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Bitter melon malt vinegar increases daily energy turnover in rats.

Vinegar is generally believed to be good for health. A mash consisting of 35% ethanolic extract from bitter melon malt vinegar-water (8:50:42) was subjected to further acetate fermentation and the resulting vinegar was converted to dried vinegar powder by spray drying after adsorption on dextrin, which was mixed with a commercial rat chow (CRF-1) in the ratio of 1:19 so as to prepare an experimental diet. Male 12-wk old rats of LETO and OLETF strains were fed this experimental diet in parallel with CRF-1 (control) and examined for respiratory quotient (RQ) and blood or plasma parameters associated with diabetes mellitus. Administration of the experimental diet increased daily food intake as well as daily energy expenditure in both strains. RQ significantly lessened in the vinegar diet-fed group of LETO strain, which was reflected not only in the increased energy consumption from fat but also in the decreased energy consumption from carbohydrate, while no significant difference was observed between both dietary groups of OLETF strain in this respect. The profiles of diurnal energy expenditure in both dietary groups of LETO strain exerted two peaks before lights-on and lights-off. Nevertheless, there was a clear difference between both dietary groups of OLETF strain: interestingly the reproduction of the two peaks became conspicuous in the vinegar diet-fed group despite the lack of such peaks in the control. As a consequence of blood or plasma inspection, it turned out that there was no change in HbA1c but a significant increase in plasma cholesterol in the vinegar diet-fed OLETF rats. From these results, a long-term administration of bitter melon malt vinegar can be expected to suppress a lowering of energy turnover inherent with aging and thereby improve anorexia rather than to bring about a preventive effect against the manifestation of NIDDM.

Acetic Acid↗

Epidemiology of bitter crab disease (Hematodinium sp.) in snow crabs Chionoecetes opilio from Newfoundland, Canada.

The parasitic dinoflagellate Hematodinium sp. causes a condition known as bitter crab disease (BCD) in snow crabs Chionoecetes opilio and Tanner crabs C. bairdi. As the name of the condition implies, crabs infected with BCD are unmarketable due to their bitter flavor. We surveyed the distribution of BCD in 3 regions within the snow crab fishery of Newfoundland from 1997 to 2003. Over time, the disease has become firmly established in Conception and Bonavista Bays and persists at low levels on the Avalon fishing grounds. An epizootic occurred within Bonavista and Conception Bays in 1999 and persisted in Conception Bay in 2000, reaching prevalences of over 2% to 9% in trapped and trawled male crabs and from 19 to 26% in trawled and trapped female crabs, respectively. Infections were highest in females and small males, i.e. the unfished and pre-recruit portions of the fishery. In a mortality study, all of the naturally infected crabs died and 50% of the experimentally inoculated crabs died. Patterns in the molting cycle and prevalence of infection indicate that transmission occurs during the post-molt condition, and that overt infections probably develop 2 to 4 mo later with mortalities occurring at least 3 to 4 mo thereafter. The hydrography of this bay may have contributed to the epizootic as infections were centered within the deeper confines of the bay. Analysis of various abiotic factors uncovered a significant positive association between prevalence, depth and mud/sand substrates; the nature of this relationship was not apparent but may be related to diet or alternate hosts. Lastly, given the increase in BCD in snow crabs in Newfoundland, we recommend that fishery management programs for Chionoecetes fisheries employ non-selective gear to monitor for Hematodinium infections in female and juvenile crabs because these under-sampled members of the population may forewarn of impending recruitment declines that might otherwise remain unexplained.

Animals↗

Effects of context on sweet and bitter tastes: unrelated to sensitivity to PROP (6-n-propylthiouracil).

In a double-shifting context paradigm, subjects gave magnitude estimates of the perceived intensity of qualitatively dissimilar taste substances (saccharin and quinine, sucrose and quinine) or qualitatively similar ones (saccharin and sucrose), with each pair of substances taking on different contextual sets of concentrations in different sessions. The dissimilar pairs produced substantial differential effects of context (e.g., a particular concentration of saccharin or sucrose was judged more intense than a particular quinine in one contextual setting, less intense in another), but the similar pair did not. This result accords with the hypothesis that differential context effects depend on qualitative similarity. Contrary to expectations, however, the magnitude of the context effect did not differ in tasters and nontasters of the bitter substance 6-n-propylthiouracil (PROP), groups previously shown to differ in sensitivity to bitterness in saccharin. Similarity judgments suggest that saccharin and sucrose were qualitatively alike for all subjects, regardless of sensitivity to PROP.

Attention↗

Variant angina associated with bitter orange in a dietary supplement.

The Food and Drug Administration has banned the sale of ephedrine-based weight-loss products because of their association with many cardiovascular adverse effects. Bitter orange is now being used as a stimulant in "ephedra-free" weight-loss supplements but was recently implicated in adverse cardiovascular sequelae. To our knowledge, this report describes the first case of variant angina associated with bitter orange in a dietary supplement.

Angina Pectoris, Variant↗

Caries experience in children with various genetic sensitivity levels to the bitter taste of 6-n-propylthiouracil (PROP): a pilot study.

PURPOSE: The objective of this pilot study was to determine the prevalence of coronal dental caries among children with different genetic sensitivity levels of taste, as determined by 6-n-propylthiouracil (PROP). METHODS: Coronal caries and restorations in permanent and primary dentition were evaluated in 150 healthy school-aged children aged 6 to 12 years. A filter paper containing 6-n-propylthiouracil was used to determine each subject's genetic ability to taste bitter and sweet substances. Supertasters perceived stronger tastes from a variety of bitter and sweet substances than both medium tasters and nontasters. The data were analyzed by ANOVA with Duncan's multiple range test, Mantel-Haenszel chi-square, multiple linear regression analyses, and Pearson's coefficient of correlation. RESULTS: The nontasters had more mean decayed, missing, and filled surfaces (dfs/DMFS) than tasters. The values of mean decayed and filled surfaces of primary dentition and mean decayed, missing, and filled surfaces of permanent dentition (dfs/DMFS) and mean decayed surfaces of primary dentition and permanent dentition (ds/DS) were significantly higher in nontasters than in medium tasters, and in medium tasters compared with supertasters. After adjusting for missing teeth, the data were expressed as a percentage of the available surfaces, and the significant differences in dfs/DMFS and ds/DS persisted (r = -0.49, P < .001 and r = -0.51, P < .0001 respectively). CONCLUSIONS: After all associated factors were controlled, taste was the only independent variable significantly related to overall caries experience. The results of this study suggested an increased prevalence of overall caries experience in nontaster children.

Analysis of Variance↗

Modulation of Immune Response of BALB/Mice Bearing Lymphoma L5178Y Treated with Bitter Yellow Juice of Aloe vera (L) in vivo.

Aloe vera (L), a plant of African origin, has been introduced in Mexico since XVIth century. It has been used in the treatment of many diseases of immune system. In the present study we investigated a specific and non-specific immune response of BALB/c mice, healthy and immunosuppressed with murine lymphoma L5178Y, treated with bitter yellow juice (extract) of Aloe vera (L). We observed that the immunosuppressed mice, treated with the whole extract of the bitter yellow juice achieved restoration of immunological parameters in cellular immune response and phagocytosis. On the other hand, the humoral immunity was not restored. Also, in the healthy rodents treated with the extract, it caused the stimulation of specific and non-specific responses, the results had significant differences with the obtained ones in untreated mice.

Journal Article↗

Oral Consumption of Bitter Gourd and Tomato Prevents Lipid Peroxidation in Liver Associated with DMBA Induced Skin Carcinogenesis in Mice.

The protective role of two commonly consumed natural dietary items- bitter gourd and tomato against endogenous as well as 7,12- dimethylbenz(a)anthracene (DMBA) induced lipid peroxidation in the livers of mice was investigated. The rationale for such an approach is that lipid peroxidation has been suggested to play a key role in human cancer development. There was a sharp rise in lipid peroxidation (measured as thiobarbituric acid reactive substances formation) during skin carcinogenesis induced by DMBA in mice. Aqueous extracts of bitter gourd and tomato juice were found to be very potent inhibitors of lipid peroxidation both in normal and DMBA treated mice. Our observations support the hypothesis that natural combinations of phytochemicals present in the fruit juices exert cancer-protective effects via a decrease in lipid peroxidation.

Journal Article↗

[Isolation and purification of ribosome-inactivating proteins from bitter melon seeds by ion exchange chromatographic columns in series].

An anion exchange chromatographic column (DEAE-650C) and a cation exchange chromatographic column (CM-650C) were connected in series on a perfusion chromatography workstation. The crude extract of bitter melon seeds flowed through the two columns and the unadsorbed fraction on the DEAE-650C column was then directly readsorbed on the CM-650C column. Two protein components with antifungal activity were eluted from the cation exchange chromatographic column by linear salt gradient. Both of them were found to be homogeneous by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and their relative molecular masses were estimated to be about 30 000. Their N-terminal amino acid sequences are DVSFRLSGADPRSYGMFI and DVNFDLSTATAK. All of the above suggested that they are alpha-momorcharin (alpha-MMC) and beta-momorcharin (beta-MMC), respectively, two type I ribosome-inactivating proteins (Rips) of bitter melon seeds. a-MMC shows antifungal activity against Fusarium oxysporum and Pythium aphanidermatum, while beta-MMC shows antifungal activity against Pythium aphanidermatum. But they are not against Sclerotium rolfsii. In the study, quantitative recoveries of alpha-MMC and beta-MMC were 13.8% and 8.0%, respectively, from decorticated seeds by ion exchange chromatographic columns in series.

Chromatography, Ion Exchange↗

Protection against 2- acetyl aminofluorene-induced toxicity in mice by garlic (Allium sativum), bitter kola (Garcina kola seed) and honey.

The effects of honey (Hoc) and aqueous suspensions of garlic (Allium sativum) (Ga) and bitter kola (Garcina kola seed) (Bi) on the toxicities induced by 2-acetylaminofluorene (2-AAF) a model carcinogen, were investigated in mice. The animals were dosed for seven consecutive days with Ho, Ga and Bi as dietary supplements. They were then challenged with a single intraperitoneal (i.p.) dose of 2-AAF at 50 mg/kg bd. wt on the seventh day. The degree of clastogenicity was assessed using the mouse micronucleus assay while liver damage was monitored by measuring the level of gamma glutamyltransferase (gamma-GT) in serum and liver homogenates respectively. The results revealed that 2-AAF induced micronuclei formation in the polychromatic erythrocytes (PCEs) of the bone marrow by about five fold in comparison to the PCEs formed in control mice. Ho, Ga, and Bi also induced micronucleus formation on their own. However. feeding of any of Ho, Ga or Bi and the administration (i.p) of 2-AAF reduced significantly, the ability of 2-AAF to induce micronuclei formation in the order Ho>Ga>Bi. Furthermore, 2-AAF induced gamma-GT activity in the serum and liver homogenate by about two and a half and three folds respectively. A combination of 2-AAF and any of Ga or Bi or Ho significantly decreased 2-AAF-induced activity of gamma-GT in the order Ho>Bi>Ga (serum) and Bi>Ga=Ho (liver). These findings suggest that honey, garlic and bitter kola protect against 2-AAF-induced gamma-GTactivity and micronuleated PCEs formation.

2-Acetylaminofluorene↗

[Determination of bitter components in citrus juice by high performance liquid chromatography].

Bitterness in citrus juice is primarily due to the presence of both limonin and naringin, and determination of them is a standard in controlling the quality of juice. A high performance liquid chromatographic (HPLC) method was developed for the rapid determination of bitter components in citrus juice. The HPLC conditions were as follows: ODS column with acetonitrile-tetrahydrofuran-water (17.5: 17.5: 65, v/v) as mobile phase, flow rate at 1 mL/min, 207 nm as detection wavelength for limonin, and methanol-100% acetic acid-water (40:1:59, v/v) as mobile phase, flow rate at 1 mL/min, 283 nm as detection wavelength for naringin. As results showed, for limonin and naringin, the linearity was good within the ranges of 1.00 - 50.00 mg/L (r = 0.9992) and 20.00 - 160.00 mg/L (r = 0.9988) respectively, and the detection limits were 0.07 microg and 0.14 microg, then the average recoveries were 98.69% and 100.13% with relative standard deviations of 2.5% and 1.5%, respectively. The method is simple, rapid and accurate for determining limonin and naringin in juice.

English Abstract↗

UDP-rhamnose:flavanone-7-O-glucoside-2''-O-rhamnosyltransferase. Purification and characterization of an enzyme catalyzing the production of bitter compounds in citrus.

The rhamnosyltransferase catalyzing the production of the bitter flavanone-glucosides, naringin and neohesperidin, was purified to homogeneity. The enzyme catalyzes the transfer of rhamnose from UDP-rhamnose to the C-2 hydroxyl group of glucose attached via C-7-O- of naringenin or hesperetin. To our knowledge this is the first complete purification of a rhamnosyl-transferase. The enzyme from young pummelo leaves was purified greater than 2,700-fold to a specific activity of over 600 pmol/min/mg of protein by sequential column chromatographies on Sephacryl S-200, reactive green 19-agarose, and Mono-Q. The enzyme was selectively eluted from the green dye column with only three other proteins by a pulse of the substrate hesperetin-7-O-glucoside followed by UDP. The rhamnosyltransferase is monomeric (approximately 52 kDa) by gel filtration and electrophoresis. The enzyme rhamnosylates only with UDP-rhamnose. Flavonoid-7-O-glucosides are usable acceptors but 5-O-glucosides or aglycones are not. It is inhibited by 10 microM UDP, its end product, but not by naringin or neohesperidin. Several flavonoid-aglycones at 100 microM inhibited the rhamnosyltransferase; UDP-sugars did not. The Km for UDP-rhamnose was similar with prunin (1.3 microM) and hesperetin-7-O-glucoside (1.1 microM) as substrate. The affinity for the natural acceptor prunin (Km = 2.4 microM) was much higher than for hesperetin-7-O-glucoside (Km = 41.5 microM). The isolation of the gene may enable its use in genetic engineering directed to modifying grapefruit bitterness.

Chromatography↗

Interaction of alpha-L-aspartyl-D-phenylalanine methyl ester with the receptor site of the bitter taste.

The analysis of the structure-activity relationship previously performed on the sweet L,L isomer of Asp-Phe-OMe was extended to the bitter L,D diastereoisomer. A combination of NMR measurements and of an original method of PEM calculations gives a description of the conformational state of the L,D isomer that can be effectively used to study the interaction with a previously proposed model of the bitter taste receptor site.

Aspartame↗

Response latency of gerbils and hamsters to nuts flavoured with bitter-tasting substances.

The unconditioned reactions of Mongolian gerbils to peanuts rolled in sucrose octa-acetate (SOA) or denatomium benzoate (Bitrex) were studied in Experiment 1. Although SOA evokes as high a bitterness rating among humans as quinine salts, the gerbils' latency to ingest a nut flavoured with the former was similar to that to an unflavoured nut. Their oral latency to a nut that was flavoured with Bitrex was longer than to either an unflavoured one or one flavoured with SOA. However, the fact that they ingested a nut flavoured with the "most bitter substance known to man" within 70 sec after contact is surprising. Experiment 2 dealt with the effects of a peanut that was either unflavoured or flavoured with SOA or quinine and then paired with a LiCl injection. The oral latency of these gerbils to a nut conveying such flavours was assessed for six days after this conditioning. A nut flavoured with quinine acquired aversive properties but not ones that were flavoured with SOA or were unflavoured. Similar results were observed in Experiment 3, when hamsters were tested under comparable conditions. The theoretical implications of these results are discussed.

Acetates↗

Bittering agents: their potential application in reducing ingestions of engine coolants and windshield wash.

Ethylene glycol automobile engine coolants and methanol-based windshield washer liquids are toxic. Despite international attempts to improve the safety of these products through better labelling and packaging, accidental and intentional ingestions continue a source of poisonings worldwide. The rejection of bitter tasting substances forms part of the human defense against ingestion of harmful substances. Denatonium benzoate (DB) is currently recognised as a means to prevent ingestion of ethyl alcohol intended for industrial use. This study investigated the use of this bitter substance also as a deterrent against ingesting ethylene glycol and methanol. The palatability of ethylene glycol and methanol with and without the addition of DB was assessed using a human taste panel; 30 ppm DB rendered each product intolerable to the panel. The addition of DB to ethylene glycol engine coolants and methanol-based windshield washer liquids at low concentrations could afford protection against accidental ingestions.

Adolescent↗

Bitter taste transduction of denatonium in the mudpuppy Necturus maculosus.

Bitter substances are a structurally diverse group of compounds that appear to act via several transduction mechanisms. The bitter-tasting denatonium ion has been proposed to act via two different G-protein-regulated pathways, one involving inositol 1,4, 5-trisphosphate and raised intracellular calcium levels, the other involving phosphodiesterase and membrane depolarization via a cyclic nucleotide-suppressible cation channel. The aim of the present study was to examine these transduction mechanisms in taste cells of the mudpuppy Necturus maculosus by calcium-imaging and whole-cell recording. Denatonium benzoate increased intracellular calcium levels and induced an outward current independently of extracellular calcium. The denatonium-induced increase in intracellular calcium was inhibited by U73122, an inhibitor of phospholipase C, and by thapsigargin, an inhibitor of calcium transport into intracellular stores. The denatonium-induced outward current was blocked by GDP-beta-S, a blocker of G-protein activation. Neither resting nor denatonium-induced intracellular calcium levels were affected by inhibition of phosphodiesterase (with IBMX) or adenylate cyclase (with SQ22536) or by raising intracellular cyclic nucleotides directly (with cell permeant analogs). Our results support the hypothesis that denatonium is transduced via a G-protein cascade involving phospholipase C, inositol 1,4,5-trisphosphate, and raised intracellular calcium levels. Our results do not support the hypothesis that denatonium is transduced via phosphodiesterase and cAMP.

1-Methyl-3-isobutylxanthine↗

Stir bar sorptive extraction-liquid desorption applied to the analysis of hop-derived bitter acids in beer by micellar electrokinetic chromatography.

Stir bar sorptive extraction-liquid desorption (SBSE-LD) has been applied as an efficient sample preparation method for the analysis of beer bitter acids. Extracts free of almost all interfering compounds were obtained, allowing simultaneous analysis of iso-alpha-acids and reduced iso-alpha-acids. A robust micellar electrokinetic chromatography (MEKC) method was developed that enables fast separation of iso-alpha-acids and reduced iso-alpha-acids. Quantitative data are in good agreement with results obtained by high-performance liquid chromatography (HPLC) using direct beer injection.

Acids↗

Dietary seed oil rich in conjugated linolenic acid from bitter melon inhibits azoxymethane-induced rat colon carcinogenesis through elevation of colonic PPARgamma expression and alteration of lipid composition.

Our previous short-term experiment demonstrated that seed oil from bitter melon (Momordica charantia) (BMO), which is rich in cis(c)9, trans(t)11, t13-conjugated linolenic acid (CLN), inhibited the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF). In our study, the possible inhibitory effect of dietary administration of BMO on the development of colonic neoplasms was investigated using an animal colon carcinogenesis model initiated with a colon carcinogen AOM. Male F344 rats were given subcutaneous injections of AOM (20 mg/kg body weight) once a week for 2 weeks to induce colon neoplasms. They also received diets containing 0.01%, 0.1% or 1% BMO for 32 weeks, starting 1 week before the first dosing of AOM. At the termination of the study (32 weeks), AOM induced 83% incidence (15/18 rats) of colonic adenocarcinoma. Dietary supplementation with 0.01% and 0.1% BMO caused significant reduction in the incidence (47% inhibition by 0.01% BMO, p<0.02; 40% inhibition by 0.1% BMO, p<0.05; and 17% inhibition by 1% BMO) and the multiplicity (64% inhibition by 0.01% BMO, p<0.005; 58% inhibition by 0.1% BMO, p<0.02; and 48% inhibition by 1% BMO, p<0.05) of colonic adenocarcinoma, though a clear dose response was not observed. Such inhibition was associated with the increased content of CLA (c9,t11-18:2) in the lipid composition in colonic mucosa and liver. Also, BMO administration in diet enhanced expression of peroxisome proliferator-activated receptor (PPAR) gamma protein in the nonlesional colonic mucosa. These findings suggest that BMO rich in CLN can suppress AOM-induced colon carcinogenesis and the inhibition might be caused, in part, by modification of lipid composition in the colon and liver and/or increased expression of PPARgamma protein level in the colon mucosa.

Adenocarcinoma↗

Transcending bitterness and early paternal loss through mourning and forgiveness.

This paper provides an in-depth account of a clinical path to forgiveness following a complicated, delayed mourning of an early loss by a man now entering old age. The search for mourning and forgiveness in light of extreme bitterness in advancing age is highlighted. Despite the intimate connection between mourning and forgiveness, this paper attempts to highlight important differences in their dynamics and psychological aims. Forgiveness is conceived as work, unconsciously motivated, to safeguard and complement the psychological gains of mourning. The distinct features of forgiveness facilitating psychic reorganization, as well as the adaptive function of refusal to forgive as a defense against melancholia, are discussed. The paper concludes that in this case, the motivation for forgiveness was to repair a powerful narcissistic injury.

Adaptation, Psychological↗