for phosphatidylinositol 4,5-bisphosphate hydrolyzing activity in vivo, while phosphorylation does not affect the catalytic activity in vitro. To study the roles of Tyr-783 phosphorylation in vivo, we developed a polyclonal antibody that recognizes PLCgamma1 containing phosphotyrosine 783 (alpha-PLCgamma1 PY). Tyr-783-phosphorylated PLCgamma1 was not detected in the absence of PDGF, appeared after stimulation, increased for 30 min, and then decreased to near the prestimulation level. Immunostaining of cells showed that PDGF-produced Tyr-783-phosphorylated PLCgamma1 localized predominantly at membrane ruffles and stress fibers where it colocalized with actin filaments within 30 min. Ninety minutes after PDGF stimulation, the actin filaments were disassembled to short fragments, and the levels of Tyr-783-phosphorylated PLCgamma1 were remarkably decreased in membrane ruffles and cytoskeleton. Furthermore, the depolymerization of actin filaments and membrane ruffling caused by PDGF stimulation were blocked by microinjecting alpha-PLCgamma1 PY, as occurred following the microinjection of the PLCgamma1-2SH2 domain, which is expected to associate with phosphorylated PDGF receptors and to block PLCgamma1 binding. It is worth noting that the microinjection of tyrosine-phosphorylated peptide (consisting of 13 amino acids containing Tyr-783) induced the disassembly of actin filaments and membrane ruffling as observed in PDGF-stimulated cells, while nonphosphorylated peptide did not cause any effect. These data suggest that the phosphorylation of PLCgamma1 on tyrosine 783 by PDGF plays an important role in cytoskeletal reorganization in addition to mitogenesis.

3T3 Cells↗

PubMed1998

Lysophosphatidylcholine upregulates CD40 ligand expression in newly activated human CD4+ T cells.

Lysophosphatidylcholine (lyso-PC) accumulates in tissues undergoing inflammation and atherosclerosis, where an infiltration of T cells is also seen. We found that lyso-PC increased IFN-gamma production and CD40L expression in CD4+ T cells stimulated with anti-CD3 Ab and recombinant CD80 molecules, whereas lyso-PC did not affect IL-2 and IL-4 production. These results suggest that lyso-PC, in combination with other stimuli, may regulate CD4+ T cell functions to propagate local inflammatory reactions and also imply a novel role played by a modified lipid in the selection of Th1/Th2 immune response as well as in the T cell mediated pathogenesis in atherosclerosis.

Antibodies↗

PubMed1998

A novel phosphatidylinositol-5-phosphate 4-kinase (phosphatidylinositol-phosphate kinase IIgamma) is phosphorylated in the endoplasmic reticulum in response to mitogenic signals.

Here, we identify a novel rat phosphatidylinositol-5-phosphate 4-kinase, phosphatidylinositol-phosphate kinase IIgamma (PIPKIIgamma). PIPKIIgamma comprises 420 amino acids with a molecular mass of 47,048 Da, showing greater homology to the type IIalpha and IIbeta isoforms (61.1 and 63.7% amino acid identities, respectively) of phosphatidylinositol-phosphate kinase than to the type I isoforms. It is predominantly expressed in kidney, with low expression in almost all other tissues. PIPKIIgamma was found to have phosphatidylinositol-5-phosphate 4-kinase activity as demonstrated in other type II kinases such as PIPKIIalpha. The PIPKIIgamma that is present endogenously in rat fibroblasts, PC12 cells, and rat whole brain lysate or that is exogenously overexpressed in COS-7 cells shows a doublet migrating pattern on SDS-polyacrylamide gel electrophoresis. Alkaline phosphatase treatment and metabolic labeling in [32P]orthophosphate experiments revealed that PIPKIIgamma is phosphorylated in vivo, resulting in a shift in its electrophoretic mobility. Phosphorylation is induced by treatment of mitogens such as serum and epidermal growth factor. Immunostaining experiments and subcellular fractionation revealed that PIPKIIgamma localizes dominantly in the endoplasmic reticulum (ER). Phosphorylation also occurs in the ER. Thus, PIPKIIgamma may have an important role in the synthesis of phosphatidylinositol bisphosphate in the ER.

1-Phosphatidylinositol 4-Kinase↗

PubMed1998

Vasorelaxant effect of olprinone, an inhibitor of phosphodiesterase 3, on mesenteric small artery and vein of rabbits.

The effects of olprinone, a cardiotonic agent that inhibits cyclic GMP (cGMP)-inhibited phosphodiesterase, was studied on isolated rabbit mesenteric small artery and vein. In the presence of indomethacin and propranolol, olprinone at concentrations of 10 nM to 10 microM and 1 microM to 100 microM relaxed norepinephrine-stimulated mesenteric artery and vein in a concentration-dependent manner, respectively. The relaxation was not endothelium-dependent in the artery. Removal of the endothelium, however, increased marginally the response of the vein to olprinone. Olprinone-induced relaxation was less pronounced in arteries contracted with high KCl solution + norepinephrine than in those contracted with norepinephrine alone. Nicardipine inhibited this attenuating effect of high KCl solution on the olprinone-induced relaxation. Olprinone (1 microM) enhanced the relaxation of artery and vein in response to a cAMP-increasing agent, 6-(3-dimethylaminopropionyl) forskolin (NKH477), but not to a cGMP- increasing agent, glyceryl trinitrate. Norepinephrine (10 microM) and caffeine (5 mM) elicited a transient, phasic contraction of the artery in Ca2+-free solution. Both olprinone and NKH477 attenuated more potently the norepinephrine-induced contraction than the caffeine-induced contraction. When norepinephrine (10 microM) and caffeine (5 mM) were successively applied in Ca2+-free solution, the contractile effect of caffeine was diminished compared to that in artery which had not been pretreated with norepinephrine. When the contraction in response to norepinephrine was partially attenuated by 1 microM olprinone, the following contraction evoked by caffeine was enlarged. It is concluded that olprinone relaxes the small artery more strongly than the vein via its direct action on smooth muscles. It is suggested that olprinone attenuates norepinephrine-induced contraction through inhibition of receptor-operated transmembrane Ca2+ influx and Ca2+ release from intracellular storage sites.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1998

A comparison of Listeria monocytogenes serovar 4b isolates of clinical and food origin in Japan by pulsed-field gel electrophoresis.

Pulsed-field gel electrophoresis (PFGE) patterns of 102 L. monocytogenes serovar 4b isolates from patients and foods examined in Japan were compared with 16 isolates from foodborne listeriosis episodes which occurred in North America or Europe. Using a combination of PFGE patterns with the restriction enzymes SmaI, ApaI, AscI and Sse8387I, 82 clinical isolates from Japan were categorized into 45 PFGE types: the largest group of 17 isolates (20.7%) were of the same PFGE type as cultures from the large foodborne outbreaks which occurred in California (1985) and Switzerland (1983-1987). Twenty cultures from foods on retail sale in Japan were classified into 12 PFGE types: four isolates were of three PFGE types also recognized among isolates of clinical origin from Japan, including the predominant clinical type.

DNA Restriction Enzymes↗

PubMed1998

Homonojirimycin isomers and N-alkylated homonojirimycins: structural and conformational basis of inhibition of glycosidases.

A series of natural epimers of alpha-homonojirimycin and its N-alkylated derivatives have been prepared to investigate the contribution of the different chiral centers and conformation of the specificity and potency of inhibition of glycosidases. These epimers and N-alkylated derivatives are alpha-homonojirimycin (1), beta-homonojirimycin (2), alpha-homomannojirimycin (3), beta-homomannojirimycin (4), alpha-3,4-di-epi-homonojirimycin (5), beta-4,5-di-epi-homonojirimycin (6), N-methyl-alpha-homonojirimycin (7), and N-butyl-alpha-homonojirimycin (8). Compound 1 was a potent inhibitor of a range of alpha-glucosidases with IC50 values of 1 to 0.01 microM. Compounds 2, 3, and 4 were surprisingly inactive as inhibitors of beta-glucosidase and alpha- and beta-mannosidases but were moderately good as inhibitors of rice and some mammalian alpha-glucosidases. Compound 4 was active in the micromolar range toward all alpha-glucosidases tested. Furthermore, compound 4, which superimposes well on beta-l-fucose, was a 10-fold more effective inhibitor of alpha-l-fucosidase than 1-deoxymannojirimycin (12) and 3, with a Ki value of 0.45 microM. Only compounds 5 and 6 showed inhibitory activity toward alpha- and beta-galactosidases (6with an IC50 value of 6.4 microM against alpha-galactosidase). The high-resolution structure of 1 has been determined by X-ray diffraction and showed a chair conformation with the C1 OH (corresponding to the C6 OH in 1-deoxynojirimycin) predominantly equatorial to the piperidine ring in the crystal structure. This preferred (C1 OH equatorial) conformation was also corroborated by 1H NMR coupling constants. The coupling constants for 7 suggest the axial orientation of the C1 OH, while in 8 the C1 OH axial conformation was not observed. The C1 OH axial conformation appears to be responsible for more potent inhibition toward processing alpha-glucosidase I than alpha-glucosidase II. It has been assumed that the anti-HIV activity of alkaloidal glycosidase inhibitors results from the inhibition of processing alpha-glucosidase I, but 1, 7, and 8 were inactive against HIV-1 replication at 500 microg/mL as measured by inhibition of virus-induced cytopathogenicity in MT-4 cells. In contrast, the EC50 value for N-butyl-1-deoxynojirimycin (11), which also inhibits processing alpha-glucosidase I, was 37 microg/mL. Compound 7 has been shown to be a better inhibitor of alpha-glucosidase I than 1 and 8 both in vitro and in the cell culture system. These data imply that inhibition of HIV by glycosidase inhibitors can be due to factors other than simply inhibition of processing alpha-glucosidase I.

1-Deoxynojirimycin↗

PubMed1998

NGF prevention of neurotoxicity induced by cisplatin, vincristine and taxol depends on toxicity of each drug and NGF treatment schedule: in vitro study of adult rat sympathetic ganglion explants.

The simultaneous administration of nerve growth factor (NGF) has been found to prevent experimental neuropathies induced by anti-cancer drugs such as cisplatin, vincristine and taxol. However, it is clinically important to know whether NGF is beneficial once the neuropathy is already manifest. We established a bioassay system to examine the preventive effects of NGF in various treatment schedules. NGF significantly prevented the inhibition of neurite outgrowth by vincristine and taxol regardless of treatment schedules. The pre-treatment and co-treatment schedules were effective against cisplatin, but the post-treatment schedule was not. With regard to the neurite and nerve cell population densities, only the cisplatin group treated with NGF showed lower values than the control. These results indicate that NGF-treatment is effective for the toxic sympathetic nerve injury induced by vincristine and taxol regardless of the treatment schedule, but is not protective against cisplatin-induced nerve cell injury.

Analysis of Variance↗

PubMed1998

Histone H1 binding does not inhibit transcription of nucleosomal Xenopus laevis somatic 5S rRNA templates.

It has long been proposed that selective binding of histone H1 is, in part, responsible for the differential developmental regulation of the oocyte and somatic 5S rRNA genes in Xenopus laevis. In this study we show that histone H1 binds both oocyte and somatic genes equally after reconstitution into mononucleosomes or oligonucleosome arrays. Furthermore, we show that the binding of histone H1 selectively represses only oocyte gene transcription and that an RNA polymerase III transcription complex is able to initiate transcription of nucleosomal somatic templates regardless of whether histone H1 is present. These results support a model in which the differential regulation of the 5S rRNA genes is not simply due to the prevention of histone H1 binding by transcription complexes on the somatic genes, but rather to a difference in the histone H1 interaction with the somatic and oocyte genes.

Acetylation↗

PubMed1998

Phosphate group requirement for mitogenic activation of lymphocytes by an extracellular phosphopolysaccharide from Lactobacillus delbrueckii ssp. bulgaricus.

The mitogenic activity of extracellular polysaccharides produced by Lactobacillus delbrueckii ssp. bulgaricus OLL 1073R-1 and NCFB2483 was examined in murine lymphocytes. The extracellular polysaccharide from Lactobacillus delbrueckii ssp. bulgaricus OLL 1073R-1 was fractionated into neutral and acidic polysaccharides by anion-exchange chromatography, while that of Lactobacillus delbrueckii ssp. bulgaricus NCFB2483 were all fractionated into neutral polysaccharide(s). The acidic polysaccharide stimulated mitogenic responses of murine splenocytes and Peyer's patches but not of thymocytes. The optimal concentration of the acidic polysaccharide at the highest stimulation was 160 microg/ml. A significant increase of mitogenic activity was initiated at 24 h, and the highest response was obtained after stimulation for 48 h. The acidic polysaccharide purified by high performance liquid chromatography also had substantial mitogenic activity, and the molecular weight was estimated to be 1.2 x 10(6). The acidic polysaccharide was a phosphopolysaccharide consisting of glucose, galactose and phosphorus. Dephosphorylation by hydrofluoric acid degradation reduced the mitogenic activity in lymphocytes. The phosphopolysaccharide produced by Lactobacillus delbrueckii ssp. bulgaricus 1073R-1 is a potent B-cell-dependent mitogen in which the phosphate group acts as a trigger of the mitogenic induction.

Animals↗

PubMed1998

Prevalence of verotoxin-producing Escherichia coli harbored in the intestine of cattle in Japan.

The production of verotoxin was examined in 2152 Escherichia coli isolates from 387 cattle in Japan from 1992 to 1994. The toxin was detected in 263 isolates from 94 cattle (detection rate: 24.3%). Verotoxin-producing E. coli (VTEC) was isolated from the cattle in 15 out of 17 prefectures, and the strains were divided into 33 serotypes. E. coli O157:H7 was isolated from 7 out of 387 cattle (detection rate: 1.8%) in four prefectures. These results suggest that VTEC is widely distributed in Japan and include a wide variety of serotypes.

Animals↗

PubMed1998

Reduced angiogenesis and tumor progression in gelatinase A-deficient mice.

Matrix proteolysis is thought to play a crucial role in several stages of tumor progression, including angiogenesis, and the invasion and metastasis of tumor cells. We investigated the specific role of gelatinase A (matrix metalloproteinase 2) on these events using gelatinase A-deficient mice. In these mice, tumor-induced angiogenesis was suppressed according to dorsal air sac assay. When B16-BL6 melanoma cells or Lewis lung carcinoma cells were implanted intradermally, the tumor volumes at 3 weeks after implantation in the gelatinase A-deficient mice decreased by 39% for B16-BL6 melanoma and by 24% for Lewis lung carcinoma (P < 0.03 for each tumor). The number of lung colonies of i.v. injections fell by 54% for B16-BL6 melanoma and 77% for Lewis lung carcinoma (P < 0.014 and P < 0.0015, respectively). These results indicated that host-derived gelatinase A plays an important role in angiogenesis and tumor progression, suggesting the usefulness of gelatinase A inhibitors for anticancer chemotherapy.

Animals↗

PubMed1998

Identification of a novel apoptosis-inducing factor derived from leukemic cells: endothelial interleukin-8, but not monocyte-derived, induces apoptosis in leukemic cells.

The human myelogenous leukemia cell line HL-60, treated with phorbol 12, 13-dibutyrate (PDBu), produces apoptosis-inducing factors (AIFs) in leukemic cells. We have purified AIF against leukemic cell line K562 as target cells, and N-terminal amino acid sequencing analysis revealed that this purified protein is identical to endothelial cell-derived interleukin-8 ([(Ala)-IL-8]77). In Western blot analysis of supernatants of PDBu-treated HL-60 cells, only [(Ala)-IL-8]77 was detected. Moreover, recombinant human [(Ala)-IL-8]77 induced apoptosis in leukemic cell lines such as K562, HL-60, KG-1, U937, THP-1 and Jurkat, but monocyte-derived IL-8 ([(Ser)-IL-8]72) did not. Therefore [(Ala)-IL-8]77 plays an important role in inducing apoptosis against leukemic cells and may lead to a new therapy for leukemia.

Apoptosis↗

PubMed1998

The histone binding protein nucleoplasmin does not facilitate binding of transcription factor IIIA to nucleosomal Xenopus laevis 5S rRNA genes.

In an attempt to understand the mechanism by which transcription factors compete with histone octamers for cognate binding sites in chromatin, the effect of the histone binding protein nucleoplasmin on the binding of TFIIIA to nucleosomal 5S rRNA genes was tested. In this study, it was shown that, despite the previously reported nucleosome remodeling ability of nucleoplasmin, the binding of TFIIIA to nucleosomal DNA cannot be facilitated by this protein. Furthermore, it was demonstrated that nucleoplasmin cannot overcome nucleosome mediated repression of transcription of reconstituted 5S rRNA genes. In contrast to earlier work, this study used a homologous system composed of the 5S rRNA gene, nucleoplasmin, and TFIIIA from Xenopus laevis.

Animals↗

PubMed1998

Joint fluid from patients with failed total hip arthroplasty stimulates pit formation by mouse osteoclasts on dentin slices.

Periprosthetic bone resorption has been implicated in the failure of total joint arthroplasty. Osteolysis is reported to be associated with bone resorption induced by bone-resorbing cytokines, which are released from macrophages and fibroblasts in periprosthetic tissues after stimulation by wear debris generated in the joint cavity. Recent reports have suggested the concept of the effective joint space, which includes all periprosthetic regions that are accessible to joint fluid and wear debris. In this study, we examined the levels of interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), and tartrate-resistant acid phosphatase (TRAP) in joint fluid after failed total hip arthroplasty (THA) with osteolysis and investigated whether the joint fluid could activate osteoclastic bone resorption using unfractionated mouse bone cells cultured on dentin slices. Histochemical analysis showed the presence of more TRAP-positive cells in synovial capsules from failed THA patients when compared with osteoarthritis (OA) patients (controls). The levels of IL-6, sIL-6R, and TRAP in joint fluid from failed THA patients were significantly higher than in OA patients. Mouse osteoclasts cultured on dentin slices with joint fluid from failed THA patients with osteolysis produced a significant increase of pit area, whereas cells cultured with joint fluid from OA patients did not. Interestingly, osteoclastic bone resorption on dentin slices was significantly correlated with TRAP activity in joint fluid (p < 0.0001). These results suggest that joint fluid containing bone-resorbing cytokines is produced by synovial capsules in failed THA patients with osteolysis and may activate osteoclasts around the prosthesis in combination with those produced by interface tissues, thus contributing to periprosthetic bone resorption.

Acid Phosphatase↗

PubMed1998

Lack of renal secretion of carbenicillin in rats: poor affinity to the organic anion transporter at renal brush border membrane.

The renal secretion of carbenicillin (CBPC) was studied in rats. The results obtained in the in vivo study indicated very poor renal secretion of CBPC in rats, which was entirely different from those observed in humans and rabbits. In humans and rabbits, significant and stereoselective renal secretion of CBPC was observed in vivo. In order to verify the poor renal secretion of CBPC in rats, the transport characteristics of the organic anion transporters were studied in vitro using basolateral and brush border membrane vesicles. Transport of p-aminohippuric acid (PAH) into the basolateral membrane vesicles (BLMVs) was inhibited by CBPC, indicating that the organic anion transporter located at the BLM may have affinity to CBPC. In contrast, the transport of PAH into the brush border membrane vesicles (BBMVs) was not inhibited by CBPC, suggesting that the organic anion transporter located at the BBM may not have affinity to CBPC. Similar results were obtained for sulbenicillin (SBPC). Since CBPC and SBPC exist as di-anions at physiological pH, the organic anion transporter located at the rat renal BBM may not exhibit affinity to water-soluble di-anions, which in turn will result in poor renal secretion of these compounds.

Animals↗