beta-Alanine-oxoglutarate aminotransferase (beta-Ala-TI) was found to be distributed mainly in liver, brain, kidney, and testis (decreasing order of enzyme activity in the rat). D-3-Aminoisobutyrate aminotransferase (beta-Ala-T II) was distributed in kidney and liver. Both beta-Ala-T I and beta-Ala-T II were localized in the mitochondrial fraction in rat kidney. beta-Ala-T I in the liver of rats fed on pyridoxine-deficient or control diets was induced by injecting with prednisolone, while beta-Ala-T II in the liver of these rats was unaffected by prednisolone injection. The activities of beta-Ala-T I and beta-Ala-T II in the liver of rats fed on pyridoxine deficient diet did not change. However, in kidney, pyridoxine deficiency suppressed both enzyme activities, while treatment with prednisolone did not induce either enzyme. The ratios of the apo- to holo-enzyme for beta-Ala-T I and beta-Ala-T II in control rat kidney were 1.04 and 0.11, respectively. The values increased to 2.69 and 1.53, respectively, in pyridoxine-deficient rat kidney. These experiments indicate that pyridoxine deficiency and prednisolone affect the activities of beta-alanine degrading enzymes, but that the degree is different between liver and kidney.

4-Aminobutyrate Transaminase↗

PubMed1988

Altered vascular beta adrenoceptor-mediated relaxation in deoxycorticosterone-salt hypertensive rats.

Beta adrenoceptor-mediated relaxation was studied on femoral and mesenteric arteries and thoracic aorta from deoxycorticosterone-salt hypertensive and age-matched normotensive rats. Maximum relaxations to isoproterenol (ISO), fenoterol and norepinephrine were less in hypertensive than in normotensive tissues. Mean negative log EC50 values of ISO and norepinephrine, but not fenoterol, were smaller in femoral and mesenteric strips from hypertensive rats than those from oil-water-treated rats. In thoracic aortas from hypertensive rats, the mean negative log EC50 values of ISO and fenoterol decreased, whereas those of norepinephrine increased as compared with those in oil-water-treated rats. In oil-salt- and deoxycorticosterone-water-treated rats, hypertension did not develop nor were the responses to ISO reduced. Relative potencies of the beta adrenoceptor agonists and Schild plot data for atenolol and butoxamine indicate that femoral arteries of normotensive and hypertensive rats possess beta-1 adrenoceptors mediating relaxation. It also is suggested that the mesenteric artery and thoracic aorta of both normotensive and hypertensive rats predominantly possess beta-2 adrenoceptors mediating relaxation. The present results suggest that an elevation in blood pressure is associated with the reduction of beta-1 adrenoceptor-mediated relaxation in femoral arteries and of beta-2 adrenoceptor-mediated relaxation in mesenteric arteries.

Animals↗

PubMed1988

[Combination intra-arterial chemotherapy with degradable starch microspheres and mitomycin C against inoperable hepatic metastases].

Intra-arterial hepatic infusion chemotherapy combined with degradable starch microspheres (DSM) and mitomycin C (MMC) was performed for 9 patients with inoperable hepatic metastases from alimentary tract primary cancer. DSM, 45 +/- 5 micron in average diameter, produces temporary obstruction of arterial blood flow in the arterio-capillary bed and are subsequently degraded by serum amylase with T 1/2 of about 30 min. This intra-arterial treatment was repeated 2.3 times on the average. The average dose of DSM in a single infusion was 721 +/- 194 mg and the average total dose of MMC was 34.4 +/- 22.3 mg. Antitumor effects were evaluated in terms of tumor regression measured by CT scan and sonography. An objective tumor response was shown in 4/9 patients (44.4%): PR, 2/9; MR, 2/9. Elevated serum CEA levels of more than 3.0ng/ml were decreased in 7/8 patients (87.5%). Marked declines in the CEA level of more than 50% were observed in 4/8 patients (50%). Nausea and vomiting as well as abdominal pain were experienced in 8/21 treatments (38.1%) and 5/21 (23.8%), respectively. Furthermore, fever (2/21 : 9.5%), hepatic dysfunction (2/21 : 9.5%), and leukopenia (1/21 : 4.8%) were observed. All these side effects, however, were mild and transient. Thus, these results suggest that combined intra-arterial administration of DSM and MMC favorably enhances the antitumor efficacy of MMC.

Carcinoma, Hepatocellular↗

PubMed1988

[A successful treatment of left ovarian pregnancy with methotrexate].

Explore the source record for details and available documents.

Adult↗

PubMed1988

[Endocrinological environment in polycystic ovarian disease (PCOD)].

Explore the source record for details and available documents.

Androgens↗

PubMed1988

[Pharmacokinetic and clinical studies on imipenem/cilastatin sodium in the perinatal period. A study of imipenem/cilastatin sodium in the perinatal co-research group].

Pharmacokinetic and clinical studies on imipenem/cilastatin sodium (IPM/CS) in the perinatal period were carried out, and the results obtained are summarized below. 1. IPM/CS transfers to umbilical cord plasma and amniotic fluid were effective. Passage of IPM/CS into mother's milk was as little as with other beta-lactam antibiotics. 2. Among 81 patients with perinatal infections, clinical efficacies were excellent in 16 patients, good in 62, poor in 3, with an efficacy rate of 96.3%. In addition, IPM/CS was effective in 6 patients for prophylaxis. 3. Out of 82 isolates examined for bacterial responses, 69 isolates were eradicated and 8 isolates were decreased. Especially, of 13 isolates of Enterococcus faecalis, 12 were eradicated. 4. In 109 patients administered with IPM/CS, vomiting was observed in 1 patient. No abnormal laboratory test values were observed. 5. IPM/CS was an effective and safe new antibiotic in perinatal infections. We recommend a normal dose of IPM/CS of 0.5 g/0.5 g twice a day and a dose for severe infections of 1 g/1 g twice a day in the perinatal period.

Amniotic Fluid↗

PubMed1988

[Pharmacokinetic and clinical evaluations of ceftriaxone in perinatal infections in obstetrics and gynecology].

Ceftriaxone (CTRX), an injectable cephem antibiotic agent, was studied for its pharmacokinetic properties and clinical usefulness in perinatal infections in obstetrics and gynecology on a multicenter basis. The study results are summarized below. 1. Following the one-shot intravenous injection of CTRX 1 g to pregnant women before labor, the maternal serum level of CTRX reached a peak at 131.8 micrograms/ml soon after the injection then it began to decrease gradually. T 1/2 was 6.7 hours. The umbilical serum level reached a peak at 16.0 micrograms/ml at 4.9 hours post-dose and decreased gradually with a half-life of 8.1 hours. The umbilical serum level was higher than the maternal serum level at about 12 hours post-dose. The amniotic fluid level reached a peak of 9.6 micrograms/ml at 12.8 hours post-dose. T 1/2 was 15.2 hours. The amniotic fluid level at about 15 hours post-dose or later exceeded the maternal serum level and was almost equal to the umbilical serum level at 24 hours post-dose. 2. Clinical usefulness was evaluated in 79 evaluable cases out of 89 treated for various infections at puerperium or for prophylaxis of infections at cesarean section or premature rupture of membranes (PROM). The efficacy rate was 100% in 7 cases of prenatal infections such as urinary tract infection and 30 cases of postnatal infections such as puerperal intrauterine infections. In 42 cases treated for prophylaxis in cases of cesarean section or PROM, the efficacy rate was 92.9%. Bacteriologically, 29 strains of pathogens were isolated from 26 cases. The disappearance rate of the pathogens was 96.0% as 23 strains were eradicated, 1 strain was substituted and no change was observed in 1 strain with unknown results in 4 strain. Skin rash and itching appeared in 1 patient as an adverse effect (1.1%). There were 10 cases of abnormal clinical laboratory test results such as elevated transaminase level were observed in 7 patients (7.9%). From the results, CTRX was considered to be a useful drug for the perinatal infection in the obstetrics and gynecology fields.

Adult↗

PubMed1988

[Chemosensitization with nitroimidazole to human gastric cancer transplanted into nude mice].

Combined chemotherapy for human gastric cancer Transplanted into nude mice has been performed to determine whether misonidazole (MIS) and metronidazole (MTR), derivatives of nitroimidazole, would enhance the antitumor activity of MMC. MTR, 500 mg/kg, MIS 500 mg/kg, and MMC 2.0 mg/kg were administered ip twice during a 48-hour interval. The antitumor efficacies of MMC only, MTR only, or MIS only were seen to be much the same as in the controls. The combined treatment with MMC and MTR surpassed the controls in antitumoral activity after the 12th day, whereas it did not surpass a regimen with MMC alone. The addition of MIS to MMC showed an enhanced antitumoral activity after the 10th day compared to the controls and, further, after the 10th day it exceeded the results of MMC only. Tumor tripling time in cases of MMC only, MTR only, MIS only, MMC plus MTR, and MMC plus MIS was 123, 132, 144, 144, and 178 hours, respectively, compared to 110 hours in the controls. Thus, these results suggest that MIS has a chemosensitizing activity under these conditions, while MTR has little activity.

Animals↗

PubMed1988

[Enhancement of hyperthermochemotherapy with hypoxic cell radiosensitizers].

Hyperthermochemotherapy with hypoxic cell radiosensitizers has been carried out using human gastric cancer xenotransplanted into the nude mouse. Misonidazole (MIS) and metronidazole (MTR), hypoxic cell radiosensitizers, were administered singularly or in combination with an ip dose of 500 mg/kg each, and after 60 minutes, an ip dose of MMC of 2.0 mg/kg was given. Subsequently, hyperthermia was applied, twice at a 48-hour interval, by a water bath at 43.5 +/- 0.1 degrees C for 23 minutes. The antitumor activity of hyperthermia with MTR was similar to that of hyperthermia alone, whereas hyperthermia with MIS surpassed hyperthermia alone, at 0.03237 less than p less than 0.05038. Hyperthermia combined with MIS and MMC enhanced the antitumor effects, as compared to hyperthermia with MMC, and with MMC plus MTR. Tumor volumetric tripling times in case of MMC plus heat, MTR, MMC plus heat, and MIS, MMC plus heat were about 229, 213, and 398 hours, respectively, compared to about 110 hours in the control and 160 hours in the case of hyperthermia alone. Thus, these data suggest that the antitumor efficacy of hyperthermochemotherapy with MIS may be the result of a synergistic phenomenon of thermo-chemosensitization.

Animals↗

PubMed1988

[Repeated intra-arterial chemotherapy combined with mitomycin C and degradable starch microspheres in inoperable metastatic hepatic cancer].

Intra-arterial chemotherapy combined with mitomycin C (MMC) and degradable starch microspheres (DSM) was prescribed repeatedly for 14 patients with inoperable hepatic metastasis. This intra-arterial treatment was repeated 2.7 times on the average. The average dose of DSM and MMC in a single infusion was 685 +/- 201 mg and 13.8 +/- 3.8 mg, respectively. To analyse the degradation time of DSM, MMC concentrations in the peripheral blood were measured by HPLC method. RI-angiography using 99mTc macroaggregated albumin(MAA) was performed to estimate the hemodynamic changes in the liver. Antitumor efficacy was evaluated in terms of tumor regression measured by CT scan. An objective tumor response was observed in 9/14 patients(64.2%): CR 1/14; PR 6/14; MR 2/14. Elevated CEA levels were decreased in 11/12 patients (91.7%). Based on the peripheral MMC blood levels after combined infusion with DSM and MMC, an occlusion of intrahepatic vessels with DSM continued at least for 30 minutes. Again, RI-angiography with 99mTc-MAA plus DSM revealed the increased accumulation in the tumor, compared to 99mTc-MAA only. Side effects possibly attributable to DSM were observed in 14/38 treatments, though they were slight and temporary. Thus, these results indicate that this combined intra-arterial infusion of DSM and MMC achieve, higher regional selectivity.

Combined Modality Therapy↗

PubMed1988

[Extended treatment for gastric cancer patients with peritoneal seeding].

Fourteen patients with far-advanced gastric cancer were treated surgically followed by intraperitoneal hyperthermic perfusion (IPHP) with mitomycin C (MMC) and misonidazole (MIS), a thermosensitizing drug. Immediately after extensive resection of the abdominal tumors, a 2-hour IPHP was performed at the inflow temperature 47.4 +/- 0.5 degrees C and at the outflow temperature 45.3 +/- 0.5 degrees C, using equipment designed for treatment of cancerous peritoneal seeding, as a closed circuit, and under hypothermic general anesthesia at 31.2 +/- 0.5 degrees C. In 6 of the 14 patients, cancerous ascites was absent after IPHP. Repeated cytologic examination of the lavage from pelvic cul-de-sac were negative, in all cases. The postoperative courses were uneventful except for 2 patients, in whom slight leakage occurred. All patients were discharged, and 4 in the 14 patients died of recurrence in the liver, abdominal and/or pleural cavities 8.8 +/- 2.1 months after IPHP. The remaining 10 are in good health 12.1 +/- 3.1 months after IPHP. Transient hepatic dysfunction and hypoproteinemia occurred after hyperthermia in all cases. This extensive surgery combined with IPHP using MMC and MIS was well tolerated and is a safe anti-tumor treatment for gastric cancer with peritoneal dissemination. Neurotoxicity due to MIS was nil.

Combined Modality Therapy↗