Composite effects of actinonin when inhibiting enkephalin-degrading enzymes.

Actinonin which has been found to be an inhibitor of aminopeptidase M (EC 3.4.11.2) also inhibited enkephalinase A (EC 3.4.24.11) and enkephalin aminopeptidase which were partially purified from the corpus striatum membrane of guinea-pig brain. The IC50 values were 5.6 microM for enkephalinase A and 0.39 microM for enkephalin aminopeptidase. Actinonin also inhibited with an IC50 value of 1.1 microM dipeptidyl aminopeptidase tested on whole brain homogenate of rats in the presence of thiorphan and bestatin. Analgesia was assessed by measuring the tail-flick latency of mice. The analgesic effect of [Met5]enkephalin injected intracisternally (i.cist., 50 micrograms) was potentiated by an intraperitoneal (i.p., 100 and 300 mg/kg) as well as an i.cist. (25 micrograms) injection of actinonin. Actinonin was found to inhibit all three enzymes of enkephalin metabolism and, when given peripherally, to potentiate enkephalin analgesia.

Biosynthetic studies of ebelactone A and B by 13C NMR spectrometry.

Biosynthetic pathways of ebelactone A and B were studied by 13C NMR spectroscopy. By using 13C labeled compounds as precursors it was determined that ebelactone A was derived from one molecule of acetic acid and six propionic acids and ebelactone B from one molecule of acetic acid, five propionic acids and one butyric acid.

Isolation of new minor benanomicins.

Four minor benanomicins, dexylosylbenanomicins A and B, 2'-demethylbenanomicin A and 7-methoxybenanomicinone have been isolated from the culture filtrate of Actinomadura sp. MH193-16F4. Their structures were confirmed by spectral analyses. Dexylosylbenanomicins A and B were derived chemically from benanomicins A and B, respectively.

Nagstatin, a new inhibitor of N-acetyl-beta-D-glucosaminidase, produced by Streptomyces amakusaensis MG846-fF3. Taxonomy, production, isolation, physico-chemical properties and biological activities.

Nagstatin, a new inhibitor of N-acetyl-beta-D-glucosaminidase (NAG-ase) was discovered in the fermentation broth of Streptomyces amakusaensis MG846-fF3. It was purified by chromatography on Dowex 50W, Avicel and Sephadex LH-20 followed by the treatment of active carbon and then isolated as colorless powder. Nagstatin has the molecular formula of C12H17N3O6. It is competitive with the substrate, and the inhibition constant (Ki) was 1.7 x 10(-8) M.

New hydroxybenanomicins produced by Actinomadura.

A soil microorganism, Actinomadura sp. MH193-16F4, produces an antifungal antibiotic benanomicin A and several related compounds. Among them, benanomicin A is the best candidate as a chemotherapeutic agent in terms of antifungal activity, toxicity and water-solubility. Three novel hydroxyl congeners, 3'-hydroxybenanomicin A, 7-hydroxybenanomicin A and 7-hydroxybenanomicinone have been isolated from the culture broth of the MH193-16F4 strain or its mutant. Interestingly, 3'-hydroxy-benanomicin A was as effective as benanomicin A, but the 7-hydroxy congeners were inactive. The inactive congeners differ from benanomicin A and 3'-hydroxyenanomicin A in their conformational structures at C-5 and C-6.

Radiation-induced apoptosis in scid mice spleen after low dose irradiation.

To assess the radioadaptive response of the whole body system in mice, we examined the temporal effect of low dose priming as an indicator of challenging irradiation-induced apoptosis through a p53 tumor suppressor protein- mediated signal transduction pathway. The p53 protein also plays an important role both in cell cycle control and DNA repair through cellular signal transduction. Using severe combined immunodeficiency mice defective in DNA-dependent protein kinase catalytic subunit, we examined the role of DNA-dependent protein kinase activity in radioadaptation induced by low dose irradiation. Specific pathogen free 5-week-old female severe combined immunodeficiency mice and the parental mice (CB- 17 Icr +/+) were irradiated with X-ray at 3.0 Gy at 1, 2, 3 or 4 weeks after the conditioning irradiation at 0.15, 0.30, 0.45 or 0.60 Gy. The mice spleens were fixed for immunohistochemistry 12 h after the challenging irradiation. The p53-dependent apoptosis related Bax proteins on formalin-fixed paraffin-embedded sections were stained by the avidin-biotin peroxidase complex method. The apoptosis incidence in the sections was measured by hematoxylin-eosin staining. The frequency of Bax- and apoptosis-positive cells increased up to 12 h after the challenging irradiation in the spleen of both mice. However, these cells were not observed after a low dose irradiation at 0.15-0.60 Gy. When pre-irradiation at 0.45 Gy 2 weeks before the challenging irradiation at 3.0 Gy was performed, Bax accumulation and apoptosis induced by challenging irradiation were depressed in the spleens of CB-17 Icr +/+ mice, but not in severe combined immunodeficiency mice. These data suggest that DNA-dependent protein kinase might play a major role in radioadaptation induced by pre-irradiation with a low dose in mice spleen. We expect that the present findings will provide useful information in the health care of space crews.

[A case report of multiple intracranial tuberculoma associated with miliary tuberculosis and review of the literature].

We reported a case of multiple intracranial tuberculoma associated with miliary tuberculosis and reviewed the cases reported as intracranial tuberculoma in the past 11 years. A 41-year-old diabetic man was admitted to our hospital for the treatment of miliary tuberculosis and respiratory insufficiency. On admissIon, he had no neurological deficits except mild consciousness disturbance due to respiratory failure. He developed headache and mental confusion three weeks after the beginning of antituberculous therapy with isoniazid, streptomycin, rifampicin, and ethambutol. Neurological examination revealed that he had progressive right hemiparesis and was in a confusional state. Enhanced CT showed multiple intracranial nodular lesions. During 6 weeks, he had progressive neurological manifestations in spite of his initial antituberculous treatment. He responded well, however, to the chemotherapy with combination of isoniazid, kanamycin, pyrazinamide and ethionamide that were sensitive to tuberculous bacilli separated from his sputum. He became minimally right-hemiparetic by 6 weeks after the change of antituberculous medication. Serial enhanced CT scan proved to be of great value in the diagnosis and follow-up study of intracranial tuberculoma. From 1978 to 1988, there were 72 reported cases of intracranial tuberculoma in Japan; 37 were male, 32 were female and 3 were uncertain because of no detailed document. The age of onset was distributed from 6 month to 81 years in age and 2 peaks were seen in the second decade and fifth to seventh decade. Thirty-three (48%) out of 69 cases had multiple intracranial lesions. A few reports commented that neurological complications tended to appear even if they were under antituberculous therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Preoperative visualization of the artery of Adamkiewicz by intra-arterial CT angiography.

BACKGROUND AND PURPOSE: CT and MR angiographies have been reported to visualize the artery of Adamkiewicz (AKA) noninvasively to prevent spinal cord ischemia in surgery of thoracic descending aortic aneurysms. The purpose of this work was to compare the usefulness of CT angiography (CTA) with intra-arterial contrast injection (IACTA) with that of conventional CTA with intravenous contrast injection (IVCTA). MATERIALS AND METHODS: We enrolled 32 consecutive patients with thoracic or thoracoabdominal aortic aneurysms who were scheduled for surgical repair or endovascular stent-graft treatment. All of the CTA images were obtained using a 16-detector row CT scanner and 100 mL of contrast material (370 mg/mL) injected at a rate of 5 mL/s. Contrast was injected via the antecubital veins of 15 patients and via a pig-tail catheter placed at the proximal portion of the descending aorta in 17 patients who underwent IVCTA and IACTA, respectively. Two datasets were reconstructed from 2 consecutive scans. The AKA was identified as a characteristic hairpin curved vessel in the anterior midsagittal surface of the spine and by the absence of further enhancement in the second rather than in the first phase. Continuity between the AKA and aorta was confirmed when the vessel could be traced continuously by paging the oblique coronal multiplanar reconstruction or original axial images. RESULTS: Intra-arterial contrast injection was significantly more sensitive in identifying the AKA than IVCTA: 16 (94.1%) of 17 versus 9 (60.0%) of 15 (P = .033). Continuity between the AKA and aorta through intercostal or lumbar artery was confirmed in 14 (87.5%) of 16 and 5 (55.6%) of 9 of the IACTA and IVCTA groups, respectively. CONCLUSION: Intra-arterial contrast injection detected the AKA at a high rate and verified continuity from the aorta to the AKA.

Secondary release of thromboxane A2 in aerosol leukotriene C4-induced bronchoconstriction in guinea pigs.

Effect of a thromboxane synthetase inhibitor (OKY-046) on bronchoconstriction induced by aerosol leukotriene C4 and histamine was studied in anesthetized, artificially ventilated guinea pigs in order to examine whether secondary release of thromboxane A2 is produced by aerosol leukotriene C4 or not. 0.01-1.0 micrograms/ml of leukotriene C4 and 12.5-400 micrograms/ml of histamine inhaled from ultrasonic nebulizer developed for small animals caused dose-dependent increase of pressure at airway opening (Pao) which is considered to be an index representing bronchial response. Pretreatment of the animals with intravenous OKY-046 (100mg/kg) significantly reduced the airway responses produced by inhalation of 0.1, 0.33 and 1.0 micrograms/ml of leukotriene C4, while the pretreatment did not affect the histamine dose-response curve. Based on these findings and previous reports (6,7), it is suggested that aerosol leukotriene C4 activates arachidonate cyclooxygenase pathway including thromboxane A2 synthesis and the released cyclooxygenase products have bronchodilating effect as a whole.

Additive effects of isoproterenol-phenylephrine aerosol following ipratropium bromide on airway obstruction in older patients with intrinsic asthma and chronic bronchitis.

The additive bronchodilating effect of isoproterenol-phenylephrine aerosol following ipratropium bromide was examined in seven intrinsic asthmatic patients and seven chronic bronchitic patients. FVC, FEV1 and Zrs were measured before and 30 min. after inhalation of ipratropium, 40 micrograms. Then inhalation of isoproterenol, 600 micrograms and phenylephrine, 570 micrograms was added and the pulmonary functions were measured 30 min. later. The age, baseline values of FVC and FEV1, and the increases in FEV1 and 1/Zrs with ipratropium did not differ between the two. Isoproterenol-phenylephrine aerosol following ipratropium produced further increases in FEV1 and 1/Zrs in asthmatic patients but no additive increases in bronchitic patients. These findings indicate that the role of autonomic nervous system, especially adrenergic system, on airway obstruction may be different between asthmatic and bronchitic patients and the method applied in this study may be helpful in differentiating these airway disorders.