Search PubMed⌕ Search

Biomedical subjects

M Otsuki

Publications and source records attributed to M Otsuki.

At least 163 records · Page 9Linked to original sources
PubMed1995

Different inhibitory effects of the newly developed CCK receptor antagonists FK480 and KSG-504 on pancreatic exocrine and endocrine secretion in the isolated perfused rat pancreas.

Cholecystokinin (CCK) receptor antagonists are shown to have therapeutic as well as preventive effects in some types of acute pancreatitis. However, there is a possibility that administration of CCK receptor antagonists with a high inhibitory potency on the endocrine pancreas to patients with acute pancreatitis exacerbates the associated glucose intolerance. In the present study we simultaneously examined the effects of the newly developed benzodiazepine derivative FK480 and proglumide-related antagonist KSG-504 on CCK octapeptide (CCK-8)-stimulated exocrine and endocrine function in the isolated perfused rat pancreas. FK480 and KSG-504 inhibited CCK-8-stimulated pancreatic juice flow, protein output, and insulin release in a dose-dependent manner. FK480 was approximately 10 times more potent than KSG-504 in inhibiting exocrine and endocrine secretion. Both antagonists inhibited CCK-8-stimulated insulin release more potently than exocrine secretion. FK480 caused a dose-dependent residual inhibition of exocrine secretion after its removal from the perfusate, whereas insulin release was only slightly impaired even at the highest dose. In contrast, termination of KSG-504 infusion resulted in an immediate increase in both exocrine and insulin responses without causing any residual inhibition. With regard to the residual inhibition, therefore, KSG-504 had no significant influences on exocrine and insulin release, whereas FK480 inhibited exocrine secretion more potently than insulin response. These results suggest that FK480 might become a useful therapeutic agent for pancreatitis with respect to its long-duration inhibitory effect on exocrine secretion and short-duration inhibitory effect on insulin release.

Animals↗
PubMed1995

Effect of the cholecystokinin receptor antagonist loxiglumide on pancreatic exocrine function in rats after acute pancreatitis.

Recent studies have demonstrated that cholecystokinin (CCK) receptor antagonists not only reduce the severity of pancreatitis but also inhibit pancreatic regeneration after pancreatitis. This study was undertaken, therefore, to examine the effects of the CCK receptor antagonist loxiglumide on the exocrine pancreas when given after an episode of acute pancreatitis that was induced in rats by a 4-h subcutaneous infusion of 20 micrograms/kg body weight/h cerulein. Biochemical changes and secretory function in response to 100 ng/kg body weight cerulein were determined after a 6-day treatment with saline, loxiglumide (50 mg/kg body weight), or CCK-8 (2.5 micrograms/kg body weight), which was given three times a day starting 24 h after the induction of acute pancreatitis. In the saline-treated rats, pancreatic enzyme contents and pancreatic juice and protein output were significantly low, whereas the pancreatic weight and protein and DNA contents were comparable to those of the controls without pancreatitis. Loxiglumide treatment, although significantly decreasing protein output, had no influence on pancreatic weight, protein and DNA contents, or pancreatic juice flow but increased the amylase and lipase contents compared to those of the saline-treated postpancreatitic rats. CCK-8 treatment also had no influence on pancreatic weight or protein and DNA contents but significantly increased the pancreatic enzyme contents and pancreatic juice and protein output compared to those of the saline-treated postpancreatitic rats. These results suggest that loxiglumide does not significantly inhibit the recovery of exocrine function but appears to accelerate the increase in pancreatic amylase and lipase contents even when given after an attack of acute pancreatitis.

Acute Disease↗
PubMed1995

Loss of sensitivity to cholecystokinin stimulation of isolated pancreatic acini from genetically diabetic rats.

Pancreatic exocrine function of a new inbred strain Otsuka Long-Evans Tokushima Fatty (OLETF) rat that develops spontaneous persistent hyperglycemia was evaluated in in vitro isolated pancreatic acini and compared with that in the control Long-Evans Tokushima Otsuka (LETO) rat. Serum glucose and insulin concentrations in the OLETF rats were significantly high (glucose: 270 +/- 12 vs. 208 +/- 10 mg/100 ml, P < 0.01; insulin: 12.4 +/- 1.7 vs. 4.9 +/- 0.6 ng/ml, P) < 0.01), whereas pancreatic wet weight was significantly low (803 +/- 20 vs. 1,138 +/- 17 mg, P < 0.01) compared with those in the LETO rat. Pancreatic acini isolated from the OLETF rat were totally insensitive to cholecystokinin (CCK)-8 stimulation at concentrations of up to 100 nM. However, neither the responsiveness nor the sensitivity to carbamylcholine, bombesin, and secretin of the acini from the OLETF rat was altered or even increased, probably due to the larger amylase content in the OLETF rat acini compared with those of the LETO rat acini (31.5 +/- 2.0 vs. 13.0 +/- 1.1 Somogyi units/micrograms DNA, P < 0.01). The responsiveness to fluoride, a direct activator of guanine nucleotide-binding protein, in the OLETF rat acini was similar to that in the LETO rat, suggesting that the transmembrane signaling and effectors and subsequent intracellular signal transduction molecules in the OLETF rat acini are normal. Moreover, 125I-CCK binding to the acini prepared from the OLETF rat was totally absent. These present results indicate that the OLETF rat has a selective defect in the binding of CCK to its receptors on the acinar cell surface.

Amylases↗
PubMed1995

[Auditory comprehension in transcortical motor aphasia due to a medial lesions of the left frontal lobe].

We assessed the anatomical findings and auditory comprehension of six patients with transcortical motor aphasia due to medical lesions of the left frontal lobe. All patients were right-handed and were initially mute for several hours after the onset, and they exhibited mild paresis of the right lower extremity. Their spontaneous speech was sparse and not fluent, and sometimes accompanied by echolalia, but their articulation was normal and repetition was excellent. They had difficulty in recalling words. A diagnosis of transcortical motor aphasia was made on the basis of their clinical symptoms. All patients were found to have an infarct in the left medial frontal region by MRI and/or CT. We administered the Western Aphasia Battery and 50 line drawing pointing task in order to evaluate auditory comprehension. Based on the results we concluded that there is no impairment of auditory comprehension of single words when lesions are limited to the superior frontal gyrus, but that lesions extending to the middle frontal gyrus interfere with auditory comprehension of single words. Our observations indicate that the middle frontal gyrus plays an important role in auditory comprehension of single words. All of the patients displayed impaired auditory comprehension of sentences even when their lesions were strictly limited to the medial frontal lobe. This suggests that the medial frontal lobe plays some role in the auditory comprehension of sentences.

Aged↗
PubMed1995

[Usefulness of amylase isoenzyme determination for the diagnosis of pancreatic diseases].

Serum amylase shows the greatest increase among the various pancreatic enzymes that increase at the onset of acute pancreatitis. However, the diagnostic value of the total serum amylase activity has been questioned due to its lack of specificity. To differentiate hyperamylasemia due to pancreatic disease from that due to other causes, the activity of pancreatic amylase should be determined by using a monoclonal antibody that specifically binds to pancreatic or salivary amylase, or by electrophoresis. The most useful and accurate method for distinguishing pancreatic from salivary-type hyperamylasemia is isoamylase analysis by electrophoresis. In patients with acute pancreatitis, increase of Amylase-1 and -2 is accompanied by the appearance of Amylase-4, a minor component of the pancreatic-type isoamylases, and by disappearance of the salivary-type isoenzymes, thereby leaving a pattern of the pancreatic isoenzymes alone. This pancreatitis pattern persists for about 10 days after the onset of illness. Therefore, if such a pattern is found in a patient with clinical findings suggesting acute pancreatitis despite a normal serum amylase level, the patient can be diagnosed as having acute pancreatitis or a recent attack of the disease. However, the existence of an inherited trait of the pancreatitis pattern in some healthy individuals must be borne in mind. Patients with recurrent chronic pancreatitis also show pancreatic-type hyperamylasemia, whereas the pancreatic amylase activity decreases when pancreatic exocrine insufficiency progresses. Hyperamylasemia due to elevated salivary amylase activity is also common in patients with diabetic ketosis or malignancies such as lung cancer (adenocarcinoma). Hyperamylasemia is also found following various types of operation. In most cases, it is salivary-type hyperamylasemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗
PubMed1995

[A case of pure alexia whose writing ability with eyes closed was superior to that with eyes open].

We compared the writing ability between eyes open (looking at one's writing) and eyes closed (without looking) in a case of pure alexia. The patient is a 84-year-old right handed man who developed pure alexia following an infarction in the distribution of the left posterior cerebral artery. He showed right homonymous hemianopsia, slight memory disorder and slight anomia. He could not read any kinds of letters and words at all though he could categorize letters: Kana (phonograms), Kanji (morphograms) and Arabic numbers, and he could distinguish the real letters from false ones. He could achieve almost 60-70% of Kana and Kanji dictation, though it was not perfect. He was often confused and could not continue writing correct letters once interrupted. He wrote poorly when looking at what he was writing. So we compared the ability of dictation with his eyes closed, and that with his eyes open. We found the former way never caused confusion and got better results, which was statistically significant (Fisher's exact test (p < 0.05)). It seemed that his visual feedback of his own writing rather caused trouble in his writing. Thus we concluded that input (reading) process and output (writing) process work simultaneously and bi-directionally. Slight impairment of writing in pure alexia patients might be caused by the effect of impairment of input (reading) process, which is simultaneously connected with the output (writing) process.

Aged↗
PubMed1995

Bile duct cancer associated with extramammary Paget's disease.

We report a case of bile duct cancer associated with anogenital Paget's disease. The patient was a 80-yr-old Japanese woman whose chief complaint was exanthema from the left vulva to the anus for the previous 4 yr. Histological examination of the skin biopsy of the vulva showed numerous Paget's cells. Resection of the lesion and the rectum were performed, and a permanent colostomy was created. More than 1 month after the operation, the patient suddenly developed obstructive jaundice. Percutaneous transhepatic cholangiography performed simultaneously with endoscopic retrograde cholangiography showed complete obstruction of the middle part of the bile duct. Bile cytology was class V. On the basis of these results, bile duct cancer associated with extramammary Paget's disease (EMPD) was diagnosed. About 5 months after the operation, the patient died of liver failure. Microscopically the tumor in the bile duct was poorly differentiated adenocarcinoma. Although EMPD has a tendency to be associated with underlying internal malignancies, this is the first reported case, to our knowledge, of bile duct cancer associated with EMPD.

Aged↗
PubMed1995

[A case of thrombocytopenia due to heparin therapy for a progressing ischemic stroke].

A 44-year-old man was admitted, complaining of weakness of his left limbs. On admission, he was oriented and cooperative. He showed positive Barré sign only on the left leg. Deep tendon reflexes were unremarkable; pathological reflexes were negative. There was no cerebellar ataxia or sensory deficit. Immediately after admission, monoplegia of the left leg progressed. He was started on heparin infusion therapy. His paralysis had been resolved by the 5th day. MRI of the brain demonstrated an infarction involving the body of the corpus callosum, the right cingulate gyrus, and the right paracentral lobule. Neuropsychologic examination demonstrated a disturbance of interhemispheric transfer of position. On the 10th day he developed Klebsiella ozaenae bacteremia. On the 11th day, platelet count was 9.2 x 10(4)/microliter. Antithrombin III, thrombin antithrombin III complex, D-dimer, and FDP levels were unremarkable, which is quite atypical for DIC associated with bacterial infection. Platelet factor 4 and beta-thromboglobulin levels were remarkably high, suggesting activated platelet aggregation. We made a diagnosis of heparin-induced thrombocytopenia and discontinued heparin infusion. Three days later, platelet count began to increase and creatinine levels returned normal. All patients receiving heparin should be monitored for platelet count.

Adult↗
PubMed1995

[Familial posterior cortical atrophy with visual agnosia and Bálint's syndrome].

We report a patient of posterior cortical atrophy with progressive visual agnosia, Bálint's syndrome and dementia in which posterior cortical atrophy with similar characteristics on CT and progressive dementia were found in a sister. The patient was a 75-year-old woman who noted the onset of a progressive visual disorder at the age of 70, and whose family first noticed disoriented behavior at around the same period. Ophthalmologic examinations revealed mild cataract but no evidence of peripheral optic nerve or retinal lesions. Neuropsychological examination showed right homonymous hemianopia, visual agnosia, Bálint's syndrome, mild transcortical sensory aphasia, Gerstmann's syndrome, constructional apraxia, mild ideomotor apraxia and memory disorder. MRI showed marked dilatation of both lateral ventricles, especially the posterior horns, and severe atrophy of the occipital lobes, hippocampus, and the parahippocampal gyrus. Assessment of regional cerebral blood flow by IMP-SPECT revealed a generalized decrease in the temporo-parieto-occipital region bilaterally. The patient's sister began to show evidence of progressive dementia at 80 years of age and CT of the brain revealed marked atrophy, predominantly in the occipital lobes, similar to that of the patient. We believe this to be the first report of posterior cortical atrophy with a positive family history, suggesting the possibility of a hereditary syndrome.

Aged↗
PubMed1994

A cholecystokinin receptor antagonist, loxiglumide, stimulates biliary secretion in conscious rats.

The effects of the CCK receptor antagonists loxiglumide [D,L-4-(3,4-dichlorobenzoylamino)-5-(N-3-methoxy-propylpentylam ino)-5-oxo- pentanoic acid, CR 1505] and MK-329 [3S(-)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzo-diazepine-3-y l)-1H - indole-2-carboxamide, L-364,718], on bile flow were investigated in conscious rats. The bile duct of male Wistar rats was cannulated to directly collect pure bile, and the second cannula was inserted into the duodenum for reinfusion of bile. On the 4th through 7th postoperative days loxiglumide (25, 50 or 100 mg/kg body weight), MK-329 (1 mg/kg body weight) or the respective solvent (saline and 80% dimethyl sulfoxide) was injected subcutaneously. Loxiglumide caused dose-dependent increases in bile flow and bile acid output with a slight non-dose-dependent increase in bilirubin output. The integrated increments of bile flow during a 3-h period after saline and 100 mg/kg body weight loxiglumide were -14 +/- 71 and 982 +/- 61 microliters/100 g body weight, respectively, and those of bile acids were 2.5 +/- 1.4 and 23.1 +/- 4.1 mumol/100 g body weight, respectively. In contrast, MK-329 markedly decreased the bile flow (-439 +/- 76 vs. control; -32.8 +/- 76 microliters/100 g body weight/3 h, P < 0.001) and bile acids output (-16.3 +/- 6.8 vs. control; 3.4 +/- 3.8 mumol/100 g body weight/3 h, P < 0.001), while it significantly increased bilirubin output (86.4 +/- 15.6 vs. 43.5 +/- 1.1 mg/100 g body weight/3 h, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1994

Treatment with cholecystokinin receptor antagonist loxiglumide enhances insulin response to intravenous glucose stimulation in postpancreatitic rats.

Pancreatic exocrine and endocrine function in postpancreatitic rats treated with cholecystokinin (CCK) receptor antagonist loxiglumide was compared with that treated with saline and CCK octapeptide (CCK-8) or with that in normal control rats. Treatment with loxiglumide (50 mg/kg body weight), CCK-8 (2.5 micrograms/kg body weight), or saline (2.5 ml/kg body weight) was given three times a day for 6 days starting 1 day after the induction of acute pancreatitis by a 4-h subcutaneous infusion of 20 micrograms/kg body weight/h of caerulein. On day 8, pancreatic exocrine and endocrine function was simultaneously determined following an intravenous injection of a mixed solution of 0.2 g/kg body weight glucose plus 100 ng/kg body weight caerulein. Basal pancreatic juice flow was significantly increased in all of the postpancreatitic rats irrespective of the treatment, whereas the maximal juice flow in the loxiglumide- and saline-treated rats was significantly low compared with the CCK-8-treated and the control rats. Basal and the peak protein outputs in the loxiglumide-treated rats were comparable to those in saline-treated rats, but were lower than those in the control or the CCK-8-treated rats. Although serum glucose concentrations in all of the postpancreatitic rats were similar to those in the control rats, stimulated as well as basal insulin release tended to be high compared with the control rats. In particular, loxiglumide-treated rats showed the exaggerated insulin response compared with other groups of rats. These present observations indicate that administration of high dose of loxiglumide for a long period decreases pancreatic enzyme output and causes insulin resistance.

Acute Disease↗
PubMed1994

[Significance of a mass survey for colorectal cancer at the workplace].

Two thousand four hundred and forty workers from 2 plants were enrolled in a mass survey for colorectal cancer using a single immunological fecal occult blood test as screening. The occult blood test was positive in 71 (4.0%) out of 1,759 subjects in whom the test was conducted. A further investigation, including total colonoscopy or barium enema, was performed on 52 (73.2%) of the 71. Colon cancer was detected in 5 cases: 1 with advanced cancer and 4 with early cancer (cancer in the adenoma). The advanced cancer was successfully resected by surgery and the early cancers were removed by endoscopic polypectomy. Adenomas were found in 21 cases, 11 of which were polypectomized. From these results, it can be seen that a survey for colorectal cancer at the workplace is important, and by expanding the number of subjects for the survey in the workplace we can expect more and earlier detections of colorectal cancer.

Adenoma↗
PubMed1994

Effects of a new benzodiazepine derivative cholecystokinin receptor antagonist FK480 on pancreatic exocrine secretion in anesthetized rats.

Inhibitory effects of a newly developed benzodiazepine derivative (S)-N-[1-(2-fluorophenyl)-3,4,6,7-tetrahydro-4-oxo-pyrrolo-[3,2,1- jk][1,4] benzodiazepine-3yl]-1H-indole-2-carboxamide (FK480), a cholecystokinin (CCK) -A receptor antagonist, on pancreatic exocrine secretion were examined in vivo in anesthetized rats. The antagonism produced by FK480 was competitive in nature because intraduodenal as well as intravenous infusion of FK480 (50-250 nmol/kg/hr) caused a parallel rightward shift of the entire dose-response curve for cerulein-stimulated pancreatic exocrine secretion without altering the maximal increase. The magnitude of the shift was proportional to the dose of FK480. The mean pA2 and ID50 values of intravenously administered FK480 were 8.2 and 24 nmol/kg/hr, respectively, and those of intraduodenally infused FK480 were 7.7 and 168 nmol/kg/hr, respectively. Thus, FK480 given by the intravenous route was about sevenfold more potent than that given by the oral route. The antagonistic effects produced by intravenous FK480 were specific for CCK receptor in that the stimulatory effects of cerulein were inhibited whereas those of bombesin and secretin were not altered. In addition, intravenous administration of 50 nmol/kg/hr FK480 completely suppressed pancreatic exocrine secretion in response to intraduodenal infusion of 10% casein (400 mg/hr). FK480 was active as a CCK receptor antagonist for more than 12 hr because oral administration of FK480 (1.0 mg/kg) had significant inhibitory effects even after 12 hr on cerulein-stimulated pancreatic exocrine secretion. These results indicate that FK480 is a potent, competitive, and specific CCK receptor antagonist on the exocrine pancreas in vivo, having oral bioavailability and a long biological half-life.

Administration, Oral↗
PubMed1994

Potentiating effect of insulin on exocrine secretory function in isolated rat pancreatic acini.

BACKGROUND/AIMS: Insulin is shown to exert various regulatory effects on the exocrine pancreatic function. We investigated the direct effect of insulin on exocrine pancreatic secretion. METHODS: The effects of insulin on amylase release, 125I-secretin binding and Na(+)- and K(+)-activated adenosine triphosphate phosphohydrolase (Na+,K(+)-ATPase) activity were measured using the isolated rat pancreatic acini. RESULTS: Insulin potentiated the amylase release elicited by secretin plus cholecystokinin (CCK), but not by either secretin or CCK alone. The potentiating effect of insulin was dependent on the concentration and preincubation time. Insulin had no effect on 125I-secretin binding. Ouabain, a specific Na+,K(+)-ATPase inhibitor, caused a concentration-dependent inhibition of the potentiated secretion by insulin without affecting the secretory response to secretin plus CCK. In membranes prepared from acini treated with insulin, Na+,K(+)-ATPase activity was significantly increased. Similar results were obtained when acini were treated with insulin in combination with secretin plus CCK. CONCLUSIONS: Insulin exerts a direct effect on pancreatic acinar cells and potentiates exocrine secretion elicited by secretin in combination with CCK, in part, by increasing Na+,K(+)-ATPase activity.

Amylases↗
PubMed1994

Characterization of a new cholecystokinin receptor antagonist FK480 in in vitro isolated rat pancreatic acini.

Biochemical and pharmacologic characteristics of a newly developed benzodiazepine derivative (S)-N-[1-(2-fluorophenyl)-3,4, 6,7-tetrahydro-4-oxo-pyrrolo-[3,2,1-jk] [1,4]benzodiazepine-3-yl]-1H-indole-2-carboxamide (FK480) as a cholecystokinin (CCK) receptor antagonist were examined in the isolated rat pancreatic acini and compared with those of MK-329 and loxiglumide. FK480, MK-329, and loxiglumide inhibited CCK octapeptide (CCK-8)-stimulated amylase release and binding of [125I]CCK-8 in a concentration-dependent manner, with a half-maximal inhibition (ID50) at 1.30 +/- 0.12 nM, 1.33 +/- 0.21 nM, and 1.27 +/- 0.23 microM, respectively, for amylase release, and 0.40 +/- 0.06 nM, 0.68 +/- 0.08 nM, and 0.38 +/- 0.03 microM, respectively, for [125I]CCK-8 binding. The antagonism was competitive in nature because these three compounds caused a parallel rightward shift of the dose-response curve for CCK-8-stimulated amylase secretion, without altering the maximal increase. The antagonism produced by FK480 was specific for CCK in that the effects of other receptor secretagogues or agents bypassing receptors were not altered. FK480 not only prevented but also reversed CCK-8-stimulated amylase release. This compound caused a residual inhibition of the action of CCK-8. When acini were preincubated with 100 nM FK480 for 30 min, the subsequent dose-response curve to CCK-8 was shifted 10-fold toward higher concentration. Similar results were obtained with MK-329 but not with loxiglumide. FK480 appeared to be bound to the receptors on acinar cells in a slowly dissociating state.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effects of cholecystokinin receptor antagonist loxiglumide on rat exocrine pancreas.

Effects of long-term administration of the cholecystokinin receptor antagonist loxiglumide on exocrine pancreas were studied in adult rats. Plasma concentrations of loxiglumide at 8 h after a single subcutaneous injection of 50 mg/kg body weight of loxiglumide were 3.2 +/- 0.8 microgram/ml, which were comparable to those at 12 h after oral administration of the same dose (3.7 +/- 0.9 microgram/ml). Eight hours' prior subcutaneous injection of loxiglumide (50 mg/kg body weight) significantly suppressed pancreatic exocrine secretion stimulated by an intravenous bolus injection of 50 ng/kg body weight caerulein compared with the control rats. Based on these results, in the first experiment, loxiglumide at a dose of 50 mg/kg body weight was given subcutaneously three times a day (low dose) for 6 days to adult rats fed a standard laboratory diet. Low dose of loxiglumide significantly decreased pancreatic wet weight (-14%) and pancreatic contents of protein (-26%), trypsin (-38%), and lipase (-68%), while having no significant effect on pancreatic contents of DNA and amylase. In the second experiment, three times higher dose of loxiglumide (150 mg/kg body weight) was given by an orogastric tube twice daily for 6 days. High dose of loxiglumide significantly decreased pancreatic weight (-11%) and contents of protein (-20%) and DNA (-22%), whereas it significantly increased amylase (+92%) and trypsin content (+20%).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

[In vitro synergistic effects of tazobactam/piperacillin with various antibiotics].

We investigated in vitro synergistic effects of tazobactam/piperacillin (TAZ/PIPC), a combination drug of tazobactam (TAZ) and piperacillin (PIPC) in the ratio of 1:4, with several other antibiotics against Pseudomonas aeruginosa, Serratia marcescens and methicillin-resistant Staphylococcus aureus (MRSA). Synergistic effects of TAZ/PIPC with each of tobramycin (TOB), netilmicin (NTL), fosfomycin (FOM), ciprofloxacin, minocycline or cefoperazone were observed against all bacteria tested in the checkerboard dilution method. No antagonistic effect was observed in combination of TAZ/PIPC with other antibiotics. Against P. aeruginosa, a combination of TAZ/PIPC with NTL was the most effective, with an average fractional inhibitory concentration (FIC) index of 0.459. And a combination of TAZ/PIPC with FOM was the most the effective against S. marcescens and MRSA. TAZ/PIPC combined with TOB or FOM showed bactericidal effect against P. aeruginosa No. 11, S. marcescens No. 39 and S. aureus O-62 at concentrations of the drugs that showed only bacteriostatic activity individually. Phase-contrast micrographic observations of P. aeruginosa No. 11 and S. marcescens No. 39 demonstrated that the bacterial cells treated with TAZ/PIPC were in filamentous forms and those treated with TOB or FOM were nearly normal. The combination of TAZ/PIPC with TOB or FOM induced filamentous cells with spheroplast-like structures and lysis. Those results suggest that the combination of TAZ/PIPC with aminoglycosides or FOM were useful in the treatment of infections by P. aeruginosa, S. marcescens and MRSA, especially those caused by beta-lactamase-producing strains.

Drug Synergism↗