Improvement of Transdermal Delivery of Tetragastrin by Lipophilic Modification with Fatty Acids

The in-vitro permeability of chemically modified tetragastrin with fatty acids through the rat skin was studied. The permeability of these compounds through intact skin and stripped skin of rat was determined with a Franz-type diffusion cell. The permeation of tetragastrin across the intact skin was improved by chemical modification with acetic acid and butyric acid. However, tetragastrin and caproyl-tetragastrin did not permeate across the intact skin up to the end of experiment. The permeation of tetragastrin across the stripped skin was improved by chemical modification, the skin flux of these acyl derivatives being in the order: acetyl > butyroyl > caproyl. The stability of tetragastrin in skin homogenate was also significantly improved by chemical modification with fatty acids. These results suggest that chemical modification of tetragastrin with fatty acids increases its lipophilicity, which makes it permeable across the stratum corneum. Moreover, the chemical modification reduced the degradation of tetragastrin in the viable skin, resulting an increase in permeation of tetragastrin across the skin.     

Fluid and Protein Secretion by the Submandibular Glands of Weanling Rats in Response to Cholinergic and Peptidergic Agonists at Various Doses

Fluid and protein secretion by the submandibular glands of 25-day-old rats were examined and compared in response to three cholinergic and four peptidergic sialogogues at various doses. All cholinergic and peptidergic agonists used were potent sialogogues for the submandibular glands of the weanling rats over the wide range of doses used. The cholinergic agonists, bethanechol and methacholine and the peptidergic agonists, substance P, substance P^Tyr8 and eledoisin-related peptide used intravenously, acted similarly to each other on the submandibular glands of the rats, late in the natural weaning period, but carbachol and physalaemin had slightly different effects. Of the peptidergic agonists, physalaemin was the most potent sialogogue among four tachykinins tested at the low dose. The types of protein secreted by the submandibular glands of the weanling rats in response to all sialogogues used here were typical of the β-type. These results indicate that all agonists used could mainly stimulate the acinar cells of the submandibular glands of the weanling rats which have already fully developed functionally at this time.     

Laparoscopic radical cystectomy and bilateral ureteric ligation for muscle-invasive bladder cancer in a patient on hemodialysis

Laparoscopic cystectomy and bilateral ureteric ligation were performed on a 52-year-old woman with end-stage renal disease on hemodialysis (HD) for muscle-invasive bladder cancer. Her volume of urine production was approximately 100 mL/day. Excisions of the bladder and uterus with ligation of the bilateral ureter were conducted completely laparoscopically. Total operative time was 280 min and the amount of blood loss was 60 mL. No complications were seen perioperatively and no adverse events regarding ureteric ligation arose. HD was performed on the second postoperative day. At a 12-month follow-up, the patient showed no evidence of disease.     

Genetic susceptibility to type 2 diabetic nephropathy in human and animal models

SUMMARY:   Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) in Japan, Western Europe, and the United States. Mega studies such as Diabetes Control and Complication Trial (DCCT), Epidemiology of Diabetes Interventions and Complications (EDIC), and the United Kingdom Prospective Diabetes Study (UKPDS) clarified that poor glycemic and blood pressure control are undoubtedly involved in the development of nephropathy. However, these factors are not sufficient to predict which diabetic patients will develop renal disease, because not all patients with poor glycemic and blood pressure control develop renal disease. Since ethnic variations and familial clustering of diabetic nephropathy have been observed, genetic factors might contribute to susceptibility to this disease. Several methods such as (genome wide) association studies, sib-pair analysis, and quantitative trait loci (QTLs) analysis are available to examine polygenic diseases. However, no mutations that could explain the majority of nephropathy cases have been identified so far. The development of most diabetic nephropathy might be explained by the polygenic effect (i.e. many minor gene-gene interactions might be very important in the development of nephropathy). Identification of candidate genes of nephropathy enables targeting of therapy in patients at risk and development of novel therapeutic agents.     

Protein Synthesis in Yolk Sac Tumor: Histochemical Studies of Human and Rat Yolk Sac Tumor

Synthesis of various serum proteins, such as albumin, prealbumin, α₁-antitrypsin, transferrin and α-fetoprotein, by human and rat yolk sac tumors was studied by indirect immunofluorescence and immunoperoxidase techniques. These serum proteins were found to be present in the cytoplasm of tumor cells forming the lining of vitelline cysts, as well as Schiller-Duval bodies and vacuolated meshwork on histological sections. Two of these tumors were cultured. Immunopathological studies revealed that albumin, prealbumin, α₁-antitrypsin, transferrin and α-fetoprotein were found in the cytoplasm of these cultured tumor cells. The immunofluorescence of these proteins was also found on the PAS-positive granules, which existed intra- and extra-cellularly.
The ability to synthesize these serum proteins of these tumor cells was not affected by tissue culture and was maintained during subcloning.
It was demonstrated by electron microscope ferritin antibody technique that α-fetoprotein was mainly synthesized on the ribosomes of the rough endoplasmic reticula of rat yolk sac tumor cells.     

Blast Crisis of Chronic Myelogenous Leukemia with Tumor Formation Characterized by T-cell Features--A Case Report

We report a case of chronic myelogenous leukemia (CML) associatedwith pronounced peripheral lymphadenopathy, with the cells havingthe Philadelphia (Phl) chromosome and T-cell features. A 23-year-oldman who was diagnosed as having CML and treated with busulfanwas admitted to our hospital because of increasing hepatosplenomegalyand pronounced lymphadenopathy. An axillary lymph node biopsydisclosed that the malignant cells formed rosettes with neuraminidase-treatedsheep red blood cells (En) (95.0%) and were positive for Leu1 (91.8%). Of the cytochemical reactions, peroxidase was negativeand periodic acid-Shiff, acid -naphthyl acetate esterase andß-glucuronidase were all positive. The karyotype ofthe bone marrow cells was 46 XY Phl positive (22q–), andthat of the lymph node cells was 51 XY Phl positive +8, +9,+18, +19, +21, 22q–. He was treated with various anti-leukemicagents and irradiation. Despite such treatments, he died ofpneumonia. This is a report of a CML patients with blast crisisand tumor formation characterized by T-cell features.     

Phagocytosis of heat‐killed Staphylococcus aureus by eosinophils: comparison with neutrophils

Eosinophils are characterized by several functional properties, such as chemotaxis, adhesion, superoxide anion production, and degranulation. In this article, we have studied the role of bacterial ingestion by eosinophils in comparison with that by neutrophils. Eosinophils and neutrophils were purified by using the Percoll gradient method followed by selection with CD16‐coated immunomagnetic beads and centrifugation through a Ficoll‐Hypaque gradient combined with dextran sedimentation, respectively. Both cells were preincubated with anti‐FcγRIIa mAb (CD32 mAb), anti‐FcγRIIIb mAb (CD16 mAb), anti‐CR3 (CD11b mAb), or anti‐CR1 (CD35 mAb) before being examined for phagocytosis of opsonized heat‐killed Staphylococcus aureus (S. aureus). Phagocytosis and production of hydrogen peroxide were simultaneously measured by flow cytometry using S. aureus labeled with propidium iodide and stained with 2′,7′‐dichlorofluorescein diacetate. Eosinophils showed significantly lower activity than neutrophils in both phagocytosis and hydrogen peroxide production. Phagocytosis by both cells was decreased by heat‐inactivated serum. Phagocytosis by neutrophils was significantly inhibited by CD16 mAb and CD32 mAb, whereas that by eosinophils was only inhibited by CD35 mAb. Whereas the mechanism of phagocytosis by neutrophils was mediated by CD16 and CD32, that of eosinophils was modulated by complement receptor 1 (CD35).     

Anti-neutrophil cytoplasmic antibodies in Japanese children with ulcerative colitis

Objective: To investigate the diagnostic value of anti-neutrophil cytoplasmic antibodies (ANCA) in the diagnosis of ulcerative colitis (UC) in Japanese children.
Methodology Serum samples from 23 children with UC (17 Japanese, 6 non-Japanese), 27 children with Crohn's disease (CD) (10 Japanese, 17 non-Japanese), 10 children with other diarrhoeal diseases, and 33 normal, healthy adult volunteers were assayed for ANCA using an indirect immunofluorescence technique.
Results ANCA were detected in 6/17 (35%) UC patients and 0/10 (0%) CD patients in Japanese children, and in 3/6 (50%) UC patients and 3/17 (18%) CD patients in non-Japanese children. The difference in prevalence between Japanese and non-Japanese children with UC was not statistically significant ( P >0.05). ANCA were not found in other diarrhoeal patients and volunteers.
Conclusions Although ANCA have been reported to be useful in the diagnosis of UC in adults, they may be of limited use in Japanese children. This might reflect the heterogeneity of UC.     

A case of granular cell tumor of the bladder successfully managed with extraperitoneal laparoscopic surgery

Granular cell tumor is a benign neoplasm which frequently occurs in the oral cavity, skin, and subcutaneous tissue. Granular cell tumor of the bladder is an extremely rare disease, and only nine cases have been reported. We present here an additional case of granular cell tumor occurring in the bladder. Unlike the other tumors reported, this tumor extruded into the Retzius' cavity. Therefore, the tumor was successfully excised through extraperitoneal laparoscopic surgery. The patient was free from recurrence 40 months after surgery. The small tumor located in Retzius' cavity could be managed with extraperitoneal laparoscopic surgery.