The multiple pharmacological actions of a unique compound are a prerequisite for classifying drugs as highly efficacious, because the multiple pharmacological actions offer the possibility of treating various symptoms of chronic diseases as described below. 1) Sustained hyperglycemia induces macrovascular and microvascular complications in type 2 diabetes mellitus. Antihyperglycemic medication and the control of postprandial hyperglycemia are essentially important for normalizing plasma glucose level. Gymnemic acid IV isolated from Gymnema sylvestre (Asclepiadaceae) leaves has antisweet, antihyperglycemic, glucose uptake inhibitory, and gut glycosidase inhibitory effects. Most of these pharmacological effects may synergistically contribute to alleviating type 2 diabetes-related symptoms. 2) Diabetic skeletal and vascular smooth muscles are hypersensitive to chemical transmitters, cytokines and autacoids. The sensitivity of neuromuscular synapses is enhanced in diabetes, which seems to be closely associated with neuropathy as one of the diabetic complications. β-Eudesmol found in Atractylodes lancea rhizome has a desensitizing channel blocking action to nicotinic acetylcholine receptors, anti-angiogenic action in vascular endothelium, and neuronal differentiation actions. These multiple pharmacological actions are favorable for treating angiogenic diseases possibly including the complications of diabetes, namely, retinopathy and nephropathy, and cancer. 3) Nipradilol is clinically utilized as a topical antiglaucoma drug. The ocular hypotensive effects of this compound are brought about by its α1- and β-adrenergic receptor blocking actions, and nitric oxide (NO) releasing action. NO directly activates cyclooxygenases. All these pharmacologic effects are beneficial for treating glaucoma. The selectivity and specificity of drug action are required for treating acute diseases, infections or for acting as useful reagents. The pleiotropic actions of natural compounds and their derivatives serve as important clues for developing new drugs for various chronic diseases.
An athymic mouse-derived immature T-cell clone, N-9F, was not maintained by interleukin-2 alone but required another soluble factor, contained in concanavalin A-stimulated rat splenocyte culture supernatant, namely T cell growth factor (TCGF), for its proliferation. An N-9F-proliferation factor (NPF) was isolated in a pure form from TCGF. N-9F cells and immature thymocytes proliferated in the presence of N-9F at 10-12-10-9M in a dose-dependent manner, but adult thymocytes were not stimulated by NPF. NPF increased DNA synthesis of N-9F. NPF increased CD4 and CD8 double negative, single positive and double positive thymocytes in fetal thymus organ culture. A hamster anti-NPF antiserum possessing the capacity to neutralize N-9F proliferation activity of NPF neutralized the increasing effect of NPF on immature thymocytes. All effects of NPF was inhibited by mAb QR6.6 to recognize a 100kDa surface molecule of N-9F. The amino-terminal 20 amino acid sequence of NPF was identified and identical to that of rat saposin A. The apparent molecular weight of NPF, 16000, was comparable to that of saposin A. A Hitrap-mouse recombinant His-tag-saposin A antibody column bound NPF, pulled down the NPF activity in TCGF, and the antibody recognized a 16kDa molecule in western-blotting of TCGF. Thus, NPF in TCGF was a saposin A-like protein possessing the capacity for growth and differentiation of immature thymocytes. The physiological significance of NPF in the growth and differentiation of immature thymocytes was discussed in view of the characteristic distributions of NPF and the molecule recognized by its mAb QR6.6 in fetal thymi.
This paper puts forward a method for estimating the infection route and speed of influenza from the daily variations in the amount of influenza formulations supplied at distant city pharmacies. The cross-correlation function between the time variations at the pharmacies indicates as for the drug sales, how many days a pharmacy lags behind another pharmacy. The comparison of the time lags between the pharmacies can lead to the estimation of the infection route of influenza. Taking into account the distance between the locations of the pharmacies, we can calculate the infection speed of influenza. Three pharmacies located in Tokyo and its vicinity (Saitama and Kanagawa) are taken as an example. The thrust of this paper is to introduce the new strategy that can take full advantage of the information every pharmacy has in possession.
The adherence of Candida albicans strain NIH A207 to plastic plates was inhibited by the addition of mannan, and plates coated with mannan also inhibited the adherence of C. albicans strains TIMM1768, TIMM2640, and JCM2076. Mannan coated the plastic plates under neutral and acidic conditions, but not under alkaline conditions. These results indicate that C. albicans cannot attach to mannan. Thus mannan-coated medical equipment might be useful to prevent C. albicans adherence.
Plant-derived phenylpropanoid compounds (4-ethyl-2-methoxyphenol, 2,6-dimethoxyphenol, 2,3-dimethoxyphenol, 3,4-dimethoxyphenol, 3,5-dimethoxyphenol, 3,4-dihydroxycinnamic acid, 4-hydroxy-3-methoxycinnamic acid, and 3-hydroxy-4-methoxycinnamic acid) were glycosidated to form glycoside compounds. We evaluated the effects of these compounds on the inhibition of tyrosinase and melanin synthesis and their cytotoxicity from the viewpoint of their use as whitening agents in cosmetics. Some compounds had more potent tyrosinase-inhibiting activity than commercial arbutin, which was used as a control, and showed no cytotoxicity at low concentration ranges.
A new type of S-protected thiol-type thiamines (prodrugs), which have a (5-methyl-2-oxo-1,3-dioxol-4-yl) methyl group recognized as a biologically safe promoiety, were designed, prepared, and confirmed to show higher serum thiamine levels after oral administration to rats than after that of thiamine itself and bisbentiamin as standards. Thus it was shown that the promoiety should be also used for improvement of poor oral absorption of drugs with a mercapto group, in addition to the absorption of drugs with carboxyl, amino, and hydroxyl groups.