Marihuana is a complex mixture containing various biologically active compounds in which cannabinoids are major components. The drug interaction of marihuana with other drugs is a serious problem in some cases since marihuana is often taken with other centrally-acting drugs. Tetrahydrocannabinol (THC), which is a main component responsible for most of the psychomimetic effects of marihuana, can potentiate the effects of many depressants, such as alcohol, barbiturates, anesthetics, morphine and anticonvulsants, in the central nervous system. The drug interaction of THC with other drugs is a functional mechanism in the central nervous system. THC has biphasic effects (stimulant and depressant) depending on, maily, doses. THC, therefore, interacts with stimulants as cocaine and phencyclidine in a complicated manner. Cross-tolerance in some effects of the components of marihuana and of other drugs has been recognized. Cannabidiol (CBD), which is another major component in marihuana but lacks psychomimetic activity, potentiates the effects of some specified drugs that terminates their effects through metabolic inactivation. The interaction of CBD with other drugs is considered to be metabolic in origin since the cannabinoid can suppress the gepatic microsomal drugmetabolizing enzymes. Drug interaction can also occur among cannabinoids, indicating the complexity of the combined effect of marihuana and other drugs. These are additives, synergistic or antagonistic, depending on the conditions used. This review describes the interactions of marihuana components with centrally-acting drugs in relation to their pharmacological and toxicological significance.

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The determination of butylated hydroxyanisole (BHA) and its conjugated metabolites (glucuronide and sulfate) in tissues and excreta of BHA administered mice was investigated by normal-phase high-performance liquid chromatography (HPLC). Male mice were orally administered BHA at 50 and 500 mg/kg, BHA and its metabolites were extracted from the liver and kidney by continuous extraction and from the blood, stomach, intestine, urine and feces by direct extraction. Conjugated metabolites were hydrolyzed with enzymes before extraction. BHA could be determined without influence from obstructive substances. In animals administered BHA at 500 mg/kg, unchanged BHA was present at high concentration in the liver, kidney and the blood 0.5 h later, but at 8 h could not be detected in any sample. The sulfate of BHA exceeded the glucuronide of BHA in the liver at 0.5 h, but the latter exceeded the former during 1 and 3 h after dosing. Mice excreted about 52% of 500 mg/kg during 8 h, and about 76% within 48 h in the urine as glucuronide (72.3±7.6%), sulfate (3.0±2.4%) and unchanged BHA (0.3±0.1%). However, about 25% of unchanged BHA was recovered from stomach at 8 h, and even after 48 h. some unchanged BHA could be found.

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The conditions for production of amines by tyramine- and histamine-producing bacterial strains (T- and H-strains) isolated from soybean paste (miso) starting materials were examined. These strains grew and produced tyramine and histamine under various conditions which may occur during miso fermentation. Namely, tyramine and histamine were produced at pH above 5.1, at salt concentrations of less than 6% and 4%, under either aerobic or anaerobic conditions and at 15-37°C in MRS medium. Both strains consumed possible precursor amino acids of the respective amines. It is assumed that tyramine and histamine were produced by T- and H-strains during the early stages of miso aging and within a short period, when the salt concentration and pH conditions were optimal. Based on their bacteriological properties, the T-strain was identified as Enterococcus faecium and the H-strain was identified as Lactobacillus sp.

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A sensitive and simple analytical method for butylated hydroxyanisole (BHA) using a high performance liquid chromatograph (HPLC) with an electrochemical detector (ECD) was described. Detection limit of BHA was 0.02 ng when BHA standard solution was analyzed. The determination of BHA by HPLC-ECD is strongly affected by the stain of the ECD electrode by contaminants in the biological samples, which causes a remarkable decrease of sensitivity. The decrease was small when BHA in the biological samples was extracted with n-hexane, the n-hexane layer was then extracted with n-hexane-saturated acetonitrile, and 0.05 M NaClO₄/80% methanol was used as the mobile phase. Free BHA was recovered in high quantities from urine, serum and liver. Total BHA (sum of free BHA and conjugated BHA) was determined after hydrolysis of conjugated BHA by enzymes (enzymatic method) or HCl (HCl method). The two hydrolysis methods were compared. For urine, the enzymatic method gave a good recovery whereas the HCl method gave a low recovery. For serum, both hydrolysis methods were applicable. For liver, recovery by the enzymatic method was very low and not constant, however, constant recoveries and analytical values were obtained by the HCl method irrespective of BHA concentration. Determination limits for free BHA and total BHA were 30 ng/g for urine and serum, and 100 ng/g for liver.

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Identification of allergen in foods is predominantly reported in relation to food and allergic response ; there have been very few reports on antiallergic components in foods. The effect of vegetable foods on immediate allergic reaction was evaluated using a newly developed assay method. This method is advantageous in that, since it uses rat basophilic leukemia cells (RBL-2H3), cells of high purity are easy to obtain, and a release of chemical mediator determines by colorimetry the enzyme activity of β-hexosaminidase. A total of 44 vegetable foods were investigated for their effects on β-hexosaminidase release from RBL-2H3 cells. Allium plants such as garlic, Chinese chive, Welsh onion, turfed stone leek, onion, and ginger and east Indian lotus showed release-inhibitory action. This inhibitory action was not caused by the cell death. For each of the vegetable foods found to inhibit β-hexosaminidase release, the median inhibitory concentration (IC₅₀) in the reaction mixture was determined. Garlic and Chinese chive showed very strong inhibitory values in IC₅₀, while sweet pepper showed release promotive action as demonstrated by its action of injurying the cells. Thus, it was suggested that vegetable foods were related to the immediate allergy.

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To investigate the induction of hepatic metallothionein (MT) after administration of strontium (Sr) and calcium (Ca), male mice of the ICR strain were injected subcutaneously with Sr and/or Ca at a dose of 2 mmol/kg body weight, respectively. Both metals induced hepatic MT, though Ca was twice as effective as Sr when observed at 24 h. When Sr and Ca were co-administered, hepatic MT induction was essentially additive and hence no synergism was observed in the induction. When intraperitoneal (i.p.) and subcutaneous (s.c.) injections were compared, the induction by s.c. injection was higher in spite of the lower hepatic concentration of Sr at 24 h. When hepatic Sr concentration was also followed during an initial period, the i.p. injection always showed a higher level than the s.c. injection. Our results showed that the higher level of MT induction observed with s.c. injection of Sr relative to i.p. injection is not due to the higher Sr level.

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The effect of nicotinamide on 7 kinds of mutagenic alkylating agents was investigated in Salmonella typhimurium TA100 without S9 mix, and its mechanism was studied. The mutagenic potency of alkylating agents other than N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was reduced to less than 50% by the addition of about 50-fold molar ratio of nicotinamide to alkylating agent. The mutagenic potency of MNNG was only reduced to 60-70% by the addition of more than 200-fold molar ratio of nicotinamide. To investigate the mechanism of the suppressive effect of nicotinamide, alkylating agents (1.0 μmol) (methyl methanesulfonate and dimethyl sulfate) were reacted with nicotinamide (1.0 μmol) alone or together with DNA or 5 kinds of nucleotides in phosphate buffer (pH 7.4) at 30°C for 24 h, and the resulting N¹-methylnicotinamide (NMN) was analyzed by HPLC with fluorometric detection after derivatization. With the addition of DNA (0.2 molar ratio or more), the amount of NMN by methyl methane-sulfonate was reduced to 80% compared with nicotinamide alone, whereas that by dimethyl sulfate was unchanged. With the addition of nucleotides like guanosine-5'-phosphate, the amount of NMN by methyl methanesulfonate was reduced to 75%, whereas no reducing effect was seen by the other 4 nucleotides. The present results strongly suggest that nicotinamide is more easily alkylated than nucleic bases in DNA or nucleotides by methyl methanesulfonate and dimethyl sulfate, and that nicotinamide scavenged alkyl species derived from them, thereby showing a suppressive effect on the mutagenicity of alkylating agents. In MNNG, nicotinamide did not act as des-mutagen in Salmonella assay.

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A high performance liquid chromatographic method for the determination of lysozyme in foods with a fluorescence detector based on measuring the fluorescence intensity of 4-methylumbelliferone (4-MU) released from 4-MU-(GlcNAc)₃ after enzymatic hydrolysis. A reversed phase chromatographic system consisting of an ODS column and a mobile phase, acetonitril-0.04 M glycine buffer, pH 12.0 ; (70 : 30) was used. The optimum pH and reaction temperature were 5.2 and 45°C. After extraction with 0.1 M sodium phosphate buffer (pH 6.2), containing 2% NaCl, the lysozyme activity was measured with 0.04% substrate in sodiumcitrate buffer (pH 5.2) at 45°C for 60 min. Under the developed conditions lysozyme can be detected in the range of 5-100 μg/g. The recoveries of lysozyme from five kinds of foods were in the range of 84.3-96.4%.

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Distribution patterns of 8 polynuclear aromatic hydrocarbons (PAHs), i.e. pyrene (Py), fluorantene (Fl), benzo [a] anthracene (B [a] A), benzo [k] fluorantene (B [k] F), benzo [b] fluorantene (B [b] F), benzo [a] pyrene (B [a] P), benzo [ghi] perylene (B [ghi] P) and perylene (Per), in environmental samples from the Niigata area were examined. The total concentrations of 8 PAHs in sediments from the mouth area of rivers, airborne dusts, street dusts and surface soils ranged from <1.6 to 16600, 4700-263000, 210-1770 and 46-170 ng/g dry weight, respectively. The concentrations of B [a] P in the street dusts and soils, 12-138 and 4.8-15 ng/g dry weight, respectively, were highly correlated (r>0.9) to those of other 7 PAHs. The concentration of B [a] P in the airborne dusts, 590-35000 ng/g dry weight, was highly correlated to those of other 5 PAHs except for Py and Fl which were collected at lower efficiencies by the collection materials. The PAHs in the airborn dusts, the street dusts and the soils were derived from artificial sources, especially from automobile. The concentration of B [a] P in the river sediments, 0.1-937 ng/g dry weight, was highly correlated to those of other 6 PAHs except for Per ; this showed a simillar distribution of PAHs in another rivers reported previously. A part of Per in the sediment seems to be derived from natural sources.

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The effect of SH reagents on the absorption of mercuric chloride through the rat small intestine was investigated by the in situ recirculation method. The concentrations of mercury in the perfusion solutions, intestine, blood, kidney and liver were determined at each time intervals. Without SH reagents, the mercury transfer into the blood increased slightly with the time proceeds and mercury was absorbed through the intestine. The addition of L-cysteine, glutathione, 3-mercapto-1, 2-propanediol, dimercaptosuccinic acid, D (-)-penicillamine, diethyldithiocarbamate (DDTC), pyridoxine-5-thiol and thiola did not promote the mercury absorption, nor decreased the mercury content in the perfusion solutions. On the other hand, 2, 3-dimercapto-1-propanol (BAL) and 2-mercaptoethanol (MET) distinctly increased the mercury concentration in the blood, and then promoted the absorption of mercury through the intestine. To investigate the mechanism of the mercury absorption, the effect of SH compounds on the partition coefficients of mercuric chloride between octanol and water was determined. BAL and MET greatly increased the partition coefficient, but most of the other SH reagents except DDTC rather decreased it. Therefore we conclude that the lipophilic chelate formation with SH reagents is the main mechanism for the promotion of mercury absorption through the intestine.

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The effect of aeration time on the efficiency of batch activated sludge treatment was experimentally investigated to treat wastewater containing higher concentration of CHG (chlorhexidine digluconate) with the activated sludge acclimated to CHG of constant concentration. 2 ppm and 10 ppm CHG-containing wastewater was charged into the aeration vessel keeping activated sludge acclimated to 0.5 ppm CHG-concentration and treated under the different conditions (6 h, 12 h, 22 h) on aeration time for one month and their treatment efficiency were compared with that of control (CHG : 0.5 ppm, aeration : 6h). The results shown were as follows. The treatment efficiency of both 2 ppm and 10 ppm CHG-containing wastewater under the same aeration time as control was remarkably inferior to that of the control. Longer time aeration, however, remarkably improved the treatment efficiency of all of TOD (Total Oxygen Demand), TOC (Total Organic Carbon), COD (Chemical Oxygen Demand), NH₄⁺ and NO₃^- except TOD, NH₄⁺ and NO₃^- in case of 10 ppm CHG-containing wastewater. In case of 10 ppm CHG-containing wastewater, long time aeration was effective for the first 5 d after the starting operation, but the treatment efficiency of TOD, NH₄⁺ and NO₃^- went down suddenly from 6th day and after then the efficiency of TOD by long time aeration was getting lower and lower day by day. Whereas the effect of long time aeration as to NH₄⁺ and NO₃^- nearly disappeared after 6th day. NO₂^- was almost absent in effluent during the experiment.

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The microdetermination of glyoxal bound to proteins in biological samples has been developed using gas chromatography with an electron capture detector (ECD-GC). The treatment of the glyoxal-bound protein with 4-chloro-o-phenylenediamine resulted in the formation of its derivative, 6-chloroquinoxaline, showing the release of glyoxal from the protein. The use of metaphosphoric acid as a precipitant of the protein is suitable because the precipitant did not inhibit the derivatization and free glyoxal in the precipitated protein can be completely rinsed out with water. The results from Sephadex G-25 gel chromatography coupled with this microdetermination method indicated that glyoxal indeed binds to bovine albumin. The amounts of glyoxal bound to the albumin, fetal bovine serum and rat liver homogenate increased with an increase of glyoxal added.

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Cannabis oil (1 g) was extracted with n-hexane-saturated acetonitrile, and 91% of oil was removed by this method. Cannabinoids in extracted cannabis oil were identified by high performance thin layer chromatography (HPTLC) and capillary gas chromatography-mass spectrometry (GC-MS). The cannabinoid contents were determined by capillary gas chromatography (GC) using 5α-cholestane as an internal standard. Contents of CBD in the cannabis oil were 121±17 μg/g. However, other cannabinoids (THC and CBN) were not detected in this cannabis oil by HPTLC, GC-MS or GC.

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