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Biomedical subjects

N Ohnishi

Publications and source records attributed to N Ohnishi.

At least 37 records · Page 2Linked to original sources

[Clinical efficacy of cefpirome sulfate against Bacteroides species, Prevotella species and Porphyromonas species. Society of Anaerobic Bacterial Infections in the fields of obstetrics and gynecology in Gifu].

The injectable cephalosporin cefpirome (CPR) was launched in Japan in 1993. It has widely been used in the various infectious diseases. We therefore studied the clinical and bacteriological efficacy of CPR against infections caused by Bacteroides species, Prevotella species and Porphyromonas species frequently isolated from the obstetric and gynecologic infections. Thirteen institutions were involved in this study which ran from March 1994 to January 1999. The administration dosage of CPR was 2 to 4 gram per day administered by drip infusion or intravenous infusion. The duration of treatment was from 3 to 15 days. The evaluations were performed before and after the treatment. CPR was administered to 194 patients with obstetric and gynecologic infections, and 146 of 194 cases were acceptable for the evaluation of drug efficacy. Bacteroides species were identified in 102 patients. Clinical efficacy in 146 cases was excellent in 12 patients, good in 110, fair in 9 and poor in 15 patients. The eradication rate for Bacteroides species could be in 37 cases out of 54 evaluable cases; Prevotella species in 38 out of 49; and Porphyromonas species in 5 out of 5. The overall assessment of bacteriological efficacy was "eradicated" in 91 cases out of 133 (68.4%). Adverse reactions including abnormal findings in laboratory tests were seen in 8 patients (4.76%). Based on these results, CPR promises efficacy and safety in the treatment of obstetric and gynecologic infections due to Bacteroides species.

Adult↗

Venous hemangioma of the scrotum: a case report.

We report a case of intrascrotal hemangioma. A 68-year-old man who had noticed a swelling in his left scrotum over the past 1 year was seen at our hospital. Under a diagnosis of intrascrotal tumor, total excision of the mass was performed. Histopathological examination revealed venous hemangioma of the scrotum.

Aged↗

Factors affecting membrane-controlled drug release for an osmotic pump tablet (OPT) utilizing (SBE)(7m)-beta-CD as both a solubilizer and osmotic agent.

PURPOSE: The purpose of this study was to define membrane controlling factors responsible for drug release from a controlled-porosity osmotic pump tablet (OPT) that utilizes a sulfobutyl ether-beta-cyclodextrin, (SBE)(7m)-beta-CD, as both a solubilizing and osmotic agent. METHOD: The OPT was spray coated with cellulose acetate solutions varying the amount and size of micronized lactose, the amount of triethyl citrate (TEC) and the composition ratio of dichlormethane to ethanol. Chlorpromazine (CLP) was used as a model drug. The release of CLP from the OPTs was studied using the Japanese Pharmacopoeia dissolution method. The membrane surface area of the OPTs were measured with multi-point analysis by the gas absorption method. RESULTS: The release rate of CLP from OPTs containing (SBE)(7m)-beta-CD increased with increasing amounts of micronized lactose and decreasing amounts of TEC and lactose particle size in the membrane. Also, the CLP release rates from the spray-coated OPTs using mixtures of varying ratios of dichlormethane to ethanol were almost identical. The membrane surface area of the OPTs following release of membrane components had a linear relationship to CLP release rates from the OPTs. CONCLUSION: The present results confirmed that the membrane controlling factors responsible for the drug release were the amount and size of micronized lactose and the amount of TEC in the membrane.

Antipsychotic Agents↗

Efficient gene transfer by hybrid retroviral vectors to murine spermatogenic cells.

Using murine spermatogenic cell lines GC-1 spg and GC-2 spd(ts) as target cells, an attempt was made to design a retroviral vector that would transduce genes efficiently. Promoter activities of various retroviral long terminal repeats (LTRs) were examined by using chloramphenicol acetyltransferase (CAT) as a reporter. The U3 region of spleen focus-forming virus (SFFVp) showed higher enhancer activity than that of Moloney murine leukemia virus (Mo-MuLV) in both cell lines. The U3 region of myeloproliferative sarcoma virus (MPSV) showed higher activity only in GC-1 spg cells. Expression was suppressed by the repressor element of the primer-binding site (PBS) of the Moloney-related virus. The efficiency of transduction of the multidrug-resistance gene (mdr-1) by an Mo-MuLV-based vector was compared with hybrid vectors consisting of the murine embryonic stem cell virus (MESV) PBS and the LTR of either SFFVp or MPSV. Rhodamine efflux assays and colchicine-resistant colony-forming assays demonstrated higher gene expression by the hybrid vectors. Amphotropic and ecotropic receptors were found to be expressed and functional in both cell lines. Thus, these hybrid vectors represent a powerful tool by which to transfer genes into spermatogenic cells.

Animals↗

Sucrose diuresis protects rat bladder from outlet partial obstruction-induced contractile dysfunction.

OBJECTIVES: Evidence is accumulating that bladder dysfunction caused by experimental partial obstruction of the bladder outlet can be reduced or reversed by treatment that results in upregulation of bladder function, even in the presence of obstruction. Inducing diuresis in rats or rabbits results in a significant increase in bladder mass and increased contractility in response to stimulation. The objective of the present study was to determine whether diuresis-induced amplification of bladder function in the rat could protect the bladder from contractile dysfunctions caused by partial outlet obstruction. METHODS: Thirty-two rats were separated into four groups of 8 rats each. Groups 2 and 4 were fed 5% sucrose instead of water; groups 1 and 3 were fed only water. Three weeks later, partial outlet obstructions were created in groups 3 and 4. After 4 weeks of obstruction, all bladders were rapidly excised and cut into longitudinal strips; each strip was mounted in an isolated muscle bath for contractile studies. RESULTS: Sucrose-induced diuresis caused a moderate but significant increase in bladder mass. Partial outlet obstruction stimulated significant increases in bladder mass in both water-drinking and sucrose-drinking groups; the bladder mass of sucrose-drinking rats, however, increased less than that of water-drinking rats. In water-drinking rats, partial outlet obstruction resulted in significantly decreased bladder strip contractility in vitro in response to field stimulation (1 to 32 Hz), carbachol (0.1 to 22 microM), and KCl (120 mM). After 3 weeks of sucrose-induced diuresis, partial obstruction of the rat bladder outlet did not result in decreased in vitro contractile responses to any form of stimulation applied. CONCLUSIONS: Sucrose-induced diuresis caused an increase in bladder mass and an increase in contractile strength, consequently protecting the rat bladder from the contractile dysfunctions that usually follow partial outlet obstruction.

Animals↗

Design and evaluation of an osmotic pump tablet (OPT) for chlorpromazine using (SBE)7m-beta-CD.

PURPOSE: The purpose of this study was to develop a controlled-porosity osmotic pump tablet (OPT) which exhibits pH-independent release profiles for a basic drug using a sulfobutyl ether-beta-cyclodextrin, (SBE)7m-beta-CD, which acts as both a solubilizer and as an osmotic agent. METHODS: Chlorpromazine free base (CLP) was chosen as a model drug for this study. The release of CLP from osmotic pump tablets was studied in vitro. In vivo absorption of CLP from the OPT was evaluated in male beagle dogs. RESULTS: The CLP release profile from an OPT prepared from a core tablet composed of a 1:10 molar ratio of CLP to (SBE)7m-beta-CD was pH-independent, and was controlled by modulating the membrane thickness of the OPT. Another cyclodextrin, hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and a sugar mixture of lactose and fructose resulted in pH-dependent release at the same molar ratio. An in vivo absorption study in dogs with an OPT containing (SBE)7m-beta-CD correlated very well with the in vitro release profiles using the Japanese Pharmacopoeia dissolution method. CONCLUSIONS: In addition to serving as a solubilizer and osmotic agent, (SBE)7m-beta-CD can also serve as the controlling agent for pH independent release of CLP from OPTs. This system successfully modified the in vivo input rate of CLP without compromising oral bioavailability.

2-Hydroxypropyl-beta-cyclodextrin↗

Membrane transport and antitumor activity of pirarubicin, and comparison with those of doxorubicin.

We have compared the membrane transport and antitumor activity of pirarubicin with those of doxorubicin in M5076 ovarian sarcoma, which exhibits low sensitivity to doxorubicin. Pirarubicin was rapidly taken up by M5076 cells and the intracellular concentration of pirarubicin reached more than 2.5-fold that of doxorubicin. In terms of the 50% cell growth-inhibitory concentration in vitro, pirarubicin was more effective than doxorubicin. Thus, the intracellular concentration influenced the cytotoxicity of these anthracycline agents. On comparison of the nuclear uptake of pirarubicin and doxorubicin, the nucleus/cell ratio of pirarubicin was found to be about 40%, whereas that of doxorubicin reached more than 80%. As the intranuclear concentration of pirarubicin is dependent on nuclear transport, the increases in not only cell membrane transport, but also nuclear membrane transport contributed to the enhancement of the efficacy of pirarubicin. In M5076 solid tumor-bearing mice, pirarubicin reduced the tumor weight to 60% of the control level, although doxorubicin had no effect. These results were supported by the intracellular uptake of pirarubicin. Moreover, theanine, which inhibited the pirarubicin efflux from M5076 cells, increased by 1.3-fold the pirarubicin concentration in the tumor and enhanced the therapeutic efficacy of pirarubicin 1.7-fold. In conclusion, our results suggest that an increase in the concentration of an anthracycline derivative in tumor cells due to alteration of cell membrane transport results in enhancement of the antitumor activity.

Animals↗

Contribution of the nucleoside transport system to doxorubicin transport in HL60 cells but not in mononuclear cells.

Previously, we reported that pirarubicin (THP), an anthracycline, was transported, at least in part, via a nucleoside transport system in human leukemic HL60 cells, but not in mononuclear cells (MNCs). In this study, the contribution of the nucleoside transport system to the transport of other anthracyclines, doxorubicin (DOX), daunorubicin (DNR) and idarubicin (IDA), in HL60 cells and MNCs was investigated. The experiments were performed after both types of cells had been pretreated with a metabolic inhibitor, 2,4-dinitrophenol, to deplete cellular ATP. The DOX uptake by HL60 cells was partially inhibited by inhibitors of equilibrative nucleoside transporters. In HL60 cells, moreover, the uptake of DOX depended on an inwardly directed Na(+)-gradient, and was inhibited by concentrative nucleoside transporters, but there was no change in the DNR or IDA uptake under any of these conditions. On the other hand, the uptake of the three drugs by MNCs was not affected by any inhibitors of the nucleoside transporters, and there was no dependence of the uptake on an Na(+)-gradient. These results suggested that DOX, but not DNR or IDA, was partially transported in HL60 cells via the nucleoside transport system, whereas in MNCs the system did not contribute to the uptake of any of these three drugs. Thus, nucleoside transport systems contributing to the transport of anthracyclines may be different among different derivatives and cell types.

Antibiotics, Antineoplastic↗

Hepatic damage induced by transcatheter arterial chemoembolization elevates serum concentrations of macrophage-colony stimulating factor.

AIMS/BACKGROUND: This study was undertaken in order to characterize the liver injury induced by transcatheter arterial chemoembolization therapy (TACE) for hepatocellular carcinoma (HCC) and to elucidate-mechanisms involved in the growth of mononuclear phagocytes in injured human liver in vivo. PATIENTS AND METHODS: The serum levels of macrophage-colony stimulating factor (M-CSF) along with clinical parameters were examined in 43 patients with HCC who underwent TACE. Ten patients who underwent angiography alone served as controls. RESULTS: Serum M-CSF increased and peaked on the third day after TACE showing significant correlations (p < 0.001, respectively) with the increases in serum alanine aminotransferase (ALT) and type IV collagen-7S (IVcol-7S). The lipopolysaccharide-stimulated production of interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha in peripheral whole blood increased and peaked on the first or on the third day after TACE. In effective cases of TACE, significantly (p < 0.05) greater increases in serum M-CSF were noted as compared with those in ineffective cases. DISCUSSION: The serum levels of M-CSF increased after TACE in correlation with hepatic inflammation and necrosis and increased production of IL-1 beta, TNF-alpha and IL-6 in peripheral whole blood. These results suggest a mechanism by which hepatic injury enhances the production of M-CSF via a cytokine cascade, which results in the proliferation of liver macrophages in vivo.

Adult↗

Serum levels of soluble tumor necrosis factor receptors and effects of interferon therapy in patients with chronic hepatitis C virus infection.

OBJECTIVE: The aim of this study was to understand the significance of the tumor necrosis factor receptor (TNFR)-mediated signaling pathway in the pathophysiology of chronic hepatitis C. METHODS: The serum levels of soluble TNFRs (sTNFRs; sTNFR p55 and sTNFR p75) were measured in 84 patients with chronic hepatitis C virus (HCV) infection (24 sustained responders and 25 nonresponders to interferon [IFN] therapy and 35 patients with persistent normal blood chemistries) and 20 healthy controls, then compared with clinical parameters. RESULTS: The serum levels of sTNFRs increased in proportion to the severity of liver disease. The levels of sTNFRs revealed significant correlations with the serum levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, and gamma-globulin, but not with the serum levels of HCV-core protein. In the sustained responder group, the levels of sTNFR p75 showed a significant decrease (p < 0.0002) 1 yr after IFN therapy, although the levels of sTNFR p55 did not. The levels of sTNFR p75 were correlated with the serum levels of macrophage-colony stimulating factor both before and after IFN therapy. In the nonresponder group, the levels of both sTNFRs were unaltered after IFN therapy. CONCLUSIONS: The TNF alpha-TNFRs system, especially the TNFR p75-mediated pathway, is involved in the hepatic inflammation-fibrosis process in chronic hepatitis C. The serum levels of sTNFR p75, but not sTNFR p55, were correlated with the serum levels of macrophage colony stimulating factor in this process.

Adult↗

Decreased amplitude of left ventricular posterior wall motion with notch movement to determine the left posterior septal accessory pathway in Wolff-Parkinson-White syndrome.

OBJECTIVE: To determine preoperatively, by analysing asynchronous left ventricular wall motion, whether to approach through the right ventricle or the left ventricle when carrying out catheter ablation of the accessory pathway in Wolff-Parkinson-White syndrome, especially in patients with the pathway located on the septum. METHODS: 73 patients with manifest Wolff-Parkinson-White syndrome who underwent successful catheter ablation were studied. Location of accessory pathway was classified as right ventricular side: right anterior paraseptum, right anterior, right lateral, right posterior, anterior septum, midseptum, right posterior septum; left ventricular side: left posterior septum, left posterior, left lateral, left anterior. Asynchronous systolic wall motion was analysed by cross sectional echocardiography. RESULTS: Echocardiography showed that the amplitude of left ventricular posterior systolic wall motion was reduced when the pathway was located on the left ventricular side as opposed to the right ventricular side (mean (SD), 11.1 (1.7) v 12.9 (1.1) mm, p < 0.001), especially in patients with left posterior septal accessory pathway (9.7 (0.8) mm). There were no overlapping values between the left posterior septal accessory pathway and the right ventricular side accessory pathway. Posterior wall notch motion was observed in all patients with a left posterior septal accessory pathway (9/9), but not at all in patients with pathways located on the right ventricular side of the septum. In patients with a septal accessory pathway, an ECG algorithm provided poor information (relatively low sensitivity, specificity, and predictive value) for determining whether the subsite faced either the left (left posterior septum) or the right ventricle (anterior septum, midseptum, right posterior septum). CONCLUSIONS: Decreased amplitude of left ventricular posterior wall motion with notch movement is an important finding for accessory pathways located on the left posterior septum. These findings provided clinically useful information for determining whether to approach catheter ablation from the right or the left ventricle.

Adolescent↗

Clinical efficacy of oxybutynin on sensory urgency as compared with that on motor urgency.

OBJECTIVE: Anticholinergic drug is widely accepted as an effective medication for frequency, urgency and urge incontinence related to detrusor overactivity (motor urgency). In order to elucidate whether anticholinergic drug is also effective for these symptoms related to bladder hypersensitivity (sensory urgency), clinical efficacy of oxybutynin on sensory urgency was compared with that on motor urgency. METHOD: Twenty-four patients with sensory urgency, and 53 patients with motor urgency were treated with oxybutynin (6 mg/day) for 4 weeks and subjective and objective efficacies were evaluated. Subjective parameters were quantified with urge score (grade 0-3) and daily numbers of voiding and incontinence. Objective efficacies were evaluated with pre-/ postcomparison of cystometric parameters. RESULTS: Excellent or good overall efficacy was obtained in 62.5% (15/24) of the sensory urgency group and 60.4% (32/53) of the motor urgency group. There was no statistical difference between these two groups. Objective cystometric parameters, bladder volume at first sensation and maximum cystometric capacity, statistically improved after the treatment in both groups. CONCLUSION: The results suggest that oxybutynin works as well on sensory urgency as it does on motor urgency.

Aged↗

Studies on interactions between traditional herbal and Western medicines. I. Effects of Sho-seiryu-to on the pharmacokinetics of carbamazepine in rats.

The effects of oral co- and pre-administration of Sho-seiryu-to extract powder (TJ-19, 1 g/kg), a widely used Kampo (traditional Chinese herbal) medicine, on the pharmacokinetics of an anti-epileptic drug, carbamazepine (CBZ), and its active metabolite (carbamazepine-10,11-epoxide, CBZ-E) after oral administration of CBZ (50 mg/kg) were examined in male rats. The simultaneous administration of TJ-19 significantly lengthened the time to reach the peak plasma concentration (Tmax), but did not influence the peak plasma concentration, area under the plasma concentration-time curve or terminal elimination half-life (t1/2). Each parameter for CBZ or CBZ-E with a single pretreatment with TJ-19 was not significantly different from that with the vehicle. Tmax and the elimination rate constant for CBZ were significantly increased by 1-week repeated pretreatment with TJ-19, by 83% (p<0.01) and 88% (p<0.001), respectively. t1/2 and the mean residence time from zero to infinity (MRT0-infinity) in the TJ-19 pretreatment group were significantly shortened, by 52 and 34% (p<0.005), respectively. No significant difference in the bound fraction of each drug at two concentrations (1 and 10 microg/ml) was observed between the control and TJ-19 pretreatment groups. These results indicate that simultaneous oral administration of TJ-19 delays the oral absorption of CBZ, while 1-week repeated pretreatment with TJ-19 accelerates the metabolism of CBZ in rats, without affecting the protein binding of CBZ.

Analysis of Variance↗

Why is transurethral microwave thermotherapy (TUMT) positively effective?

Between 1992 and 1994, 157 patients with benign prostatic hyperplasia were treated with transurethral microwave thermotherapy (TUMT). In evaluating the efficacy of TUMT with the International PrOstate Symptom Score (I-PSS) in 121 patients, 18 (15%) showed excellent and 42 (35%) showed good response. In evaluation of QOL, the result was 43 patients (33%) excellent and 42 patients (35%) good response. In objective evaluation of uroflow in 93 patients, 12 (13%) showed excellent and 13 (14%) showed good response. The prostatic volume did not show a significant decrease after treatment. In terms of overall improvement, according to the criteria proposed at the 2nd International Consultation on BPH, the treatment was considered effective in 53 of 108 patients (48%). Histological examination of the prostate enucleated from a patient 7 months after TUMT revealed degenerative changes of nerve fibres on S-100 protein immunohistochemical staining, which were more extensive than those in smooth muscle cells on HE staining. In in vitro tests the isometric contraction force of the rabbit prostatic tissue was measured after exposure to different temperatures, ranging from 37 to 50 degrees C. No significant change was observed up to 45 degrees C vs. 37 degrees C. After exposure to 48 degrees C, the nerve mediated contractions became completely depressed, although phenylephrine or KCl induced contractions were only partially suppressed. After exposure to 50 degrees C, no contraction was induced by any type of stimuli. In conclusion, it is suggested that good symptomatic improvement after TUMT results from both neural and muscular damage to the prostate. As TUMT is not aiming at a relief of anatomical obstruction, 50 degrees C is thought to be a sufficient thermal condition to cause an irreversible damage to prostatic tissue, which will provide a relief from functional obstruction and urethral instability.

Aged↗

Gut bacterial translocation during total parenteral nutrition in experimental rats and its countermeasure.

BACKGROUND: The use of total parenteral nutrition (TPN) is commonly associated with mucosal lining of the intestinal tract, causing degenerative changes within the gut-associated lymphoid tissue (GALT). These phenomena are probably caused by the translocation of indigenous intestinal bacteria into other organs and tissues where they induce infections. METHODS: Using TPN model rats, this paper looks at the result of the investigation of the action of PSK (proteoglycan), a biological response modifier, which appears to suppress bacterial translocation and maintain local immunity activity. RESULTS: Culture of mesenteric lymph nodes obtained post-TPN demonstrate a bacterial rate as high as 60%. Immunohistochemical examination indicates a reduction in the number of plasma cells and a decrease in S-IgA production and secretion. A similar reduction in S-IgA within bile and portal venous blood was also confirmed. Continuous oral administration of PSK in a daily dose of 1,000 mg/kg had a protective effect against the degeneration of GALT. A staining in immunocytes of Peyer's patches using immunohistochemical study was performed after administration of PSK and revealed constant levels of MHC-I, MHC-II, T helper cells, and interleukin-2 producing cells, supporting the protective role of PSK against degeneration of GALT with a subsequent reduction in bacterial translocation. CONCLUSIONS: Proteoglycan can restore the impaired local immunity in the intestinal tract to normal levels and suppression of the bacterial translocation to provide an important function for patients receiving TPN treatment.

Administration, Oral↗

Design and evaluation of an osmotic pump tablet (OPT) for prednisolone, a poorly water soluble drug, using (SBE)7m-beta-CD.

PURPOSE: The purpose of this study was to develop a controlled-porosity osmotic pump tablet (OPT) for poorly water soluble drugs using a sulfobutyl ether-beta-cyclodextrin, (SBE)7m-beta-CD or Captisol, which acted as both a solubilizer and as an osmotic agent. METHODS: Prednisolone (PDL) was chosen as a model drug for this study. The release of PDL from osmotic pump devices and tablets was studied. In vivo absorption of PDL from OPT was evaluated in male beagle dogs. RESULTS: PDL release from the osmotic pump tablet with (SBE)7m-beta-CD was complete. Another cyclodextrin, hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and a sugar mixture of lactose and fructose resulted in incomplete release. Although PDL release from the OPT with (SBE)7m-beta-CD and the sugar formulation displayed mainly zero-order release characteristics, the tablet utilizing HP-beta-CD showed apparent first-order release characteristics. An in vivo absorption study in dogs correlated very well with the in vitro release profiles using the Japanese Pharmacopoeia dissolution method. CONCLUSIONS: The present results confirm that (SBE)7m-gamma-CD can serve as both the solubilizer and the osmotic agent for OPT of PDL, and modify the input rate of PDL without compromising oral bioavailability.

Absorption↗

Possibility of contribution of nucleoside transport systems to pirarubicin uptake by HL60 cells but not mononuclear cells.

Previously, we reported that pirarubicin (THP), an anthracycline, was taken up, at least in part, by both human leukemic HL60 cells and mononuclear cells (MNCs) via a carrier-mediated system. In this study, the possibility of a contribution of nucleoside transport systems to the uptake of THP by HL60 cells and MNCs was investigated. The experiments were performed after both types of cells had been pretreated with a metabolic inhibitor, 2,4-dinitrophenol, to deplete cellular ATP. In HL60 cells, THP uptake was increased and decreased significantly by treatment with equilibrative nucleoside transport inhibitors, nitrobenzylthioinosine (NBMPR), nitrobenzylthioguanosine and dilazep, in the presence and absence, respectively, of an inwardly directed Na+-gradient. THP uptake by HL60 cells showed an overshoot in the presence of the gradient, and was decreased by treatment of the cells with monensin, indicating that the uptake partially depended on the Na+-gradient. In HL60 cells in which equilibrative nucleoside transport was inhibited by NBMPR, THP uptake in the presence of the gradient was inhibited by Na+-dependent concentrative nucleoside transport inhibitors, but no inhibition was observed in the absence of the gradient. In MNCs, conversely, there was no effect of any equilibrative nucleoside transport inhibitor or the Na+-gradient on THP uptake. These results suggested that THP was taken up, at least in part, via both equilibrative and concentrative nucleoside transport systems in HL60 cells, but not in MNCs.

2,4-Dinitrophenol↗