Biomedical subjects

Y Kumamoto

Publications and source records attributed to Y Kumamoto.

At least 109 records · Page 6Linked to original sources

PubMed1995

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1993). III. Secular changes in susceptibility].

Susceptibilities of Enterococcus faecalis, Staphylococcus aureus, Citrobacter spp., Enterobacter spp., Escherichia coli, Klebsiella spp., Proteus mirabilis, Pseudomonas aeruginosa and Serratia spp. isolated from patients with urinary tract infections (UTIs) in 10 hospitals during June 1993 to May 1994 to various antimicrobial agents were compared with those in the same period of previous years according to a classification, uncomplicated UTIs, complicated UTIs without indwelling catheter, and complicated UTIs with indwelling catheter. The susceptibilities of E. faecalis to chloramphenicol decreased. As for S. aureus, susceptible strains to minocycline (MINO) decreased in complicated UTIs. As for Citrobacter spp., and Enterobacter spp., their susceptibilities were not observed an obvious change. Against E. coli, the activities of cefotiam decreased in complicated UTIs, and aminoglycosides decreased. As for Klebsiella spp., susceptible strains to aminoglycosides decreased. The susceptibilities of P. mirabilis to all drugs except aminoglycosides and MINO were good. The susceptibilities of P. aeruginosa to quinolones isolated from complicated UTIs with indwelling catheter increased, but susceptible strains to aminoglycosides decreased. The susceptibilities of Serratia spp. to MINO has decreased. These data should be considered in clinical treatment of various urinary tract infections.

Anti-Bacterial Agents↗

PubMed1994

Markedly increased amounts of messenger RNAs for vascular endothelial growth factor and placenta growth factor in renal cell carcinoma associated with angiogenesis.

The presence of mRNAs for vascular endothelial growth factor (VEGF) and a VEGF-related protein, placenta growth factor (PIGF) was examined in 29 cases of renal cell carcinoma tissues and adjacent normal kidney tissues and in 4 human renal cell carcinoma cell lines. Northern blot analysis showed that 26 of 27 hypervascular renal cell carcinoma tissues (96%) exhibited a markedly elevated level (3-13 fold) of VEGF mRNA compared to the adjacent normal kidney tissues. Even tumors of small size, whenever they were hypervascular, overexpressed VEGF mRNA. We also demonstrated that mRNA for PIGF was expressed in 21 of 23 hypervascular renal cell carcinoma tissues (91%) but was not detected in the adjacent normal kidney tissues. Two hypovascular carcinoma tissues neither overexpressed VEGF mRNA nor had PIGF mRNA. VEGF mRNA was detected in four human renal cell carcinoma cell lines, while PIGF mRNA was not. There was no difference in the level of basic fibroblast growth factor mRNA between tumor tissues and normal kidney tissue, although our previous study demonstrated elevated basic fibroblast growth factor protein in the serum of renal cell carcinoma patients (K. Fujimoto et al., Biochem. Biophys. Res. Commun., 180: 386-392, 1991). Taken together, these results suggest that VEGF, PIGF, and basic fibroblast growth factor are cooperatively working to increase the angiogenesis in renal cell carcinoma in vivo.

Angiogenesis Inducing Agents↗

PubMed1994

Decrease in lymphokine-activated killer sensitivity of a human renal-cell carcinoma cell line after cytokine treatment.

Recent studies have shown that cytokine treatment of tumor cells alters the sensitivity of these cells to lymphokine-activated killer (LAK) cells, depending on the cell line. In this study, we analyzed the decrease in LAK sensitivity of a human renal-cell carcinoma cell line (SMKT-R-3). The LAK sensitivity of SMKT-R-3 was decreased by treatment with a combination of interferon gamma (IFN gamma) and tumor necrosis factor (TNF). However, the cytokine treatment increased the expression of intercellular adhesion molecule-1 (ICAM-1) on the renal-cell carcinoma cell surface. The conjugate-formation assay also confirmed a slight increase in the binding rate of LAK cells to the renal-cell carcinoma cells. When actinomycin D (a protein synthesis inhibitor) was added to the culture medium prior to treatment with IFN gamma and TNF, the LAK sensitivity of SMKT-R-3 recovered to the level demonstrated by the cells that had not received any cytokine treatment. These results suggest that the effect of cytokines in reducing LAK sensitivity of SMKT-R-3 is mediated by protein synthesis occurring when LAK cells are bound to SMKT-R-3 cells.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Carotid body tumor associated with differentiated thyroid carcinoma.

We report a case of a carotid body tumor associated with a primary differentiated thyroid carcinoma. A 44-year-old woman presented with a 10-year history of an asymptomatic mass in her neck. Physical examination revealed a pulsatile submandibular mass in her right neck as well as multiple nodules in the thyroid. Magnetic resonance imaging, computed tomography and, in particular, angiography were diagnostic of the carotid body tumor. Slight changes in serum thyroglobulin levels and thyroid scintigraphy led us to suspect thyroid carcinoma. Embolization of the arteries feeding the carotid body tumor was performed, and was followed by tumor resection 24 h later. At surgery, histopathology confirmed the presence of follicular and papillary carcinomas of the thyroid, resulting in concurrent resection of the gland. There were no residual cranial nerve deficits. The patient subsequently received radiotherapy. Diagnosis and surgical management are discussed, together with pathogenetic factors.

Adult↗

PubMed1994

Influence of growth factors on in vitro invasiveness and type IV collagenolysis of human renal cell carcinoma cells.

We investigated the influence of epidermal growth factor (EGF) and transforming growth factor (TGF)-beta 1 on the in vitro invasion and type IV collagenolytic activity of two new cell lines of renal cell carcinoma (SRCC-1P and SRCC-1M). When cells were treated with EGF or with TGF-beta 1, EGF increased the number of cells penetrating through the reconstituted basement membrane in SRCC-1P. In contrast, TGF-beta 1 suppressed the number of cells penetrating through the membrane in SRCC-1M. In accordance with the invasiveness, EGF enhanced the activity of type IV collagenolysis in SRCC-1P, and TGF-beta 1 suppressed it in SRCC-1M. The growth factors did not affect DNA synthesis of the cells as evaluated by 3H-thymidine incorporation. These results suggest that EGF and TGF-beta 1 can influence the in vitro invasive process of renal cell carcinoma cells through their actions on proteolysis such as type IV collagenolysis.

Carcinoma, Renal Cell↗

PubMed1994

Inhibitory effect of minocycline on in vitro invasion and experimental metastasis of mouse renal adenocarcinoma.

Degradation of the extracellular matrix by metalloproteinases is a critical phenomenon in cancer invasion and metastasis. Recent studies have revealed that minocycline (minocycline hydrochloride, a tetracycline) suppresses in vivo and in vitro mammalian collagenolytic activity. We investigated whether minocycline inhibited in vitro invasion and experimental pulmonary metastasis in subline-2 of streptozotocin-induced mouse renal adenocarcinoma (MRAC-PM2) cells. In vitro invasion assay demonstrated that treatment with 0.5 microgram/ml or 5.0 micrograms/ml minocycline significantly inhibited the invasion of MRAC-PM2 cells. In addition, intraperitoneal administration of 0.5 mg per mouse minocycline reduced the number of metastatic nodules in the lung when MRAC-PM2 cells were injected intravenously. Minocycline also suppressed type IV collagenolytic activity of the cells. However, the drug did not affect [3H]-thymidine uptake, growth of subcutaneously inoculated cells, attachment to the extracellular matrices, or haptotactic migration of the cells. These results indicated that the inhibitory action of type IV collagen degradation by minocycline can contribute, in part, to suppression of the in vitro invasion and metastatic potential of MRAC-PM2 cells.

Adenocarcinoma↗

PubMed1994

[Study on local immune response in mice with an impaired function of T cells--in Escherichia coli induced experimental urinary tract infection].

An ascending urinary tract infection was induced by transurethral instillation of Escherichia coli mice which had an impaired T cell function from the administration of cyclosporine (impaired T cell function group). We investigated the time course fluctuation of local immune response at the infected sites in terms of immune response cells as compared with that in normal mice (control group). 100 mg/kg of Cyclosporine was administered a total of 4 times at 7, 5, 3 days and 1 day before the day of infection. Using this method of administration, the T cell function, for which we used delayed type hypersensitivity as an indicator, significantly suppressed the impaired T cell function group. When the ascending urinary tract infection was induced by Escherichia coli, the occurrence of pyelonephritis increased and the survival rate significantly decreased in the impaired T cell function group compared to the control group, indicating a high incidence of infection. By the time course observation of the immune response cells at the infected sites, marked infiltration of neutrophils was recognized in the impaired T cell function group as compared with that in the control group and such infiltration remained on the same higher level thereafter. On the other hand, T, B cell infiltration was weaker in the impaired T cell function group compared to the control group. It was therefore suggested that other immune response cells compensated for the infiltration of T cells when their function was suppressed, and that these cells on the whole possibly responded toward the preservation of their protective mechanism against infection.

Animals↗

PubMed1994

[Investigation of Chlamydia trachomatis-specific IgA, IgG antibody with EIA method].

Recently, two new kits, HITAZYME (Hitachi Chemical Co., Ltd.) and SERO IPALISA (Savyon Diagnostics, Ltd.), for the assay of anti-C. trachomatis antibodies by the enzyme immunoassay (EIA) method have been developed and put into clinical application. In the study reported here, the authors investigated the clinical usefulness of these assay kits, together with the IPAzyme and micro-IF test, in the diagnosis of cases of urogenital tract C. trachomatis infections. 1. The positive rates for IgA antibodies, which are considered to be an indicator of active infection, obtained with the HITAZYME and SERO IPALISA kits in the 82 antigen-positive cases were significantly (p < 0.005) higher than the rates obtained with the IPAzyme and micro-IF test. These results showed the usefulness of the HITAZYME and SERO IPALISA kits for detecting C. trachomatis infections. 2. A comparison was made of the assay results obtained with the HITAZYME and SERO IPALISA kits, and it was found that there was a large number of cases (142) that tested negative for IgA antibodies with the HITAZYME but positive with the SERO IPALISA kit. We carried out a confirmatory test on the specimens of cases for which the results obtained with the HITAZYME and SERO IPALISA kits were not in agreement. This test employed the Western blotting method using COMC (the antigen extracted from EB of C. trachomatis strain L2 and used in the HITAZYME kit) and whole EB of C. trachomatis strain L2 (the antigen used in the SERO IPALISA kit). The results showed a significantly higher degree of agreement between the HITAZYME kit data and the Western blotting data than between the SERO IPALISA kit data and the Western blotting data. 3. In addition, with the objective of investigating the existence of cross reactivity with anti-C. pneumoniae antibodies, we performed Western blotting using as the antigen crude whole EB of C. pneumoniae strain TW-183. The results showed that anti-C. pneumoniae antibodies were detected in 25 of 35 (71.4%) cases that were negative with C. trachomatis antigen and the HITAZYME kit and positive with the SERO IPALISA kit. These findings indicate a strong possibility that these cases positive with the SERO IPALISA kit are due to a cross reaction with anti-C. pneumoniae antibodies.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Bacterial↗

PubMed1994

[Inhibition of biofilm formation by clarithromycin (CAM) in an experimental model of complicated bladder infection--in vitro study using automated simulation of urinary antimicrobial concentration].

The role of clarithromycin (CAM) in biofilm formation has recently been reported. Inhibition of the production or promotion of the dissolution of the glycocalyx, a major component of biofilm, has been implicated in its mechanism of action. However, the details remain unclear. We used an experimental model of complicated urinary bladder infection and automated simulation of the variations in urinary antimicrobial concentration to study the efficacy of CMA in inhibiting biofilm formation and obtained the following results. 1) Prior to biofilm formation, Pseudomonas aeruginosa (P. aeruginosa) was exposed to ciprofloxacin (CPFX, MIC: 8 micrograms/ml), which was active against the organism, at a dose of 200 mg t.i.d. for 7 days. The bacteria were apparently eradicated from the culture medium in the experimental model of bladder infection (model bladder) after 32 hours. However, when the medium was changed to eliminate the antimicrobial agent on Day 7, bacterial regrowth was initiated after 4 hours. Scanning electron microscopy demonstrated sequential biofilm formation on the surface of glass beads in the model bladder diverticulumn, suggesting inside the biofilm were a source of regrowth. 2) Prior to biofilm formation, P. aeruginosa was also exposed to CAM alone, which has no antimicrobial activity against the organism (MIC: > 128 micrograms/ml) at a dose of 200 mg t.i.d. for 7 days. In this situation, CAM was not active against P. aeruginosa and the bactericidal concentration in the model bladder did not decrease markedly, reaching the initial level (10(7) CFU/ml) within 48 hours. However, although numerous bacteria were attached to the glass beads in the diverticulum, no biofilm was formed. 3) Exposure to a combination of CPFX and CAM (each at 200 mg t.i.d. for 7 days) resulted in the eradication of bacteria from the model bladder at 32 hours, and no bacterial regrowth was demonstrated after the medium was exchanged on Day 7. In addition, no biofilm was formed and the bacteria did not become attached to the glass beads. 4) The content of alginate, a major component of P. aeruginosa biofilm, was measured per 5 glass beads on Day 3, 5, and 7 after starting drug administration. The alginate content increased with time when CPFX was given alone at a dose of 200 mg t.i.d..(ABSTRACT TRUNCATED AT 400 WORDS)

Biofilms↗

PubMed1994

[Studies on local immune response in mouse model of experimental Escherichia coli intrauterine infections].

Studies were conducted to elucidate the immune cell response at infection sites by performing immunostaining of immune cells with a monoclonal antibody in an experimental Escherichia coli (E. coli) mouse uterine infection model. 1. The incidence of uterine infection by E. coli decreased with the passage of time: 4/4 on Day 1, 4/6 on Day 3, 2/6 on Day 7, and 1/6 on each of Days 14 and 21. It was surmised that clearance of the bacteria from the infection sites was being carried out by immune cells. 2. Beginning from infection Day 1, the infected uterine tissue was observed to undergo a moderate degree of invasion by neutrophils, macrophages, CD4+ T cells, CD8+ T cells and IgA+ B cells. Then, beginning from infection Day 3, there was a mild degree of invasion of the infected uterine tissue by IgM+ B cells and IgG+ B cells. The number of neutrophils in the tissue decreased beginning from infection Day 14, but the degree of invasion of the infected tissue by the other kinds of immune cells remained almost constant through infection Day 21. 3. A comparison was made of the immune responses to local infection by E. coli, and Chlamydia trachomatis (C. trachomatis), an intracellular parasite. It was found that the invasion of the infection site by immune cells occurred earlier in the case of E. coli infection than C. trachomatis infection. In addition, the C. trachomatis infection site was observed to contain greater numbers of macrophages and CD8+ T cells play important roles in the immune defense at sites of infection by C. trachomatis.

Animals↗

PubMed1994

[Tissue gamma/delta T cells in experimental urinary tract infection relationship between other immuno-competent cells].

We studied the gamma/delta T cells, which are thought to be one of the local immune-defense system, in an experimental ascending urinary tract infection model in mouse. The experimental infection was induced in the BALB/c mouse by transurethral instillation of Escherichia coli. gamma/delta T cells were stained immunohistochemically with ABC method and the localization in the uninfected and infected murine urinary tract was determined. Then, to determine the CD4 or CD8 phenotype of gamma/delta T cells in the infected site, a two-color immunohistological study was done. In the uninfected state, gamma/delta T cells were observed in the bladder epithelium and submucosa, not in the kidney. It is thought that the difference of gamma/delta T cell distribution between kidney and bladder is affected by the bacteriological milieu, because the chance for foreign antigen exposure of bladder may be greater than that of the kidney. Six hours after inoculation of E. coli, the gamma/delta T cells infiltrated in to the bladder and kidney, following a gradual increase in number. Especially at 105 days after inoculation, severe accumulation of gamma/delta T cells in the renal scarring lesion was observed. Two-color immunohistological study revealed that the phenotypes of gamma/delta T cells in the renal scarring lesion were both CD4-CD8- double negative and CD4-CD8+ single positive. The CD4-CD8+ gamma/delta T cells were probably activated by the bacterial antigen.

Animals↗

PubMed1994

[Studies on immune response in mouse model of experimental Chlamydia trachomatis intrauterine infections].

An experimental model of Chlamydia trachomatis (C. trachomatis) intrauterine infections was established in mice. Using this model, studies were conducted on the immune response at the site of infection by applying the ABC staining method and monoclonal antibodies directed against each of the various species of immunocompetent cells. At the same time, the serum levels of C. trachomatis-specific IgA and IgG antibodies were also measured. The immunological correspondence of these serum antibodies to C. trachomatis elementary bodies was also investigated. 1. With regard to the immunological response at the site of infection, there was greater infiltration by T cells than by B cells. Determination of the subsets of the T cells revealed that CD8+ T cells outnumbered CD4+ T cells. In addition, among the B cell lineage, there was moderate infiltration by IgA-positive B cells, whereas the infiltration by IgM-positive B cells and IgG-positive B cells was very slight. 2. C. trachomatis-specific IgA and IgG antibodies came to be detected beginning on the 7th day of infection. When the immunological correspondence of these serum antibodies to C. trachomatis elementary bodies was investigated by western blot analysis, one band reacted with the major outer membrane protein (MOMP; 39.5 Kd), while a second band reacted with a 60-Kd protein. On the basis of these findings, it was surmised that, as the immunological response to C. trachomatis infections, the host recognizes the MOMP and a 60-Kd protein in C. trachomatis elementary bodies, thus initiating a series of immune responses. It was also surmised that, at the sites of infection, cells belonging to the T-cell lineage, especially CD8+ cells, play an important role in the host's defense mechanism against the infection by C. trachomatis.

Animals↗

PubMed1994

[An experimental examination of the significance of the peak antimicrobial concentration value in urine and time above MIC on the effect of antimicrobial agents--an examination using a severely complicated in vitro bladder model with an autosimulation system for antimicrobial concentration in urine].

Using a severely complicated in vitro bladder model with a computer-controlled autosimulation system for antimicrobial concentration in urine, we examined the significance of the peak concentration value and time above MIC, and obtained the following results. 1. Regarding the initial bactericidal speed, the higher the peak concentration value was, the more quickly the bacterial concentration decreased. 2. Concerning the minimum value of bacterial concentration in the model bladder, the higher the peak concentration value was, the more the level tended to decrease. 3. Regarding inhibition of regrowth of bacteria (ERT) 1) When a particular antimicrobial agent had no PAE on bacteria, the viable bacterial count curve was similar in cases of peak antimicrobial concentration values of higher than 8 MIC. 2) On the other hand, when an antimicrobial agent had PAE on bacteria, regrowth of bacteria occurred quickly below a certain peak concentration (24 MIC or 64 MIC value), although there was some difference depending on the type of antimicrobial agents. Thus, it was suggested that the peak concentration above that level be attained and maintration above that level be attained and maintained for some time were in order to obtain PAE adequately. 4. It is concluded from the aforementioned facts that two factors, a certain high concentration and a certain continued time are necessary for both antimicrobial agent with metabolic disorder and antimicrobial agent with cell wall synthetic inhibition to obtain proper antimicrobial effect. The condition of their necessity differed slightly according to the two different agents.

Adult↗

PubMed1994

[Study on MIC breakpoint and method of antimicrobial chemotherapy for moderately complicated urinary tract infection--study using an automatic simulator of urinary antimicrobial agent concentrations].

We experimentally investigated an efficient administrating method of antimicribials prior to the clinical treatment of complicated urinary tract infection without catheter. An experimental model of moderately complicated urinary tract infection, which can simulate changes in the urinary concentration of antimicrobials by means of previously reported computer control method, was used for the experiment. The following results were obtained. 1. At first, for complicated UTI cases without an indwelling catheter, an investigation was made of the clinical therapy results to determine the upper MIC range of bacteria, including isolated strains, that can be nearly eliminated following treatment, by the administration method. We then estimated the clinical breakpoint. 2. By adjusting the size of the diverticulum in a urinary bladder model, we prepared a model which gave comparatively good agreement between the clinical and experimental breakpoints. 3. The clinical therapy results revealed that by the clinical breakpoint was higher in degree of coverage of the MIC distribution of causative bacteria associated with a higher actual clinical elimination rate and a higher efficacy rate. 4. It was surmised that an efficient administration method for complicated UTI without an indwelling catheter can be established if the urinary bladder model and the following approach are applied: prior to clinical treatment it should be determined what would be high enough to cover 70% of the MIC distribution of the estimated causative bacteria of UTI, and then an administration method which would yield that concentration as the experimental breakpoint should be devised.

Anti-Bacterial Agents↗

PubMed1994

[Therapeutic study on biofilm of the urinary tract using a severely complicated bladder model (biofilm model of the urinary tract)--experimental study using an automatic simulator of urinary antimicrobial agent concentration, and clinical study].

For the purpose of conducting a therapeutic study on biofilm of the urinary tract, we devised a computer-controlled severely complicated bladder model (biofilm model of the urinary tract) enabling us to simulate the time-course of the concentration of antimicrobial agents in the urine. Using this model, we investigated clarithromycin (CAM), which has been reported to have anti-biofilm action, at concentrations close to its urinary levels at the time of clinical use in order to predict its effect on biofilm of the urinary tract. On the basis of those experimental results, we also conducted a clinical examination. The following results were obtained. 1. The action of ciprofloxacin (CPFX, MIC: 8 micrograms/ml) alone, which shows anti-P. aeruginosa activity, caused apparent elimination of P. aeruginosa from the model. However, regrowth of the microbes occurred when CPFX was removed from the bladder model. Moreover, the biofilm was not eliminated by the antimicrobial action of CPFX, and this was surmised to be the cause of the regrowth. 2. CAM (MIC: above 128 micrograms/ml), which has no anti-P. aeruginosa activity, was similarly tested as anti-biofilm agent when added alone to the biofilm model. The P. aeruginosa recovered to its initial concentration within 48 hours, but the biofilm disappeared due to the action of CAM. 3. The combined action of CPFX and CAM caused microbial elimination from the bladder model without microbial regrowth, even after these antimicrobial agents were removed from the bladder model. After the action of CPFX and CAM, the biofilm disappeared, and no microbial adherence was noted. 4. Measurement of time-course of the alginate content, which is the main component of P. aeruginosa biofilm, in the presence of CAM found that the alginate content decreased below the limit of detection after day 5. 5. The clinical study of complicated urinary tract infection revealed the microbial elimination rate and the efficacy rate to be higher in the combined CPFX-CAM administration group than in the CPFX-only administration group. 6. Based on the above results, we surmise that the combined use of an antimicrobial agent which is active against the causative microbe and anti-biofilm agent such as CAM will show some degree of efficacy in eliminating biofilm of the urinary tract.

Ciprofloxacin↗

PubMed1994

[Fundamental and clinical studies on MIC breakpoint of SY5555 for Enterococcus faecalis in complicated urinary tract infections of moderate severity].

A multicenter clinical study was carried out to investigate the clinical efficacy of SY5555 from viewpoint of its MIC breakpoint for Enterococcus faecalis. SY5555 was administered in dosages of 150 mg x 3/day and 300 mg x 3/day, for 7 days, to patients with complicated urinary tract infections of moderate severity (no indwelling catheter). Based primarily on the bacteriological efficacy (eradication) as the criterion for evaluation, the MIC breakpoint of SY5555 was investigated. SY5555 showed potent antimicrobial activity towards E. faecalis, and its MIC80 value for the clinical isolates of this bacterial species was 1.56 micrograms/ml. Analysis was carried out to determine the extent to which this in vitro activity is corroborated by the drug's clinical efficacy in eradicating E. faecalis. 1. Experimental study In a study employing an experimental model of complicated bladder infections of moderate severity, it was judged that the MIC breakpoints of SY5555 administered at 150 mg x 3/day and 300 mg x 3/day were 2 micrograms/ml and 8 micrograms/ml. 2. Clinical study SY5555 was administered at 150 mg x 3/day (7 days) to six patients and at 300 mg x 3/day (7 days) to 32 patients, and the clinical efficacy of these treatments was investigated. 2.1. Investigation of the clinical MIC breakpoint showed it to be 12.5 micrograms/ml for both the 150 mg x 3/day and 300 mg x 3/day regimens. However, since the number of cases in this study was small, analysis was performed of the data from a large number of cases by including the cases registered in a nation-wide Phase II study of SY5555. That analysis showed the clinical MIC breakpoint for the two dosages to be 3.13 micrograms/ml and 6.25 micrograms/ml. Thus, this analysis of large number of cases yielded clinical MIC breakpoint that are in agreement with the abovementioned experimental MIC breakpoints. 2.2. In the evaluation of the efficacy rate using the UTI drug efficacy evaluation criteria, cases rated as "good" or "excellent" numbered five of the six patients in the 150 mg x 3/day treatment group and 25 of the 32 (78.1%) patients in the 300 mg x 3/day treatment group, or 30/33 (78.9%) cases overall. These efficacy rates are about the same as the 82.0% reported for the nation-wide Phase II study. 2.3. Each of the strains of E. faecalis isolated from the patients was found to be eradicated by the SY5555 treatment: four strains in the 150 mg dosage group (the MIC of each was 3.13 micrograms/ml or less) and 18 strains in the 300 mg dosage group (the MIC of each was 6.25 micrograms/ml or less). Moreover, in both dosage groups, E. faecalis was not found to recur after the SY5555 treatment. 3. Conclusions In consideration of the above findings in the investigations of treatment of patients with complicated urinary tract infections of moderate severity, the following conclusions can be drawn. 3.1. In antimicrobial treatment employing SY5555 in a regimen consisting of 300 mg x 3/day for 7 days, the clinical breakpoint is in the range of 6.25-12.5 micrograms/ml. 3.2. In particular, as would be surmised from the fact that the MIC80 value of SY5555 for E. faecalis isolated is 1.56 micrograms/ml, this drug shows quite strong efficacy in the eradication of E. faecalis from cases of complicated urinary tract infection.

Adult↗

PubMed1994

[Study on local immune response in diabetic mice, in which bactericidal capacity of the neutrophils had been damaged--Escherichia coli induced experimental urinary tract infection].

An experimental ascending urinary tract infection was induced by transurethral instillation of Escherichia coli in streptozotocin (STZ)-induced diabetic mice, in which bactericidal capacity of the perineal exudating neutrophils had been damaged. The local immune response in uninfected diabetic mice and the response time fluctuation of local immune responses in diabetic mice following infection were compared with those in normal mice, and the nature of induced changes in the local immune response was determined. The diabetic model was prepared by a single administration of 280 mg/kg of STZ after it had been fasted for 15 hours. The mouse was then fasted an additional 2 hours to induce the diabetic state. Compared with the normal mice, the diabetic mice prepared using this method were found to have a significant suppression of the bactericidal capacity of the perineal exudating neutrophils, 3 weeks after induction of diabetes. The study of the cellular distribution in uninfected urinary tract tissue demonstrated a reduction in CD4-positive T cell distribution in bladder submucosa of diabetic mice at 3 weeks after induction of diabetes (diabetic group), compared with that in the normal mice (control group). In the diabetic group, probably in order to compensate for the reduction in CD4-positive T cell distribution in the bladder submucosa, the distribution of macrophages was increased in the bladder epithelium, compared with the control group. This finding suggested that diabetic mice are thought to have protective mechanisms against infection different from those of normal mice in the uninfected state. The study of the response time fluctuation of local immune response at the infected sites demonstrated infiltration of macrophages was the same grade as that of neutrophils in the control and the diabetic group. However, in the diabetic group, a marked infiltration of macrophages was recognized when compared with the control group in the early phase of infection. These findings suggested that macrophages aid in protection against infection when damage to the bactericidal capacity of neutrophils results in insufficient elimination of microorganisms. On the other hand, infiltration of T and B cells was weaker in the diabetic group, than in the control group.

Animals↗

PubMed1994

[Adaptation study for biofilm of the urinary tract via highly complicated bladder model (biofilm model of the urinary tract)--experimental study using automatic simulator of the urinary antimicrobial agent concentration].

With the view of making an adaptation study for biofilm of the urinary tract, we devised a computer-controlled highly complicated bladder model (biofilm model of the urinary tract) that allowed the simulation of time-course changes in the urinary concentration of antimicrobial agents. Clarithromycin (CAM), which is reported to have an anti-biofilm action, was examined at urinary levels approximating clinical concentrations and its effect on biofilm was determined. The following results were obtained. 1) Ofloxacin (OFLX, 200 mg x 2/day, MIC; 8 micrograms/ml), which is active against Pseudomonas aruginosa, caused apparent microbial elimination from the model at 42 hours, but bacterial regrowth occurred 4 hours after withdrawal of this agent. No disappearance of the biofilm was noted with OFLX suggesting that this was the cause of bacterial regrowth. 2) The combination of OFLX (200 mg x 2/day) and CAM (MIC; > 128 micrograms/ml, 200 mg x 2/day) on anti-biofilm agent, with no effect on P. aeruginosa, eliminated bacteria from the bladder model more rapidly and prolonged the regrowth time to 10 hours after withdrawal of the antimicrobial agents. Disappearance of most of the biofilm and only slight microbial adhesion was noted. 3) The combination of OFLX (200 mg x 2/day) and CAM (400 mg x 3/day) caused microbial elimination from the bladder model with no regrowth at 30 hours after withdrawal of the antimicrobial agents. The biofilm disappeared completely and no microbial adhesion was noted. 4) CAM alone (400 mg x 3/day) allowed microbial recovery to the initial level within 48 hours after withdrawal, but led to disappearance of the biofilm and the adhesion of microbes without a glycocalyx. 5) These results suggest that the anti-biofilm action of CAM is dose-dependent, and that combined use of an appropriate antimicrobial agent and anti-biofilm agent like CAM may be effective for biofilm infections of the urinary tract.

Anti-Bacterial Agents↗