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F Ikeda

Publications and source records attributed to F Ikeda.

At least 37 records · Page 2Linked to original sources

Efficacy of FK463, a new lipopeptide antifungal agent, in mouse models of pulmonary aspergillosis.

The efficacy of FK463, a novel water-soluble lipopeptide, was evaluated in mouse models of pulmonary aspergillosis and was compared with that of amphotericin B (AMPH-B). In the pulmonary aspergillosis models induced by intranasal inoculation, FK463 exhibited good efficacy, with 50% effective doses in the range of 0. 26 to 0.51 mg/kg of body weight; these values were comparable to those of AMPH-B. In an Aspergillus target organ assay with immunosuppressed mice, under conditions of constant plasma levels of FK463, using a subcutaneously implanted osmotic pressure pump, a significant reduction in viable fungal cells was observed at plasma FK463 levels of 0.55 to 0.80 microgram/ml or higher. We conclude that FK463 is highly effective in the treatment of pulmonary aspergillosis in this animal model. These results indicate that FK463 may be a potent parenterally administered antifungal agent for pulmonary aspergillosis.

Amphotericin B↗

Prophylactic effect of FK463, a novel antifungal lipopeptide, against Pneumocystis carinii infection in mice.

The prophylactic effect of FK463, a new water-soluble echinocandin-like lipopeptide with inhibitory activity against 1, 3-beta-D-glucan synthase, against Pneumocystis carinii infection was investigated with the severe combined immunodeficient (SCID) mouse model. Treatment with FK463, pentamidine, and saline only was performed for 6 weeks from the day after the SCID mice were inoculated intranasally with infected lung homogenates. FK463 at 0.2 or 1.0 mg/kg of body weight, pentamidine at 4 mg/kg, or saline was subcutaneously administered daily into the backs of the SCID mice. The effects of the drugs were evaluated by detection of P. carinii cysts in mouse lung homogenates by toluidine blue O staining, lung histology, and PCR amplification of a P. carinii-specific DNA fragment from the lungs. P. carinii cysts were detected in the lungs of all mice administered saline. In contrast, no cysts were detected in mice administered both doses of FK463 and pentamidine. A specific DNA fragment was amplified from all mice administered saline and at least half or more of the mice administered FK463 and pentamidine. These results indicate that FK463 acts on cyst wall formation but not on trophozoite proliferation and is extremely effective in preventing P. carinii-associated pneumonia. These results suggest that FK463 is potentially useful as a prophylactic agent against P. carinii infection.

Animals↗

Effects of MS-31-038, a novel Na(+)-H+ exchange inhibitor, on the myocardial infarct size in rats after postischemic administration.

The abilities of 2-(2-methylphenyl)-5,7-dimethoxy-4-quinolyl carbonylguanidine dihydrochloride (CAS 181048-29-3, MS-31-050) and 2-phenyl-8-(2-methoxyethoxy)-4-quinolyl carbonylguanidine bismethanesulfonate (CAS 181048-36-2, MS-31-038) in inhibiting Na(+)-H+ exchange, ischemia- and reperfusion-induced injury were determined and compared with those of 4-isopropyl-3-methylsulfonylbenzoyl guanidine methanesulfonate (CAS 159138-81-5, IMGM), a selective inhibitor of Na(+)-H+ exchange. MS-31-050 and IMGM exhibited comparable inhibitory effects on Na(+)-dependent pH recovery and antiarrhythmic effects during ischemia in anesthetized rats. In rats subjected to ischemia and reperfusion, MS-31-050 (10 mg/kg i.v.) significantly reduced the infarct size when given prior to the onset of ischemia. However, postischemic treatment with either MS-31-050 or IMGM failed to protect reperfused hearts. In contrast, MS-31-038 reduced the infarct size dramatically from 65.4 +/- 7.4% in control to 29.9 +/- 11.6% at 3 mg/kg and 9.8 +/- 3.4% at 10 mg/kg even when administered before the onset of reperfusion. These results suggest the beneficial effects of Na(+)-H+ exchange inhibitors on myocardial ischemia/reperfusion injury.

Anesthesia↗

Primary cardiac angiosarcoma associated with cardiac tamponade: case report.

A 57-year-old male with primary cardiac angiosarcoma was initially admitted for cardiac tamponade. Pericardiocentesis was performed twice preoperatively, but the bloody pericardial fluid was cytologically negative for malignant cells. The tumor in the right atrium was resected during cardiopulmonary bypass. The resected tumor was 5.5x4.5x3.0cm in size and the diagnosis of cardiac angiosarcoma was made histologically. There were no tumor cells in the surgical margin. Unfortunately the patient died 3.5 months after surgery due to multiple recurrence in the pericardium. A suitable therapy for cardiac angiosarcoma is still controversial, but early antemortem diagnosis and more aggressive combined treatment should be considered.

Cardiac Tamponade↗

Human complement component C1q inhibits the infectivity of cell-free HTLV-I.

Human T cell leukemia virus type I (HTLV-I) is a retrovirus that is not lysed by human serum or complement. It has not been determined, however, whether HTLV-I directly binds to complement components or whether it retains infectivity after incubation with human serum. We investigated the effects of human serum on the infectivity of cell-free HTLV-I produced by human and animal cells. Plating of vesicular stomatitis virus (HTLV-I) pseudotypes prepared in cat or human cells and formation of HTLV-I DNA after infection of cell-free HTLV-I produced by cat or human cells were markedly inhibited by treatment with fresh human serum, but not by heat-inactivated serum. HTLV-I infection was also inhibited by treatment with C2-, C3-, C6-, or C9-deficient serum, but not by C1q-deficient serum. Inhibitory activities of normal human serum against HTLV-I were neutralized by anti-C1q serum. Furthermore, purified C1q inhibited HTLV-I infection. The direct binding of C1q to HTLV-I was confirmed by comigration of C1q with HTLV-I virion upon sucrose density gradient ultracentrifugation of HTLV-I virion treated with C1q. Binding assay using synthetic envelope peptides indicated that C1q bound to an extramembrane region of the gp21 transmembrane protein. These findings indicate that the human complement component C1q inactivates HTLV-I infectivity.

Animals↗

Low prevalence of Helicobacter pylori infection in patients with hamartomatous fundic polyps.

Helicobacter pylori infection of the gastric mucosal surface was investigated in patients with hamartomatous fundic polyps or hyperplastic polyps and in patients without endoscopic evidence of disease (healthy subjects). Presence of H. pylori infection was determined by culture, histologic examination, and the endoscopic phenol red test. Adherence of H. pylori was evaluated with scanning electron microscopic examination of antral biopsy specimens. Both prevalence of H. pylori infection (P < 0.001) and H. pylori adherence (P < 0.05) were less in patients with hamartomatous fundic polyps than in healthy subjects and patients with hyperplastic polyps. However, the percentages of plasma cells in gastric mucosa that contained IgA and of gastric epithelial cells that expressed Lewis b did not differ significantly among the three groups. These findings suggest that defense mechanisms against the attachment of H. pylori other than IgA or Lewis b antigen are present in patients with hamartomarous fundic polyps.

Biopsy↗

Prevalence of hepatitis B and C virus markers in outpatients of Mongolian general hospitals.

In East Asian countries, the prevalence of viral hepatitis has been reported to be high, but precise data for each country remained to be investigated. Here we report the prevalence of viral markers of hepatitis B and hepatitis C in outpatient volunteers visiting two general hospitals in Ulaanbaatar, Mongolia. One hundred fifty sera were tested for HBs antigen (HBsAg), anti-HBs, and anti-HCV by Counting Immunoassay. The backgrounds of groups of patients positive for HBsAg and negative for anti-HCV (group 1; n = 18), negative for HBsAg and positive for anti-HCV (group 2; n = 47), positive for both HBsAg and anti-HCV (group 3; n = 25), and negative for both HBsAg and anti-HCV (group 4; n = 60) were compared. The prevalence of HBsAg, anti-HBs, and anti-HCV in this study group was 28.7%, 39.3% and 48.0%, respectively. Subjects of group 1 (mean +/- SD; 31.3 +/- 12.4 years old) were younger than those of group 4 (39.2 +/- 14.3; p < 0.05), while patients of group 2 (48.7 +/- 15.5) were older than those of group 4 (p < 0.01). More group 2 subjects had histories of jaundice (23/47) than those of group 4 (15/60; p < 0.05). Transaminase levels were higher in group 1 (median (range) IU/l of AST, ALT; 29 (13-95), 32 (9-144) and group 3 (25 (15-187), 22 (8-185)) than in group 4 (18 (9-13), 15 (6-133); p < 0.05, p < 0.005 vs. group 1, and p < 0.005, p < 0.001 vs. group 3, respectively). In HBsAg-negative subjects, those with higher titers of anti-HCV (cut-off index > 15) were older, and had more histories of jaundice and higher levels of AST and ALT than anti-HCV negative subjects (50.3 +/- 14.8 vs. 39.1 +/- 14.3, p < 0.01; 15/28 vs. 15/60, p < 0.01; 22.5 (12-127) vs. 18 (9-93), p < 0.05; 20.5 (7-362) vs. 15 (6-133), p < 0.05; respectively). In conclusion, this preliminary surveillance for hepatitis B and C viral markers showed that both hepatitis viruses are prevalent and may cause liver diseases in Mongolia. A nation-wide survey for these viruses should be urged and preventive measures should be taken to suppress the spread and development of liver diseases in this country.

Adult↗

Comparative analysis on the distribution of heterochromatin in Citrus, Poncirus and Fortunella chromosomes.

Double fluorochrome staining with chromomycin A3 (CMA) and 4'-6-diamidino-2-phenylindole (DAPI) was used to characterize and compare the distribution of constitutive heterochromatin along chromosomes of Citrus, Poncirus and Fortunella species. Only CMA-positive bands were distinguishable in metaphase chromosomes. Preferential distribution of heterochromatin in terminal regions, mainly of the long arm, and centromeric regions of a few long chromosomes was a common feature of these genera. Heteromorphism between possible homologous chromosomes was present in the majority of species. Citrus and Poncirus revealed some remarkably uniform chromosomes without any intensively fluorescing region, whereas Fortunella cultivars were differentiated by the presence of CMA bands in all chromosomes. Through measurements assisted by a computer, amounts of CMA-positive regions were shown to be highest in Fortunella. Similarities between Citrus and Poncirus suggest little heterochromatin diversification among karyotypes of these genera, whereas Fortunella, with higher amounts and more homogenous distribution of heterochromatin, is more divergent.

Chromomycin A3↗

Induction of ulceration and severe gastritis in Mongolian gerbil by Helicobacter pylori infection.

Specific pathogen-free Mongolian gerbils were infected orally with Helicobacter pylori to establish a new small animal model of severe gastritis H. pylori was recovered by culture from both antrum and body over a 16-week period after a single inoculation. The number of H. pylori colonising the antrum was about 100-fold higher than in the body, and this was consistent throughout the experiment. Histological examination showed that all animals developed severe inflammation with infiltration of polymorphonuclear leucocytes and mononuclear cells into the lamina propria and submucosa of the antrum from 4 weeks after infection. From 8 weeks after infection, multifocal lymphoid follicles appeared in the lamina propria and submucosa, and micro-erosions were also observed in the epithelial layer. At 16 weeks after infection, ulceration with disruption of the lamina muscularis mucosae was observed in the antral mucosa. To determine whether H. pylori caused gastritis or not, infected gerbils were treated with amoxycillin. After the treatment, gastritis could not be seen in the gastric mucosa. Therefore, the Mongolian gerbil is a useful small animal model to study the pathogenesis of H. pylori in gastric ulceration and severe gastritis and to assess anti-H. pylori treatment.

Amoxicillin↗

Appearance of a metronidazole-resistant Helicobacter pylori strain in an infected-ICR-mouse model and difference in eradication of metronidazole-resistant and -sensitive strains.

We tested whether antibiotic-resistant strains appeared in vivo after the failure of treatment using the Helicobacter pylori-infected euthymic mouse model. The numbers of colonies isolated from 56 ICR mice 2 weeks after 4 days of treatment with metronidazole (3.2, 10, or 32 mg/kg of body weight) or amoxicillin (1, 3.2 or 10 mg/kg), with treatment started 4 days after H. pylori CPY2052 inoculation, were counted, and the isolated strains were tested for their sensitivities to two antibiotics to rule out the presence of antibiotic-resistant strains. One metronidazole-resistant strain was detected in a mouse treated with 10 mg of metronidazole per kg, and the MIC of metronidazole for this strain was 25 microg/ml, compared to a MIC of 1.56 microg/ml for the original strain. However, no resistant strain was detected in the amoxicillin treatment group. After the examination described above, mice challenged with a metronidazole-resistant or -sensitive strain isolated from the stomach of a mouse were treated with metronidazole or amoxicillin. The metronidazole-resistant strain was more difficult to eradicate in vivo than the sensitive strain after treatment with metronidazole but not after treatment with amoxicillin. Thus, a metronidazole-resistant H. pylori strain was selected by insufficient treatment, but no resistant strain was selected with amoxicillin. Eradication of a metronidazole-resistant H. pylori strain in vivo required a higher dosage than eradication of a metronidazole-sensitive H. pylori strain. These results may explain one of the reasons for H. pylori treatment failure.

Amoxicillin↗

Remodelling of choroidal circulation in carotid cavernous sinus fistula.

BACKGROUND: Carotid cavernous sinus fistula may induce drastic changes in choroidal circulation secondary to elevated orbital venous pressure. CASES AND METHODS: Three patients affected by spontaneous carotid cavernous sinus fistula were studied for 3-15 months. The angioarchitecture and hemodynamics of the choroid were evaluated repeatedly by indocyanine green angiography using a montage panoramic technique. RESULTS: Choroidal vessels underwent drastic restructuring including patchy nonperfusion of the choriocapillaris, attenuation of vortex veins, preferential venous dilatations, and drainage into outflow channels near the optic disc or into anterior ciliary veins. CONCLUSIONS: Choroidal veins were very versatile in remodelling their structure and hemodynamics after sustained elevation of orbital venous pressure. The presence of numerous anastomoses between choroidal veins appeared to be a major underlying cause of this versatility. The observed remodelling of choroidal vessels seemed to be guided by the principle that the venous blood flowed toward sites of lesser pressure resistance.

Aged↗

[Choroidal vascular lesions in serous retinal detachment viewed with indocyanine green angiography].

In serous retinal detachment due to damaged retinal pigment epithelium (RPE), fluorescein angiography shows dye leakage into the subretinal space from the choroid. We performed indocyanine green (ICG) angiography in 110 eyes with serous retinal detachment comprising 71 eyes with central serous chorioretinopathy (CSC), 19 with bullous retinal detachment, 18 with Harada's disease, and 2 with toxemia of pregnancy. Choroidal tissue staining was present around the site of subretinal leakage in late-phase ICG angiograms from 63 eyes with CSC and 18 with bullous retinal detachment. ICG angiography also showed leakage from choroidal vessels in 16 eyes with Harada's disease and 2 with toxemia of pregnancy. As a common feature, ICG angiography showed choroidal vascular hyperpermeability in various types of serous retinal detachment. Choroidal circulation was delayed in Harada's disease and toxemia of pregnancy. Choroidal hypoperfusion and hyperpermeability of choroidal vessels probably contribute to the damage of RPE, and choroidal vascular hyperpermeability probably provides fluid pressure to move fluid into the subretinal space from the choroid.

Adult↗

[Antibacterial activity of cefdinir and omeprazole against Helicobacter pylori and their inhibition on H. pylori-producing urease].

Since Helicobacter pylori is isolated very frequently from gastric ulcer specimens, the combination therapy of antimicrobial agent and proton pump inhibitor has recently been used. A study was made on whether cefdinir (CFDN), amoxicillin (AMPC), metronidazole (MNZ), omeprazole (OPZ), and omeprazole-M (OPZ-M) have antimicrobial activity against H. pylori and whether they can inhibit H. pylori-producing urease. 1) CFDN, AMPC and MNZ showed a potent antimicrobial activity against H. pylori, and especially, AMPC showed a marked bactericidal activity in a short time. 2) OPZ is reported to be converted to OPZ-M, and active form, in the body. OPZ and OPZ-M showed a moderate antimicrobial activity against H. pylori, and scarcely any bactericidal activity. 3) CFDN and OPZ or AMPC and OPZ in combination did not show any synergistic effect on the antimicrobial activity, but MNZ and OPZ in combination showed additive effect on the antimicrobial activity against H. pylori. 4) OPZ and OPZ-M inhibited H. pylori-producing urease and the inhibitory effect of OPZ-M was more stronger than that of OPZ. CFDN, AMPC and MNZ did not show any inhibitory effect on H. pylori-producing urease at 10 micrograms/ml. From these data, antimicrobial agents and proton pump inhibitors in combination are expected to exert the in vivo synergistic effect since these drugs eradicate H. pylori and inhibit H. pylori-producing urease.

Cefdinir↗

Calcium concentration during anoxic perfusion modifies post-ischemic hypercontraction in the canine heart.

The purpose of this study was to clarify the role of calcium flux in the pathogenesis of transient overshoot in regional myocardial contractile function after brief ischemia (post-ischemic hypercontraction). Six open-chest anesthetized dogs were examined. The left anterior descending coronary artery (LAD) was cannulated with a bypass system from the left carotid artery. Two minutes of total coronary occlusion of the LAD resulted in a post-ischemic hypercontraction 1 minute after reperfusion. Post-ischemic hypercontraction was abolished after reperfusion following 2 minutes of perfusion with anoxic Krebs-Henseleit solution containing 2.5 mM calcium. Post-ischemic hypercontraction occurred after calcium-free anoxic perfusion. The regional myocardial contractile function remained depressed 1 minute after reperfusion following anoxic perfusion with 5.0 mM calcium solution. Thus, post-ischemic hypercontraction was modified by the calcium concentration during anoxia. Alteration in transsarcolemmal calcium influx during reperfusion, which was modified by alterations in the calcium environment during anoxia, could be responsible for this phenomenon.

Animals↗

Postischaemic hypercontraction is enhanced in ischaemically injured canine myocardium.

OBJECTIVE: The aim was to identify the role of calcium flux in the pathogenesis of transient overshoot of regional myocardial contraction after brief ischaemia, ie, postischaemic hypercontraction. METHODS: Ten anaesthetised mongrel dogs were examined under open chest conditions. The left anterior descending coronary artery was initially occluded for 2 min and reperfused for 10 min. A further period of coronary occlusion of 15 min duration was followed by 15 min reperfusion to produce postischaemic regional dysfunction. A third occlusion of 2 min duration was followed by 10 min reperfusion to induce postischaemic hypercontraction. Coronary blood flow was measured using an ultrasonic transit time flow meter. Segment length was measured by ultrasonic microcrystals. RESULTS: Postischaemic hypercontraction after 2 min coronary occlusion was exaggerated in ischaemically injured myocardium. The 10 dogs were divided into two groups, a control group (n = 5) and a verapamil treated group (n = 5), and were exposed to a final 2 min period of coronary occlusion with or without verapamil in the ischaemically injured myocardium. Postischaemic hypercontraction was attenuated in the verapamil treated group compared with the control group. CONCLUSIONS: Exaggeration of postischaemic hypercontraction in ischaemically injured myocardium may be mediated by a trans-sarcolemmal calcium flux. Changes in calcium flux may play a role in the pathogenesis of this phenomenon in the normal myocardium.

Animals↗

Antibacterial activity of cefixime against Streptococcus pneumoniae, Streptococcus pyogenes, and Haemophilus influenzae in the presence of Moraxella (Branhamella) catarrhalis.

We measured the sizes of the inhibition zones of oral beta-lactam antibiotics for Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae in the presence of beta-lactamase-producing-Moraxella (Branhamella) catarrhalis by the agar double-layer method. The sizes of the zones of amoxicillin for S. pneumoniae alone were the largest, followed in a descending order by those of cefixime and cefaclor. In the presence of 10(7) CFU/ml of M.(B.) catarrhalis, however, significant reduction of the sizes of the zones was seen with amoxicillin and cefaclor; inhibition with cefixime was nearly unchanged. Similar results were observed in those for S. pyogenes. These variable findings were attributed to the difference in stability of these drugs to the beta-lactamase produced by M.(B.) catarrhalis. When the susceptibility of H. influenzae in the presence of 10(8) CFU/ml of M.(B.) catarrhalis to cefixime, cefoteram, cefpodoxime, cefotiam and cefuroxime was examined, the sizes of the inhibition zones of all the drugs were reduced by the presence of 10(8) CFU/ml of M.(B.) catarrhalis, but those of cefixime were the largest of all the drugs tested. Our agar double-layer method is simple and useful for evaluating the influence of beta-lactamase-producing organism, as M.(B.) catarrhalis, on the disk susceptibility of other pathogens to antibiotics.

Cefixime↗

Mechanisms of transient augmentation of myocardial contraction after a brief coronary occlusion.

The purpose of this study was 1) to clarify whether augmented myocardial contraction after a brief coronary occlusion, i.e. post-ischemic hypercontraction, depends on a transient increase in coronary blood flow or preceding myocardial ischemia, and 2) to identify the role of catecholamines or calcium flux in this phenomenon. Sixteen mongrel dogs were examined in open-chest anesthetized condition. One-minute reperfusion after two-minute total coronary occlusion of the left anterior descending artery resulted in a transient increase in segment shortening. Intracoronary administration of adenosine caused hyperemia without any changes in segment shortening. Two minutes of total coronary occlusion with adenosine caused post-ischemic hypercontraction to the same degree, but without any additional hyperemia. Two minutes of partial occlusion with 75% flow reduction caused less post-ischemic hypercontraction. Post-ischemic hypercontraction did not occur after partial occlusion with 50% flow reduction, irrespective of hyperemia with adenosine during reperfusion. Propranolol or verapamil did not prevent this phenomenon. Thus, post-ischemic hypercontraction is not dependent on the transient increase in coronary blood flow, but is related to the preceding myocardial ischemia. Local release of catecholamines is not likely to be the cause. A calcium antagonist, verapamil, did not modify this phenomenon. The precise mechanism of this phenomenon is still uncertain, although some alterations in cellular hemostasis, such as ionic changes, are likely to be the cause.

Animals↗