The kinetics of peritoneal insulin absorption

This study examined the relationship between the delivery of insulin into the peritoneal space and its absorption into the peripheral circulation. Studies were performed in conscious dogs receiving somatostatin (5.0 μg/min) to suppress endogenous insulin secretion, and intravenous glucose (50 mg/min) to prevent hypoglycemia. The biologic effectiveness of the absorbed insulin was determined by its hypoglycemic effect. The possibility of direct absorption of insulin into the portal circulation from the peritoneal space in anesthetized, portal vein-catheterized dogs was examined with radiolabeled I¹²⁵ insulin. Our results suggest that absorption of insulin from the peritoneal space is volume, concentration, and time-dependent. Maximal absorption of insulin was observed at 50 min when 1.92 U of insulin in a volume of 3 ml was infused intraperitoneally over 30 min. More rapid absorption was observed at 30 min when this quantity of insulin was given in a 1-min intraperitoneal bolus, compared to 30 min of intraperitoneal infusion. Least rapid absorption of insulin followed the delivery of 1.92 U of insulin in a volume of 15 ml. Intermediate absorption of insulin was observed at 40 min when the 1.92 U was delivered in a volume of 0.6 ml. Peripheral intravenous insulin delivery of 1.92 U reached a maximal plasma concentration at 20 min, which was more than three times the concentration observed with intraperitoneal insulin. Isotopic tracer studies, in which radioiodinated insulin was placed into the peritoneal space in anesthetized dogs, demonstrated greater radioactivity in the portal vein than in the aorta throughout a 30-min observation period. These studies demonstrate that intraperitoneal administration of insulin results in absorption of insulin which is volume, concentration, and time-dependent. Thus, the peritoneal space may be an appropriate site for insulin delivery through a transcutaneous catheter.     

A histological study of changes in the lingual papillae of streptozotocin-induced diabetic rats.

This study examined the effect of experimental diabetes mellitus on the dorsal tongue of rats which were made diabetic by tail-vein injections of streptozotocin (50 mg/kg) and then raised for either 5 or 10 months. Lingual papillae were observed by scanning electron microscopy (SEM) and light microscopy. Morphological changes in lingual mucosal capillaries in 10-month diabetic rats were observed by electron microscopy (TEM). In the study of cellular movement in the lingual dorsal epithelium, bromodeoxyuridine (BrdU) was applied as a tracer for studying DNA replication. In diabetic rats, lingual papillae showed morphological atrophic changes. The lingual mucosal capillaries' alterations included endothelial cells with numerous cell projections into the lumen, degenerated cell organs, increased basement membrane width, and narrowed capillary lumen. BrdU labeling index among the basal cells was reduced in diabetic rats which indicates a possible retardation of their epithelial-tissue activity. In diabetes mellitus, direct metabolic disturbances to the epithelia because of insulin deficiency first occurred, successively diabetic microangiopathy appeared on the lingual mucosal capillaries. The appearance of diabetic microangiopathy caused tissue hypoxia, which induced atrophic changes to the epithelia.     

Low-titer cold agglutinin disease following Salmonella gastroenteritis

We encountered a patient with cold agglutinin disease (CAD) that worsened after Salmonella gastroenteritis. A 52-year-old male complained pain in the left fingers with cyanosis and was admitted in a local hospital. After treatment for ischemia, he demonstrated diarrhea with fever. Because of progressive anemia, he was referred to our hospital. Salmonella gastroenteritis was diagnosed based on the results of microbiological examination. Severe hemolysis was noted at admission, and Coombs test was positive (IgG-, C3d+). Cold agglutinin titer was elevated (x256). There were no findings of malignancy or infection demonstrating CA. A diagnosis of CAD with Salmonella gastroenteritis was made. Because spherocytosis was noted during admission, we measured the mean channel fluorescence (MCF) of eosin-5-maleimide (EMA) in erythrocytes from patients. MCF of EMA of the patient's erythrocytes was similar to that of normal subjects. Therefore, we concluded that coexisting hereditary spherocytosis was unlikely. We also examined the in vitro hemolytic effect of Salmonella infection on his blood and on blood from normal subjects. Treatment with Salmonella enteritidis isolated from this patient was found to induce hemolysis in the patient's blood, but not in blood from a normal subject. Moreover, treatment with Salmonella increased the titer of cold agglutinin in vitro. These data suggested that Salmonella infection might worsen hemolysis in CAD.     

Transition-Metal-Catalyzed Diarylation of Isocyanides with Triarylbismuthines for the Selective Synthesis of Imine Derivatives

The transition-metal-catalyzed diarylation of isocyanides with triarylbismuthines was investigated in detail, and rhodium catalysts such as [RhCl(nbd)]₂ were found to selectively afford N-alkyl diaryl ketimines. On the other hand, palladium-catalyzed diarylation proceeded with the incorporation of two molecules of isocyanide, preferentially yielding N,N’-dialkyl or N,N’-diaryl α-diimines. In addition, a cascade synthesis of 2,3-diarylquinoxalines starting from the palladium-catalyzed diarylation of isocyanides with triarylbismuthines was successfully achieved.     

Phase II study of S-1 as first-line treatment for elderly patients over 75 years of age with advanced gastric cancer: the Tokyo Cooperative Oncology Group study

Purpose

This prospective multicenter phase II study was carried out to investigate the efficacy, safety and pharmacokinetics of S-1 monotherapy in elderly patients over 75 years of age, with unresectable advanced or recurrent gastric cancer.

Methods

Patients had measurable or evaluable lesions according to the Japanese Classification of Gastric Carcinoma. S-1 (25–60 mg determined by the body surface area and creatinine clearance) was given orally, twice daily. A course of treatment consisted of 4-week administration followed by a 2-week rest period, and the patients received repeated courses.

Results

Thirty-three patients were enrolled. Pharmacokinetics of S-1 was studied in six patients, and the maximum plasma concentrations of respective metabolites after S-1 administration were found to be similar to those reported for younger cancer patients. The overall response rate in 33 patients was 21.2% (95% CI, 10.7–37.8%), and median progression-free survival was 3.9 months, with a median overall survival of 15.7 months. Frequently noted adverse events include leukopenia, neutropenia, anemia, anorexia, and fatigue. As for serious adverse events, relatively higher frequencies of anemia (9%) and anorexia (12%) of grade 3 severity were found, but there were no grade 4 episodes.

Conclusions

The results suggest that S-1 monotherapy is safe and useful for elderly patients with unresectable advanced or recurrent gastric cancer when the dose is selected with caution, taking into account renal function.     

Morphological study on the human developing vitreous collagen fibrils and persistent hyperplastic primary vitreous

The human primary vitreous fibrils were similar to the secondary vitreous fibrils on electron microscopic observation. On the other hand, the intravitreal strand in a persistent hyperplastic primary vitreous (PHPV) contained large numbers of collagenous fibrils with 40-50 nm diameters and about 65 nm cross-striation periodicity. Besides these, other types of noncross-striated fibrils, ranging in diameter from 10 to 30 nm were observed in the circumferential region of the intravitreal strand. Moreover, there was complete morphological continuation between the intravitreal strand and the optic disc. Their histochemical properties were very likely collagenous and in part glial. Although the results are based only on 1 case of PHPV, present observations showed that components of the intravitreal strand of PHPV considerably differed from the primary vitreous.