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Biomedical subjects

L D Lawson

Publications and source records attributed to L D Lawson.

At least 19 recordsLinked to original sources
PubMed2001

Low allicin release from garlic supplements: a major problem due to the sensitivities of alliinase activity.

Most garlic supplements are standardized on allicin potential and are enteric-coated to prevent gastric acid inactivation of the allicin-producing enzyme, alliinase. To determine whether these products release the claimed amount of allicin under simulated gastrointestinal conditions, USP dissolution method 724A for drug release was applied to all 24 known brands of enteric-coated tablets. It was found that nearly all brands employed effective coatings and that they met their claims for allicin potential when crushed and suspended in water. However, all brands except one gave low dissolution allicin release, with 83% of the brands releasing less than 15% of their potential. The low allicin release was found to be due to both impaired alliinase activity, mostly caused by tablet excipients, and to slow tablet disintegration, which also impairs alliinase activity. Only when tablets had high alliinase activity and disintegrated rapidly did they show high allicin release. The ability of USP 724A to estimate allicin release in vivo was validated by monitoring breath levels of the allicin metabolite, allyl methyl sulfide. In conclusion, garlic powder supplements should no longer be standardized on allicin potential, but rather on dissolution allicin release.

Antioxidants↗
PubMed2001

Allicin release under simulated gastrointestinal conditions from garlic powder tablets employed in clinical trials on serum cholesterol.

The failure of five recent clinical trials to show significant reduction in elevated serum cholesterol by a single brand of allicin-standardized garlic powder tablets is in contrast to many prior positive studies with the same brand. The hypocholesterolemic activity of garlic is mainly due to allicin, a compound that is produced by the acid-sensitive garlic enzyme, alliinase, only after tablet consumption. Therefore, the allicin-releasing ability of ten lots of these tablets--manufactured over the same years that the positive and negative clinical trials were conducted (1989-1997)--was determined under simulated gastrointestinal dissolution conditions, as defined by U.S. Pharmacopeia Method 724A. It was found that the older lots were more resistant to acid-disintegration (2.5 h vs. 1.3 h, P < 0.001) and that they released three times as much allicin (44% vs. 15 % of their potential, P < 0.001) as the newer lots. A second brand of tablets employed in a recent negative trial released no detectable amount of allicin, while a third set of tablets with high allicin release was used in a trial that gave positive effects. Hence, the persons involved in the recent negative clinical trials probably received considerably less allicin than did those in the older positive studies, possibly accounting for much of the discrepancy in the outcomes. In conclusion, clinical trials using garlic powder tablets to assess any effect of garlic that might be related to allicin, as most are, cannot be considered valid for garlic when the trial shows no effect, unless the expected allicin release from the tablets has at least been determined under standardized drug release conditions (USP 724A).

Cholesterol↗
PubMed1997

Allyl sulfides from garlic suppress the in vitro proliferation of human A549 lung tumor cells.

The present studies compared the antiproliferative effects of diallyl trisulfide (DATS) and diallyl disulfide (DADS) on cultured human neoplastic (A549) and nonneoplastic (MRC-5) lung cells. Addition of 10 microM DATS reduced A549 growth by 47%, whereas 10 microM DADS decreased growth by only 20%. DATS treatment (10 microM) did not alter MRC-5 cell growth. DATS (10 microM) caused a marked and progressive increase in intracellular Ca2+ in A549 cells during the first four hours after treatment. Intracellular Ca2+ in A549 cells exposed to DATS returned to near control levels within one hour after refeeding complete medium without DATS. Exposure to 1 microM DATS for 24 hours significantly induced apoptosis, as indicated by increased DNA fragmentation. The ability of DATS and DADS to suppress neoplastic growth is consistent with increasing evidence that several garlic components have anticarcinogenic and antitumorigenic properties.

Allyl Compounds↗
PubMed1996

Enhanced diallyl trisulfide has in vitro synergy with amphotericin B against Cryptococcus neoformans.

Although amphotericin B remains the drug of choice for systemic fungal infections, its use is limited by considerable side effects. In The Peoples' Republic of China, commercial Allium sativum derived compounds are widely used as an antifungal drug to treat systemic fungal infections. To evaluate the scientific merit of using A. sativum derived compounds as antifungal agents, we studied a Chinese commercial preparation, allitridium. This preparation contained mainly diallyl trisulfide as confirmed by high performance liquid chromatography. Allitridium, with and without amphotericin B, was tested to determine its efficacy in killing three isolates of Cryptococcus neoformans. The minimum inhibitory concentration of the commercial preparation was 50 micrograms/ml and the minimum fungicidal concentration was 100 micrograms/ml against 1 x 10(5) organisms of C. neoformans. In addition, the commercial preparation was shown to be synergistic with amphotericin B in the in vitro killing of C. neoformans. This study demonstrates that diallyl trisulfide and other polysulfides possess potent in vitro fungicidal effects and their activity is synergistic with amphotericin B. These observations lend laboratory support for the treatment of cryptococcal infections with both amphotericin B and the Chinese commercial preparation.

Allyl Compounds↗
PubMed1992

Inhibition of whole blood platelet-aggregation by compounds in garlic clove extracts and commercial garlic products.

The inhibitory effects of adenosine and 16 quantitatively determined organosulfur compounds derived from garlic cloves or commercial garlic preparations on collagen stimulated in vitro platelet aggregation in whole blood were determined. An estimation of the anti-aggregatory activity of several brands of the major types of commercial garlic preparations was determined from the activities of the individual compounds present in each sample. In platelet rich plasma (PRP) most of the anti-aggregatory activity of garlic clove homogenates was due to adenosine; however, in whole blood neither adenosine nor the polar fraction had any effect and all of the anti-aggregatory activity was due to allicin and other thiosulfinates. Allicin was equally active in whole blood and PRP. Among brands there was a several-fold variation in content of the organosulfur compounds and activity for all types of garlic products tested. The best garlic powder tablets were equally as active as clove homogenates whereas steam-distilled oils were 35% as active and oil-macerates (due to low content) only 12% as active. A garlic product aged many months in aqueous alcohol had no activity. For steam-distilled oils, most of the activity was due to diallyl trisulfide. For the oil-macerates, most of the activity was due largely to the vinyl dithiins. Ajoene, an exclusive component of the oil-macerates, had highest specific activity of all the compounds tested but, because of its low concentration, had only 13% of the activity of diallyl trisulfide and 3% of the activity of allicin. Compounds which may be active in vivo are discussed.

Adenosine↗
PubMed1992

Characterization of the formation of allicin and other thiosulfinates from garlic.

The effects of pH, neutralization after acidification, time, and temperature on the yield of dialkyl thiosulfinates released from garlic powder and garlic cloves were determined. All dipropenyl thiosulfinates (allicin, 1-propenyl allyl, and allyl 1-propenyl) were formed at an optimum pH of 4.5-5.0. The methyl propenyl thiosulfinates (allyl methyl + methyl allyl and 1-propenyl methyl + methyl 1-propenyl) and dimethyl thiosulfinate were optimally formed at pH 6.5-7.0 and pH 5.5, respectively. Below pH 3.6 no thiosulfinates were formed. Neutralization of the pH failed to restore thiosulfinate generation from garlic previously incubated at pH 3 or below. Thus, alliinase is completely and irreversibly inhibited by the acidic conditions found in the stomach. The dipropenyl thiosulfinates were completely formed in 0.3 min at 37 degrees C, while the methyl thiosulfinates were not completely formed until 3.5 min. Allyl 1-propenyl thiosulfinate was the most rapidly formed, and the most unstable, thiosulfinate. The stability of the dipropenyl thiosulfinates was improved at pH 4.5 or lower. Drying garlic at 60 degrees C had no effect on alliin or the rate of formation of the dipropenyl thiosulfinates, but decreased trans-1-propenylcysteine sulfoxide (isoalliin) and the rate of formation of the methyl thiosulfinates. The results demonstrate that there are two alliinase activities in garlic, that a stomach acid-resistant coating on garlic powder tablets is necessary for thiosulfinate release, and that carefully prepared garlic powder can release similar amounts of total thiosulfinates to whole garlic cloves.

Journal Article↗
PubMed1992

In vitro virucidal effects of Allium sativum (garlic) extract and compounds.

Garlic (Allium sativum) has been shown to have antiviral activity, but the compounds responsible have not been identified. Using direct pre-infection incubation assays, we determined the in vitro virucidal effects of fresh garlic extract, its polar fraction, and the following garlic associated compounds: diallyl thiosulfinate (allicin), allyl methyl thiosulfinate, methyl allyl thiosulfinate, ajoene, alliin, deoxyalliin, diallyl disulfide, and diallyl trisulfide. Activity was determined against selected viruses including, herpes simplex virus type 1, herpes simplex virus type 2, parainfluenza virus type 3, vaccinia virus, vesicular stomatitis virus, and human rhinovirus type 2. The order for virucidal activity generally was: ajoene > allicin > allyl methyl thiosulfinate > methyl allyl thiosulfinate. Ajoene was found in oil-macerates of garlic but not in fresh garlic extracts. No activity was found for the garlic polar fraction, alliin, deoxyalliin, diallyl disulfide, or diallyl trisulfide. Fresh garlic extract, in which thiosulfinates appeared to be the active components, was virucidal to each virus tested. The predominant thiosulfinate in fresh garlic extract was allicin. Lack of reduction in yields of infectious virus indicated undetectable levels of intracellular antiviral activity for either allicin or fresh garlic extract. Furthermore, concentrations that were virucidal were also toxic to HeLa and Vero cells. Virucidal assay results were not influenced by cytotoxicity since the compounds were diluted below toxic levels prior to assaying for infectious virus. These results indicate that virucidal activity and cytotoxicity may have depended upon the viral envelope and cell membrane, respectively. However, activity against non-enveloped virus may have been due to inhibition of viral adsorption or penetration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

HPLC analysis of allicin and other thiosulfinates in garlic clove homogenates.

Reversed-phase high Performance liquid chromatography (C18-HPLC) was used to separate and quantitate all the detectable alkyl and alkenyl thiosulfinates, including configurational isomers, of garlic homogenates. Pure thiosulfinates were synthesized or isolated and identified by (1)H-NMR, and their extinction coefficients determined. Some configurational isomers required Separation by silica-HPLC. Five previously unreported thiosulfinates have been found, four of which contain the TRANS-1-propenyl group and increase several-fold to over half the content of allicin upon storage of garlic bulbs at 4 degrees C with a concomitant decrease in a gamma-glutamyl peptide. The variation in thiosulfinate yield between different countries, stores, bulbs, cloves, and storage times was investigated. A method for standardizing the quantitation of allicin yield from garlic is proposed and compared to other methods of allicin analysis.

Journal Article↗
PubMed1991

Identification and HPLC quantitation of the sulfides and dialk(en)yl thiosulfinates in commercial garlic products.

The content of dialk(en)yl thiosulfinates, including allicin, and their degradation products has been determined by high performance liquid chromatography (HPLC), using the respective determined extinction coefficients, for a number of commercially available garlic products. Quantitation has been achieved for the thiosulfinates; diallyl, methyl allyl, and diethyl mono-, di-, tri-, tetra-, penta-, and hexasulfides; the vinyldithiins; and (E)- and (Z)-ajoene. The thiosulfinates were found to be released only from garlic cloves and garlic powder products. The vinyldithiins and ajoenes were found only in products containing garlic macerated in vegetable oil. The diallyl, methyl allyl, and dimethyl sulfide series were the exclusive constituents found in products containing the oil of steam-distilled garlic. Typical steam-distilled garlic oil products contained about the same amount of total sulfur compounds as total thiosulfinates released from freshly homogenized garlic cloves; however, oil-macerated products contained only 20% of that amount, while garlic powder products varied from 0 to 100%. Products containing garlic powder suspended in a a gel or garlic aged in aqueous alcohol did not contain detectable amounts of these non-ionic sulfur compounds. A comparison of several brands of each type of garlic product revealed a large range in content (4-fold for oil-macerates and 33-fold for steam-distilled garlic oils), indicating the importance of analysis before garlic products are used for clinical investigations or commercial distribution.

Alkenes↗
PubMed1988

Absorption of eicosapentaenoic acid and docosahexaenoic acid from fish oil triacylglycerols or fish oil ethyl esters co-ingested with a high-fat meal.

The absorption of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil triacylglycerols and fish oil ethyl esters consumed in a high-fat meal (44 g total fat) by male volunteers was measured and compared to values previously reported for consumption in a low-fat meal (8 g total fat). Absorption of EPA, but not of DHA, from fish oil triacylglycerols was significantly improved from 69% to 90% by co-ingestion with the high-fat meal. Absorption of both EPA and DHA from fish oil ethyl esters was increased three-fold, to about 60%, by co-ingestion with the high-fat meal, indicating that absorption of fatty acid ethyl esters is highly dependent on the amount of co-ingested fat.

Absorption↗
PubMed1988

Human absorption of fish oil fatty acids as triacylglycerols, free acids, or ethyl esters.

The transient rise in plasma triacylglycerol fatty acids after single-dose ingestion of fish oil as triacylglycerols, free acids, or ethyl esters with linseed oil as an absorption standard was used to determine the relative absorption of fish oil fatty acids in eight men. As free acids, the fish oil fatty acids were well absorbed (greater than or equal to 95%). As triacylglycerols, eicosapentaenoic acid (1.00 g) and docosahexaenoic acid (0.67 g) were absorbed only 68% and 57% as well as the free acids. The ethyl esters were absorbed only 20% and 21% as well as the free acids. The incomplete absorption of eicosapentaenoic and docosahexaenoic acids from fish oil triacylglycerols correlates well with known in vitro pancreatic lipase activity.

Adult↗
PubMed1987

Selective immunotoxic effects in mice treated with the adenosine deaminase inhibitor 2'-deoxycoformycin.

Mice were administered the adenosine deaminase inhibitor 2'-deoxycoformycin by daily intraperitoneal injection for five days and evaluated 24 h, 72 h and 6 days after the final dose. Spleen weight was decreased in treated mice for up to 6 days after treatment whereas body weight was significantly affected only at 24 h in mice administered 4 micrograms 2'-deoxycoformycin/g of body weight. The number and relative percentage of circulating lymphocytes were decreased 24 and 72 h after the last injection. Lymphoproliferative responses to T cell mitogens were suppressed for at least 72 h post-treatment whereas the mixed lymphocyte response was normal at 24 h but was depressed at 72 h post-treatment. Conversely, natural killer cell activity was greater in treated mice than in controls for the entire observation period. Data from cell surface marker analysis provided indirect evidence that natural killer effector cells lack sensitivity to 2'-deoxycoformycin. The antibody responses of mice treated with 2 or 4 micrograms 2'-deoxycoformycin/g over four days prior to or after immunization with sheep erythrocytes were suppressed or enhanced, respectively, compared to controls. These results indicate selective effects of 2'-deoxycoformycin on immune function and suggest that subpopulations of lymphocytes differ in the degree of sensitivity to 2'-deoxycoformycin.

Adenosine Deaminase Inhibitors↗
PubMed1987

Bradykinin-stimulated eicosanoid synthesis and secretion by rabbit ileal components.

The eicosanoid profiles, sites of production, and response to bradykinin stimulation were determined in rabbit ileum and its various components by radioimmunoassay of various prostanoids and 5-lipoxygenase products in the incubation media. The profile of eicosanoid synthesis and secretion by the epithelial cell fraction was PGF2 alpha greater than 6-keto-PGF1 alpha greater than dihydro-keto-PCM = PGE2 greater than TxB2 much greater than 5-HETE greater than LTB4 and by the deepitheliated ileum was PGE2 = 6-keto-PGF1 alpha greater than PGF2 alpha greater than dihydro-keto-PGM greater than TxB2 much greater than LTB4 greater than 5-HETE. PGD2 was not sought in these studies. Rates of eicosanoid production by the deepitheliated ileum were over 200 times that of the epithelial cells. The epithelial cells accounted for 67% of the protein but only 0.2% of the PGE2 produced, while the lamina propria and submucosa contained only 12-30% of the protein but produced 80-90% of the PGE2. Bradykinin (1 microM), A23187 (10 microM), arachidonic acid (20 microM), and melittin (0.7 microM) stimulated PGE2 and 6-keto-PGF1 alpha production by 200% in deepitheliated (or subepithelial) ileum, but bradykinin failed to stimulate production of any eicosanoid by the epithelial cell fraction. Thus the subepithelium (predominantly the lamina propria) is the major eicosanoid producer of rabbit ileum and is the major site of bradykinin-stimulated eicosanoid synthesis and secretion. Eicosanoids released from subepithelial components may be important regulators of epithelial function.

1-Methyl-3-isobutylxanthine↗