The mechanism of the inhibitory effect of protease inhibitors on platelet aggregation and cellular synthesis of prostaglandins. I. The effect on the release of arachidonic acid from phospholipids

The inhibitory effect of proteinase inhibitors on platelet aggregation was investigated. The proteinase inhibitors tested were SBTI, leupeptin and FOY (a synthetic proteinase inhibitor). Also, synthetic substrates for serine proteinases (TLME, ATEE) were tested. They completely inhibited the secondary aggregation of platelets induced by ADP or epinephrine. They also completely inhibited the platelet aggregation induced by collagen or thrombin. The aggregation induced by arachidonic acid was completely inhibited by all the proteinase inhibitors and synthetic substrates. The aggregation induced by Ca ionophore A 23187 was completely inhibited by leupeptin, FOY, TLME or ATEE but not by SBTI. It is generally accepted that platelet prostaglandin metabolism plays an important role in platelet aggregation. As the first step to elucidate the possible mechanism of the inhibitory effect of the proteinase inhibitors, their effect on the release of arachidonic acid from platelet phospholipids was investigated. The release of arachidonic acid from ¹⁴C-arachidonate incorporated gel filtered platelets (¹⁴C-AA-GFP) by thrombin or A 23187 was directly measured in the presence or absence of a proteinase inhibitor or synthetic substrate, utilizing thin layer chromatography (TLC) and a scintillation counting. The release was almost completely blocked when the aggregation of ¹⁴C-AA-GFP by thrombin or A 23187 was completely inhibited by a proteinase inhibitor or a synthetic substrate.     

Constituents of the chinese crude drug "Sāng-Bái-Pí" (morus root bark)

From the benzene extract of the Chinese crude drug "Sāng-Bái-Pí" (Japanese name Sōhakuhi), the root barks of MORUS sp. (Moraceae), a novel isoprene substituted flavanone derivative, named sanggenon B, was isolated; its structure was shown to be I on the basis of spectral and chemical data. Sanggenon B (I) is regarded biogenetically as a variation of a Diels-Alder adduct of a chalcone derivative and a dehydroprenylflavanone derivative.     

Constituents of the Chinese crude drug "sāng-bái-pí" (Morus root bark)

From the benzene extract of the Chinese crude drug "Sāng-Bái-Pí" (Japanese name Sōhakuhi), the root bark of MORUS sp. (Moraceae), a novel isoprene substituted flavanone, named sanggenon A, was isolated whose structure was shown to be I on the basis of spectral data. A known isoprene substituted flavone derivative, morusin (II), was also obtained from the extract.     

Quality of life (QOL) and nutrition

We thought that nutritional parameters in laboratory data might be able to express quality of life (QOL). Therefore, in 70 patients with malignant chest diseases (NSCLC, 42 patients; SCLC, 15; lung metastasis, 7; others, 6), the correlation between nutritional parameters of total protein (Tp), serum albumin (Alb), and serum (cholinesterase (ChE] and Karnofsky Performance Status scale (KPS) was investigated. Then, in 24 patients with them (NSCLC, 12; SCLC, 6; lung metastasis, 4; others 2), Alb and ChE were compared to the EORTC Core Quality of Life Questionnaire and Lung Cancer-Specific Questionnaire Module (QS). Results were as follows: 1) KPS and nutritional parameters correlated (Tp. r = 0.55, p less than 0.001; Alb, r = 0.60, p less than 0.001, ChE, r = 0.60; p less than 0.001). 2) The cores for Functional Status (FS) and Disease and Treatment-related symptoms (Sym) in QS and parameters of Alb and ChE correlate (FS v.s. Alb, p less than 0.01; Sym v.s. Alb, p less than 0.01; FS v.s. ChE, p less than 0.05; and Sym v.s. ChE, p less than 0.05). Moreover, the scores of Psychological Distress in QS and Alb showed a correlation (p less than 0.05). It is considered that nutrition and part of QOL (KPS and FS + Sym in QS, that is to say, "objective" functional activity and "subjective" functional activity and symptoms) correlate, and that nutritional parameters are useful to evaluate QOL.     

The increase of cardiac beta 1-subtype of beta-adrenergic receptors in adult rats following neonatal 6-hydroxydopa treatment

An analysis of Hofstee plots of specific [3H]dihydroalprenolol ([3H]DHA) binding in the presence of various concentrations of practolol showed that KD and Bmax in beta 1-subtype adrenoceptors were 19.2-fold lower and 2.76-fold higher than those in beta 2-subtype in adult rat hearts, respectively. Neonatal treatment with 6-hydroxydopa produced a significant increase only in Bmax in beta 1-adrenoceptors without changing Bmax and KD in beta 2-receptors. "Up' regulation in the density of beta 2-type of adrenoceptors seems to be caused by the 6-hydroxydopa-induced sympathetic lesion.     

Psychological changes of Japan Self-Defense Forces personnel during selection and training for the peacekeeping mission in the Golan Heights

We sought to determine whether a selection process for deployment had a measurable effect on psychological symptoms by comparing scores on the Yatabe-Guilford Personality Index, the Manifest Anxiety Scale, and the 30-item version of the General Health Questionnaire between deployed and nondeployed mission candidates from the Japan Self-Defense Forces. The studies were undertaken in Japan during education and training for the United Nations peacekeeping mission in the Golan Heights. The participants included 80 candidates for deployment. Personnel who were not deployed had significantly higher measures of manifest anxiety and general psychological distress than deployed personnel, whereas deployed personnel showed more symptoms suggesting somatization. The selection process and training for deployment appear to have been stressful for all personnel, whether deployed or not.     

The McCoy laryngoscope, external laryngeal pressure, and their combined use

The efficacy of the McCoy laryngoscope, external laryngeal pressure, and their combination to improve the laryngoscopic view was evaluated in 219 patients and compared with the Macintosh laryngoscope. An experienced laryngoscopist performed laryngoscopy twice using the Macintosh laryngoscope and the McCoy laryngoscope in a random sequence, and external laryngeal pressure was applied in each laryngoscopy with the laryngoscopist's right hand. The laryngoscopic view obtained was graded on our modified Cormack's method. Without external laryngeal pressure, the McCoy laryngoscope provided a better laryngoscopic view than that obtained by the Macintosh laryngoscope (P < 0.001, signed rank test), but the view was worse than that with the Macintosh laryngoscope under external laryngeal pressure (P < 0.001). The McCoy laryngoscope combined with external laryngeal pressure provided a better view than the Macintosh laryngoscope with external laryngeal pressure (P < 0.001).     

Randomized controlled trial comparing oral doxifluridine plus oral cyclophosphamide with doxifluridine alone in women with node-positive breast cancer after primary surgery.

PURPOSE: We compared the therapeutic usefulness of doxifluridine (5'-DFUR) alone and a combination of 5'-DFUR plus cyclophosphamide (CPM), both of which are considered effective against advanced and recurrent breast cancer, to determine which treatment is more beneficial as postoperative adjuvant chemotherapy. PATIENTS AND METHODS: A total of 1,131 women with node-positive primary breast cancer were randomly assigned after primary surgery to receive 5'-DFUR alone or 5'-DFUR plus CPM. All patients initially received 5'-DFUR in an oral dose of 1,200 mg/d for 4 weeks, starting 4 weeks after surgery. Chemotherapy was then not given for 2 weeks. Patients in the 5'-DFUR group subsequently received five 4-week cycles of treatment consisting of oral 5'-DFUR (1,200 mg/d) for the first 2 weeks and no chemotherapy for the next 2 weeks. Those assigned to the 5'-DFUR plus CPM group also received oral CPM 100 mg/d for the first 2 weeks and no chemotherapy for the next 2 weeks. Women 50 years or older concurrently received 20 mg/d of tamoxifen for 2 years in both groups. RESULTS: Of the 1,088 eligible women, 546 were assigned to receive 5'-DFUR alone and 542 were assigned to receive 5'-DFUR plus CPM. Overall disease-free survival was significantly better in women who received 5'-DFUR plus CPM than in those who received 5'-DFUR alone (log-rank test, P =.021). Toxic effects occurred in 20.0% of patients (109 of 546) in the 5'-DFUR group and 32.3% of patients (175 of 542) in the 5'-DFUR plus CPM group (chi(2) test, P <.001). CONCLUSION: Combination therapy with 5'-DFUR plus CPM is more effective in preventing recurrence than 5'-DFUR alone.