The most important problem in cancer research is to increase comfortably the survival time and to prevent completely recurrence after surgical resection in cancer patients. Cytocidal anticancer chemotherapeutics have detrimental side effects and destroy host defence mechanisms, and are not useful for cancer patients. On the other hand, there is several evidence suggesting the existence of intrinsic resistance to cancer. The examples are an equilibrium state with proliferation and regression in a small amount of cancer cells and spontaneous regression of cancer. An increase in this resistance may be one of the most important problem to find new anticancer drugs. In Oriental medicine practiced in Asian countries from olden times, the fundamental principle is to regulate homeostasis of the whole body and to bring the diseased person to a normal state, rather than to attack the focus directly. On the basis of such a concept, the antitumor activity of numerous folk remedies has been reexamined and isolated a polysaccharide with marked antitumor activity and named as lentinan. Lentinan is a strictly purified β-1, 6 : β-1, 3-D-glucan, and exerts prominent antitumor activities in murine allogeneic, syngeneic and autochthonous hosts, prevents chemical and viral oncogeneses, and suppresses tumor metastasis in several clinical models. The antitumor action of lentinan is host-mediated. Comparing with other well-known immunostimulants, such as BCG, C. parvum and LPS, lentinan appears to represent a unique class of immunopotentiator, a T-cell oriented adjuvant in which macrophages play some parts. First, lentinan triggers the increased production of various kinds of bioactive serum factors associated with immunity and inflammation, such as CSF, IL-1, IL-3, vascular dilatation hemorrhage inducer and acute-phase protein inducer, by direct impact of macrophages or indirectly via lentinan-stimulated T-cells, which results in the induction of many immunobiological changes in the host. Augmented IL-1 production amplifies the maturation of immature effector cells to mature cells capable of responding to IL-2 and other cytokines, but lentinan do not augment production of IL-2. This is the most important characteristics of lentinan, because this suggests a contact point between new immunology and Oriental medicine. Lentinan augments differentiation of various kinds of important cells in the host defence. These results clearly explain the requirment of intact macrophages and T-cell compartments for antitumor activity of lentinan. Lentinan has only a little toxic side effect in in vivo application to animals and human. An excellent result was obtained in 4 year's follow-up of the randomized control study of lentinan in Phase III on the patients with advanced and recurrent stomach, colo-rectal, breast cancer and malignant lymphoma. These results suggest that lentinan might be more effective for micrometastasis after surgery. Lentinan is a hopeful drug for cancer patients.

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Since polyamines are essential components of cell proliferation, mechanism of polyamine stimulation of cell growth has been studied. It has been found that polyamines play several important roles in protein synthesis : (a) they stimulate the synthesis of specific proteins; (b) they decrease misincorporation of amino acid into polypeptides; and (c) they stimulate the assembly of Escherichia coli 30S ribosomal subunits from their constituents. Effect of polyamines on nucleic acid synthesis is briefly summarized.

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Within the past decade, more than 30 peptides have been identified in the central nervous system (CNS). Of all these peptides, substance P (SP) is one of the best characterized neuropeptides in the mammalian tissues. In addition to SP, two novel tachykinin peptides have recently been identified in the mammalian CNS, namely neurokinin A and neurokinin B. This review will describe our present knowledge on the distribution of tachykinins, its pharmacological properties, especially tachykinins peptide receptors and cardiovascular effects in the CNS.

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The oxidation of ethyl acetoacetate with peracetic acid in the presence of sulfuric acid in acetic acid has been followed by iodometry. The rate satisfied the following equation; -dC_PAA/dt={k_d+k_tC_H2SO4}C_PAA+{k₂+k₂'C_H2SO4}C_PAAC_EAA. The first and the second terms correspond to the decomposition of peracetic acid and the acid-catalyzed reversible transformation to acetyl peroxide, while the third and the fourth terms represent the neutral and the acid-catalyzed oxidation of ethyl acetoacetate, respectively, with peracetic acid. Hammett plots of the third and the fourth terms for the oxidation of substituted phenyl acetoacetates gave straight lines with slopes of -0.91 and -1.36, respectively. As products, acetic and oxalic acids, acetaldehyde, ethanol, ethyl glyoxylate, ethyl glycolate, ethyl acetate and diethyl oxalate were confirmed by means of gaschromatography and/or thin layer chromatography. No Baeyer-Villiger reaction product was formed at all. From these findings, a mechanisms is postulated and discussed which involves an epoxidation of enol form of ethyl acetoacetate, as the rate determining step, by an attack of the positive oxygen atom of peracetic acid and/or of protonated one.

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A fraction causing diarrhea to mice with a hemolytic activity was previously isolated from the aqueous extract of a poisonous mushroom Rhodophyllus rhodopolius. In order to clarify the relationship between the enterotoxicity and hemolytic activity, the hemolysin was purified. The hemolysin which was partially purified by DEAE-cellulose column chromatography, ammonium sulfate precipitation, and Sephacryl S-300 column chromatography, caused diarrhea and intestinal hemorrhage to suckling mice. The molecular weight of the hemolysin was estimated to be about 40000 by SDS-slab polyacrylamide gel electrophoresis and gel filtration. The hemolytic activity of the hemolysin was observed to be relatively heat-stable in the crude extract and dependent on the temperature and concentration of erythrocytes.

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Flunarizine (flu) is a calcium entry blocker and widely used in the treatment of cerebral and peripheral vascular diseases. It has been also reported to have an anticonvulsant effect. We developed an analytical method of flu serum concentration by high performance liquid chromatography for therapeutic drug monitoring. By using the present method, pharmacokinetic parameters were determined for seven healthy volunteers after a single oral administration and serum concentrations of flu were monitored for seventeen patients with add-on treatment in therapy-resistant epilepsy or cerebrovascular disease. The peak-height ratio of flu to the internal standard (cinnarizine) was linealy related (r=0.9994) to concentrations over the range 5-200ng/ml in the serum. The detective limit was 2 ng/ml in the human serum. The overall average recovery was 99.1±5.1% (n=30). The within-day precision was 3.3% (n=5) and the between-day reproducibility was less than 5% over 5 d. Commonly used antiepileptic agents were found not to interfer in this method. The seven healthy volunteers received a single oral dose 20 mg of flu tablets after overnight fast. The average of the maximal serum concentration and the area under the curve from 0 to 24 h were 55.0±13.4 ng/ml and 552.1±136.1 ng·h/ml, respectively. The elimination from the serum showed a biphasic pattern, with the elimination half-life of 18.8±4.6 h. Flu showed the effect only for the impairment of consciousness in complex partial seizure in two epileptic children, and at this time, the trough concentrations in the serum were 25 and 45 ng/ml.

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The hamster cheek pouch has generally been used in oral mucosal irritation test. However, whether the hamster cheek pouch is suited for this test is questionable, because it differs from the oral mucosa histologically. Therefore, we tried to search for a more suitable mucosa for irritation tests in place of the hamster cheek pouch, and found that the rabbit sublingual mucosa was quite ideal for this purpose. That is, the rabbit sublingual mucosa showed a higher sensitivity than the hamster cheek pouch to irritants such as acetic acid and sodium lauryl sulfate. And it showed a similar pattern of injury for each irritant. These results indicated that the rabbit sublingual mucosa was ideal for irritation tests. We also devised a new apparatus by which the tested drug is kept in uniformly close contact with the mucosa for prolonged periods of time. By using our new apparatus, we examined a relationship between the duration of drug application and the intensity of the resulting injury, and a relationship between the concentration of irritants and the intensity of the resulting injury. We determined the duration of application, the appropriate observation time and criteria of the test condition based on our findings that the intensity of injury was dependent on the duration of application or the concentration of irritants, and that the time when the injury reached its peak was the same regardless of the concentration of irritants. The results of our study suggest that our new method would be a highly sensitive technique for the evaluation of the irritancy of drugs on the oral mucosa.

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The effects of ethyl eicosapentaenoate (EPA-E) and docosahexaenoic acid (DHA) on the rat hepatic drug and fatty acid metabolizing enzyme systems were studied after single or repeated oral administration for 14 d. The ratio of liver to body weight and protein concentration in each fraction of microsomes, mitochondria and peroxisomes were not affected after single or repeated administration of EPA-E or DHA. Neither induction nor inhibition of hepatic drug metabolizing enzymes was not observed in EPA-E group. A single administration of DHA decreased aniline p-hydroxylase activity. This decrease in activity, however, was neither enhanced nor reduced after repeated administration of DHA. Other hepatic drug metabolizing enzymes were not affected by DHA. No effects on fatty acid oxidizing enzyme systems of mitochondria and peroxisomes were observed after administration of EPA-E or DHA. No effects on fatty acid elongation and desaturation on microsomes were observed after administration of EPA-E or DHA.

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In order to develop a new tumor-detecting agent with D-amino acid as a parent compound, the preparation of ¹²⁵I labeled D- and L-iodophenylglycines and their distribution in Ehrlich solid tumor-bearing mice were investigated. Each labeled compound was synthesized via the corresponding diazonium compound. The distribution pattern of the D-form was similar to that of the L-form. Although the tumor uptake of D-form, as well as L-form, at 60 min after the injection was higher than other organs except kidney, stomach, duodenum and thyroid, its uptake ratio was insufficient for use as a tumor-imaging agent.

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