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Biomedical subjects

K Katsu

Publications and source records attributed to K Katsu.

At least 55 records · Page 3Linked to original sources
PubMed1997

In vitro and in vivo antibacterial activities of ER-35786, a new antipseudomonal carbapenem.

ER-35786 is a new parenteral 1 beta-methyl carbapenem with a broad antibacterial spectrum and a potent antipseudomonal activity. It showed high in vitro activity, comparable to those of meropenem and a new carbapenem, BO-2727, against methicillin-susceptible Staphylococcus aureus and streptococci, with MICs at which 90% of strains tested are inhibited (MIC90S) of < or = 0.39 microgram/ml. Against methicillin-resistant S. aureus, ER-35786 was the most active among the compounds tested, yet its MIC90 was 12.5 micrograms/ml. Against members of the family Enterobacteriaceae, Moraxella catarrhalis, and Haemophilus influenzae, ER-35786 inhibited 90% of strains tested at a concentration of < or = 1.56 micrograms/ml. The MIC90 of ER-35786 for Pseudomonas aeruginosa was 3.13 micrograms/ml, and the compound was more active than meropenem. In addition, the activity of ER-35786 against imipenem-, meropenem-, cefclidin-, or ceftazidime-resistant P. aeruginosa was equal to or higher than that of the most active reference compound. The in vivo activity of ER-35786 was consistent with this in vitro activity. The in vivo activity of ER-35786 was highest for systemic infection models with methicillin-resistant S. aureus and beta-lactam-resistant P. aeruginosa strains. In acute pneumonia caused by P. aeruginosa, ER-35786 produced a greater reduction in the viable cell count in the lungs than did imipenem-cilastatin or meropenem.

Animals↗
PubMed1997

[A case of recurrent advanced colon cancer treated with CPT-11 for second-line chemotherapy].

A 59-year old male patient had been operated on for sigmoid colon cancer in July, 1990. Operative findings were, P0, H0, S1, N (-), Stage I, and histological findings were ss, ly 2, v0, n (-). In July 1994, the CEA level elevated, and be was diagnoted as having para-aortic LN swelling and stenosis of anastomosis of colon. He was admitted for treatment of recurrent colon cancer. Initially, he was treated with continuous injection of 5-FU, low-dose CDDP and Leucovorin. His CEA level decreased and para-aortic LN diminished in size. But, in December 1995, the CEA level and para-aortic LN relapsed. 5-FU, CDDP and Leucovorin were administered, but the CEA level became more and more elevated. This regimen was not considered responsible for drug resistance. CPT-11 was administered at 60 mg/week 6 times, and 80 mg/week 3 times. The side effects disappeared, LN sightly diminished in size, and the CEA level decreased. Judging by the anticancer effect without severe side effect, we found CPT-11 a useful drug for second-line chemotherapy.

Antineoplastic Agents, Phytogenic↗
PubMed1996

In vitro and in vivo antifungal activities of ER-30346, a novel oral triazole with a broad antifungal spectrum.

ER-30346 is a novel oral triazole with a broad spectrum of potent activity against a wide range of fungi. ER-30346, with MICs at which 90% of the strains tested are inhibited (MIC90s) ranging from 0.025 to 0.78 microgram/ml, was 4 to 32 times more active than itraconazole, fluconazole, and amphotericin B against Candida albicans, Candida parapsilosis, and Candida glabrata. Against Candida tropicalis, ER-30346, with an MIC90 of 12.5 micrograms/ml, was 2 to > 8 times more active than itraconazole and fluconazole, but was 16 times less active than amphotericin B. ER-30346 (MIC90, 0.78 microgram/ml) was four to eight times more active than fluconazole and amphotericin B and had activity comparable to that of itraconazole against Trichosporon beigelli. The MIC90s of ER-30346 were 0.10 microgram/ml for Cryptococcus neoformans and 0.39 microgram/ml for Aspergillus fumigatus. ER-30346 was 2 to 8 times more active than itraconazole and amphotericin B and 32 to > 256 times more active than fluconazole. ER-30346 also showed good activity against dermatophytes, with MICs ranging from 0.05 to 0.39 microgram/ml, and its activity was comparable to or 2 to 16 times higher than those of itraconazole and amphotericin B and > 32 times higher than that of fluconazole. In vivo activity was evaluated with systemic infections in mice. Against systemic candidiasis and cryptococcosis, ER-30346 was comparable in efficacy to fluconazole and was more effective than itraconazole. Of the drugs tested, ER-30346 was the most effective drug against systemic aspergillosis. We studied the levels of ER-30346 in mouse plasma. The maximum concentration of drug in plasma and the area under the concentration-time curve for ER-30346 showed good linearity over a range of doses from 2 to 40 mg/kg of body weight.

Animals↗
PubMed1996

Efficacy of ER-30346, a novel oral triazole antifungal agent, in experimental models of aspergillosis, candidiasis, and cryptococcosis.

ER-30346 is a novel oral triazole with a broad spectrum of potent activity against a wide range of fungi. In the present study, we investigated the therapeutic effects of oral ER-30346 on experimental local infections caused by Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans and compared them with those of itraconazole and fluconazole. In experimental murine models of pulmonary aspergillosis, candidiasis, and cryptococcosis, ER-30346 reduced the numbers of CFU in the lungs significantly compared with the numbers of CFU in the lungs of the controls (P < 0.05). ER-30346 was as effective as or more effective than itraconazole against pulmonary aspergillosis. Against pulmonary candidiasis and cryptococcosis, ER-30346 was more effective than itraconazole and was as effective as fluconazole. ER-30346 was also effective against pulmonary candidiasis caused by fluconazole-resistant C. albicans. In mice with intracranial cryptococcosis, ER-30346 reduced the numbers of CFU in the brains significantly compared with the numbers of CFU in the brains of the controls (P < 0.05) and was more effective than itraconazole and as effective as fluconazole. In an experimental model of oral candidiasis in rats, ER-30346 reduced the numbers of CFU in oral swabs significantly compared with the numbers of CFU in oral swabs from the controls (P < 0.05) and was more effective than itraconazole and as effective as fluconazole. Thus, ER-30346 shows efficacy in murine aspergillosis, candidiasis, and cryptococcosis models. Further studies are needed to determine the potential of ER-30346 for use in the treatment of these infections.

Animals↗
PubMed1996

Fecal lactoferrin as a marker for disease activity in inflammatory bowel disease: comparison with other neutrophil-derived proteins.

OBJECTIVES: 1) To investigate which neutrophil-derived proteins in feces most accurately reflect disease activity in inflammatory bowel disease. 2) To examine the extracellular release of these proteins by activated neutrophils and their stability in feces by in vitro study. METHODS: We studied 41 patients (91 samples) with ulcerative colitis (UC), 34 patients (105 samples) with Crohn's disease (CD), and 25 control subjects. Fecal levels of lactoferrin (Lf), polymorphonuclear neutrophil elastase (PMN-E), myeloperoxidase (MPO), and lysozyme (Lys) were measured by ELISA. We also measured fecal hemoglobin (Hb) and alpha 1-antitrypsin (alpha 1-AT), useful markers of disease activity in UC and CD, respectively. For the in vitro study, blood samples were stimulated with phorbol myristate acetate or latex beads. For the assessment of stability, homogenized stool samples were stored at 4 degrees C, 25 degrees C, and 37 degrees C for various periods. RESULTS: 1) Fecal Lf, PMN-E, MPO, and Lys concentrations were significantly increased in the active phase of the disease compared to the inactive phase in both UC and CD. 2) Fecal Lf, PMN-E, MPO, and Lys concentrations correlated significantly with fecal Hb concentration in UC, whereas fecal Lf, PMN-E, and MPO concentrations correlated significantly with alpha 1-AT concentration in CD. In UC, fecal Lf, PMN-E, MPO, and Lys concentrations were high in 15, 9, 14, and 14 samples, respectively, of 25 samples with normal Hb concentration. In CD, fecal Lf, PMN-E, and MPO concentrations were high in 19, 10, and 16 samples, respectively, of 30 samples with normal alpha 1-AT concentration. 3) The extracellular release of Lf was the most efficient and this molecule was the most stable in feces. CONCLUSIONS: Both our clinical and our in vitro studies suggested that Lf is the most suitable of these proteins to use as neutrophil-derived fecal marker of inflammation for clinical application.

Adult↗
PubMed1995

Suppressive action of lansoprazole on gastric acidity and its clinical effect in patients with gastric ulcers: comparison with famotidine.

We studied the action on acid secretion of lansoprazole compared with famotidine by 24-h intragastric pH monitoring, evaluated its clinical effects prospectively, and assessed the importance of acid inhibition in gastric ulcer patients. Twenty symptomatic patients with active gastric ulcers diagnosed by endoscopy were assigned to a lansoprazole (LAN) group (lansoprazole 30 mg q.d., n = 10) or a famotidine (FAM) group (famotidine 20 mg b.i.d., n = 10). There were no differences between the groups in pretreatment pH profiles or background factors such as age, sex, smoking, previous ulcer therapy, ulcer site, or Helicobacter pylori infection. The FAM group showed a continuous increase in intragastric pH during the night, with low pH values except for a transient increase associated with food intake during the day. However, the LAN group showed a more neutral pH throughout the day, with pH-3 holding time ratios of 99.0% for 24 h, 98.3% at night, and 99.8% during the day, compared with 68.0, 76.5, and 59.4%, respectively, in the FAM group. The healing rate was also higher in the LAN group. We conclude that inhibition of gastric acidity is important in ulcer therapy and that lansoprazole is superior to famotidine in promoting ulcer healing.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Clinical study on the pathophysiology and treatment of PPI-resistant ulcers.

We studied the gastric acidity, gastric emptying, and proton pump inhibitor (PPI) plasma levels in 10 patients with PPI-resistant ulcers. The pH3 holding-time ratio was low in nine of these patients, with an average ratio of only 39%. PPI plasma levels in those patients were also much lower than in those with nonresistant ulcers. Gastric emptying, determined by the acetaminophen method, was reduced in all 10 patients. Therefore, PPI-resistant ulcers appear to result from insufficient inhibition of gastric acidity, with reduced gastric emptying interfering with the absorption of PPIs. In patients with mild reductions in gastric emptying, PPI plasma levels increased after a change from single-unit enteric-coated tablets (omeprazole) to multiunit enteric-coated granules in capsules (lansoprazole). This change in formulation markedly inhibited gastric acidity and led to rapid healing. In patients with moderate reductions in gastric emptying, doubling the dose of lansoprazole was effective. In patients with severely reduced gastric emptying, there appeared to be a limit to the effectiveness of oral administration of PPIs. Changing the formulation and doubling the dose to compensate for reduced gastric emptying are effective approaches in the treatment of patients with PPI-resistant ulcers.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

A micro-suspension-test for evaluation of disinfectants against human immunodeficiency virus.

We devised a micro-suspension-test to evaluate disinfectants against human immunodeficiency virus type-1 (HIV-1) and confirmed its reliability. Suspensions of persistently HIV-1-infected Molt-4 cells were used as targets of disinfectants and residual infectivity was measured by an infectivity assay: after cocultivation with uninfected Molt-4 cells reverse transcriptase activity (RTA) in the supernatant and giant cell formation (GCF) were monitored. Our new infectivity assay consists of a short-term assay, that is RTA and GCF monitoring on the second day of co-culture, and a long-term assay, that is RTA monitoring up to the 28th day of co-culture. The sensitivity of the short-term assay was 1 x 10(3) infected cells and that of the long-term assay 1 x 10(1) infected cells. All the chemical disinfectants examined in this study showed dose- and time-dependent inactivation of HIV-1. By 5-minute contact with ethanol, glutaraldehyde, formalin, sodium hypochlorite and povidone-iodine, HIV-1 was effectively inactivated at concentrations of 20, 0.01, 5, 0.05 and 0.1%, respectively. Since the micro-suspension-test is easy and sensitive, we recommend it as a method for evaluating disinfectants against HIV-1.

Cells, Cultured↗
PubMed1995

The forms and the levels of fecal PMN-elastase in patients with colorectal diseases.

OBJECTIVES: To compare the form of polymorphonuclear leukocyte (PMN)-elastase in feces with that in plasma and to investigate the usefulness of measuring fecal PMN-elastase levels in patients with colorectal diseases. METHODS: We examined PMN-elastase complexed with alpha 1-antitrypsin (alpha 1-AT), chymotrypsin, and alpha 2-macroglobulin by ELISA in feces and plasma. Fecal levels of total PMN-elastase were determined in patients with colonic polyp (N = 19), colonic cancer (N = 20), ulcerative colitis (UC; N = 36), colonic Crohn's disease (CD; N = 26), and in control subjects (N = 20). RESULTS: Most PMN-elastase was not complexed with alpha 1-AT, chymotrypsin, or alpha 2-macroglobulin in feces, whereas most plasma PMN-elastase was complexed with alpha 1-AT. Fecal concentrations and daily fecal excretion of PMN-elastase were significantly increased in patients with active UC (medians 54.8 micrograms/g, 15.14 mg/day) and active CD (41.5 micrograms/g, 10.24 mg/day) compared to those values in control subjects (0.6 micrograms/g, 0.11 mg/day) and in patients with colonic cancer (2.5 micrograms/g, 0.33 mg/day). In inactive UC and CD, these values (3.4 micrograms/g, 0.52 mg/day and 5.2 micrograms/g, 0.59 mg/day, respectively) were significantly lower than in active UC and CD, respectively. In UC, all patients whose rectal biopsies showed infiltration of PMN had high fecal PMN-elastase levels. CONCLUSIONS: Our results suggest that the measurement of fecal PMN-elastase concentrations are useful for monitoring the disease activity of UC and CD, especially when evaluating whether intestinal inflammation has disappeared completely.

Adult↗
PubMed1994

Studies on orally active cephalosporins. I. Synthesis and structure-activity relationships of new 3-substituted carbamoyloxymethyl cephalosporins.

The synthesis and antibacterial activities of 7 beta-[2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3-N,N - dimethylcarbamoyloxymethyl-3-cephem-4-carboxylic acid (E1100) and its analogs are described, as well as oral absorbability and in vivo activities of the 1-(isopropoxycarbonyloxy)ethyl ester (E1101) and its analogous esters. The introduction of acyclic and cyclic lower alkyl groups at the N-position of 3-carbamoyloxymethyl cephems influences antibacterial activities, especially against H. influenzae, and oral absorbability of their prodrug esters. The structure-activity relationships are also discussed.

Administration, Oral↗
PubMed1994

Studies on orally active cephalosporins. II. Synthesis and structure-activity relations of new [(E) or (Z) 3-substituted carbamoyloxy]-1-propenyl cephalosporins.

In an effort to find a new oral cephalosporin with well-balanced antibacterial spectrum, good oral absorbability and long plasma half-life, a series of oxyimino aminothiazolyl 3-[(E)- or (Z)-N-substituted carbamoyloxy]propenyl cephems was synthesized and evaluated for antibacterial activity and oral absorbability. The substituents of the carbamoyloxy group affected their in vitro activity and bioavailability after oral administration of their pivaloyloxymethyl esters at the C-4 position. The compound possessing an N,N-dimethylcarbamoyloxy moiety at the C-3 position showed good oral absorption and well-balanced antibacterial activity. In this report, the structure-activity relationships and the structure-oral absorbability relationships of 3-(N-substituted carbamoyloxy)-propenyl cephems are described.

Administration, Oral↗
PubMed1993

Affinity of E1077, a new cephalosporin, for penicillin-binding proteins of Staphylococcus aureus and its antistaphylococcal activity.

Potent antistaphylococcal activity was conferred on E1077 by the introduction of the propenylammonium group at the 3-position in the cephem nucleus and of the fluoromethoxyimino group in the 7 beta-side chain. Antistaphylococcal activity was more markedly increased by the former group than by the latter. This effect seemed likely to be due to the increased high affinity for penicillin-binding protein (PBP) 3, which may be one of the essential PBPs of Staphylococcus aureus, and secondly for PBP 4. E1077 also showed more potent bactericidal activity than did cefpirome at concentrations above the MICs, although the MICs of E1077 for S. aureus were only half those of cefpirome. While cefpirome showed little killing activity within 4 hours at its MIC, the addition of cefoxitin (0.05 micrograms/ml), a specific inhibitor for PBP 4, enhanced the killing activity of cefpirome to match that of E1077. In addition, peptidoglycan (PG) obtained from cells grown with the subinhibitory E1077 concentration was more susceptible to lytic enzymes than that from untreated cells or cefpirome-treated cells. These results indicated that the increased inhibition of PBPs 3 and 4 by E1077, which was brought about by the introduction of two distinctive functional groups, led to the enhanced antistaphylococcal activity and to the production of poorly cross-linked PG, and thereby to rapid bactericidal activity.

Autolysis↗
PubMed1993

Pharmacological effects of cefclidin on the central nervous system.

The effects of cefclidin (CFCL), a novel antibacterial agent, on the central nervous system (CNS) were examined in a variety of animal models. The effects of cefazolin (CEZ) were also examined for comparative purposes. In the animal models used CFCL whilst having some effects at the doses examined, failed to show an overall consistent effect on the CNS. In contrast CEZ produced changes in the parameters measured which were generally consistent with a proconvulsant action.

Animals↗
PubMed1992

Bactericidal activity of cefclidin (E1040) against Pseudomonas aeruginosa under conditions simulating plasma pharmacokinetics: lack of development of chromosomally-mediated resistance to beta-lactams.

The bactericidal activity of cefclidin (E1040), a new cephalosporin, against Pseudomonas aeruginosa was compared with that of ceftazidime and imipenem in an in-vitro model in which antibiotic concentration was varied continuously. A two-compartment open in-vitro model was used to simulate the plasma pharmacokinetics of each antibiotic in man for 12 h after a 1 h infusion of 1 g iv. The bactericidal activity of each antibiotic was observed for 6 h; however, it was diminished or absent after 6 h when the antibiotic concentration fell near to the MIC. With ceftazidime and imipenem, marked regrowth was observed after 6 h. Moreover, selection of resistant variants was observed with ceftazidime, and these variants produced 200 to 500 times more beta-lactamase than the corresponding wild-type strains. With cefclidin neither marked regrowth nor emergence of resistant variants was observed. The affinity of cefclidin for the chromosomal beta-lactamase produced by P. aeruginosa was much lower than the affinities of other new beta-lactams, and cefclidin was hydrolyzed more slowly than ceftazidime at a low concentration (2 microM). The high activity of cefclidin against P. aeruginosa, which results mainly from the low affinity of cefclidin for the pseudomonal beta-lactamase, and may play a major role in the absence of regrowth and lack of selection of resistant variants.

Ceftazidime↗
PubMed1992

Comparative in-vitro activities of newer cephalosporins cefclidin, cefepime, and cefpirome against ceftazidime- or imipenem-resistant Pseudomonas aeruginosa.

Three hundred and thirty-four recent clinical isolates of Pseudomonas aeruginosa were examined for susceptibility to cefclidin, cefepime, and cefpirome. Of these strains, 28.7% were resistant to ceftazidime, and 23.4% were resistant to imipenem. About half of those resistant to ceftazidime were also resistant to imipemem. Although 37.4% and 59.6% of the isolates were resistant to cefepime and cefpirome respectively, and most or all ceftazidime-resistant strains showed resistance to cefepime and cefpirome, only 3.9% were resistant to cefclidin. Ceftazidime-resistant, but cefclidin-susceptible, P. aeruginosa produced high levels of chromosomal cephalosporinases. Of the compounds tested, cefclidin showed the lowest affinity for these enzymes, suggesting that its high activity against P. aeruginosa resistant to several beta-lactams was mainly due to its high resistance to enzymatic hydrolysis. Thirteen strains resistant to cefclidin were also resistant to both cefepime and cefpirome, and eight and three of these strains were resistant to ceftazidime and imipenem, respectively. A penicillinase, which hydrolyzed cefclidin, was detected in the cefclidin-resistant P. aeruginosa, which was similar to the OXA-1 beta-lactamase.

Cefepime↗
PubMed1992

In vitro evaluation of E1077, a new cephalosporin with a broad antibacterial spectrum.

E1077 is a novel parenteral cephalosporin with a wide spectrum of potent antibacterial activity against aerobic and anaerobic gram-positive and gram-negative bacteria. Against methicillin-susceptible Staphylococcus aureus, E1077 was twice as active as cefpirome, with an MIC for 90% of strains tested (MIC90) of 0.78 micrograms/ml. Methicillin-resistant S. aureus was moderately to highly resistant to E1077, but E1077 was at least twice as active as other beta-lactams tested. Against Enterococcus faecalis, E1077 was the most active of the cephalosporins tested (MIC90, 12.5 micrograms/ml) and was at least fourfold more active than cefpirome and ceftazidime. At concentrations of less than or equal to 0.78 micrograms/ml, E1077 inhibited 90% of streptococci and most of the members of the family Enterobacteriaceae tested, with the exceptions of Serratia marcescens and Proteus vulgaris, for which the MIC90s of E1077 were both 3.13 micrograms/ml. Against Pseudomonas aeruginosa, E1077 was two- to fourfold more active than cefpirome and ceftazidime. For the anaerobes, E1077 was as active against Bacteroides fragilis as was cefuzonam, and its activity was fourfold higher than those of cefpirome and ceftazidime. E1077 was at least as resistant as cefpirome to hydrolysis by various beta-lactamases, and these enzymes had a low affinity for E1077.

Cephalosporins↗