Ninjin-yoei-to (NYT), a Kampo medicine, has ameliorative effects on cognitive dysfunction via enhancing cholinergic neuron activity. To explore an efficacy of NYT administration for prevention and cure of Alzheimer's disease, here we examined the effect of NYT on amyloid β1-42 (Aβ1-42)-induced neurodegeneration in the dentate gyrus.A diet containing 3% NYT was administered to mice for 2 weeks and human Aβ1-42 was intracerebroventricularly injected. Neurodegeneration in the dentate granule cell layer of the hippocampus, which was determined 2 weeks after the injection, was rescued by administration of the diet for 4 weeks. Aβ staining (uptake) was not modified in the dentate granule cell layer by pre-administration of the diet for 2 weeks, while Aβ1-42induced increase in intracellular Zn 2+ was reduced, suggesting that pre-administration of NYT prior to Aβ injection is effective for reducing Aβ1-42-induced Zn 2+ toxicity in the dentate gyrus. As a matter of fact, Aβ1-42-induced neurodegeneration in the dentate gyrus was rescued by pre-administration of NYT. Interestingly, the level of metallothioneins, intracellular Zn 2+ -binding proteins, which can capture Zn 2+ from Zn-Aβ1-42 complexes, was elevated in the dentate granule cell layer by pre-administration of NYT. The present study suggests that pre-administration of NYT prevents Aβ1-42mediated neurodegeneration in the dentate gyurs by induced synthesis of metallothioneins, which reduces intracellular Zn 2+ toxicity induced by Aβ1-42.
Despite tremendous success of pneumococcal conjugated vaccine and antimicrobial treatment by amoxicillin, acute otitis media (AOM) still remains as a great medical concern. Failure of antimicrobial treatment includes several factors. The middle ear cavity is surrounded by bone tissue, which makes it difficult to maintain sufficient concentration of antibiotics. Tympanic membrane of AOM patients thickens and actually becomes a barrier for topical therapy. This review discusses novel antimicrobial treatment strategies based on drug delivery systems (DDS) for AOM. To deliver drugs enough to kill the pathogenic bacteria without systemic side effects, the development of new antimicrobial treatment strategy applying innovative drug DDS has been expected. The sustained-release DDS can achieve sufficient time for antimicrobial concentrations to exceed minimum inhibitory concentration (MIC) for time-dependent antibiotics as well as enough maximum concentration for dose-dependent antibiotics to eradicate causative pathogens in the middle ear. The development of trans-tympanic membranes of DDS, such as hydrogels with chemical permeation enhancers (CPEs), is another attractive strategy. Phage is a promising strategy for developing DDS-based therapies. The DDS formulations enable antimicrobial treatment of AOM by a single dose and thus, an attractive future antimicrobial treatment for AOM.
SummaryTo understand the molecular basis of glucose concentration-responsive insulin synthesis and secretion from pancreatic islet beta cells, a group of pancreatic islet beta-cell-related cDNAs was cloned. A pair of cDNA libraries was constructed from a mouse pancreatic islet beta-cell line of MIN6, which was cultured in either high glucose or low glucose media. By applying a random cDNA sequencing approach, 503 and 395 independent species were obtained from a total of 1,011 and 762 clones in the high glucose and low glucose library, respectively. The unknown genes comprised the majority of about 70 % independent clones in both libraries. In Northern blot analysis, 311 (69.4%) of 448 independent clones showed positive signals within 72 h of autoradiographic exposure. Surprisingly, 150 (48.2 %) out of 311 positive clones showed positive signals to MIN6 cells, but not to NIH/3T3 fibroblasts. The expression level of three unknown clones were glucose-concentration dependent. Combination of a random cDNA sequencing approach and Northern blot analysis is useful to obtain a large number of novel genes and islet beta-cell-related genes. [Diabetologia (1995) 38: 381-386] Key words Random cDNA sequencing, MIN6, pancreatic islet beta cell.Understanding the molecular basis of pancreatic islet beta cells is essential in order to develop a logical treatment for diabetes. In addition to glucokinase [1][2][3] and mitochondrial genes [4][5], which are known to be aetiological for non-insulin-dependent diabetes or maturity-onset diabetes of the young, there are others which are related to islet beta-cell Received: 12 July 1994 and in revised form: 20 September 1994Corresponding author: Professor M. Itakura, Otsuka Department of Clinical and Molecular Nutrition, School of Medicine, University of Tokushima, Kuromoto, Tokushima-city, Tokushima, 770, Japan Abbreviations: DMEM, Dulbecco's modified Eagle's medium; FCS, fetal calf serum; AGPC, acid guanidinium thiocyanatephenol-chloroform; bp, base pair(s); IAPR islet amyloid polypeptide; HUMMHBA 123, human MHC protein homologous to chicken B complex protein; PACAR pituitary adenylate cyclase activating polypeptide precursor. function and diabetes. It is speculated that the highly-differentiated functions of islet beta cells are based on a group of cell-specific genes. Recently, large,scale cDNA analysis has become a valuable way to examine and register expressed genes in various tissues by determining expressed sequence tags [6][7][8][9]. Abundant transcripts, which are frequently encountered in random sequencing, are assumed to play relatively more important roles than rare transcripts with exceptions including transacting factors and rate-limiting enzymes among others. With this in mind we randomly sequenced cDNA to clone unknown genes which are abundantly expressed and are presumably important for islet beta-cell functions. In this study we report the acquisition of a group of islet beta-cell-related genes by combining a random cDNA sequencing of a total of 1,773 clones from a m...
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