In vitro activity of β-lactams and quinolones against AmpC β-lactamase-producing Escherichia coli

We studied the antimicrobial susceptibility of AmpC -lactamase-producing Escherichia coli isolates collected at ten medical institutions in the Kinki area of Japan during a 6-month period (November 2002 through April 2003). Of 2845 E. coli isolates tested, 29 (1.0%) showed a minimum inhibitory concentration (MIC) for cefazolin of more than 8µg/ml and were three-dimensional extract test positive. In standard inoculum susceptibility tests against these 29 strains, the MIC90s for the four carbapenems tested ranged from 0.06µg/ml to 0.5µg/ml, and these compounds were more active than the other -lactams, with meropenem being the most active. The MIC90s for -lactams, except carbapenems, ranged from 4µg/ml to 32µg/ml, with cefepime being the most active. In high inoculum susceptibility tests against these strains, the MIC90s for the four carbapenems and cefepime were 8µg/ml or less, and these compounds were more active than other -lactams. The MIC90s for -lactams, except carbapenems and cefepime, were 32µg/ml or more. The MIC90s for the five quinolones tested ranged from 4µg/ml to 16µg/ml, and the order of increasing susceptibility was ciprofloxacin > levofloxacin, gatifloxacin and pazufloxacin > prulifloxacin.     

Optimization of dose and dose regimen of biapenem based on pharmacokinetic and pharmacodynamic analysis

Pharmacokinetic and pharmacodynamic (PK/PD) parameters, which are important indices of the therapeutic efficacy of antimicrobials, and the minimum inhibitory concentration (MIC) predictive of clinical efficacy at common clinical doses, were examined for biapenem (BIPM; 300mg b.i.d.), imipenem/cilastatin (IPM/CS; 500mg/500mg b.i.d.), meropenem (MEPM; 500mg b.i.d.), and ceftazidime (CAZ; 1000mg b.i.d.), using a mouse model of thigh infection caused by Pseudomonas aeruginosa. The PK/PD parameter that most closely correlated with the therapeutic efficacy of all these antimicrobials was time above MIC (T MIC). The values of T MIC predictive of clinical efficacy against P. aeruginosa infection varied among antimicrobials and were 17%, 17%, 23%, and 33% for BIPM, IPM/CS, MEPM, and CAZ, respectively. From these values and the known plasma concentrations of the antimicrobials in humans after administration at the common clinical doses, the MIC for bacterial strains at which clinical efficacy can be expected was estimated to be 4.4µg/ml for BIPM, 6.1µg/ml for IPM/CS, 2.2µg/ml for MEPM, and 13.6µg/ml for CAZ. These MICs nearly coincided with the MIC₈₀ of the antimicrobials for 104 clinical isolates of P. aeruginosa strains. These results indicate that, even at a low dose, of 300mg b.i.d., the clinical efficacy of BIPM against P. aeruginosa infection can be expected to be comparable to that of IPM/CS, MEPM, and CAZ.     

Penetration of oral telithromycin into female genital tissues

To estimate the potential efficacy of telithromycin in the treatment of gynecological infections, a pharmacokinetic study was conducted in 13 Japanese subjects. Telithromycin was administered orally, at a dose of 600mg, to patients undergoing hysterectomy, 3.0 to 7.5h prior to the hysterectomy. At surgical operation, cubital venous blood, uterine arterial blood, vaginal cervix uteri (portio vaginalis), supravaginal uterine cervix, uterine endometrium, uterine myometrium, oviduct, and ovary specimens were collected separately. The blood and tissue concentrations of telithromycin were measured with a bioassay, using Micrococcus luteus ATCC 9361 as the test organism. The concentrations of telithromycin in these tissues and their proportions in relation to that in cubital venous blood (in parentheses) were as follows: cubital venous blood, 0.119 to 1.270mg/l; uterine arterial blood, 0.111 to 1.230mg/l; vaginal cervix uteri (portio vaginalis), 0.356 to 1.850mg/kg (1.324 to 5.640), supravaginal uterine cervix, 0.376 to 4.520mg/kg (1.108 to 16.807), uterine endometrium, 0.234 to 5.300mg/kg (0.975 to 12.185), uterine myometrium, 0.309 to 5.050mg/kg (1.288 to 19.832), oviduct, 0.375 to 5.550mg/kg (1.563 to 10.000); and ovary, 0.495 to 5.250mg/kg (1.835 to 6.851). From these results, it was concluded that the concentrations of telithromycin in female genital tissues are generally higher than those in blood. Taking the antimicrobial spectrum of telithromycin into consideration, it was suggested that telithromycin could potentially be a good candidate for the treatment of gynecological infections, including cases associated with sexually transmitted diseases.     

The activity of grepafloxacin in two murine models of <Emphasis Type="Italic">Mycobacterium avium</Emphasis> infection

The activity against Mycobacterium avium complex (MAC) of varying doses of grepafloxacin (GRE; 25mg/kg, 50mg/kg, 100mg/kg, and 200mg/kg) were compared to clarithromycin (CLA; 100mg/kg and 200mg/kg), ethambutol (EMB; 100mg/kg), and rifabutin (RBT; 10mg/kg) using an intranasal (IN) infection model compared to an intravenous (IV) infection model. Beige mice (C57BL6/J-Lyst bg J/+) were infected intranasally with about 10⁶ organisms and for the IV model about 10⁷ organisms. Treatment for both models was started 1 week postinfection and given by gavage 5 days/week for 4 weeks. At the initiation of therapy, an early control group was killed to determine the initial organism load. Three days following the completion of therapy, drug-treated groups of mice and the late control group were killed and the response to therapy measured. The most effective agents were CLA and RBT. GRE and EMB had modest activities in both the IN and the IV models. A matched comparison between IN and IV challenges for each of the agents used revealed greater suppression of MAC in the IN model compared to the IV model.     

Development of a lipoprotein based molecular imaging MR contrast agent for the noninvasive detection of early atherosclerotic disease

Introduction: Currently there are no clinically available means of noninvasively detecting early atherosclerotic disease because these lesions are characterized by an accumulation of extracellular lipid and foam cells, but a lack of significant wall thickening or architectural distortion. Objective: We hypothesize that a paramagnetically labeled low density lipoprotein (LDL) could serve as a functional probe to detect sites of abnormal lipid metabolism in the vessel wall that represent sites of early disease. Methods: Isolated LDL was first incubated with manganese–mesoporphyrin, a hydrophobic MR contrast agent (MnMeso). Size exclusion chromatography and absorption mass spectroscopy were performed on the resulting samples to prove that an association between the two occurred. Subsequently, foam cell cultures (n=7) were incubated (10–30g/ml for 48h) with these labeled lipoproteins and the T1 relaxivity of centrifuged pellets of these cells was determined by using an inversion recovery sequence on a 1.5T scanner. These results were compared to control measurements made from foam cell cultures fed unlabeled lipoproteins (n=7). Results: Measured T1 relaxation times of the cells fed the MnMeso–LDL (443.3±51.8ms) was significantly different from the T1 relaxivity obtained from cells fed unlabeled lipoproteins (661.3±60.9ms). These findings indicate that the amount of contrast bound to the constructed lipoproteins is sufficient to produce measurable MR signal changes noninvasively. Conclusions: The study results support the feasibility of future in vivo MR experiments with labeled lipoproteins to assess lipoprotein kinetics in the vessel wall, which will hopefully provide a means of detecting early atherosclerotic disease.     

Experimental confirmation of <Emphasis Type="Italic">Serratia marcecsens</Emphasis> contamination in multiple-dose vials of heparin-saline solution

The initial contamination of heparin-saline solution (HS) in multiple-dose vials (MDVs) by Serratia marcescens was experimentally investigated using various isolates. Isolates I2 and S1 were from blood specimens from patients with a hospital-acquired infection (HAI). Isolates I13 and FHSM9043 were from urine and blood specimens, respectively, from patients without HAI. Isolate I124, with a pulsed-field get electrophoresis pattern identical to that of isolate I2, was from the hospital environment. Viable cells of isolate I2 were carried over into the HS of MDVs when the contaminated rubber septum was pierced with a syringe needle. When the outside surface of the septum was contaminated by inoculating it with wet-cell suspensions in HS or Müller-Hinton broth, the viable cells carried over were detected at a minimum inoculum size (MIS) of 10³scfu/ml. However, when the surface was contaminated by inoculating it with dry-cell suspensions, the viable cells carried over were detected at an MIS of 10⁷scfu/ml. The viable cells in the internal lumen of the needle much more than those on its outside surface spread to the HS of MDVs. For exposures of 24h and 72h at 4°C to HS with 1% benzyl alcohol as a preservative in MDVs, viable cells of all isolates tested were detected at MIS values of 1s and 10scfu/ml, respectively, increases three orders of magnitude smaller than those of reference strain IFO3736. These results suggest that S. marcescens isolates are readily carried over into the HS of MDVs by piercing a wet, contaminated rubber septum with a syringe needle. Also, despite the sterilization action of 1% benzyl alcohol, the organism persistently survived at 4°C, even when initial contamination was with a small amount of inoculum.     

Pharmacokinetics of panipenem/betamipron in patients with end-stage renal disease

Panipenem/betamipron (Carbenin), a parenteral carbapenem antibiotic, is used for the treatment of severe and intractable bacterial infections caused by gram-positive and gram-negative bacteria. Because 30% of panipenem and most of the betamipron are excreted in the urine in an unchanged form, renal function is the important determinant of the dosage regimen of panipenem/betamipron. In this study, the pharmacokinetics of panipenem/betamipron were investigated in patients with end-stage renal disease (ESRD) undergoing hemodialysis treatment to establish an appropriate dose regimen. We further attempted to predict the in vivo clearance in patients undergoing hemodialysis based on the in vitro dializability. The pharmacokinetics of panipenem/betamipron were investigated in eight patients after a 1-h intravenous infusion of panipenem/betamipron (500mg/500mg). The in vitro extraction ratios of panipenem/betamipron through a high-flux dialyzer were obtained, and compared with those obtained in vivo. The clearances of panipenem in patients were 9.53 ± 1.26l/h with hemodialysis, and 2.92 ± 0.238l/h without hemodialysis. In contrast, those of betamipron were 4.18 ± 0.643l/h and 0.615 ± 0.511l/h, respectively. The clearance of panipenem with hemodialysis were predicted well from in vitro extraction ratios, while that of betamipron was overestimated about 1.4-fold, probably due to high plasma protein binding and the binding difference between patients and healthy subjects. After comparing the pharmacokinetic behavior of panipenem in patients with ESRD and that of a surrogate marker of efficacy, we recommend that these patients be treated with 500mg/500mg of panipenem/betamipron once daily, which gives a similar clinical result in a patient with normal renal function.     

Cowden disease: CT findings in three patients

Cowden disease, also known as multiple hamartoma syndromes, is an autosomal dominant disease characterized by numerous benign mucocutaneous tumors, hamartomas of multiple organs, and malignancies of the breast and thyroid. In this report, we present the computed tomographic findings in three patients with Cowden disease. In addition to the classic findings, the patients were diagnosed with spinal neurinoma (n=1), meningioma (n=1), and hepatic hemangioma (n=3). We also review current clinical and genetic concepts that unify Cowden disease.     

A comparative evaluation of phenotypic and molecular methods for the detection of oxacillin resistance in coagulase-negative staphylococci

Detection of oxacillin resistance in coagulase-negative staphylococci (C-NS) by phenotypic methods is often difficult. The present study compared the National Committee for Clinical Laboratory Standards (NCCLS) revised guidelines of phenotypic methods with a mecA-based polymerase chain reaction (PCR) for C-NS. Ninety clinical C-NS isolates were tested for oxacillin resistance by disk diffusion (1-µg disk), minimum inhibitory concentration (MIC) breakpoint (0.5µg/ml) after 24h, and mecA-based PCR. The sensitivity and specificity of disk diffusion was 80% and 93%, and the sensitivity and specificity of the MIC breakpoint after 24h was 84% and 91%, respectively, against PCR as gold standard. Eleven strains (7 mecA-positive and 4 mecA-negative) showed discordant results between MIC breakpoint after 24h and PCR. Six of the 7 mecA-positive and all 4 mecA-negative discordant strains had inducible oxacillin resistance and -lactamase hyperproduction, respectively. The present study concludes that inducible oxacillin resistance and -lactamase hyperproduction are the major causes of discordant results between phenotypic methods and mecA-based PCR, and need special attention.     

Subcutaneous tissue release of amikacin from a fibrin glue/polyurethane graft

We investigated whether fibrin glue (FG) might be useful as a carrier of amikacin (AMK) for prevention of local graft infection. After AMK (4.0mg)-treated FG (AMK-FG) polyurethane grafts were implanted subcutaneously in the anterior abdominal region of Sprague-Dawley rats, AMK concentrations in tissues surrounding the implantation sites were compared over time with concentrations at the same sites in rats given an intravenous injection of AMK (4.0mg). In the injection group, AMK concentrations in serum were detectable only for 4h, whereas AMK released from AMK-FG grafts remained detectable over 24h. Until 4h after implantation, AMK concentrations in tissues near implantation sites were significantly higher in the AMK-FG graft group than in the injection group; peak local concentrations during that time were 210 times higher for the AMK-FG graft group than for the injection group. Areas under the tissue concentration–time curve (AUC) for AMK were 171µg·h/g and 1.35µg·h/g in the AMK-FG graft and injection groups, respectively. FG therefore was considered to control release of AMK and to maintain a high AMK concentration in tissues surrounding the implantation site. Thus, AMK-FG polyurethane graft delivery may be useful in preventing local infection by local delivery of AMK.     

Changes in serum KL-6 after intravenous fosfomycin administration in idiopathic interstitial pneumonia

Changes in serum KL-6 levels after intravenous fosfomycin (FOM) administration in idiopathic interstitial pneumonia (IIP) were studied. Seventeen patients who were diagnosed with usual interstitial pneumonia by surgical lung biopsy were selected as subjects. In these patients, FOM was administered intravenously, at a dose of 2g twice daily, for 14 days, and serum KL-6 was determined before and after its administration. FOM administration resulted in a reduction of serum KL-6 in all 17 patients (1273 ± 132U/ml [mean ± SEM] to 1023 ± 101U/ml; P 0.01). FOM may reduce serum KL-6 in IIP and may be an appropriate therapeutic drug for this condition.     

Clinical course of acute hemorrhagic infarction of a thyroid nodule

A 27-year-old woman patient with acute hemorrhagic infarction of a thyroid nodule had experienced abrupt painful swelling of the thyroid gland soon after being involved in an automobile accident. We diagnosed her thyroid mass, based on clinical symptoms and laboratory findings, as acute hemorrhagic infarction of a thyroid nodule. The mass diameter gradually decreased from 4.4cm to 1.9cm over the following 12 months but did not change thereafter. The serum thyroglobulin level rapidly decreased from 312.4ng/ml to 14.2ng/ml during the first 3 months and presented no change during the next 21 months. Fine-needle aspiration biopsy was repeated during the 24th month, when preexistence of a benign neoplasm had become clear. The clinical course of acute hemorrhagic infarction of the thyroid nodule was made apparent by ultrasonography, which readily identified the thyroid mass and accurately measured its dimensions at any time.     

Augmented inhibition of <Emphasis Type="Italic">Candida albicans</Emphasis> growth by murine neutrophils in the presence of a tryptophan metabolite,picolinic acid

The effects of picolinic acid (PLA), a product of tryptophan catabolism, on anti-Candida activity of neutrophils were studied. Casein-induced peritoneal neutrophils of C3H/He mice partially inhibited mycelial growth of Candida albicans when cultured with C. albicans for 16h in vitro. The growth inhibition of Candida was augmented by a combination of neutrophils and more than 4mM picolinic acid. Especially in the presence of 200U/ml murine interferon- (IFN-), 2mM picolinic acid augmented the anti-Candida activity of neutrophils. The physiological significance of the augmenting effects of picolinic acid is discussed.     

An epidemiological study of the susceptibility and frequency of multiple-drug-resistant strains of Pseudomonas aeruginosa isolated at medical institutes nationwide in Japan

The susceptibility of 3233 strains of Pseudomonas aeruginosa, isolated primarily in 2001, as agents of infection at 37 medical institutes with various specialties in seven regions of Japan (ranging from Hokkaido to Kyushu/Okinawa), to 18 antipseudomonal agents known to be active against P. aeruginosa was evaluated, in accordance with the National Committee for Clinical Laboratory Standards (NCCLS) guidelines. Of the 18 antipseudomonal agents, including some combinations of -lactamase inhibitors and antibacterial agents, ciprofloxacin had the lowest minimum inhibitory concentration (MIC)₅₀ (0.25µg/ml) against P. aeruginosa, followed by meropenem, with an MIC₅₀ of 0.5µg/ml. The MIC₅₀ of 7 of the examined antibacterial agents (ceftazidime, cefozopran, imipenem, biapenem, gentamicin, tobramycin, and levofloxacin) was between 1 and 2µg/ml. Among the antipseudomonal agents tested, tobramycin showed the lowest MIC₉₀ (2µg/ml), which was not significantly different from its MIC₅₀ (1µg/ml). The MIC₉₀ of the other antibacterial agents examined ranged from 8 to 64µg/ml and more. The susceptibility of the 3233 strains to the 12 antibacterial agents covered by the NCCLS guidelines was determined according to the standard method of the NCCLS guidelines. The frequency of strains resistant to meropenem, gentamicin, or tobramycin was relatively low (7.5%–8.3%). The frequency of strains showing intermediate to severe resistance to tobramycin was particularly low (8.0%). The frequency of strains resistant to aztreonam, imipenem, or levofloxacin was 16.7%–19.0%, about twice as high as the frequency of strains resistant to tobramycin. The susceptibility pattern of the 3233 strains (isolated from seven regions of Japan) to five antibacterial agents (ceftazidime, piperacillin, imipenem, gentamicin, and ciprofloxacin) was evaluated in relation to the regions from which they were isolated. The MIC₅₀ values of these antibacterial agents did not differ significantly among the regions. However, the MIC₉₀ values of ceftazidime and gentamicin were higher for strains isolated from the Kansai region than for strains isolated from other regions. The MIC₉₀ of ciprofloxacin was higher for strains isolated from the Tohoku, Kansai, and Kyushu/Okinawa regions than for strains isolated from other regions. Of the 3233 strains, 89 were classified as multiple-drug-resistant (imipenem, gentamicin, and ciprofloxacin) strains. Of these 89 strains, 42 were isolated from urine, 17 from sputum or pharyngeal mucus, 13 from pus, 8 from blood, 1 from cerebrospinal fluid, and 8 from other specimens. The frequency of multiple-drug-resistant strains was higher among strains isolated from the Tohoku and Kansai regions than in strains isolated from other regions.     

Pharmacokinetics of single-dose intravenous ciprofloxacin in blood and ascites of patients with pelvic peritonitis

To estimate the efficacy of ciprofloxacin in the treatment of pelvic peritonitis, a pharmacokinetic study was conducted in four Japanese subjects. Ciprofloxacin was administered intravenously at a dose of 300mg for 1h to patients with pelvic peritonitis. Ascites was collected by culdocentesis. The concentrations of ciprofloxacin in blood and ascites were measured by a bioassay, using Escherichia coli Kp as the test organism and heart infusion agar as the medium. The ciprofloxacin concentration in ascites ranged from 3.01 to 9.41µg/ml. The values for the arithmetic mean of ascites/serum ranged from 4.01 to 19.37, which showed that the penetration of ciprofloxacin was higher in ascites than in serum. The concentrations of ciprofloxacin are generally higher in ascites than in blood. Taking the antimicrobial spectrum of ciprofloxacin and the causative organisms of pelvic peritonitis into account, intravenous ciprofloxacin could be a good candidate for use in the treatment of pelvic peritonitis from the point of view of pharmacokinetics.     

Patient assessment of a combined medical and nursing preparation to cytotoxic chemotherapy

At Auckland hospital there is a combined medical and nursing preparation for patients receiving cytotoxic chemotherapy. The aim of the current study was to assess whether patients felt that this combined approach had prepared them adequately for chemotherapy. Patients were asked to complete three questionnaires anonymously at different times in their treatment programme: Immediately prior to chemotherapy, after three cycles of chemotherapy and 2 months after completion of chemotherapy. A high level of satisfaction with the programme was demonstrated: 68% of patients thought the orientation programme had prepared them very well, 32% adequately and none poorly for their chemotherapy. Separate interviews with medical and nursing staff were thought a good idea by 86% of patients and only 1 of 100 medical and 100 nursing interviews was assessed as not worthwhile. This study suggests that a combined medical and nursing preparation is a worthwhile practice in preparing patients for cytotoxic chemotherapy.     

Ultrasonic-enhanced gentamicin transport through colony biofilms of <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> and <Emphasis Type="Italic">Escherichia coli</Emphasis>

The hypothesis that ultrasound increases antibiotic transport through biofilms of Escherichia coli and Pseudomonas aeruginosa was investigated using colony biofilms. Biofilms grown on membrane filters were transferred to nutrient agar containing 50µg/ml gentamicin. A smaller filter was placed on top of the biofilm and a blank concentration disk was situated atop the filter. Diffusion of antibiotic through the biofilms was allowed for 15, 30, or 45min at 37°C. Some of these biofilms were exposed to 70-kHz ultrasound and others were not. Each concentration disk was then placed on a nutrient agar plate spread with a lawn of E. coli. The resulting zone of inhibition was used to calculate the amount of gentamicin that was transported through the biofilm into the disk. The E. coli and P. aeruginosa biofilms grown for 13 and 24h were exposed to two different ultrasonic power densities. Ultrasonication significantly increased the transport of gentamicin through the biofilm. Insonation of biofilms of E. coli for 45min more than doubled the amount of gentamicin compared to their noninsonated counterparts. For P. aeruginosa biofilms, no detectable gentamicin penetrated the biofilm within 45min without ultrasound; however, when insonated (1.5W/cm²) for 45min, the disks collected more than 0.45µg antibiotic. Ultrasonication significantly increased transport of gentamicin across biofilms that normally blocked or slowed gentamicin transport when not exposed to ultrasound. This enhanced transport may be partially responsible for the increased killing of biofilm bacteria exposed to combinations of antibiotic and ultrasound.     

In vitro antifungal activity of luliconazole (NND-502), a novel imidazole antifungal agent

The in vitro activity of luliconazole (NND-502), a novel imidazole antifungal agent, against dermatophytes and several other groups of medically important fungi including the rare causative agents of dermatomycoses, was studied. The luliconazole susceptibility tests were performed with a total of 58 fungal strains of 23 species of fungi grouped into dermatophytes, dematiaceous fungi, hyaline hyphomycetes, yeastlike fungi, and zygomycetes using a broth microdilution method with RPMI 1640 medium. The minimum inhibitory concentration (MIC) values for luliconazole were compared with those of three reference drugs, lanoconazole (LCZ), bifonazole (BFZ), and terbinafine (TBF), all of which have been popular for the topical treatment of dermatophytosis, cutaneous candidiasis, and other superficial fungal infections in Japan. Luliconazole inhibited growth of all filamentous fungi except zygomycetes at low concentrations (MIC, 0.004–0.125µg/ml), with dermatophytes being most susceptible (MIC, 0.004–0.008µg/ml). The susceptibility of these filamentous fungi to luliconazole was almost equal to that to LCZ, and surpassed TBF and BFZ, although to a lesser extent; yeastlike fungi were also susceptible to luliconazole (MIC, 0.125–4µg/ml). Again the antiyeastlike fungi activity of luliconazole was at the same level as LCZ and was greater than that of BFZ and TBF. In contrast to BFZ and TBF, however, luliconazole and LCZ were virtually inactive against zygomycetes.     

Detachment activity of human saliva in vitro for Candida albicans cells attached to a plastic plate

The effects of human saliva on Candida albicans attached to plastic plates were investigated. C. albicans cells were cultured for attachment to the bottoms of the wells of a 96-well plate, and saliva preparations collected from healthy adults were then added to each well. After various periods of incubation, the number of Candida cells attached to the bottom of each well was measured by the crystal violet staining method. The results showed that, when incubated with human saliva (final concentration, 10% or higher) for 3h, Candida cells that were attached to the plates became detached from the wells. For characterization of the detachment factor(s), the saliva was divided into three fractions by ultrafiltration. The detachment activity recovered in fractions with molecular weights of 50K or higher. When the saliva was heated at 100°C for 20min, its ability to detach Candida cells completely disappeared. When the saliva was treated with 0.025% trypsin, the detachment activity decreased by 57%. These findings suggested that human saliva contains factors for detachment of Candida cells, which are considered to be proteins with molecular weights of 50K or higher.     

Ultrasonically induced cell damage and membrane lipid peroxidation by photofrin II: mechanism of sonodynamic activation

Purpose Ultrasonically induced cell damage and active oxygen generation with photofrin II were compared using the same in vitro insonation setup.Methods Sarcoma 180 cells suspended in an air-saturated phosphate-buffered saline solution were exposed to ultrasound at 2MHz for not more than 60s in the presence and absence of photofrin II. The trypan blue exclusion test was used to determine viability. Lipid peroxidation in cell membranes was estimated by measuring the quantity of reactive substance produced from thiobarbituric acid added immediately after the cells had been exposured to ultrasound.Results Significant enhancement of the rates of ultrasonically induced cell damage and lipid peroxidation was demonstrated with photofrin II (20–80µg/ml), and the two rates were closely associated. Enhancement of both rates by photofrin II was suppressed by 10mM of histidine.Conclusion These results suggest that ultrasonically generated active oxygen is a primary factor in ultrasonically induced cell damage in the presence of photofrin II.