All-trans retinoic acid suppresses liver injury induced by Propionibacterium acnes and lipopolysaccharide in rats

All-trans retinoic acid (ATRA) has been reported to exert major effects on the immune system, including monocytes/macrophages. The present study was designed to determine whether ATRA would modulate macrophage-associated liver injury induced by Propionibacterium acnes and lipopolysaccharide (LPS) in rats. All-trans retinoic acid administration alleviated the liver injury and reduced the incidence of death following hepatic failure. Serum alanine aminotransferase (ALT) levels 5 h after, and survival rates within 12 h after the administration of LPS were significantly lower in the ATRA-treated group (134 ± 119 IU/L and 72.7%) compared with the control group (713 ± 411 IU/L and 18.2%; P < 0.05). Histological findings supported these results. These effects may be due to suppression of tumour necrosis factor-α (TNF-α) and superoxide anions produced by activated macrophages. Serum levels of TNF-α 1 h after LPS administration were significantly lower in the ATRA-treated group (60.5 ± 7.0 ng/mL) as compared with the control group (105.2 ± 39.3 ng/mL; P < 0.05). Formazan deposition that was generated by the perfusion of the liver with nitroblue tetrazolium, also suggested suppression of the release of superoxide anions from hepatic macrophages. These results suggest that ATRA acts as an immunomodulator in liver injury by suppressing the activation of liver macrophages.     

Cytotoxin and urease activities of Helicobacter pylori isolates from Japanese patients with atrophic gastritis or duodenal ulcer

The vacuolating cytotoxin and urease secreted by Helicobacter pylori are thought to be virulent factors. Because vacuolation is potentiated by the presence of ammonium ion, which is produced by urease in vitro, it is of interest to examine whether cytotoxin and urease work reciprocally in the development of atrophic gastritis or duodenal ulcer. In the present study, patients (all H. pyloripositive) were divided into four groups: mild atrophic gastritis (group 1; nine patients), severe atrophic gastritis (group 2; 36 patients), duodenal ulcer with mild atrophic gastritis (group 3; 19 patients) and duodenal ulcer with severe atrophic gastritis (group 4; 12 patients). Cytotoxin production and urease activity of H. pylori isolated from these patients were analysed. Cytotoxin production was observed in four of nine (44.4%), 28 of 36 (77.8%), 11 of 19 (57.9%) and eight of 12 (66.7%) isolates from groups 1, 2, 3 and 4, respectively. Cytotoxin-producing H. pylori isolates were found significantly more in patients with severe atrophy than in patients with mild atrophy (P= 0.048). The mean of relative activity of cytotoxin in H. pylori isolate was 1. 6. ± 2. 3, 7. 9. ± 7. 4, 5. 8. ± 6. 0 and 9. 0 ± 9. 1 in groups 1, 2, 3 and 4, respectively. Helicobacter pylori isolates from severe atrophy or duodenal ulcer patients in groups 2 or 4 possessed significantly higher activity than those from non-ulcer patients in group 1 (P= 0.017 and 0.030, respectively). The mean of urease activity was 8. 6 ± 4. 6, 10. 0 ± 5. 9, 10. 0 ± 8. 5 and 11. 2 ± 7. 7 IU/mg in groups 1, 2, 3 and 4, respectively. These differences indicated no statistical significance. In each H. pylori isolate, the production of cytotoxin and urease were independent, which indicated that there was no reciprocal effect between them in vivo. Thus, cytotoxin-producing H. pylori isolates were more prevalent in patients with severe atrophic gastritis and the cytotoxin activities of H. pylori isolates from the patients with severe atrophic gastritis or duodenal ulcer were much higher than those from the patients with mild atrophic gastritis, which suggested that vacuolating cytotoxin may be a disease-inducing factor.     

Nonulcerative Lesion Detected by Endoscopy as an Early Expression of Gastric Malignancy: --Retrospective Observation of 72 Cases of Gastric Carcinoma--

To evaluate the endoscopic criteria for early malignant findingsof gastric carcinoma more precisely, a retrospective examinationof endoscopic pictures of 72 patients with gastric carcinomawas carried out. The patients had received endoscopic examinationsrepeatedly for years and proceeded finally to surgery on thebasis of a diagnosis of carcinoma by gastric biopsy. The macroscopicas well as microscopic findings of the resected specimens werecompared with the previous endoscopic observations. Ulcerative lesions were predominantly found at the initial endoscopyin patients whose final diagnosis was the lie type of earlygastric cancer or IIc-like advanced cancer. These patients usuallyreceived endoscopic examinations repeatedly and their lesionswere diagnosed as malignant by the adopted criteria of earlygastric cancer 2 to 6 yr after the initial examination. In contrast, nonulcerative lesions were observed more frequentlyat the initial examination in patients with the final diagnosisof the IIa+IIc type of early gastric cancer or Borrmann typeof advanced cancer. In most of those patients endoscopic examinationwas not carried out so frequently, and in some of those whohad been closely followed the malignant findings appeared rathersuddenly with tumorous formation as well as deeper invasionduring less than a few years from the previous examination atwhich the tumor had been considered benign. These data indicate that the nonulcerative lesions which wereconsidered benign could be the early expression of gastric carcinoma.It should be stressed that nonulcerative lesions such as "irregularerythematous change, discoloration, flat granular change" and"simple mucosal depression" observed in some parts of the stomachwould be important site for the detection of early gastric carcinoma,and that these lesions need to be biopsied more frequently.     

Struggles of neonatology staff and the network system in the Hanshin-Awaji earthquake disaster

More than 5500 people were killed in the Hanshin-Awaji earthquake disaster. Most of the neonatal intensive care units (NICU) could not offer proper services as a result of the earthquake and the Hyogo Emergency System for Neonates could not function. No one imagined that such a great disaster would occur in their home town, Kobe; however, the devastation of the quake has raised the opportunity to examine the operation of neonatal medicine in an emergency. We sent out questionnaires to perinatologists in the damaged area 2–3 months after the quake. Some hospitals in the demolished area suffered such serious damage that they could not continue work as NICU, and some in the surrounding area had problems in a number of areas, including staff, room capacity and transport methods. Under these difficult circumstances the greatest problem encountered by staff was maintaining fundamental care in NICU, that is to say keeping temperature, formula (nutrition) and prevention of infection techniques operating. In this report we discuss the effects on neonatal medicine of the earthquake in Kobe. Medical staff struggled patiently and made great efforts to recover and maintain the functioning of NICU. We believe this information will be useful for neonatology staff in other areas which may experience an earthquake in the future.     

Antitumor Activity and Pharmacokinetics of Estra-1,3,5 (10)-Triene-3,17{beta}-Diol, 3-Benzoate, 17-((4-(4-(Bis (2-Chioroethyl)Amino)Phenyl)-1-Oxobutoxy) Acetate) (Bestrabucil) in Human Tumor Xenografts Serially Transplanted into Nude Mice

Bestrabucil (KM2210), the benzoate of an estradiol-chlorambucilconjugate, was used experimental cancer chemotherapy against13 human tumor xenografts serially transplanted into nude mice,and its pharmacokinetics was studied. The tumors were one esophageal,two gastric, six colon, one cholecystic and three breast carcinomas.Two tumor tissue fragments approximately 3x3x3 mm were inoculatedinto BALB/cA nude mice, which were then treated with KM2210at doses of 100, 200 and 300 mg/Kg/day orally starting 24 hrafter the transplantation or when the tumor reached a weightof 100–300 mg. The concentration of KM2210 and its derivativesin the tumor xenografts, normal muscular tissue and blood wereassayed by high performance liquid chroma-tography. Six out of 13 xenografts were found to be sensitive to KM2210.The concentrations of KM2210 and its derivatives in the tumortissues of the sensitive xenografts were five to 10 times higherthan those in blood and muscular tissue, and the antitumor activitycorrelated well with the area under the curve of active metabolitesof KM2210 in the tumor.     

Decreased cyclosporin A absorption after treatment with GoLytely lavage solution in rats

Abstract— Recently we observed a case in which the cyclosporin A absorption decreased after treatment with GoLytely lavage solution in a kidney transplant patient. In this study, we confirmed the decrease of the blood concentration of cyclosporin A after oral administration by GoLytely (Macrogol 3350) based on experiments with rats. The peak blood cyclosporin A concentration, and the area under the blood drug concentration-time curve from 0 to 24 h in the GoLytely-administered group were significantly lower than the control group. In the case of gastrointestinal dysfunction such as diarrhoea, or in treatment with laxatives such as GoLytely lavage solution, whole blood cyclosporin levels must be carefully monitored, and intravenous cyclosporin A may be more suitable for providing adequate immunosuppression.     

Long-term prognosis and prognostic factors of liver cirrhosis in the 1980s

Abstract The prognosis of 174 patients with cirrhosis during the 1980s (1981–89) was analysed. The estimated survival rates were 87.3% in 3 years and 68.5% in 5 years. During the follow-up period, 58 patients died: 20 of hepatocellular carcinoma (37.7%); 11 of hepatic failure (20.8%); eight of gastrointestinal bleeding (15.1%); and 14 of other causes (26.4%). Multivariate analysis revealed that serum albumin, indocyanine green retention rate at 15 min and white blood cell count were significantly associated with prognosis. The results were also compared to our previous study covering the 1970s (1971–80). The estimated survival rate was significantly improved compared to that during the 1970s (54.3% in 5 years, P < 0.001). In the 1980s, hepatic failure mortality significantly decreased ( P < 0.01), and non-liver-related mortality significantly increased ( P < 0.05). In summary, the prognosis of cirrhosis has improved in recent years, and changes of death cause and prognostic factors were observed. It was concluded that to evaluate the severity and prognosis of cirrhosis, new indices and appropriate classification were necessary.     

Deficiency of endogenous prostanoids in gastric and duodenal ulcer diseases

The levels of prostaglandin E₂ (PGE₂), 6-keto-prostaglandin F₁α (PGF₁α) and thromboxane B₂ (TXB₂) in endoscopic biopsy specimens from the gastric and duodenal mucosa of healthy volunteers and ulcer patients were measured by radio-immunoassay. The PGE₂ and PGF₁α levels in the mucosa of the corpus of the stomach were lower and the TXB₂ level was higher in 10 patients with gastric ulcer in the corpus than in the 16 healthy subjects. The PGE₂ level in the antral mucosa of 14 patients with gastric ulcer in the antrum was lower than in the controls. In 18 patients with duodenal ulcer, PGE₂ deficiency was more widespread in the entire gastric and duodenal mucosa while the reduced PGF₁α level was limited in the gastric corpus. Lower levels of PGE₂ in patients with antral or duodenal ulcer and of PGE₂ and PGF₁α in patients with corpus ulcer in the anatomical mucosal area including the ulcer site may predispose the mucosa to ulceration.