Biomedical subjects

K Nakajima

Publications and source records attributed to K Nakajima.

At least 127 records · Page 7Linked to original sources

PubMed2001

Impaired glucose tolerance without hypertriglyceridemia does not enhance postprandial lipemia.

Postprandial lipemia has been thought to be one of risk factors for coronary heart disease, and enhances in potential patients for atherosclerotic disease. Patients with impaired glucose tolerance (IGT) often show hypertriglyceride, which is caused by enhanced portprandial lipemia. Therefore, postprandial lipemia in patients with IGT and without hypertriglyceridemia has not been cleared. We have examined the levels of plasma triglyceride and chylomicron remnants after a high fat meal load (1250 kcal, 40% fat and 420 mg cholesterol) in 13 normotriglyceridemic subjects with IGT and 10 controls with normal glucose tolerance (NGT). Chylomicron remnants were evaluated as remnant-like particles (RLP) that were not bound to an immunoaffinity gel mixture containing apo A-I and apo B-100 monoclonal antibody. RLP cholesterol levels 4 hours after the fat load were significantly lower in IGT subjects than in NGT subjects. Increase of RLP cholesterol after the fat meal load only significantly correlated with increase of insulin during the first 30 min after a 75 g oral glucose tolerance test, but not fasting lipid, insulinogenic index and HOMA-R (homeostasis model) in all subjects. These results suggest that postprandial response does not enhance in IGT subjects, and may associate with early-phase insulin secretion and without insulin resistance in normotriglyceridemic men with IGT or NGT.

Antibodies, Monoclonal↗

PubMed2001

Increased QT dispersion does not reflect the increased regional variation of cardiac sympathetic nervous activity in hypertrophic cardiomyopathy.

BACKGROUND: QT dispersion (QTD) reflects regional variation of ventricular repolarization. However, the relationship between QTD and the regional variation of cardiac sympathetic nerve activity in hypertrophic cardiomyopathy (HCM) is not yet elucidated. METHODS: Cardiac sympathetic nerve activity was evaluated in 25 patients with HCM by iodine 123 metaiodobenzylguanidine (MIBG) myocardial scintigraphy. With planar MIBG imaging, heart and mediastinum ratios (H/M) at early (20 minutes) and delayed (3 hours) acquisition and the washout rate (WR) were calculated. Polar maps of left ventricular myocardium were divided into 20 segments. The SD of early uptake (EU-SD), delayed uptake (DU-SD), and WR (WR-SD) in 20 segments as indices of regional variation were calculated. QT intervals were corrected by use of the Bazett formula. RESULTS: Maximum QTc correlated positively with H/M early, WR, and left ventricular wall thickness (LVWT). Minimum QTc correlated positively with WR and LVWT. Corrected QTD (QTDc) correlated negatively with EU-SD, DU-SD, and WR-SD and positively with the interventricular septal thickness/posterior wall thickness ratio. Stepwise regression analysis revealed that the most powerful determinants for maximum QTc, minimum QTc, and QTDc were WR, LVWT, and EU-SD, respectively. CONCLUSIONS: QTD correlated negatively rather than positively with the regional variability index of cardiac sympathetic nerve activity. These results suggest that increased QTD in patients with HCM may not reflect increased heterogeneity of cardiac sympathetic nerve activity.

Arrhythmias, Cardiac↗

PubMed2001

Monitoring of p53 autoantibodies after resection of colorectal cancer: relationship to operative curability.

OBJECTIVE: To investigate the clinical use of p53 autoantibodies as a marker in the postoperative monitoring of colorectal cancer. DESIGN: Retrospective study. SETTING: Teaching hospital, Japan. SUBJECTS: 40 patients with colorectal cancer who had p53 autoantibodies in their serum preoperatively. INTERVENTIONS: Serial assay of p53 autoantibodies by ELISA before and after resection. MAIN OUTCOME MEASURES: Interpretation by a qualitative analysis. RESULTS: A significant correlation was observed between curability by surgical resection and postoperative disappearance of p53 autoantibodies. Twenty-seven (96%) of 28 patients, who had p53 autoantibodies and whose cancer was completely removed, had no such antibodies after resection and no recurrence after 7 to 26 months. CONCLUSIONS: Postoperative assays of p53 autoantibodies are potentially useful for predicting recurrence of colorectal cancer in patients who have p53 autoantibodies preoperatively.

Colorectal Neoplasms↗

PubMed2001

Amiodarone stimulates interleukin-6 production in cultured human thyrocytes, exerting cytotoxic effects on thyroid follicles in suspension culture.

To investigate whether amiodarone increases interleukin-6 (IL-6) production in thyrocytes, human follicles obtained from subtotally thyroidectomized patients with Graves' disease were cultured in serum-free medium supplemented with various concentrations of bovine thyrotropin (bTSH) and amiodarone. The follicles gradually formed monolayer cells and secreted triiodothyronine (T3), thyroglobulin (Tg), and IL-6 for at least 14 days. TSH dose-dependently increased T3 and Tg but not IL-6 levels in the conditioned medium. Amiodarone exerted no significant effect on T3, Tg, or IL-6 concentrations at 0.1-1 microM. In contrast, at 10-20 microM, it decreased T3 and Tg, but increased IL-6 levels, and these changes were accompanied by increased expression of IL-6 mRNA. Amiodarone-induced IL-6 production was inhibited by prednisolone at 10(-7) M. Electron microscopic examination revealed that the thyroid follicles in the suspension culture remained intact at 1 microM, but that cytotoxic effects (decreased microvilli and increased onion-like inclusion bodies) occurred at higher concentrations (10-25 microM). These in vitro findings indicate that amiodarone does not impair thyroid function at clinically attainable serum levels (1 microM), but exerts cytotoxic effect by inducing the production of a proinflammatory cytokine (IL-6) at higher concentrations. Because amiodarone-induced IL-6 production was inhibited by prednisolone, it is reasonable to administer glucocorticoids to patients with amiodarone-induced destructive thyrotoxicosis (type II).

Amiodarone↗

PubMed2001

Microglia: activation and their significance in the central nervous system.

Microglia are resident monocyte-lineaged cells in the brain. Their characteristic feature is that they react to injury and diseases of the brain and become morphologically and functionally activated. Although some trigger molecules which activate microglia are predicted to be released from injured or affected cells, such molecules have not yet been identified. The main role of activated microglia is believed to be in brain defense, as scavengers of dead cells, and as immune or immunoeffector cells. Recent biochemical and neurobiological studies have further indicated that they significantly affect the pathological state and/or regulate the regenerative state and remodeling of the brain by producing a variety of biologically active molecules including cytotoxic and neurotrophic molecules.

Brain↗

PubMed2001

Neutralization of fibroblast growth factor-2 reduces intraarticular adhesions.

Adhesion is a serious complication after trauma or surgery. Because adhesion formation is essentially a fibrogenetic process, a series of growth factors are assumed to be involved in its development. If this is true, it may be possible that inhibition of the growth factor activity suppresses adhesion formation. The current study was conducted to verify this hypothesis on fibroblast growth factor-2 using an intraarticular adhesion model in the rabbit knee. Forty Japanese White rabbits were used. They were divided randomly into five groups of eight animals, and in three of them, activity of endogenous fibroblast growth factor-2 was suppressed locally by a neutralizing antibody. The remaining two groups served as controls, and formation of adhesions was evaluated 4 weeks after surgery. The results showed that the administration of the antibody reduced the extent of adhesions macroscopically, whereas histologic observation and collagen content measurement suggested the adhesion tissue was not affected significantly. Corresponding to the macroscopic findings, contraction of the knee was improved in the antibody groups. The findings showed that suppression of fibroblast growth factor-2 activity reduces adhesions. It is expected that control of the cytokine activity may become a novel method for reducing adhesions.

Animals↗

PubMed2001

Tumor necrosis factor-alpha gene mutations and genotype changes in renal cell carcinoma.

PURPOSE: We tested the hypothesis that genotype changes in the promoter region of tumor necrosis factor-alpha and exon 1 are associated with renal cell carcinoma. MATERIALS AND METHODS: We analyzed genotypic changes at the 3 polymorphic loci of tumor necrosis factor-alpha -238, -308 and 488 using tumor and normal tissues from 81 Japanese patients with renal cell carcinoma. RESULTS: Of the 81 patients 14 (17%) had point mutations from G to A, including 8 (57%) with point mutations at multiple loci. Six of the 8 patients (75%) with point mutations at multiple loci were classified with stage 4 renal cell carcinoma. Of the 81 patients 14 were classified with stage 4 carcinoma, including 9 (64%) with point mutation from G to A. Normal tissue from cancer patients showed an increased frequency of the GA genotype at loci -238 and 488 compared to healthy controls (37% versus 9% and 30% versus 12%, respectively). The relative risk of renal cell carcinoma was 6.5-fold higher in patients with the GA genotype at locus -238 (p <0.001) and 2.9-fold higher in those with the GA genotype at locus 488 (0.01 < p <0.025) when comparing normal tissue from renal cell carcinoma patients with that of healthy controls. CONCLUSIONS: Point mutation from G to A, and the GA genotype at loci -238 and 488 of the TNF-alpha gene were common in patients with advanced renal cell carcinoma. The genotype change at loci -238 and 488 of the TNF-alpha gene are associated with renal cancer pathogenesis.

Adult↗

PubMed2001

Pseudomonas alcaliphila sp. nov., a novel facultatively psychrophilic alkaliphile isolated from seawater.

Facultatively psychrophilic alkaliphilic strains were isolated from seawater obtained off the coast of Rumoi, Hokkaido, Japan. They were Gram-negative, aerobic straight rods with polar flagella. The isolates were catalase- and oxidase-positive and able to grow at 4 degrees C, but not at 40 degrees C. They produced acid from D-glucose under aerobic conditions. The isolates reduced nitrate to nitrite and hydrolysed casein and gelatin, but not starch or DNA. NaCl was required for growth at pH 10 but was not required at neutral pH. The major isoprenoid quinone was ubiquinone-9 (Q-9) and the DNA G+C content was 62.3-63.2 mol%. The whole-cell fatty acids mainly consisted of C16:0, C16:1(9c) and C18:1(9c), with 3-OH C10:0 and 3-OH C12:0 as the hydroxyl fatty acids. A larger amount of trans-unsaturated fatty acid, C16:1(9t) was observed when the cells were grown at pH 7 compared to when cells were grown at pH 10. Phylogenetic analysis based on 16S rRNA gene sequencing indicated that the bacteria are members of the genus Pseudomonas. Analysis of DNA-DNA relatedness data with several close phylogenetic neighbours revealed a low level of hybridization (less than 61%). On the basis of phenotypic characteristics, phylogenetic analysis and DNA-DNA relatedness data, it is concluded that these isolates represent a separate new species. Accordingly, the name Pseudomonas alcaliphila is proposed. The type strain is AL15-21T (= JCM 10630T = IAM 14884T).

Alkalies↗

PubMed2001

Remnant lipoproteins and atherogenesis.

Remnant lipoproteins are reported to play a causative role in atherogenesis. They consist of chylomicron remnants and very low-density lipoprotein remnants. They are heterogeneous in composition and metabolic pathway and are rapidly taken up from the circulation as soon as they are formed in normal lipid metabolism. These characteristics make it difficult to separate and subsequently analyze remnant lipoproteins. Recently, however, we developed a simple and reliable immunoseparation method to separate remnant lipoproteins, and the cellular mechanism(s) by which they contribute to atherogenesis have been elucidated.

Arteriosclerosis↗

PubMed2001

Tissue-specific autoregulation of the stat3 gene and its role in interleukin-6-induced survival signals in T cells.

Signal transducer and activator of transcription 3 (STAT3) mediates signals of various growth factors and cytokines, including interleukin-6 (IL-6). In certain IL-6-responsive cell lines, the stat3 gene is autoregulated by STAT3 through a composite IL-6 response element in its promoter that contains a STAT3-binding element (SBE) and a cyclic AMP-responsive element. To reveal the nature and roles of the stat3 autoregulation in vivo, we generated mice that harbor a mutation in the SBE (stat3(mSBE)). The intact SBE was crucial for IL-6-induced stat3 gene activation in the spleen, especially in the red pulp region, the kidney, and both mature and immature T lymphocytes. The SBE was not required, however, for IL-6-induced stat3 gene activation in hepatocytes. T lymphocytes from the stat3(mSBE/mSBE) mice were more susceptible to apoptosis despite the presence of IL-6 than those from wild-type mice. Consistent with this, IL-6-dependent activation of the Pim-1 and junB genes, direct target genes for STAT3, was attenuated in T lymphocytes of the stat3(mSBE/mSBE) mice. Thus, the tissue-specific autoregulation of the stat3 gene operates in vivo and plays a role in IL-6-induced antiapoptotic signaling in T cells.

Animals↗

PubMed2001

Differential effects of growth hormone and insulin-like growth factor I on human endothelial cell migration.

Effects of growth hormone (GH), insulin-like growth factor I (IGF-I), and endothelin-1 (ET-1) on endothelial cell migration and the underlying molecular mechanisms were explored using a human umbilical cord endothelial cell line, ECV304 cells, in vitro. Treatment of the cells with IGF-I or ET-1, but not GH, stimulated the cell migration. Interestingly, however, ET-1-induced, but not IGF-I-induced, migration of the cells was inhibited by GH. Both ET-1 and IGF-I caused activation of mitogen-activated protein kinase (MAPK) in the cells, and GH eliminated the MAPK activation produced by ET-1 but not that produced by IGF-I. On the other hand, migration of the cells was stimulated by protein kinase C (PKC) agonist, phorbol 12-myristate 13-acetate. ET-1 promoted PKC activity, and a PKC inhibitor, GF-109203X, blocked ET-1-induced cell migration. Although GH inhibited ET-1-induced cell migration and MAPK activity, it did not block ET-1-induced PKC activation. Thus ET-1 stimulation of endothelial cell migration appears to be mediated by PKC/MAPK pathway, and GH may inhibit the MAPK activation by ET-1 at the downstream of PKC.

Cell Line↗

PubMed2001

Investigation into non-monosynaptic corticospinal excitation of macaque upper limb single motor units.

There has been considerable recent debate as to relative importance, in the primate, of propriospinal transmission of corticospinal excitation to upper limb motoneurons. Previous studies in the anesthetized macaque monkey suggested that, compared with the cat, the transmission of such excitation via a system of C3-C4 propriospinal neurons may be relatively weak. However, it is possible that in the anesthetized preparation, propriospinal transmission of cortical inputs to motoneurons may be depressed. To address this issue, the current study investigated the responses of single motor units (SMUs) to corticospinal inputs in either awake (n = 1) or lightly sedated (n = 3) macaque monkeys. Recordings in the awake state were made during performance of a precision grip task. The responses of spontaneously discharging SMUs to electrical stimulation of the pyramidal tract (PT) via chronically implanted electrodes were examined for evidence of non-monosynaptic, presumed propriospinal, effects. Single PT stimuli (up to 250 microA; duration, 0.2 ms, 2 Hz) were delivered during steady discharge of the SMU (10-30 imp/s). SMUs were recorded from muscles acting on the thumb (adductor pollicis and abductor pollicis brevis, n = 18), wrist (extensor carpi radialis, n = 29) and elbow (biceps, n = 9). In all SMUs, the poststimulus time histograms to PT stimulation consisted of a single peak at a fixed latency and with a brief duration [0.74 +/- 0.25 (SD) ms, n = 56], consistent with the responses being mediated by monosynaptic action of cortico-motoneuronal (CM) impulses. Later peaks, indicating non-monosynaptic action, were not present even when the probability of the initial peak response was low and when there was no evidence for suppression of ongoing SMU activity following this peak (n = 20 SMUs). Even when repetitive (double-pulse) PT stimuli were used to facilitate transmission through oligosynaptic linkages, no later peaks were observed (16 SMUs). In some thumb muscle SMUs (n = 8), responses to PT stimulation were compared with those evoked by transcranial magnetic stimulation, using a figure-eight coil held over the motor cortex. Responses varied according the orientation of the coil: in the latero-medial position, single peak responses similar to those from the PT were obtained; their latencies confirmed direct excitation of CM cells, and there were no later peaks. In the posterio-anterior orientation, responses had longer latencies and consisted of two to three subpeaks. At least under the conditions that we have tested, the results provide no positive evidence for transmission of cortical excitation to upper limb motoneurons by non-monosynaptic pathways in the macaque monkey.

Anesthesia↗

PubMed2001

Nitric oxide synthase gene and protein expression are upregulated by Bacille Calmette-Guérin in the rat bladder.

OBJECTIVE: We hypothesize that Bacille Calmette-Guérin (BCG) may act through the regulation of various isoforms of nitric oxide synthase (NOS) [inducible (iNOS), endothelial (eNOS), and neuronal (nNOS)] genes and protein expression in rat bladder. METHODS: Adult female Sprague-Dawley rats (200-250 g) were injected transurethrally with BCG (22 rats) and phosphate-buffered saline (22 control rats), and after 2, 4, 6, and 12 h, and 1, 2, 3, 5, 7, 10, and 14 days, the bladders were harvested. Normal and BCG-treated rat bladders were analyzed for mRNA expression for iNOS, eNOS, and nNOS by reverse-transcriptase polymerase chain reaction. Protein expression was determined by Western blotting and immunohistochemistry. RESULTS: mRNA expression for iNOS was induced after 2 h of BCG injection in the rat bladder. Gene expression for iNOS was highest at 6 h to 1 day followed by decreased expression, reaching its lowest level at 5 days. eNOS mRNA expression was detected in control bladders, but its level was higher in the BCG-treated animals. nNOS mRNA expression was present in all samples, but did not change after BCG treatment. Western blotting confirmed these findings. Immunohistochemistry analysis demonstrated that eNOS was present mainly in endothelium, while iNOS was detected in stroma and nNOS in epithelium and smooth muscle of the rat bladder. CONCLUSION: The present study demonstrates, for the first time, that BCG treatment up-regulates gene and protein expression of iNOS and eNOS in normal rat bladders, suggesting that BCG action may be mediated through NOS pathways.

Animals↗

PubMed2001

Changes in plasma triglyceride levels shift lipoprotein(a) density in parallel with that of LDL independently of apolipoprotein(a) size.

Lipoprotein(a) [Lp(a)] represents a class of low density lipoprotein (LDL) particles that have as a protein moiety apolipoprotein B-100-linked covalently to a single molecule of apolipoprotein(a) [apo(a)], a specific multikringle protein of the plasminogen family. Lp(a) is polymorphic in density because of either the density heterogeneity of constitutive LDL, apo(a) size, or both. Authentic LDL also represents a set of heterogeneous particles whose density is affected by metabolic events. Whether in vivo these events may also affect Lp(a) density is not clearly established. To this effect, we studied 75 subjects with plasma Lp(a) protein levels between 7 and 50 mg/dL and containing a single apo(a) size isoform. We used density gradient ultracentrifugation to simultaneously monitor the changes in the peak density of LDL and Lp(a) at entry and during the course of treatments directed at reducing plasma triglyceride levels. In each case, we found that at entry, Lp(a) peak density was correlated with LDL peak density (r=0.71, P<0.0001) and that during treatment, changes in plasma triglycerides were associated with shifts of Lp(a) peak density that paralleled those of LDL peak density. A high correlation (r=0.94, P<0.0001) was particularly evident in subjects with initial plasma triglycerides in the 300-mg/dL range. In vitro assembly studies showed that an apo(a) isoform containing 14 kringle IV type 2 repeats, exhibited, on incubation with LDL, a comparable degree of incorporation into LDL species varying in density between 1.035 and 1.057 g/mL Taken together, our results indicate that metabolically dependent changes in the peak density of Lp(a) can occur independently of apo(a) size. These changes may have to be taken into account in assessing the cardiovascular pathogenicity of this lipoprotein particle in hypertriglyceridemic subjects.

Apolipoproteins A↗

PubMed2001

Somatic mutations of the MEN1 gene and microsatellite instability in a case of tertiary hyperparathyroidism occurring during high phosphate therapy for acquired, hypophosphatemic osteomalacia.

Somatic mutations of the MEN type 1 (MEN1) gene were recently shown to be responsible for tumorigenesis in 13-26% of sporadic, nonfamilial primary hyperparathyroidism. However, it is unknown whether these mutations are also involved in tumorigenesis of parathyroid glands occurring during high phosphate therapy for hypophosphatemic rickets or osteomalacia. A male patient with adult-onset, hypophosphatemic osteomalacia had been treated with 1alpha-OHD3 and oral phosphate for 13 yr when tertiary hyperparathyroidism developed. After total resection of four enlarged parathyroid glands and autotransplantation of a hyperplastic gland, the patient has continued to do well for the last 2 yr. Sequence analysis of the coding exons of MEN1 gene revealed a 36-bp deletion with a 2-bp insertion (exon 2) in the right upper parathyroid gland accompanied with loss of heterozygosity at 11q13 locus and a heterozygous mutation of 2-bp deletion (AG) in exon 10 in the right lower gland, in which microsatellite instability was also found. No MEN1 gene mutation was detected in the other two hyperplastic parathyroid glands or in the peripheral blood. These findings indicate that MEN1 gene mutations contributed to tumorigenesis of the right upper parathyroid gland in this case of phosphate-induced tertiary hyperparathyroidism. Very recently a bone tumor was found in the right femoral neck, and the tumor (chondroblastoma) was resected.

Adult↗

PubMed2001

Postprandial remnant-like lipoproteins in hypertriglyceridemia.

It has been proposed that remnants of chylomicrons and very-low-density lipoproteins (VLDL) are atherogenic. We have used an immunochemical method to isolate remnant-like particles (RLP) and measured them in terms of their cholesterol and triglycerides (TG). RLP consist of apoB-48-containing triglyceride-rich lipoproteins and remnant-like VLDL containing apoB-100. The study aim was to look for information from postprandial RLP data that could not be known from other markers of triglyceride-rich lipoproteins and fasting TG and RLP data alone. A total of 41 subjects were studied. Eight subjects had hypertriglyceridemia (HTG) and low high-density lipoprotein (HDL), 14 had combined hyperlipidemia (CH), 5 had the apo E2/2 genotype receiving gemfibrozil, 10 were normolipidemic (NL) controls, and 4 had hypercholesterolemia. As a whole group, there was correlation among 1) fasting TG, RLP cholesterol (RLP-C), and RLP-TG but not VLDL apo B100, VLDL apo B48 and their respective postprandial responses measured as incremental area under the curve (IAUC), 2) fasting TG and postprandial IAUC of RLP-C and RLP-TG, 3) RLP-C IAUC, RLP-TG IAUC, and TG IAUC, retinyl palmitate (RP) IAUC, and VLDL apo B48 IAUC but not VLDL apo B100 IAUC. The HTG/low HDL-C and CH groups had higher IAUC for RLP-C, RLP-TG, TG, and RP than the NL group. Fasting and postprandial RLP were triglyceride enriched in the HTG/low HDL-C group and to a lesser extent in the CH group. The HTG/low HDL-C and CH groups had a delay in their RLP-C but not RLP-TG peaks suggesting a delay in hepatic clearance of RLP and/or a protracted period of lipolysis and/or processing of RLP. The fasting and postprandial RLP-C/RLP-TG and RLP-C/TG ratios were elevated in the apo E2/2 group in spite of gemfibrozil therapy. The increment in postprandial RLP was, however, not exaggerated. Our data indicate that 1) postprandial RLP lipemia is enhanced in HTG subjects when compared with NL subjects, 2) postprandial RLP lipemia is proportional to fasting RLP and TG levels and mirrors, to a large extent, increases in postprandial TG, RP, and VLDL apo B48 but not VLDL apo B100, 3) there are compositional differences in fasting and postprandial RLP in the three forms of HTG studied, RLP being triglyceride enriched in the HTG/low HDL-C group and to a lesser extent in the CH group, and cholesterol-enriched in the apo E2/2 group, and 4) apo E2/2 subjects had high fasting and postprandial RLP-C concentrations in spite of being on treatment with gemfibrozil and having normal fasting and postprandial TG concentrations.

Apolipoprotein B-100↗

PubMed2001

[Pharmaceutical investigation of vancomycin hydrochloride eye drops and their topical application to MRSA eye infection].

Two formulations of 0.5% vancomycin hydrochloride (VM) eye drops (VM-B and VM-C eye drops) were prepared by dissolving commercial VM powder for injection with preserved water B (PWB) containing phosphate buffer and preserved water C (PWC) containing only antimicrobial preservative, respectively. The VM-B eye drops have neutral pH (about 6.3), and the VM-C eye drops acidic pH of about 3.5. The pharmaceutical examination of these eye drops was performed regarding its clinical application to MRSA eye infection. In an irritability test using a rabbit's eye, the average number of winks after instillation of one drop of VM-B eye drops was 0.8 times/min and significantly smaller than that of VM-C eye drops (2.0 times/min). In dark storage at 4 degrees C, no change of VM concentration in both eye drops was observed for 25 weeks after preparation and the mean residual concentrations as determined by the HPLC-UV (240 nm) method were constant over 90% for 8 weeks, of the initial concentration. However, the residual VM concentration of VM-B eye drops under a room condition declined to 58% after 4 weeks and 20% after 8 weeks, and VM in light storage at 40 degrees C was not detectable after 8 weeks. The drug concentration of VM-C eye drops declined to 83% after 4 weeks and 74% after 8 weeks under a room condition, and to 46% after 4 weeks and 20% after 8 weeks under light storage at 40 degrees C. Under these storage conditions, the precipitation of VM related crystals was observed in both the eye drops when the residual percentage of VM was lower than 80%. Judging from HPLC chromatograms of a solution of the precipitated crystals, it was suggested that this crystal was degradation products of VM. The VM-B eye drops was applied to a patient with MRSA eye infection, because other medication was not effective. After continuous instillation of a drop per times every hour to both eyes, MRSA in corneal culture turned out negative after one week, and the clinical condition was remarkably improved. On the basis of the result of eye-irritability, VM-B eye drops with neutral pH was suggested to be superior to acidic VM-C eye drops from a safety point of view. It was also indicated that VM-B eye drops can be effectively used for 8 weeks under dark storage at 4 degrees C for MRSA eye infection, which is a useful piece information for the proper usage of the VM eye drops.

Aged↗

PubMed2001

Effects of nipradilol, a nitric oxide-releasing beta-adrenoceptor blocking agent, on phosphoenolpyruvate carboxykinase gene transcription in a rat hepatoma cell line.

Effects of nipradilol, a beta-adrenoceptor blocker with a nitroxy moiety, on phosphoenolpyruvate carboxykinase (PEPCK) gene transcription were examined using a rat hepatoma cell line, H4IIE cells. Dexamethasone was employed as an enhancer of PEPCK gene transcription. Nipradilol, but not timolol (a beta-blocker without a nitroxy moiety), attenuated PEPCK gene transcription both in the control and the dexamethasone-treated cells. The effects of nipradilol were eradicated by methylene blue (an inhibitor of cellular guanylate cyclase). Nipradilol is a unique beta-blocker that suppresses PEPCK gene transcription in hepatocytes likely through liberation of nitric oxide and resultant activation of guanylate cyclase.

Adrenergic beta-Antagonists↗