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H Sakamoto

Publications and source records attributed to H Sakamoto.

At least 559 records · Page 31Linked to original sources
PubMed1993

High sensitivity of LEC rats with chronic hepatitis to hepatocarcinogenesis: decreases in unscheduled and replicative DNA synthesis of the hepatocytes.

We carried out the following three experiments to clarify the mechanism of hepatocarcinogenesis in Long-Evans Cinnamon (LEC) rats. (1) Sensitivity to diethylnitrosamine (DEN): LEC rats (8 and 25 weeks old) without and with hepatitis and age-matched F344 rats were administered an intraperitoneal injection of a low dose of DEN. Eight weeks after the injection, the numbers of glutathione-S-transferase placental-form (GST-P)-positive foci in the 33-week-old LEC rat liver were significantly higher than those in the livers of the other three groups of rats. (2) Potential for unscheduled DNA synthesis (UDS): Isolated hepatocytes of 25-week-old LEC rats with chronic hepatitis showed about one-third the level of UDS induced by UV irradiation, as compared to that of age-matched F344 rats, while no significant difference was found between the UDS of isolated hepatocytes of 8-week-old LEC rats and age-matched F344 rats. (3) Potential for proliferation: Isolated hepatocytes from 8-week-old LEC rats responded well to epidermal growth factor (EGF) in culture, to almost the same degree as F344 rat hepatocytes, while a remarkable decrease in the responsiveness of hepatocytes isolated from 25-week-old LEC rats to EGF was found. These results suggested that LEC rat hepatocellular carcinoma could be naturally initiated after the onset of hepatitis by carcinogens contaminating food and the environment, probably due to the reduction of DNA repair activity, after which initiated hepatocytes selectively proliferate in response to growth stimuli endogenously produced as a result of continuous loss of hepatocytes (chronic hepatitis), because of a decrease in growth activity of non-initiated hepatocytes.

Animals↗
PubMed1993

Time course of dopamine-D2 and serotonin-5-HT2 receptor occupancy rates by haloperidol and clozapine in vivo.

In vivo occupancy of dopamine-D1, D2 and serotonin-5-HT2 receptors by haloperidol 10 mg/kg and clozapine 20 mg/kg were studied. Rats were injected intravenously with [3H]-YM-09151-2, [3H]-SCH23390, or [3H]-ketanserin 10 min after the administration of the tested drugs. Fifteen to 240 min after the ligand injection, the receptor occupancy rates of the drugs in the striatum and frontal cortex were calculated. Clozapine demonstrated the higher 5-HT2 and lower D2 occupancies in the respective regions. A dose-response analysis of D2 and 5-HT2 receptor occupancy by the drugs consolidated the higher 5-HT2 binding affinity of clozapine in comparison with haloperidol. The present methodology may serve as an accurate tool to evaluate the peculiarity of various antipsychotics.

Animals↗
PubMed1993

The effect of nicardipine on maternal and fetal hemodynamics and uterine blood flow in chronically instrumented pregnant goats.

This study was designed to clarify the maternal and fetal hemodynamics of nicardipine (0.02 mg/kg) administered intravenously to unanesthetized, chronically instrumented pregnant goats. Nicardipine produced a significant increase in maternal heart rate and cardiac output, and a significant decrease in maternal mean arterial blood pressure and systemic vascular resistance. These changes persisted for about 30 minutes. There were no consistent changes in maternal pulmonary hemodynamics. Uterine arterial blood flow (UBF) decreased significantly (about 15%) after 5 minutes of the injection and returned to the control value within 30 minutes. A significant correlation between the decreases in UBF and maternal diastolic blood pressure was observed after 5 minutes of the injection. The fetal heart rate, blood pressure and acid-base status did not change after the injection of nicardipine. These observations of pregnant goats suggest that nicardipine might be a useful agent for the treatment of acutely hypertensive crises in pregnant patients.

Animals↗
PubMed1993

Ramification of the intercostal nerves in the rhesus monkey (Macaca mulatta) with special reference to the innervation of the intercostal muscles.

Detailed dissection was performed on the ventral primary rami from the first thoracic to the second lumbar nerves in order to obtain more comprehensive data of the ramification of the intercostal nerves in the rhesus monkey. The nerves to the intercostalis intimus and internus and the obliquus externus abdominis tended to arise as a common trunk from the main intercostal nerve. A comparison of the intercostal nerve ramification with that in man is included.

Animals↗
PubMed1993

[Stress management].

Stress management is an important health demand in developed and rapidly developing countries. The principle of stress management consists of four strategies. That is, reduction of stressors, culture of stress tolerance, enrichment of supporting resources, and early detection of manifestations of physical and mental disorders. Accordingly, a comprehensive approach is needed for stress management. For reduction of stressors, methods of quantitatively measuring not only physico-chemical stressors, but also psycho-social stressors, have been explored. However, both the absolute level and the varying degrees of stress are valuable stress indicators. Techniques of behavioral therapy are admirable for avoiding new stress through a culture of stress tolerance. Enrichment of supporting resources is realized by two dimensions: one is man-power and the other is space and time for relaxation. For early detection of the manifestations of physical and/or mental disorders, we must pay attention to alexithymia and alexisomia in order to prevent delays in detection.

Humans↗
PubMed1993

Evaluation of phlebotomy-induced erythropoietin production in the dog.

Erythropoietin (EPO) production in dogs was studied by reducing red blood cells with phlebotomy. In this study, the hemoglobin reduction rate (delta %Hb) was newly taken into account as the regulating factor for EPO production, and its usefulness to estimate the stimulating intensity to EPO production was examined. As the result, plasma EPO was highly correlated with delta %Hb showing the importance related to regulation of EPO production, in the increasing plasma EPO by different degrees of phlebotomy, in the change of plasma EPO through the anemia progress and recovery period after severe phlebotomy, and in the initial variation of plasma EPO induced by chronic mild phlebotomy. On the other hand, increasing EPO production appeared at least within 6 hr after acute severe phlebotomy, which revealed significantly higher plasma level compared with the mild chronic phlebotomy, suggesting the effect of time leading to red blood cell reduction on EPO production response. Simultaneously, considering an in vivo EPO half life of 8.4 hr calculated from plasma EPO disappearance after bilateral nephrectomy, endogenous plasma EPO accumulation should be taken into consideration in rapidly increasing of delta %Hb.

Anemia↗
PubMed1993

Evaluation of erythropoietin production in dogs with reduced functional renal tissue.

This study was designed to determine the quantity of functional renal tissue needed to maintain homeostasis of red blood cell production by evaluating the erythropoietin (EPO) production response to phlebotomic stimulation in the 1/2- and 1/4-kidney dogs surgically prepared. The results showed that the reduction in functional renal tissue caused a decrease in EPO production, which led to the delay in recovery from anemia. In the anemic progress stage, the plasma EPO level showed a transition proportional to the quantity of functional renal tissue immediately after the operation for tissue reduction. The 1/2-kidney dog group still kept such proportional relation even in the recovery stage. Thus, the half of the normal renal tissue was considered sufficiently contributory to EPO production needed to maintain homeostasis of red blood cell production. However, the 1/4-kidney dog group precipitously decreased in plasma EPO level in the recovery stage and fell into an extremely unfavorable anemia. This indicated that homeostatic maintenance in erythropoiesis would be impossible more below a quarter of normal renal tissue. These findings disclosed that reduction in functional renal tissue quantity would sensitively influence homeostatic maintenance of red blood cell production through the decrease in EPO production, even if it does not affect renal function concerned with urine production.

Anemia↗
PubMed1993

Left ventricular wall thickness in normal mongrel dogs.

To clarify the normal value of ventricular wall thickness we directly measured the ventricular wall thickness of 50 normal mongrel dogs of one year old. Because of a wide range in body weight from 6.0 to 16.0 kg of these 50 dogs, we selected 34 dogs weighing 8 to 12 kg to calculate the mean ventricular wall thickness as normal value of one year old. The results obtained were as follows; (1) The mean and standard deviation of the left ventricular wall thickness was 7.1 +/- 1.2 mm at anterior, 6.3 +/- 1.6 mm at posterior, 7.1 +/- 1.3 mm at lateral, 10.3 +/- 1.8 mm at the interventricular septum, and that of the right ventricular wall thickness was 3.4 +/- 1.0 mm. (2) Although any site of the ventricular wall thickness correlated significantly to heart weight, only the anterior left ventricular wall and interventricular septum barely correlated to body weight. (3) There was no significant correlation between arterial blood pressure and the ventricular wall thickness. Further study should be necessary to clarify influences of aging on the ventricular thickness and to determine the criteria of ventricular hypertrophy.

Alanine Transaminase↗
PubMed1993

Assessment of pulmonary edema based on extravascular thermal volume in dogs.

To establish criteria of pulmonary edema by extravascular thermal volume (ETV), ETV and a roentgenogram of the thorax were compared in normal and experimental hydrostatic pulmonary edema dogs. ETV was measured by the double indicator dilution technique using heat as a diffusible indicator and sodium ions as a non-diffusible indicator (thermal-Na method). Mean ETV in 14 dogs under physiologic conditions was 8.20 +/- 1.44 ml/kg. Comparison of ETV with the roentgenogram indicated the density of thoracic the roentgenogram to increase when ETV exceeded 11 ml/kg. Pulmonary edema was recognized clearly in the thoracic roentgenogram at more than 15 ml/kg of ETV. Further increase in ETV did not occur with additional radiographic change. ETV was significantly (P < 0.01) correlated with arterial oxygen tension (PaO2) but not statistically correlated with colloid oncotic pressure (COP), pulmonary arterial wedge pressure (PAWP) or PAWP-COP. Measurement of ETV would thus, appear to be a reliable method for evaluating the severity of pulmonary edema, which has been difficult to diagnose by roentgenography and should facilitate the early diagnosis and management of pulmonary edema.

Animals↗
PubMed1993

Effects of environmental temperature on atrial natriuretic peptide (ANP)-granules of auricular cardiocytes and plasma ANP level in pregnant rats.

The atrial natriuretic peptide (ANP) levels of auricular cardiocytes and plasma were examined by immunohistochemistry, ultrastructural morphometry, and radioimmunoassay (RIA) in pregnant rats (4th, 12th, 20th day of gestation) under 22 degrees C and 33 degrees C environmental conditions. Immunohistochemically, ANP immunoreactivity was stronger on the 20th day of gestation in the 22 degrees C environmental groups, but weaker on the 12th and 20th days of gestation in the 33 degrees C environmental groups. According to the results of ultrastructural morphometry, the number of ANP-granules had increased significantly by the 20th day of gestation in the 22 degrees C environmental groups, but was decreased on the 12th and 20th days of gestation in the 33 degrees C environmental groups. RIA demonstrated that the maternal plasma ANP concentration decreased gradually during pregnancy in the 22 degrees C environment. The plasma ANP concentration in the 33 degrees C environmental groups tended to be lower than that at the same stage of pregnancy in the 22 degrees C environmental groups.

Animals↗
PubMed1993

Autoxidation of human hemoglobin: kinetic analysis of the pH-profile.

The autoxidation reaction of human hemoglobin A was studied over the pH range of 5.3-10.4 in 0.1 M buffer at 37 degrees C. In the first-order plot, hemoglobin showed a biphasic reaction, which consisted of a rapid initial reaction and was followed by a slower second phase in the acidic or neutral pH range (5.3-8). However, this difference decreased with increase of pH of the solution and only a single-phase reaction was observed in alkali solutions above pH 8. For the kinetic analysis of the time course of the reaction, computer fitting was made to obtain curves as a function of time by a non-linear least squares method using a biphasic first-order equation with rate constants of kf and ks for the initial fast component reaction and for the slower second reaction, respectively. The parameter of the molar fraction (P) with a rate constant of kf was computed in the range of 0.45-0.55, which means that hemoglobin was autoxidized with half of the component via the reaction process with the initial rapid rate (kf) and the other half via the reaction with the following slower rate (ks). kf and ks thus obtained versus pH plot also indicated that (1) both rate constants increase markedly with increase in hydrogen ion concentrations, but (2) when pH > 8, kf becomes equal to ks with P = 1.0, and (3) there appears a rate minimum at pH 8-8.5, followed by a considerable elevation of the rate with increase in hydroxyl ion concentration. In order to examine these complicated pH-profiles, some mechanistic models were proposed for the autoxidation reaction of hemoglobin. Fitting of their rate equations as a function of pH was examined for the experimental rate constants kf and ks versus pH plot by the least squares method with use of a computer. Both pH-profiles could be best explained by the "acid-base catalyzed model." This revealed not only the catalytic role of hydrogen ions but also the involvement of hydroxyl ions and water molecules in the autoxidation reaction of human hemoglobin.

Hemoglobin A↗
PubMed1993

Preservation of alpha rhythm shortly after photic driving.

EEG responsiveness to intermittent photic stimulation (IPS) with repetitive flashes was examined just after the pause of IPS. By omitting 5, 10, 15 and 20 flashes in the course of IPS at 10 Hz, 2 s IPS responses at the midline occipital area were compared between flash trains before (train 1) and after the pause (train 2). Amplitude, peak frequency and bandwidth (reflecting the degree of rhythmicity) of an alpha peak in the power spectrum of averaged IPS responses were each obtained every 50 ms with the power spectrum based on a time-varying AR model. Bandwidth was more sensitive to IPS responses, because significant differences in bandwidth between trains 1 and 2 occurred earlier than differences in amplitude. There were greater differences in bandwidth for the omission of 5, 10 and 15 flashes, suggesting increased responsiveness to train 2, while there were no significant differences in bandwidth for the omission of 20 flashes. These findings show that rhythmicity in IPS responses can be preserved up to 1.6 s after the pause of IPS.

Adult↗
PubMed1993

Inhibitory effect of beta-carotene and astaxanthin on photosensitized oxidation of phospholipid bilayers.

Large unilamellar liposomes comprising of egg yolk phosphatidylcholine (PC) was exposed to photoirradiation in the presence of methylene blue (water-soluble photosensitizer) or 12-(1-pyrene)dodecanoic acid (P-12, lipid-soluble photosensitizer) to estimate the inhibitory effect of beta-carotene and astaxanthin on photosensitized oxidation of phospholipid bilayers. Without sensitizers, astaxanthin decreased much slower than beta-carotene and other hydrocarbon carotenoids (lycopene, alpha-carotene). Astaxanthin lasted longer than beta-carotene even in the presence of methylene blue or P-12. Decrease of astaxanthin was also much slower than that of beta-carotene when egg yolk PC was replaced by dimyristoyl PC. However, inhibitory effect of astaxanthin was lower than beta-carotene in the case of P-12 sensitized photooxidation. These results suggest that effectiveness of carotenoids as antioxidants on photosensitized oxidation (Type II) in phospholipid bilayers depends on the site of singlet oxygen to be generated, as well as their stability on photoirradiation.

Carotenoids↗
PubMed1993

Animal pharmacokinetics of FK037, a novel parenteral broad-spectrum cephalosporin.

Single-dose pharmacokinetics of FK037 has been investigated in laboratory animals. After bolus intravenous dosing with 20 mg/kg, the elimination half-life of FK037 varied in the species; with values of 0.27, 0.30, 0.97, 1.29 and 1.76 hours in mice, rats, rabbits, dogs and monkeys, respectively. The volume of distribution ranged between 260 ml/kg in rats and 390 ml/kg in dogs. These parameters approximated those of ceftazidime and cefpirome used as reference drugs. The renal clearance of FK037 was almost equal to glomerular filtration rate (GFR) in rabbits. Probenecid did not affect the elimination half-life of FK037 and its clearance ratio to GFR. These findings suggest that FK037 is solely excreted by glomerular filtration. FK037 readily penetrated into the tissues and inflammatory exudate fluid in rats, and the tissue level was highest in the kidneys, and decreased in the following order; lungs > heart > liver > spleen. Penetration of FK037, cefpirome and ceftazidime into the cerebrospinal fluid were determined using induced staphylococcal meningitis in rabbits. The penetration percentage ranged from 14.2 to 16.0% for these drugs with no significant differences. The major route of excretion of FK037 was via the kidney, with more than 74% of the dose being excreted in the urine within 24 hours after dosing to each species. Biliary excretion was low, 0.79% in rats. Bioautograms showed only unchanged drug in the plasma, urine and bile. Serum protein binding was low (8.8 to 17.6%) in all the species studied.

Animals↗
PubMed1993

In vitro antibacterial activity of FK037, a novel parenteral broad-spectrum cephalosporin.

FK037 is a new parenteral cephalosporin, which offers some advantages over the commercially available parenteral cephalosporins. It demonstrated potent broad-spectrum activity against clinical isolates of Gram-positive bacteria including methicillin-resistant staphylococci, and Gram-negative bacteria including Pseudomonas aeruginosa. Against clinical isolates of aerobic Gram-positive bacteria, FK037, like cefpirome, demonstrated more potent activity than ceftazidime, cefoperazone and ceftizoxime. It is noteworthy that FK037, on the basis of the MIC90s, was the most active of all the cephalosporins tested against methicillin-resistant Staphylococcus aureus (MRSA). It was similar in activity to cefpirome against methicillin-sensitive S. aureus (MSSA). Against clinical isolates of aerobic Gram-negative bacteria, FK037, like cefpirome, was superior to cefoperazone, similar to ceftazidime and inferior to ceftizoxime in activity. Against P. aeruginosa, FK037 was superior to cefoperazone, similar or slightly superior to cefpirome and inferior to ceftazidime in activity. However, FK037 exhibited significant activity against Citrobacter and Enterobacter which were highly resistant to ceftazidime, cefoperazone and ceftizoxime. FK037 had an advantage in that its bactericidal activity against S. aureus, Escherichia coli and P. aeruginosa at sub-MICs (1/2 or 1/4 the MIC) was much stronger than those of cefpirome and ceftazidime. Moreover, it exhibited potent bactericidal activity against MSSA, MRSA and P. aeruginosa in a pharmacokinetic in vitro model simulating human plasma concentrations after intravenous dosage of 0.125, 1.0 and 1.0 g, respectively. FK037 inhibited essential penicillin-binding proteins (PBPs), 1, 2 and 3 of S. aureus with a 50% inhibitory concentration (I50) of 0.58 micrograms/ml or lower. Of essential PBPs 3, 1a and 1b of E. coli and P. aeruginosa, FK037 inhibited PBP 3 at the lowest I50 (0.03 and 0.04 micrograms/ml, respectively) and PBPs 1a and 1b with I50 values of 2.7 micrograms/ml or lower. FK037, like cefpirome, was highly stable to hydrolysis by various beta-lactamases except Ic cephalosporinase from Bacteroides fragilis, and had extremely low affinity for beta-lactamases. Therefore, FK037 was more potent than ceftazidime in activity against beta-lactamase-producing bacteria except P. aeruginosa and Serratia marcescens. The ability of FK037 to penetrate the outer membrane of E. coli was slightly higher than that of ceftazidime, but slightly lower than that of cefpirome.

Anti-Bacterial Agents↗
PubMed1993

In vivo antibacterial activity of FK037, a novel parenteral broad-spectrum cephalosporin.

FK037 has potent therapeutic activity against lethal systemic infections and experimental local infections due to a wide variety of Gram-positive and Gram-negative bacteria such as staphylococci, Streptococcus pneumoniae, Enterobacteriaceae and Pseudomonas aeruginosa in mice. In murine systemic infections, FK037 was the most effective of the cephalosporins and imipenem tested against highly methicillin-resistant Staphylococcus aureus (H-MRSA). It was more effective than ceftazidime against selected strains of S. aureus and Enterobacteriaceae, except Serratia marcescens and P. aeruginosa against which FK037 was as effective as ceftazidime and was as effective as cefpirome against all organisms tested, except MRSA and P. aeruginosa against which FK037 was more effective than cefpirome. These results correlated well with its in vitro activity. In murine local infections, with few exceptions, FK037 was more effective than ceftazidime and cefpirome against Klebsiella pneumonia in ED50 values and against methicillin-sensitive S. aureus (MSSA) subcutaneous abscess, pyelonephritis with Staphylococcus epidermidis, E. coli and P. aeruginosa, intrauterine infections with S. aureus and E. coli in reducing the number of viable bacteria in the abscess, kidneys and uterus. It is noteworthy that the therapeutic effects of FK037 were more potent than had been anticipated from its in vitro activity against local infections with staphylococci and P. aeruginosa when compared with ceftazidime or cefpirome. In addition, the therapeutic effects of FK037 were equipotent or superior to those of cefpirome and ceftazidime against pneumonia due to MSSA, K. pneumoniae and P. aeruginosa in reducing the number of viable bacteria in the lungs in mice using an in vivo pharmacokinetic model simulating human plasma concentrations after drip infusion of usual clinical doses (0.25 to 1.0 g for MSSA, 0.063 to 0.125 g for K. pneumoniae and 1.0 to 2.0 g for P. aeruginosa). FK037 induced an in vivo post-antibiotic effect (PAE) of 3.4 hours against a thigh infection with MSSA in neutropenic mice. These results strongly suggest that it has potential for clinical use against various infections due to bacteria which include staphylococci and P. aeruginosa.

Abscess↗
PubMed1993

Excellent activity of FK037, a novel parenteral broad-spectrum cephalosporin, against methicillin-resistant staphylococci.

FK037 exhibits potent in vitro and in vivo antibacterial activity against methicillin-resistant staphylococci. In in vitro studies, FK037 was the most active of the cephalosporins and imipenem tested against the highly methicillin-resistant staphylococci (MIC > 100 micrograms/ml). Only 2 of 57 strains of highly methicillin-resistant Staphylococcus aureus (H-MRSA) had a FK037 MIC value of 50 micrograms/ml. On the other hand, 55, 40 and 19 strains had MICs of 50 or > or = 100 micrograms/ml to cefpirome, flomoxef and imipenem, respectively. Against 13 strains of highly methicillin-resistant coagulase-negative staphylococci (H-MRCNS), FK037 inhibited all the strains at < or = 50 micrograms/ml, but there were many strains highly resistant to the reference drugs with MICs of > or = 100 micrograms/ml. The influence of culture conditions such as low temperature, high inoculum and supplementation with 4% NaCl on the anti-MRSA activity of FK037 was less than those with cefpirome, flomoxef and imipenem. The in vitro frequency of spontaneous mutant cells highly resistant to FK037 in MRSA was lower than that to cefpirome and flomoxef. These findings were supported by lack of colonies inside the inhibition zone demarcated by FK037 in a disk sensitivity test, although many colonies proliferated inside the inhibition zone demarcated by flomoxef and imipenem. The increase in MIC of FK037 against a MRSA strain during subculture in the presence of the drug was smaller than that noted with the reference drugs. FK037 had higher affinity and faster binding for the PBP 2a of MRSA than that of the reference drugs. Moreover, the capacity to induce PBP 2a was lower for FK037 than that of cefpirome but higher than that of flomoxef. In an in vitro pharmacokinetic model simulating human plasma concentrations, FK037 showed potent bactericidal activity against H-MRSA in the plasma concentrations after intravenous infusion dosing with 1.0 g. FK037 was synergistically active against H-MRSA in combination with either imipenem of fosfomycin. The in vitro post-antibiotic effect (PAE) of FK037 against H-MRSA ranged from 1.2 to 1.7 hours at one to four times the MIC. FK037 had potent therapeutic effects against lethal systemic infections and experimental local infections in mice such as pneumonia, endocarditis, subcutaneous abscess, intrauterine infection and granuloma pouch infection due to MRSA or methicillin-resistant Staphylococcus epidermidis (MRSE). FK037 was about 4, 8 and 1.5 times more effective than cefpirome, flomoxef and imipenem, respectively, against lethal systemic infections with H-MRSA.(ABSTRACT TRUNCATED AT 400 WORDS)

Abscess↗