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There has been increasing interest in finding natural antioxidants to prevent free radical damage and retard the progress of chronic inflammatory diseases. Our previous data demonstrated the strong antioxidant properties of polyphenolics in Mamao seed (MS) and Mamao marc (MM) extracts. In this study we further investigated the effect of MS and MM polyphenolics on hydrogen peroxide (H 2 O 2 )-induced apoptosis and tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation, using human breast epithelial (MCF10A) cells. MS and MM extracts conferred dose-dependent protection against H 2 O 2 -induced apoptosis by inhibiting PARP/caspase-3 cleavage, inducing anti-apoptotic Bcl-2 expression, and down-regulating pro-apoptotic Bax. Moreover, MS and MM polyphenolics inhibited TPA-induced COX-2 and NF-κB activation by blocking the degradation of cytoplasmic IκBα, as well as subsequent nuclear translocation of p65 and attenuation of the activation of ERK, but not JNK and p38. These data establish the molecular mechanism for the anti-apoptotic and anti-inflammatory effects of MS and MM polyphenolics.

Ethanolic extracts from various parts of 26 Thai indigenous plants were examined for phenolic constituents and free radical scavenging capacity, to determine their potential as a source of natural antioxidants. Total phenolic content and total flavonoid content were evaluated according to the Folin-Ciocalteu procedure, and a colorimetric method, respectively. The results showed that total phenolic compounds and flavonoid content were higher in seed extracts of berries used in wine production, while the levels in extracts obtained from herbs and vegetables were lower. Chewing plants which have an astringent taste gave a significantly higher total phenolic content and flavonoid content. Antiradical activity determined from 1/EC50 by the DPPH radical-scavenging method was highest in wine production seeds and chewing plants. The correlation coefficient from regression analysis showed a positive relationship between total phenolic and total flavonoid content (r = 0.9). The results suggest that ethanolic extracts of some Thai indigenous plants exhibit a potential for use as natural antioxidants.

The recent case-control studies in Thailand indicate that a high incidence of liver cancer in Thailand has not been associated with common risk factors such as hepatitis B infection, aflatoxin intake and alcohol consumption. While the infestation by the liver fluke Opisthorchis viverrini (OV) accounted for the high risk in north-east Thailand, there was no such exposure in the other regions of the country where the incidence of liver cancer is also high. Case-control studies suggest that exposure to exogenous and possibly endogenous nitrosamines in food or tobacco in betel nut and cigarettes may play a role in the development of hepatocellular carcinoma (HCC), while OV infestation and chemical interaction of nitrosamines may also be aetiological factors in the development of cholangiocarcinoma (CCA). Over 1800 samples of fresh and preserved food were systematically collected and tested between 1988 and 1996. All the food items identified by anthropological studies to be consumed frequently in four major regions of Thailand were analysed for volatile nitrosamines using gas chromatography combined with a thermal energy analyser. Relatively high levels of N -nitrosodimethylamine (NDMA), N -nitrosopiperidine (NPIP) and N -nitrosopyrrolidine (NPYR) were detected in fermented fish (“Pla-salid”). NDMA was also detected at levels ranging from trace amounts to 66.5 μ g/kg in several salted and dried fish (“Larb-pla” and “Pla-siu”). NDMA and NPYR were frequently detected in several vegetables, particularly fermented beans (“Tau-chiau”) at levels ranging between 1 and 95.1 μ g/kg and 0–146 μ g/kg, respectively. The possible role of nitrosamines in Thai food in the aetiology of liver cancer (HCC, CCA) is discussed.

Weight for age, weight for height, the concentration ofalbumin, prealbumin, and transferrin together with the proteinase inhibitors ai-antitrypsin, a1-antichymotrypsin, a2-macro- globulin, and the acute-phase reactants a,-acid glycoprotein and haptoglobin were determined in six marasmus and seven kwashiorkor children; marasmus-kwashiorkor children were admitted with diarrhea. The results were compared with those from six healthy preschool children. Serum protein concentration from the children suffering from protein-energy malnutrition were measured at the 2nd, 8th, 29th, and 50th day after hospital admission. The anthropometric measurements, prealbumin, albumin, and transferrin were lower in the protein-energy malnutrition children compared with the healthy preschool children. Prealbumin and albumin indicated a lower nutri- tional status in the kwashiorkor, marasmus-kwashiorkor group compared with the marasmus group. a2-Macroglobulin and ai-antitrypsin were lower in the protein-energy malnutrition groups compared with the healthy preschool children. Both serum proteins were significantly lower at the 2nd day compared with the 50th day in the kwashiorkor, marasmus-kwashiorkor group, whereas ai-antitrypsin values remained almost the same level in the marasmus group from the 2nd day up to the 50th day. ai-Acid glycoprotein and ai-antichymotrypsin were higher in the marasmus group at the 2nd day compared with the healthy preschool children. ai-Acid glycoprotein at the 2nd day of the kwashiorkor, marasmus-kwashiorkor group were higher compared with the 50th day of that group. ai-Antichymotrypsin levels at the 2nd day of the marasmus group were higher compared with the 2nd day of the kwashiorkor, marasmus-kwashiorkor group. Haptoglobin did not differ between the groups. Variations of armacroglobulin, ai-antitrypsin, and albumin during treatment for one marasmus and one kwashiorkor case complicated by frequent periods of fever were compared with one marasmus and one kwashiorkor case with straight recovery. The results are discussed in respect of the possible role of ai-antitrypsin and a2-macroglobulin in the influence of these inhibitors on the balance of catabolism and anabolism of protein in protein-energy malnu- trition complicated by infection, where the proteinase inhibitors might also inhibit the mobilization of body's own protein. Am. J. Clin. Nuir. 32: 14 15-1422, 1979.

The action of N-acetylneuraminic acid aldolase on 7- and 8-carbon analogues of N-acetylneuraminic acid has been studied. The 8-carbon analogue was slowly and reversibly cleaved by the aldolase to yield 2-acetamido-2-deoxy-d-lyxose and pyruvic acid. The 7-carbon analogue was not cleaved by the enzyme. The 8-carbon analogue competed with N-acetylneuraminic acid for the active site of the enzyme, but the 7-carbon analogue exhibited no inhibitory effect even when present at a 10-fold greater concentration than N-acetylneuraminic acid.

Glycoprotein substrates for neuraminidase and glycoprotein inhibitors of the agglutination of erythrocytes by influenza virus were subjected to oxidation by very low concentrations of periodate under conditions which selectively oxidize N-acetylneuraminic acid (NANA), to the 8carbon and 7-carbon aldehydes. Molar ratios of periodate to NANA were varied from 0.2 to 4.5. Reduction of the oxidized glycoproteins with sodium borohydride yielded glycoproteins containing the 8- and 7-carbon analogues of NANA as well as the parent 9-carbon compound in amounts depending on the quantity of periodate employed. These were quantitated in the mixture by means of gas-liquid chromatography. Under the conditions used, periodate oxidation of other sugars in the glycoproteins could not be detected. The capacity of neuraminidases from Vibrio cholerae, Clostridium perfringens, and PR-8 influenza virus to cleave N-acetylneuraminic acid or its 8-carbon (NANA-8) or 7-carbon (NANA-7) analogues from native and modified orosomucoid and from NANA-, NANA-8-, and NANA-7-N-acetylgalactosaminitol were studied. NANA-8 was hydrolyzed from the glycoproteins and the reduced disaccharide at an initial rate about 30% of that for NANA. The 7-carbon analogue of NANA was not cleaved from the reduced disaccharide, but was slowly cleaved from modified orosomucoid at an initial rate of 5 to 10% of that for NANA. It was concluded that the optimum activity of neuraminidase requires the intact structure of the polyhydroxy side chain of NANA. When the molar ratio of periodate to NANA exceeded 1.5, all of the NANA was converted to the 8- and 7-carbon analogues, and the capacity of the glycoproteins to inhibit agglutination of human erythrocytes by PR-8 influenza virus was reduced by 95 to 100%. It is concluded that carbon atoms 7, 8, and 9 in the polyhydroxy side chain of NANA acid in glycoproteins are involved in their binding to influenza virus.

Ovine and human follicle-stimulating hormone (FSH) were modified by periodate oxidation followed by borohydride reduction, yielding FSH-containing analogues of N-acetylneuraminic acid (NANA) shortened by 1 or 2 carbon atoms. The FSH activity of the modified preparations was assayed by the human chorionic gonadotropin augmentation assay. The treatment decreased the biological activity of FSH somewhat, but, even when no unmodified NANA remained, the potency was still about half that of untreated FSH. Treatment of either native or modified FSH with neuraminidase resulted in the release of all NANA and NANA-8 and some NANA-7, and the loss of hormonal activity. It appears, therefore, that an intact 3-carbon polyhydroxy side chain in NANA is not required for full FSH activity.

The 8-carbon and the 7-carbon analogues of N-acetyl-neuraminic acid were necessary in order to study some of the structural requirements of N-acetylneuraminic acid in its role as substrate for certain enzymes. The 8-carbon analogue of N-acetylneuraminic acid was synthesized by the alkaline condensation of 2-acetamido-2-deoxy-d-lyxose and di-tert-butyloxaloacetate. This same 8-carbon compound and the 7-carbon analogue of N-acetylneuraminic acid were isolated after acid hydrolysis of Collocalia mucoid which had been modified by periodate oxidation followed by borohydride reduction. The two analogues could also be detected when periodate oxidation and borohydride reduction were applied to crystalline β-methoxy-N-acetylneuraminic acid methyl ester.