Enhancement by hyperthermia of the in vivo antitumour effect of doxorubicin hydrochloride (DOX) and buthionine sulfoximine (BSO)-hydroxyapatite (HAP) complex

We have developed a new type of drug delivery system (DDS) comprising a complex of porous hydroxyapatite (HAP) with the anticancer drug doxorubicin hydrochloride (DOX) and the glutathione inhibitor buthionine sulfoximine (BSO) (DOX and BSO-HAP complex). We then studied the antitumour effect of DOX and BSO-HAP combined with 44 degrees C hyperthermia for 40 min. It was found that in mice this combined treatment suppressed the growth of sarcoma 180 in terms of tumour volume to 36% in comparison viith mice given plain HAP, and was more effective than HAP + hyperthermia or DOX- and BSO-HAP. These results were also confirmed by histological observation.     

Interleukin-6 and granulocytic elastase levels following laparoscopic cholecystectomy

Interleukin-6 (IL-6) levels have been shown to correlate well with the magnitude of surgical stress. Serum IL-6 and plasma granulocytic elastase levels, 24 h after surgery, were determined in 12 patients who underwent open major surgery [MS group; esophageal carcinoma (n=5), gastric carcinoma (n=3), colorectal carcinoma (n=4) 5 patients who had open cholecystectomy [OC group] and 17 patients who had laparoscopic cholecystectomy [LC group]. IL-6 levels correlated significantly with the duration of surgery (r=0.685,P < 0.01) and with intraoperative blood loss (r=0.583,P < 0.02). However, there was no significant correlation between granulocytic elastase and the duration of surgery or blood loss. Plasma IL-6 levels in the LC group (21±3 pg/ml) were significantly lower than those in the OC group (47±5 pg/ml) and the MS group (186±36pg/ml) (P<0.05;P<0.01). However, there was no significant difference in granulocytic elastase levels between the LC group (318±8g/l), the OC group (360±130 gmg/ml), and the MS group (701±344 g/l). Increased IL-6 levels correlated well with increased duration of surgery. The lower IL-6 levels following laparoscopic cholecystectomy may therefore be indicative of lower surgical stress associated with laparoscopic cholecystectomy.     

REP-1 gene mutations in Japanese patients with choroideremia

· Background: Choroideremia (CHM) is an X-linked progressive dystrophy of the choroid, retinal pigment epithelium, and retina. Recently, the REP-1 gene was isolated and the causative mutations in the gene were detected in patients with CHM. In a previous study, we described a Japanese family with CHM who had a mutation in the REP-1 gene. In the present study, we performed extensive analysis of the REP-1 gene in patients with CHM from several institutions in Japan. · Methods: Twenty-six patients with CHM and 5 unaffected females from 22 independently ascertained families were examined. Exons 1–15 of the REP-1 gene were screened by single-strand conformation polymorphism. The DNA fragments suspected of any variations were directly sequenced. · Results: Fifteen different mutations, including one previously reported mutation, were detected in 18 families. In addition, carrier status was proven in four unaffected females found to be heterozygous for the mutant allele. · Conclusions: Fifteen different mutations of the REP-1 gene were detected in 18 Japanese families. There were no hot spots for the mutations and no missense mutations. The results show that REP-1 gene defects cause CHM in Japanese patients, and the mutations in these Japanese patients differed from the mutations reported for CHM patients in Europe, Canada, and America except for R267X and 1313delTC. These findings suggest that the mutations occurred independently in the Japanese patients. Received: 13 August 1998 Revised version received: 16 November 1998 Accepted: 9 December 1998     

Immunocytochemical localization of aromaticl-amino acid decarboxylase and catechol-O-methyltransferase in blood vessel wall of the human dental pulp

Relatively large amounts of DOPA as compared with the concentration of norepinephrine are found in human dental pulp. AADC and COMT are localized in blood vessel walls of human dental pulp. This localization suggests a functional relationship between COMT and AADC with regard to the metabolism of DOPA.     

Evidence of cross-link formation of vitreous collagen during experimental ocular inflammation

Purpose: To determine the mechanisms of vitreous changes during ocular inflammation. Methods: We investigated vitreous changes, with special emphasis on collagen, in an experimental model of ocular inflammation induced by intravitreal injection of endotoxin (Escherichia coli) in rabbits. Results: Inflammation caused gel contraction and loss of elasticity, accompanied by release of a water-like liquid from the gel, and increases in the amount of insoluble material and highmolecular-weight components of vitreous collagen, presumably due to extensive cross-links of the collagen molecules. Those changes were partially inhibited by intravitreal injection of superoxide dismutase. Conclusions: The crosslinks of vitreous collagen may promote vitreous gel contraction and release of a water-like liquid from the gel. Superoxide anion may play a role in this process.     

Potential applicability of clinical hyperthermia using a Thermotron-RF8 as assessed from thermal distribution in an agar phantom containing hydroxyapatite

We have already reported the antitumour effect of hydroxyapatite (HAP) containing anticancer drugs. In this study, we found an increased temperature effect around HAP particle(s) in an agar phantom in comparison with other areas when a Thermotron-RF8 (RF generator) was used for heating. Furthermore, it was revealed that the quantity of doxorubicin hydrochloride (DOX) released from HAP containing the drug (DOX-HAP complex) was increased by raising the temperature. These results indicated that the antitumor effect of the DOX-HAP complex + hyperthermia system was greater than that of either the DOX-HAP complex or hyperthermia system alone.     

Effects on atrio-ventricular conduction of calcium-antagonistic coronary vasodilators,local anaesthetics and quinidine injected into the posterior and the anterior septal artery of the atrio-ventricular node preparation of the dog

Summary The effects on atrio-ventricular (A-V) conduction and blood flow of calcium-antagonists (verapamil, nifedipine and diltiazem), local anaesthetics (procaine and lidocaine) and quinidine were investigated in the isolated, cross-circulated A-V node preparation of the dog. The drugs were injected individually into the posterior septal artery (PSA) through which the upper part of the A-V node is mainly perfused or into the anterior septal artery (ASA) through which the lower part of the node and the more distal conduction system are perfused. Single injections into the PSA of nifedipine (0.3–10 g), verapamil (1–30 g), diltiazem (1–30 g), quinidine (30–300 g), lidocaine (100 g–1 mg) and procaine (300 g–3 mg) produced a dose-related increase in the A-V conduction time and with higher doses of these drugs a second or third degree block of A-V conduction occurred. Nifedipine (0.3–30 g) and verapamil (1–100 g) injected into the ASA scarcely affected A-V conduction. Quinidine (30 g–1 mg) and lidocaine (100 g–3 mg) injected into the ASA prolonged the A-V conduction time in a dose-related manner, although the effects were less prominent than those produced upon injection into the PSA. High doses of quinidine (3 mg) and lidocaine (3–10 mg) injected into the ASA altered the shape of ventricular bipolar electrograms and prolonged the time interval between an electrogram of the right bundle branch and that of the ventricle. The results are consistent with the hypothesis that in excitation of A-V nodal cells a slow calcium current rather than a fast sodium current plays an important role and that in the His-Purkinje-ventricular system the fast sodium current is predominant. Single injections of the 6 drugs into the PSA produced a doserelated increase in blood flow through the PSA. All drugs but nifedipine increased the blood flow in almost the same dose range that caused impairment of A-V conduction. Nifedipine was 10 times more potent in increasing the blood flow than in impairing A-V conduction.     

Isoline两个新代谢物的制备及其理化性质

目的：为进一步研究isoline的代谢和毒理，采用化学方法制备其代谢产物。方法：分别采用水解，氮氧化和脱氢化反应将isoline转化为与代谢和毒理研究相关类型的产物。结果与结论：成功地制备了五个化合物，其中两个为新化合物，其结构经UV，IR.MS和NMR分析得以鉴定。     

An infant case of bilateral small kidneys with both proximal and distal tubular dysfunction

Abstract A male infant with bilateral small kidneys associated with both proximal and distal tubular dysfunction, who showed chronic renal failure soon after birth, is reported. He was also noted to have both proximal and distal type of renal tubular acidosis. The small kidneys were thought to be due to renal hypodysplasia associated with bilateral severe vesicoureteral reflux, by radiological findings. An alkalization therapy with chemo-prophylaxis seemed to be of benefit in slowing the progression of renal failure in this case.