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Biomedical subjects

H Masuda

Publications and source records attributed to H Masuda.

At least 253 records · Page 14Linked to original sources

Studies on the preparation of bioactive lignans by oxidative coupling reaction. IV. Oxidative coupling reaction of methyl (E)-3-(3,4-dihydroxy-2-methoxyphenyl)propenoate and lipid peroxidation inhibitory effects of the produced lignans.

The oxidative coupling reaction of the hydroxycinnamate 11 derived from daphnetin has been investigated. The reaction with silver oxide afforded, after acetylation, a dihydrobenzofuran derivative 17 and a benzodioxane derivative 16a as major products accompanied with a small amount of a bis(benzylidene)succinate 18 and a dihydronaphthalene 19, while the oxidation with iron(III) chloride gave the dihydronaphthalene derivative 20 corresponding to 19. The reaction with potassium hexacyanoferrate(III) and Na2CO3 produced, after acetylation, 16a and 19 in lower yields. The propensity for product formation in the reaction of 11 is discussed in relation to data for the reactions of hydroxycinnamate derivatives studied so far. The obtained compounds were tested for inhibitory effects on lipid peroxidation in rat brain homogenate and rat liver microsomes. In the rat brain homogenate the five compounds showed inhibitory activity more potent than that of idebenone. Compounds 17 and 20 were then tested in rat liver microsomes, and found to be more potent than schizotenuin A and much more potent than (+/-)-alpha-tocopherol.

Animals↗

Studies on the preparation of bioactive lignans by oxidative coupling reaction. V. Oxidative coupling reaction of methyl (E)-3-(2-hydroxyphenyl)propenoate derivatives and lipid peroxidation inhibitory effects of the produced lignans.

The oxidative coupling reactions of 2-hydroxycinnamates were investigated as a continuation of our previous studies on 4-hydroxy derivatives. The reaction of 2-hydroxycinnamate 1 and 2-hydroxy-4-methoxycinnamate 3 with silver oxide afforded polymerized lignin-like products, while that of 2-hydroxy-bis(methoxymethoxy)cinnamates 5 and 6, after acetylation, gave the enol acetates, 8 and 14, of oxotetrahydrobenzoxanthene derivatives, respectively. These two products were also obtained by the oxidation of 5 and 6 with potassium hexacyanoferrate(III). In the reactions of 5 and 6 with iron(III) chloride, the major products were the partially demethoxymethoxylated compounds 9 and 15, respectively. Thus, the course of the reactions in the oxidation of 2-hydroxycinnamates is quite different from that in the case of 4-hydroxy derivatives. The product 8 and the corresponding oxotetrahydrobenzoxanthene derivative were found to show moderate inhibitory effects upon lipid peroxidation.

Animals↗

Male reproductive toxicity study of nitrazepam in rats.

The main focus of this study is the optimal administration period concerning toxic effects on male fertility in rats. To assess functional and morphological changes induced in the testis by nitrazepam, male rats were administered the drug at doses of 0, 20, 40 or 80 mg/kg during pre-mating periods of 2, 4 or 9 weeks and then the 2 weeks of mating. At the end of the administration period the animals were sacrificed and sperm number, motility, abnormalities and histopathological changes in the testis were examined. Decreases in testis weight, epididymis weight, number of sperm in the testis and sperm motility were observed in the 40 and 80 mg/kg sections of the 2, 4 and 9 week pre-mating treated groups. Mating with untreated females revealed no adverse effects on copulation rate in any group; however, a remarkable decrease in pregnancy rate was noted in the 80 mg/kg section of the 2, 4 and 9 week treated groups. On histological examination, various degrees of localized necrosis in the seminiferous epithelium and Leydig cell hyperplasia were observed in the testis. No clear changes were observed in the 20 mg/kg section of the 2 week pre-mating administration group, but at the 4 week time point, necrosis of spermatogenic cells began to appear. The primary morphological event was evident in spermatocytes with necrosis of the cytoplasm observed from 4 weeks after administration of nitrazepam, although sperm motility and sperm head counts were unaffected. From these findings, examination of sperm characteristics and histopathological changes in the testis are important parameters for evaluation of drugs inducing testicular damage. We conclude that a 4 week administration period is sufficient to detect effects of nitrazepam on male fertility.

Animals↗

Influence on HMG-COA reductase inhibitors on plaque-forming cell (PFC) response in mice.

Effects of pravastatin and simvastatin on the humoral immune response were studied using Cunningham's method of the IgM plaque-forming cell (PFC) assay system in mice. The vehicle (0.5% CMC), pravastatin (1 mg/body : about 50 mg/kg) or simvastatin (0.5 mg/body : about 25 mg/kg) were given orally for 14 days in experiment Exp-I and Exp-II. The vehicle, pravastatin (0.5 mg/body : about 25 mg/kg) or simvastatin (0.25 mg/body : about 12.5 mg/kg) were given orally 29 times for 32 days in Exp-III. There were no significant differences in the mean numbers of PFCs per 10(6) splenocytes between the pravastatin groups and the vehicle groups. In the simvastatin groups, however, there were significant reductions of the numbers of PFCs in Exp-I, Exp-II and Exp-III, as compared with the vehicle group. Based on these results, it was considered that suppressive effect on IgM antibody production was induced by simvastatin, whereas such a suppression was not observed with pravastatin.

Animals↗

[An analysis of familial prostate cancer].

BACKGROUND: Clinical and pathological features of familial prostate cancer patients were examined. METHODS: We compared 7 pairs (14 patients) of familial prostate cancer patients (Group F) with those of 1741 prostate cancer patients diagnosed in around Gunma Prefecture between 1987 and 1993 (Group G). Relative survival rates were compared because the average age was different in two groups. RESULTS: In Group F and Group G, age at diagnosis ranged from 54 to 86 and 47 to 97 years old, and the averages were 68.1 +/- 8.5 (S.D.) and 74.2 +/- 8.3, respectively. The average age tended to be younger in Group F. The ratio of early stage cancer tended to be higher and that of poorly differentiated cancer tended to be lower in Group F. The 3- and 5-year relative survival rate was 82.4% and 57.6% in Group F, and 84.3% and 73.9% in Group G, respectively. The 5-year survival rate tended to be lower in Group F, but almost no difference was observed between two groups on the whole. In Group F, of 6 patients whose causes of death were clear, 4 (66.7%) died of prostate cancer, while in Group G, of 398 patients whose causes of death were elaar, 224 (56.3%) died of prostate cancer. Family history of other cancer sites was positive in 3 of 6 families in Group F. CONCLUSIONS: Familial prostate cancer patients tended to be young, in early stage and low ratio of poorly differentiated cancer.

Aged↗

[The experimental evaluation of the difference in closing dynamics of internal urethral ostium on the urinary continence and on the ejaculation induced by an administration of phenylephrine].

BACKGROUND: The internal urethral ostium is usually closed both on the ejaculation and on the urine collection, although the difference of the closing characteristics have not been known. METHODS: The difference in closing style of bladder neck (internal urethral ostium) between on the phenylephrine administration corresponding state to the ejaculation and on the filling of urinary bladder corresponding state to the urinary continence was evaluated by Stereo-UPP method using mongrel dogs. RESULTS: On phenylephrine administration, the length between verumontanum and bladder neck was lengthened, and a remarkable pressure increase was observed in the area. On the urinary continence filling physiological saline in the bladder, the length of the urethra on the UPP curve of the anterior wall of urethra was lengthened (10%) and the base of bladder was gradually become flat. The pressure in the bladder neck was not relatively increased. CONCLUSIONS: The internal urethral ostium was closed both on the phenylephrine administration and on the urine collection, although the closing characteristics of each was very different. It was demonstrated that on the phenylephrine administration the area between the verumontanum and the bladder neck was lengthened, together with the rise of pressure in the area, whereas on the urine collection bladder neck was closed in low pressure by flattening the base of bladder.

Adrenergic alpha-Agonists↗

Disposition characteristics of recombinant human interleukin-11 after a bolus intravenous administration in mice.

The pharmacokinetics and disposition characteristics of recombinant human interleukin-11 (rhIL-11) after systemic administration of 10 to 1000 micrograms/kg was investigated in mice. After a bolus i.v. injection of 100 micrograms/kg of 111In-labeled rhIL-11, radioactivity disappeared rapidly from the circulation after a biexponential function. Plasma clearance profiles based on immunoreactivity and biological activity were identical to the disappearance pattern of radioactivity in the early phase after injection. In the range of 10 to 100 micrograms/kg, pharmacokinetic parameter estimates such as the T1/2 alpha and total body clearance were almost constant, suggesting that pharmacokinetics of rhIL-11 were linear within this dose range. 111In-labeled rhIL-11 distributed mainly to the kidney and liver; within 10 min, 40 and 20% of the dose, respectively, accumulated. On the other hand, the urinary excretion ratio was very small (ca., 1% of the dose), suggesting that rhIL-11 was cleared rapidly by glomeruler filtration followed by efficient tubular reabsorption. Pharmacokinetic analysis of the tissue distribution data demonstrated large kidney and hepatic uptake clearances. At the highest dose (1000 micrograms/kg), total body clearance significantly decreased, due primarily to saturation of hepatic uptake. These findings will provide useful information for the development of rhIL-11.

Animals↗

Gasless laparoscopy-assisted nephrectomy without tissue morcellation for renal carcinoma.

PURPOSE: The efficacy of gasless laparoscopy-assisted nephrectomy for renal tumors is determined. MATERIALS AND METHODS: Seven patients with renal tumors underwent gasless laparoscopy-assisted nephrectomy. The results were compared to those of patients undergoing open nephrectomy. RESULTS: Although a long operating time was required, convalescence was significantly more rapid. En bloc removal of the kidney and complete pathological examination were possible in all patients. CONCLUSIONS: This procedure may be useful for the treatment of noninvasive renal carcinoma, especially in patients with cardiovascular and/or ventilatory complications. However, long-term followup is necessary to confirm the efficacy in preventing recurrence.

Adult↗

[Complete remission of prostate cancer after LH-RH agonist neoadjuvant therapy: a case report].

We report a case of prostate cancer showing a complete remission after LH-RH agonist neoadjuvant therapy. A 69-year-old man was referred to our department complaining of pain on urination and urge incontinence. The serum prostate specific antigen (PSA) level was 41.6 ng/ml. Needle biopsy specimens from both lobes revealed moderately differentiated adenocarcinoma. Chest X-ray, computed tomographic (CT) scan, and bone scintigraphy demonstrated neither distant metastasis nor local invasion. LH-RH agonist was administered on a monthly basis as neoadjuvant therapy. After 4 injections, pelvic lymph node dissection and radical prostatectomy were performed on January 11, 1993. Thorough examination did not reveal any cancer cells in the removed specimen. The patient was discharged 30 days after the operation and has shown no evidence of distant metastasis or local recurrence as long as 19 months later.

Adenocarcinoma↗

[Valvular surgery for the patients 70 years old or older].

From January 1986 to June 1993, twenty one patients aged 70 years or older with valvular heart disease underwent open heart surgery. There were 12 males and 9 females with a mean age of 71.2 years (range 70 to 76). Eight patients were in NYHA class III, and 4 in class IV preoperatively. AVR was performed in 10 patients, MVR, MVR with TAP, OMC, AVR with MAP, DVR with TAP in 4, 4, 1, 1, and 1, respectively. Mechanical and bioprosthetic valves were replaced in 11, and 9 patients respectively. There were 6 early death (4 operative, 2 hospital). Longer duration of cardiopulmonary bypass (p < 0.05) and aortic crossclamp time (p < 0.05) were the risk factors independently for early mortality. Follow-up of 15 hospital survivors was 100% (8 months-7.7 years, mean: 3.2 years) and cumulative follow-up was 47.6 patients years (PY). There was one late death, and one prosthetic valve endocarditis (2.1%/PY). No other valve-related complications was occurred. Actuarial survival rate and freedom from valve-related morbidity at seven years were 83.3%, and 93.3%, respectively. These results show that operative mortality of valvular disease in elderly patients remains high, but the late results is acceptable one. Valve surgery for these elderly patients is reasonably acceptable.

Aged↗

[Reservoir system for bronchial arterial injection against lung cancer patients in an outpatient clinic].

We completed a reservoir system for injection to bronchial artery. A slender catheter was indwelled in bronchial artery through left subclavian artery or right femoral artery in five cases with lung cancer. Reservoir was embedded subcutaneously, and injection to bronchial artery was performed repeatedly on an outpatient basis. Used drugs were CDDP, bleomycin and adriamycin. RI angiography confirmed the accumulation of 99mTc-MAA in primary lung tumor. Satisfactory therapeutic effect can be expected by the use of reservoir system for bronchial arterial injection, and seemed to become one of the established therapies, improving quality of life with advanced lung cancer.

Adult↗

Expression of IL-8, TNF-alpha and IFN-gamma m-RNA in ulcerative colitis, particularly in patients with inactive phase.

OBJECTIVE: The etiology of ulcerative colitis (UC) remains uncertain. It has been said that in patients with an active phase of UC the levels of the proinflammatory cytokines increased. Paying particular attention to patients with inactive UC, we investigated several cytokines' m-RNA transcripts. METHODS: In 27 patients with UC, the mucosal cytokine expression of m-RNA including IL-8, TNF-alpha, IFN-gamma and IL-6 were examined using the reverse transcription-coupled polymerase chain reaction (RT-PCR) and oligonucleotide hybridization. RESULTS: 1) The expression ratios of m-RNA of IL-8, IFN-gamma and TNF-alpha in cases with UC (92.6%, 70.4% and 77.8%, respectively) were significantly higher than in normal controls (17.6%, 0.0% and 5.9%, respectively) (p < 0.01). Regarding IL-8 and IFN-gamma, those in UC cases were also significantly higher than in cases with other types of colitis (p < 0.05). 2) No significant difference was noted between active and inactive cases with UC in terms of the expression ratios of m-RNA of IL-8, TNF-alpha and IFN-gamma. 3) Only the expression ratio of IL-6 m-RNA correlated with the macroscopic score according to Matts. In addition, expression of IL-6 m-RNA in the colon tissue was observed in 9 out of 10 cases with other types of colitis (90.0%). CONCLUSION: The expression of IL-8, TNF-alpha and IFN-gamma m-RNA increased even in inactive UC, suggesting that these three cytokines play an important role in the pathogenesis of repeated inflammation of UC.

Adult↗

Release of alpha-neoendorphin from the anterior pituitary gland of conscious rats.

alpha-Neoendorphin (alpha-NEO) is a proenkephalin B-derived opioid peptide and kappa type opioid receptor agonist. In the present study, we used a combination of microdialysis and a highly sensitive radioimmunoassay to measure the extracellular levels of immunoreactive (ir)-alpha-NEO from the anterior pituitary gland of conscious free-moving rats. When rats were given water ad libitum under a 12:12 h light-dark cycle with lighting from 06.00 to 18.00 h, ir-alpha-NEO showed circadian rhythmicity that peaked at 00.00-03.00 h and reached a minimum at 12.00-15.00 h. Furthermore, we investigated whether naloxone (10(-6) to 10(-8) M) affected ir-alpha-NEO level. The alpha-NEO release induced by naloxone was optimum at 10(-7) M, and 10(-6) M naloxone seemed to induce alpha-NEO release to a lesser degree. These results suggested that alpha-NEO release by naloxone might be mediated via anterior pituitary cell auto-receptor (kappa type) inhibition.

Animals↗

Regulation of slow calcium channels of myocardial cells and vascular smooth muscle cells by cyclic nucleotides and phosphorylation.

The slow Ca2+ channels (L-type) of the heart are stimulated by cAMP. Elevation of cAMP produces a very rapid increase in number of slow channels available for voltage activation during excitation. The probability of a Ca2+ channel opening and the mean open time of the channel are increased. Therefore, any agent that increases the cAMP level of the myocardial cell will tend to potentiate ICa, Ca2+ influx, and contraction. The action of cAMP is mediated by PK-A and phosphorylation of the slow Ca2+ channel protein or an associated regulatory protein (stimulatory type). The myocardial slow Ca2+ channels are also regulated by cGMP, in a manner that is opposite or antagonistic to that of cAMP. We have demonstrated this at both the macroscopic level (whole-cell voltage clamp) and the single-channel level. The effect of cGMP is mediated by PK-G and phosphorylation of a protein, as for example, a regulatory protein (inhibitory-type) associated with the Ca2+ channel. Introduction of PK-G intracellularly causes a relatively rapid inhibition of ICa(L) in both chick and rat heart cells. Such inhibition occurs for both the basal and stimulated ICa(L). In addition, the cGMP/PK-G system was reported to stimulate a phosphatase that dephosphorylates the Ca2+ channel. In addition to the slower indirect pathway--exerted via cAMP/PK-A--there is a faster more-direct pathway for ICa(L) stimulation by the beta-adrenergic receptor. This latter pathway involves direct modulation of the channel activity by the alpha subunit (alpha s*) of the Gs-protein. In vascular smooth muscle cells the two pathways (direct and indirect) also appear to be present, although the indirect pathway produces inhibition of ICa(L). PK-C and calmodulin-PK also may play roles in regulation of the myocardial slow Ca2+ channels. Both of these protein kinases stimulate the activity of these channels. Thus, it appears that the slow Ca2+ channel is a complex structure, including perhaps several associated regulatory proteins, which can be regulated by a number of factors intrinsic and extrinsic to the cell, and thereby control can be exercised over the force of contraction of the heart.

8-Bromo Cyclic Adenosine Monophosphate↗

Cisplatin generates superoxide anion by interaction with DNA in a cell-free system.

Cisplatin [cis-Diamminedichloroplatinum (II), DDP] generated superoxide anion (O2-), as measured by chemiluminescence from a Cypridina luciferin analog (CLA), by interaction with calf thymus DNA (ct-DNA) in phosphate-buffered saline (PBS) at pH 7.6. The intensity of chemiluminescence of CLA (CCLA) increased with increased concentration of DDP, ct-DNA or CLA in the limited range of concentrations of these agents tested. DDP-induced CCLA was completely inhibited by the addition of an O2- scavenger, superoxide dismutase (SOD), or an antioxidant, ascorbic acid. Heat-inactivated SOD did not affect CCLA. The hydroxyl radical (OH.) scavengers, mannitol, ethanol, and formic acid, also caused a partial suppression of CCLA, suggesting that DDP produced OH. as well as O2- in the cell-free system used.

Animals↗