Effect of gastrointestinal maturation on absorption of beta-lactam antibiotics.

Gastrointestinal absorption of cefazolin, which is poorly absorbed in adults, and of cephradine, which is well absorbed in adults, was studied in rats during their development. Significantly higher concentrations of cefazolin in plasma after oral administration were observed in 1- and 2-week-old rats compared with 3-week-old and adult rats. A marked difference in the absorption of cefazolin by 2- and 3-week-old rats (at weaning period) was observed. No such marked difference in the absorption of cephradine by rats of various age groups was found. With cefazolin, a similar pattern of developmental change in jejunal uptake was observed. Cortisone, which causes early maturation of the intestinal membrane, was given as a preweaning injection to 2-week-old rats. This treatment decreased concentrations of cefazolin in plasma and jejunal uptake of cefazolin. Thus, the absorption of cefazolin in 1- and 2-week-old rats seems to depend on the permeability of the immature intestinal membrane before weaning. Cephradine absorption from the intestine of 1-week-old rats became saturated and inhibited by carnosine and glycylglycine when studied by the in situ loop method. Cefazolin absorption was proportional to luminally administered doses and was not affected by carnosine and glycylglycine. A nonsaturable process for cefazolin and a saturable process for cephradine were also observed in an in vitro uptake experiment.     

Glial localization of four‐repeat tau in atypical progressive supranuclear palsy

In the present case, a patient in whom limb apraxia and asymmetrical parkinsonism developed suggesting corticobasal degeneration, is reported. Neuropathologic examination revealed numerous tufted astrocytes in the precentral cortex in addition to the characteristic pathologic findings of PSP. Therefore, on the basis of clinicopathologic features, atypical progressive supranuclear palsy was diagnosed. In addition, the brain tissue of the present patient was investigated with an antibody specific for four‐repeat tau (4R‐tau). In the precentral cortex, numerous tau‐positive tufted astrocytes, pretangles, and threads were positive for 4R‐tau. Using a confocal microscopy we demonstrated that tufted astrocytes positive for 4R‐tau were adjacent to astrocytes positive for GFAP. The present findings suggest that accumulation of four‐repeat tau in astrocytes is a degenerative process rather than a reactive process.     

Improvement in Wound Healing by Epidermal Growth Factor (EGF) Ointment. I. Effect of Nafamostat,Gabexate, or Gelatin on Stabilization and Efficacy of EGF

The healing effect of human epidermal growth factor (hEGF) on open wounds was studied in rats. No improvement in wound healing was found by topical application of EGF alone to open wound sites. We found an ointment containing EGF and a protease inhibitor, nafamostat mesilate or gabexate mesilate, or gelatin accelerated the healing rate of open wounds. Significant increases in the dry weight of the wound site granulation tissue, uronic acid (as an index of acid mucopolysaccharide) and hydroxyproline (as an index of collagen) were observed by treatment with EGF ointment containing nafamostat compared with the controls. The effects of the protease inhibitor on wound healing were dose dependent. Nafamostat was more efficient than gabexate or gelatin on wound healing. The degradation of ¹²⁵I-EGF in wound tissue homogenate was significantly decreased in the presence of a protease inhibitor, such as nafamostat or gabexate, or gelatin. These findings indicate that the stabilization of EGF at the wound site is an important factor in permitting the expression of its healing effects and suggest that the ointment containing EGF and a stabilizing agent would be a suitable dosage form for acceleration of wound repair.     

Immunoreactive opsin and glial fibrillary acidic protein in persistent hyperplastic primary vitreous

An 8-month-old boy had an anterior type of persistent hyperplastic primary vitreous in the right eye. Results of needle biopsy, performed because of elevated intraocular pressure, disclosed clusters of blastic cells. The eye was enucleated on the suspicion of retinoblastoma. Histological examination showed retrolental fibrovascular tissue and retinal dysplasia. Immunoreactive opsin was detected in the innermost structures and in photoreceptor-like cells of rosettes. We conclude that photoreceptor cells differentiated to express opsin, even when neighbouring cells were abnormally arranged. An immunocytochemical study of glial fibrillary acidic protein demonstrated glial proliferation in the inner layer of the retina but not in the preretinal space.     

Surgical treatment for carcinoma of the papilla of vater

Eighty of 89 patients who underwent radical resection (resectability 89.9%) for carcinoma of the papilla of Vater between 1976 and 1992 were retrospectively reviewed. Seventy-three patients underwent pancreaticoduodenectomy (PD) and 7 underwent pylorus-preserving pancreaticoduodenectomy (PPPD). The postoperative mortality rate was only 3.8% (3 patients). The 3- and 5-year survival rates were 63.6% and 57.4%, respectively. Important factors influencing long-term survival were Stage (clinical stage = Stage), microscopic lymph node metastasis (n), duodenal wall invasion (d), vascular invasion (v), and the epithelium of origin. Early carcinoma of the papilla of Vater is defined as tumor in which invasion is limited within the papilla of Vater; in particular, carcinomatous invasion is within the muscle of Oddi (d₀) with n₀. PD and/or PPPD with radical lymph node dissection should be performed for carcinoma of the papilla of Vater, as these procedures can be performed with low morbidity and mortality.     

Virucidal activity and viral protein modification by myeloperoxidase: a candidate for defense factor of human polymorphonuclear leukocytes against influenza virus infection.

Influenza virus (IFV) was inactivated by treatment with degranulated fluid (DF) or myeloperoxidase (MPO) from human polymorphonuclear leukocytes in the presence of H2O2. Hemagglutinin and neuraminidase activities of the virus were also reduced by DF treatment. In addition, treatment with DF or MPO in the presence of H2O2 resulted in delayed migration of viral proteins in SDS-PAGE, indicating extensively modified viral proteins. Parallel with this aberrant migration, the radioactivity of each protein band on SDS-PAGE using [35S]methionine-labeled IFV was greatly reduced. Moreover, some of the modified viral protein did not migrate. A small amount of acid-soluble degraded viral peptide was also generated. The modification of the proteins was exhibited in all major viral proteins, including the inner proteins in the envelope. These results suggest that inactivation of IFV and protein modification by DF is due to MPO present in DF.     

A nonspecific colonic ulcer occurring after hepatectomy: Report of a Case

We herein report the case of a 53-year-old man with a nonspecific acute colonic ulcer whose liver function deteriorated after he had undergone hepatectomy. He was referred to our hospital for a hepatoma caused by hepatitis B virus and a right hemihepatectomy was performed. His liver function was poor after the operation, and minor complications such as pleural effusion and biliary fistula developed. A large amount of melena was seen 29 days after the hepatectomy and he developed hemorrhagic shock. Superior mesenteric arteriography revealed pooling of blood in both the hepatic flexure of the ascending colon and the cecum. An emergency right hemicolectomy was performed. There was a 5 x 1-mm ulcer 18 cm distal to the ileocecal valve. Numerous erosions were observed to be scattered throughout the colonic mucosa. The patient recovered slowly and was discharged 6 months after the hepatectomy. This is the first report of an acute colonic ulcer that could have been caused by liver dysfunction.     

Differences in enhancing effects of zolpidem and benzodiazepine drugs on recurrent inhibition in rat hippocampal slices

It has been reported that the clinical and electroencephalographic profiles of zolpidem, a non-benzodiazepine drug which binds preferentially to the ω₁ benzodiazepine recognition sites located within the GABA_A receptor complex, are different from those of benzodiazepine drugs, which bind non-selectively to the ω₁ and ω₂ sites. In order to clarify the electrophysiological mechanism underlying the unique profile of zolpidem, the present study compared the enhancing effects of zolpidem and two benzodiazepine drugs, triazolam and diazepam, on recurrent inhibition. This inhibition was expressed as suppression of the orthodromically induced population spikes by the preceding antidromic stimulation of the alveus in the CA1 region of rat hippocampal slices. The rank order of potency for enhancing recurrent inhibition was triazolam > diazepam > zolpidem. From the present results and previously reported findings that zolpidem has a lower affinity for the ω₂ sites than diazepam while both have the same affinity for the ω₁ sites, we concluded that the hippocampal recurrent inhibition appears to be enhanced mainly by activation of the ω₂ sites, but not by that of the ω₁ sites. Furthermore, the lower potency of zolpidem for enhancing recurrent inhibition may underlie its unique profile in terms of its clinical and electroencephalographic effects. Received: 1 November 1996/Final version: 22 January 1997