RESUMEN
The accuracy of the Halimeter, an inexpensive, simple instrument that measures total breath volatile sulfur compounds (VSCs), has not been adequately tested. We compared Halimeter measurements with those obtained with a specific and sensitive gas chromatographic (GC) technique. The Halimeter gave different, biexponential responses to a constant concentration of different VSCs: The relative response rate and sensitivity were hydrogen sulfide > methyl mercaptan > dimethylsulfide. The transient peak VSC concentration of oral samples was reached long before the sulfide detector fully responded. The GC measurement of initial total VSCs in breath samples was 2.7+/-0.48 times greater than the peak concentration of the Halimeter. However, the plateau phase measurement of the Halimeter was 25% greater than that of GC. While GC and Halimeter measurements positively correlated, appreciable differences were observed. In studies where relatively precise VSC measurements are required, GC is the preferable technique.
Asunto(s)
Halitosis/metabolismo , Sulfuros/análisis , Compuestos de Azufre/análisis , Cromatografía de Gases , Diseño de Equipo , Humanos , Sulfuro de Hidrógeno/análisis , Mediciones Luminiscentes , Metano/análisis , Sensibilidad y Especificidad , Compuestos de Sulfhidrilo/análisis , VolatilizaciónRESUMEN
Breath hydrogen sulfide (H2S) and methyl-mercaptan (CH3SH) concentrations are used as quantitative indicators of halitosis. However, measurements of these gases in duplicate oral samplings often show poor reproducibility. To determine if this poor reproducibility is an artifact of the collection/analytical procedure or a true biological phenomenon, we used a standardized technique to collect from 20 to 30 oral gas samples at two-minute intervals from 11 healthy subjects. The samples were analyzed for sulfur gases and CO2. Sizable variations in H2S and CH3SH concentrations were not associated with alterations in CO2, indicating that the variations did not reflect variable contamination with atmospheric or pulmonary gas. In addition, fluctuations in H2S and CH3SH were not identical and often were not random. We conclude that minute-to-minute variability in oral sulfur gas concentrations is a true biological phenomenon. This fluctuation complicates experimental studies designed to show that interventions alter halitosis.
Asunto(s)
Pruebas Respiratorias/métodos , Halitosis/diagnóstico , Sulfuro de Hidrógeno/análisis , Compuestos de Sulfhidrilo/análisis , Adulto , Artefactos , Dióxido de Carbono/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Espectrofotometría InfrarrojaRESUMEN
Colonic bacteria release large quantities of the highly toxic thiols hydrogen sulfide (H(2)S) and methanethiol (CH(3)SH). These gases rapidly permeate the colonic mucosa, and tissue damage would be expected if the mucosa could not detoxify these compounds rapidly. We previously showed that rat cecal mucosa metabolizes these thiols via conversion to thiosulfate. The purpose of the present study in rats was to determine if this conversion of thiols to thiosulfate is (a) a generalized function of many tissues, or (b) a specialized function of the colonic mucosa. The tissues studied were mucosa from the cecum, right colon, mid-colon, ileum, and stomach; liver; muscle; erythrocytes; and plasma. The metabolic rate was determined by incubating homogenates of the various tissues with H(2)(35)S and CH(3)(35)SH and measuring the rate of incorporation of (35)S into thiosulfate and sulfate. The detoxification activity of H(2)S (expressed as nmol/mg per min) that resulted in thiosulfate production was at least eight times greater for cecal and right colonic mucosa than for the non-colonic tissues. Thiosulfate production from CH(3)SH was at least five times more rapid for cecal and right colonic mucosa than for the non-colonic tissues. We conclude that colonic mucosa possesses a specialized detoxification system that allows this tissue to rapidly metabolize H(2)S and CH(3)SH to thiosulfate. Presumably, this highly developed system protects the colon from what otherwise might be injurious concentrations of H(2)S and CH(3)SH. Defects in this detoxification pathway possibly could play a role in the pathogenesis of various forms of colitis.
Asunto(s)
Sulfuro de Hidrógeno/metabolismo , Mucosa Intestinal/metabolismo , Compuestos de Sulfhidrilo/metabolismo , Tiosulfatos/análisis , Animales , Colon/citología , Colon/metabolismo , Técnicas In Vitro , Inactivación Metabólica , Masculino , Oxidación-Reducción , Ratas , Ratas Sprague-DawleyRESUMEN
We describe a simple technique to measure sulfide in fecal homogenates (or any other liquid milieu), which involves acidification followed by the G.C. measurement of H2S in a gas space equilibrated with a small quantity of homogenate. An internal standard of Zn35S added to the homogenate permits correction for incomplete recovery of H2S in the gas space. The use of a sulfur chemiluminescence detector, which specifically and sensitively responds to sulfur-containing compounds, greatly facilitates this measurement.
Asunto(s)
Cromatografía de Gases/métodos , Heces/química , Sulfuro de Hidrógeno/análisis , Humanos , Concentración de Iones de Hidrógeno , Mediciones Luminiscentes , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Sulfuros , Azufre/análisis , Compuestos de ZincRESUMEN
We assessed the effects of several treatments on the concentrations of oral sulfur-containing gases, compounds thought to be responsible for morning breath. Upon awakening in the morning, healthy volunteers collected oral gas samples before and for eight hours after the following treatments: no treatment, brushing the teeth with toothpaste, brushing the tongue, rinsing with 5 mL of 3% hydrogen peroxide, breakfast ingestion, or swallowing two BreathAsure capsules. The gas samples were analyzed for sulfur-containing volatiles via gas chromatography. Baseline collections usually contained three sulfur gases: hydrogen sulfide, methanethiol, and dimethylsulfide. The effectiveness of a treatment was determined via comparison of the areas under gas concentrations-time curves with and without treatment. Brushing the teeth or ingestion of BreathAsure had no apparent influence on the sulfur gases. Ingestion of breakfast and tongue brushing resulted in strong trends toward decreased sulfur gases. Hydrogen peroxide significantly reduced the sulfur gas concentrations for eight hours.
Asunto(s)
Desodorantes/uso terapéutico , Halitosis/terapia , Compuestos de Azufre/análisis , Adulto , Análisis de Varianza , Área Bajo la Curva , Pruebas Respiratorias , Cromatografía de Gases , Ritmo Circadiano , Ingestión de Alimentos , Gases/análisis , Halitosis/diagnóstico , Halitosis/metabolismo , Humanos , Sulfuro de Hidrógeno/análisis , Persona de Mediana Edad , Higiene Bucal , Estadísticas no Paramétricas , Compuestos de Sulfhidrilo/análisis , Sulfuros/análisis , Insuficiencia del TratamientoRESUMEN
Several lines of evidence suggest that ulcerative colitis could be caused by excessive bacterial production of H2S in the colon. A rodent model of colitis involves the feeding of nonabsorbable, carbohydrate-bound sulfate in the form of dextran sulfate or carrageenan. The observation that metronidazole blocks the development of this colitis suggested that the injurious agent could be a sulfur-containing compound (such as H2S) that is released during the bacterial metabolism of the nonabsorbed sulfate. We tested this possibility by feeding rats dextran sulfate, with or without bismuth subsalicylate, a compound that avidly binds H2S. Bismuth subsalicylate reduced the fecal release of H2S in dextran sulfate-treated rats to values well below that of controls. Nevertheless, all the animals developed colitis. We conclude that excessive H2S production does not play a role in the dextran sulfate model of colitis.
Asunto(s)
Bismuto/metabolismo , Colitis/inducido químicamente , Colitis/prevención & control , Sulfato de Dextran , Sulfuro de Hidrógeno/metabolismo , Compuestos Organometálicos/metabolismo , Salicilatos/metabolismo , Animales , Bismuto/farmacología , Colitis/metabolismo , Colitis/patología , Colon/patología , Heces/química , Sulfuro de Hidrógeno/antagonistas & inhibidores , Masculino , Compuestos Organometálicos/farmacología , Ratas , Ratas Sprague-Dawley , Valores de Referencia , Salicilatos/farmacologíaRESUMEN
Colonic bacteria liberate large quantities of the highly toxic gases hydrogen sulfide (H(2)S) and methanethiol (CH(3)SH). The colonic mucosa presumably has an efficient means of detoxifying these compounds, which is thought to occur through methylation of H(2)S to CH(3)SH and CH(3)SH to dimethylsulfide (CH(3)SCH(3)). We investigated this detoxification pathway by incubating rat cecal mucosal homogenates with gas containing H(2)S, CH(3)SH, or CH(3)SCH(3). Neither CH(3)SH nor CH(3)SCH(3) was produced during H(2)S catabolism, whereas catabolism of CH(3)SH liberated H(2)S but not CH(3)SCH(3). Thus, H(2)S and CH(3)SH are not detoxified by methylation to CH(3)SCH(3). Rather, CH(3)SH is demethylated to H(2)S, and H(2)S is converted to nonvolatile metabolites. HPLC analysis of the homogenate showed the metabolite to be primarily thiosulfate. Analysis of cecal venous blood obtained after intracecal instillation of H(2)(35)S revealed that virtually all absorbed H(2)S had been oxidized to thiosulfate. The oxidation rate of H(2)S by colonic mucosa was 10,000 times greater than the reported methylation rate. Conversion to thiosulfate appears to be the mechanism whereby the cecal mucosa protects itself from the injurious effects of H(2)S and CH(3)SH, and defects in this detoxification possibly could play a role in colonic diseases such as ulcerative colitis.
Asunto(s)
Ciego/metabolismo , Sulfuro de Hidrógeno/metabolismo , Compuestos de Sulfhidrilo/metabolismo , Animales , Euryarchaeota/metabolismo , Sulfuro de Hidrógeno/toxicidad , Inactivación Metabólica , Mucosa Intestinal/metabolismo , Hígado/metabolismo , Masculino , Metano/metabolismo , Metiltransferasas/antagonistas & inhibidores , Oxígeno/análisis , Ratas , Ratas Sprague-Dawley , Compuestos de Sulfhidrilo/toxicidadRESUMEN
OBJECTIVE: Activated charcoal is used to treat excessive volume or malodor of intestinal gas. Our previous studies demonstrated that activated charcoal failed to bind appreciable quantities of the volumetrically important gut gases. However, the odor of feces and flatus derives primarily from trace quantities of sulfur-containing gases, primarily H2S and methanethiol, which should avidly bind to activated charcoal. The goal of this study was to determine if ingestion of activated charcoal reduces the fecal release of sulfur gases. METHODS: Five healthy human volunteers ingested 0.52 g of activated charcoal four times daily for 1 wk and the fecal liberation of intestinal gases was measured before and after the activated charcoal treatment. In an effort to explain the in vivo results, additional in vitro studies were performed to compare the binding capacity of charcoal to the sulfur gas released by feces. RESULTS: Ingestion of activated charcoal produced no significant reduction in the fecal release of any of the sulfur-containing gases, nor was total fecal gas release or abdominal symptoms significantly influenced. In vitro studies suggested that the failure of ingested charcoal to reduce liberation of sulfur gases probably is explained by the saturation of charcoal binding sites during passage through the gut. CONCLUSION: Commonly employed doses of activated charcoal do not appreciably influence the liberation of fecal gases.
Asunto(s)
Bacterias/metabolismo , Carbón Orgánico/farmacología , Colon/microbiología , Heces/química , Gases/análisis , Sulfuros/análisis , Adulto , Femenino , Flatulencia/fisiopatología , Humanos , Sulfuro de Hidrógeno/análisis , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Compuestos de Sulfhidrilo/análisisRESUMEN
Utilizing the sulfur-containing gases of garlic as probes, we investigated the gut versus mouth origin of odoriferous breath gases. Five individuals ingested 6 g of garlic, and sulfur gases in mouth, alveolar air, and urine samples were measured. The mouth normally contained low concentrations of hydrogen sulfide, methanethiol, and dimethyl sulfide. Immediately after garlic ingestion, transient high concentrations of methanethiol and allyl mercaptan and lesser concentrations of allyl methyl sulfide (AMS), allyl methyl disulfide, and allyl disulfide were observed. With the exception of AMS, all gases were present in far greater concentrations in mouth than alveolar air, indicating an oral origin. Only AMS was of gut origin as evidenced by similar partial pressures in mouth, alveolar air, and urine. After 3 h, AMS was the predominant breath sulfur gas. The unique derivation of AMS from the gut is attributable to the lack of gut and liver metabolism of this gas versus the rapid metabolism of the other gases. Breath odor after garlic ingestion initially originates from the mouth and subsequently from the gut.
Asunto(s)
Ingestión de Alimentos , Ajo , Halitosis/etiología , Intestinos/fisiología , Boca/fisiología , Plantas Medicinales , Adulto , Ingestión de Alimentos/fisiología , Femenino , Gases , Humanos , Mucosa Intestinal/metabolismo , Masculino , Persona de Mediana Edad , Boca/metabolismo , Concentración Osmolar , Alveolos Pulmonares/fisiología , Compuestos de Azufre/metabolismo , Compuestos de Azufre/orinaRESUMEN
BACKGROUND: Ingestion of soy products may cause excessive intestinal gas. This gas results from colonic bacterial fermentation of the indigestible oligosaccharides raffinose and stachyose, which are present in high concentrations in legumes. OBJECTIVE: The objective of the study was to compare gas production and gaseous symptoms in healthy volunteers after ingestion of 34 and 80 g soy flour made from either conventional soybeans or soybeans naturally low in indigestible oligosaccharides. DESIGN: In a double-blind, randomized, crossover protocol, breath hydrogen (an indicator of carbohydrate malabsorption), flatus frequency, and abdominal symptoms were assessed after subjects ingested the soy products and after 2 control meals (rice or lactose-hydrolyzed milk). RESULTS: The sum of breath-hydrogen concentrations for 8 h was significantly greater (P < 0.005) after 34 g conventional soy (60.4+/-9.4 ppm) than after low-oligosaccharide soy (34.3+/-8.1 ppm). Greater differences were observed with 80-g doses: 157.9+/-19.4 ppm after conventional soy and 50.8+/-6.8 ppm after low-oligosaccharide soy (P < 0.001). Flatus frequency (7.5+/-1.9 times/12 h) was significantly greater (P = 0.039) after ingestion of 80 g conventional soy than after the control, rice meal (3.2+/-0.8 times/12 h), whereas flatus frequency after the low-oligosaccharide soy meal (3.9+/-0.7 times/12 h) was comparable with that after the rice meal. There were no significant differences in the severity of other abdominal symptoms. CONCLUSION: Soy flour derived from low-oligosaccharide soybeans resulted in less gas production than that derived from conventional soybeans.
Asunto(s)
Flatulencia/fisiopatología , Harina , Glycine max , Intestinos/efectos de los fármacos , Oligosacáridos/farmacología , Adulto , Pruebas Respiratorias , Estudios Cruzados , Método Doble Ciego , Femenino , Gases , Humanos , Hidrógeno/análisis , Intestinos/fisiología , Masculino , Persona de Mediana Edad , Oligosacáridos/administración & dosificaciónRESUMEN
BACKGROUND/AIMS: While the social significance of flatus derives mainly from its odour, previous studies have focused on the non-odoriferous components of rectal gas. The aims of the present study were to determine the role of sulphur-containing gases in flatus odour and test the efficacy of a device purported to reduce this odour. METHODS: Flatus was quantitatively collected via rectal tube from 16 healthy subjects who ingested pinto beans and lactulose to enhance flatus output. The concentrations of sulphur-containing gases in each passage were correlated with odour intensity assessed by two judges. Odour intensity was also determined after treatment of flatus samples with zinc acetate, which binds sulphydryl compounds (hydrogen sulphide and methanethiol), or activated charcoal. Utilising gastight Mylar pantaloons, the ability of a charcoal lined cushion to adsorb sulphur-containing gases instilled at the anus of eight subjects was assessed. RESULTS: The main sulphur-containing flatus component was hydrogen sulphide (1.06 (0.2) mumol/l), followed by methanethiol (0.21 (0.04) mumol/l) and dimethyl sulphide (0.08 (0.01) mumol/l) (means (SEM)). Malodour significantly correlated with hydrogen sulphide concentration (p < or = 0.001). Zinc acetate reduced sulphur gas content but did not totally eliminate odour, while activated charcoal removed virtually all odour. The cushion absorbed more than 90% of the sulphur gases. CONCLUSION: Sulphur-containing gases are the major, but not the only, malodorous components of human flatus. The charcoal lined cushion effectively limits the escape of these sulphur-containing gases into the environment.
Asunto(s)
Flatulencia/metabolismo , Gases/análisis , Odorantes/análisis , Recto/metabolismo , Adolescente , Adulto , Análisis de Varianza , Carbón Orgánico , Cromatografía de Gases , Método Doble Ciego , Estudios de Evaluación como Asunto , Femenino , Humanos , Sulfuro de Hidrógeno/análisis , Pañales para la Incontinencia , Masculino , Persona de Mediana Edad , Odorantes/prevención & control , Compuestos de Sulfhidrilo/análisis , Sulfuros/análisisRESUMEN
BACKGROUND & AIMS: Hydrogen sulfide is one of the main malodorous compounds in human flatus. This toxic gas also has been implicated in the pathogenesis of ulcerative colitis. Therefore, a treatment that reduces colonic H2S levels could be clinically useful in the treatment of flatus odor and of ulcerative colitis. In this study the ability of bismuth subsalicylate, a compound that binds H2S, to reduce H2S release in the colon, was tested. METHODS: Homogenates made from human and rat feces were incubated with and without bismuth subsalicylate, and gas production was measured. Fecal samples from 10 healthy subjects were analyzed before and after ingestion of bismuth subsalicylate (524 mg four times a day) for 3-7 days. RESULTS: Fecal homogenates showed a dose-dependent relationship between the concentration of bismuth subsalicylate and H2S release. Treatment of subjects with bismuth subsalicylate produced a >95% reduction in fecal H2S release. CONCLUSIONS: The ability of bismuth subsalicylate to dramatically reduce H2S could provide a clinically useful means of controlling fecal and/or flatus odor and of decreasing the putative injurious effects of H2S on the colonic mucosa.
Asunto(s)
Bismuto/farmacología , Colon/metabolismo , Sulfuro de Hidrógeno/metabolismo , Compuestos Organometálicos/farmacología , Salicilatos/farmacología , Adulto , Animales , Relación Dosis-Respuesta a Droga , Heces/química , Femenino , Humanos , Sulfuro de Hidrógeno/análisis , Masculino , Persona de Mediana Edad , Concentración Osmolar , RatasRESUMEN
Highly toxic sulfur-containing gases have been pathogenetically implicated in ulcerative colitis. Utilizing a rat model, we studied the production and elimination of sulfur-containing gases within the unperturbed colon. The major sulfur-containing gases were hydrogen sulfide (H2S), methanethiol, and dimethyl sulfide with cecal accumulation rates of 2.6, 0.096, and 0.046 microliter/min, respectively. The dependence of H2S production on dietary components was demonstrated via a sixfold reduction with fasting and a fivefold increase with carrageenan (a nonabsorbable, sulfur compound) feeding. Zinc acetate reduced cecal H2S by fivefold, indicating the importance of H2S binding by divalent cations. During passage from the cecum to the rectum, > 90% of the sulfur gases were absorbed or metabolized. An H2 35S turnover of 97%/min was observed in the isolated cecum. Thus mucosal exposure is > 10 times the measured accumulation rate. Cecal mucosal tissue very rapidly metabolized H2S and methanethiol via a nonmethylating reaction.
Asunto(s)
Colon/metabolismo , Gases/metabolismo , Azufre/metabolismo , Animales , Dióxido de Carbono/metabolismo , Ciego/metabolismo , Hidrógeno/metabolismo , Sulfuro de Hidrógeno/metabolismo , Mucosa Intestinal/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Recto/fisiologíaRESUMEN
OBJECTIVE: Sulfide, a product of sulfate-reducing bacteria, has been proposed to play an etiologic role in ulcerative colitis. Ulcerative colitis feces have increased numbers and activity of sulfate-reducing bacteria, but only modestly increased sulfide. However, fecal sulfide exists largely in the volatile, highly toxic H2S form that moves rapidly from feces to surrounding gas. Our aim was to quantify the fecal release of H2S and other volatiles (CO2, H2, CH4, methanethiol, and dimethylsulfide). METHODS: Fecal samples from 25 subjects with ulcerative colitis and 17 controls were incubated in 4-L containers, and gas release was assessed at intervals over 24 h. RESULTS: H2S release by ulcerative colitis feces was elevated 3-4-fold at every measurement point compared with normal feces (p < 0.003 at 24 h). The only other significant difference was increased CO2 release by ulcerative colitis feces at 1 h. Supplementation of fecal homogenates with sulfur-containing substrates showed that organic compounds (mucin, cysteine, taurocholate) provided more readily utilizable substrate for H2S production than did sulfate. CONCLUSIONS: Increased H2S release is a relatively localized metabolic aberration of ulcerative colitis feces. This increased H2S may reflect abnormalities of the fecal bacteria and/or substrate availability.
Asunto(s)
Colitis Ulcerosa/etiología , Heces/química , Sulfuro de Hidrógeno/análisis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bacterias/metabolismo , Dióxido de Carbono/análisis , Monóxido de Carbono/análisis , Cromatografía de Gases , Colitis Ulcerosa/metabolismo , Interpretación Estadística de Datos , Heces/microbiología , Femenino , Humanos , Hidrógeno/análisis , Sulfuro de Hidrógeno/metabolismo , Masculino , Metano/análisis , Persona de Mediana Edad , Sulfatos/metabolismo , Compuestos de Sulfhidrilo/análisis , Factores de TiempoRESUMEN
To better understand the physiology of colonic gas production, each flatus passage of 16 subjects over a 4-h period was analyzed by gas chromatography for N2, O2, H2, CO2, CH4, and for odoriferous sulfur-containing gases. Appreciable intraindividual and enormous interindividual variability was observed, indicating that each gas passage reflected the interaction of highly variable liberation and/or removal mechanisms. The predominant flatus gas was CO2, H2, and N2 in seven, six, and three subjects, respectively. Gases produced intraluminally (H2, CO2, and CH4) comprised approximately 74% of flatus, and rapid CO2 and H2 productions were responsible for high passage rates. A positive correlation between flatus H2 and CO2 suggested that CO2, like H2, mainly was a bacterial product. Whereas methanogens and H2S-producing bacteria usually are mutually exclusive in feces, CH4 and H2S did not negatively correlate, indicating coexistence of both organisms in the colon. We conclude that analysis of flatus composition provides a novel means of assessing colonic physiology, particularly ongoing bacterial metabolism throughout the unperturbed colon.
Asunto(s)
Colon/fisiopatología , Flatulencia/fisiopatología , Adolescente , Adulto , Cromatografía de Gases , Femenino , Gases/análisis , Humanos , Masculino , Persona de Mediana Edad , Recto/fisiopatologíaRESUMEN
This paper shows that a variety of carbon-containing materials (wool, cotton, wood, paper, latex, Tygon) release CO during incubation at ambient temperature. This CO production was enhanced by aerobic versus anaerobic incubation, increasing temperature, and exposure to fluorescent light. CO production from glucose solutions was enhanced by alkaline pH or prior boiling or autoclaving and reduced by the presence of superoxide dismutase or catalase. We conclude that a variety of materials are constantly undergoing oxidation at ambient or physiological temperature as evidenced by the release of CO. Measurements of this CO production could provide a simple, rapid and sensitive means of assessing oxidative damage.
Asunto(s)
Monóxido de Carbono/química , Hidrocarburos/química , Oxidantes/química , TemperaturaRESUMEN
Literature values for breath pentane, an indicator of lipid peroxidation, vary by 1,000-fold in healthy subjects. This report describes multiple technical artifacts that may explain this disparity. First, we found that a major component of human breath (probably isoprene) co-eluted with pentane on columns used by some investigators, resulting in erroneously high determinations. Second, despite washouts using pentane-free air, ambient pentane dissolved in body fat may result in breath concentrations many times greater than that due to endogenous production. True endogenous breath pentane may never have been accurately determined.
Asunto(s)
Pruebas Respiratorias , Peroxidación de Lípido , Pentanos/análisis , Animales , Cromatografía de Gases , Reacciones Falso Positivas , Humanos , Ratas , Ratas ZuckerRESUMEN
Ethanol metabolism by gastric alcohol dehydrogenase (ADH) is thought to be an important determinant of peripheral ethanol time-concentration curves (AUCs) in rats and humans. We quantitated this metabolism in rats by measuring the gastric absorption of oral ethanol (0.25 g/kg) and the gastric venous-arterial (V-A) difference of ethanol versus ethanol metabolites (acetate, acetaldehyde, and bicarbonate). Over 1 h, approximately 20% of the ethanol was absorbed from the stomach and 70% was emptied into the duodenum. The gastric V-A difference of ethanol metabolites was less than 4% of that of ethanol. Thus, gastric metabolism accounted for less than 1% (less than 4% of 20% absorbed) of the dose. This negligible metabolism was predictable from the low affinity of gastric ADH for ethanol. In contrast, gastric ADH has a high affinity for octanol, and 66% of this compound was metabolized during gastric absorption. Evidence supporting gastric metabolism of ethanol largely derives from the lower AUCs observed after oral than after intravenous administration; however, we observed increasingly higher AUCs with increasingly rapid portal vein infusions of identical ethanol doses. We conclude that gastric metabolism of ethanol is negligible in the rat, and differences in AUCs ascribed to gastric metabolism may reflect differences in ethanol absorption.
Asunto(s)
Etanol/farmacocinética , Mucosa Gástrica/metabolismo , Absorción , Animales , Masculino , Ratas , Ratas EndogámicasRESUMEN
Bovine serum albumin (BSA) catalyzes the o-rearrangement of the reactive electrophile, N-sulfooxy-2-acetylaminofluorene (NSF), a potential ultimate hepatocarcinogen in the rat, to the nonmutagenic sulfuric acid esters of 1- and 3-hydroxy-2-acetylaminofluorene. Conversion of NSF was proportional to BSA concentrations ranging from 0.25 to approximately 4 mg BSA/ml incubation mixture. At concentrations greater than or equal to 5 mg BSA/ml, approximately 90% of NSF was converted to the sulfuric acid esters of the o-amidofluorenols. Human serum albumin (HSA) likewise catalyzed the o-rearrangement of NSF. However, the catalytic activity of HSA was only approximately 50% of the activity of BSA. The catalytic effect of BSA was abolished by heat denaturation. However, it was not changed by dialysis or by anion exchange chromatography. These observations indicated that the catalytic effect requires intactness of the tertiary structure of BSA and is not due to a contaminant(s) of low or high molecular weight. There were no differences in the catalytic activity of three separate fractions of chromatographed BSA, suggesting that the catalytic activity is associated with the entire BSA molecule. In contrast to serum albumin, gamma-globulin (bovine or human) did not catalyze the o-rearrangement of NSF. The solvolytic degradation of NSF to 4-hydroxy-2-acetylaminofluorene, a major reaction in the absence of BSA, occurred only to a minor extent in the presence of BSA. These data indicated that the BSA-catalyzed o-rearrangement determines the rates of concurrent reactions involved in the degradation of NSF. BSA and HSA did not catalyze the o-rearrangement of N-acetoxy-2-acetylaminofluorene (N-OAC-2-AAF), the acetate ester of N-hydroxy-2-acetylaminofluorene (N-OH-2-AAF), to the acetic acid esters of the o-amidofluorenols. These findings suggest that the albumin-catalyzed o-rearrangement occurs preferentially with esters of fluorenylhydroxamic acids that readily ionize in aqueous media.
Asunto(s)
2-Acetilaminofluoreno , Hidroxiacetilamino Fluoreno , Neoplasias Hepáticas Experimentales/inducido químicamente , Albúmina Sérica Bovina/farmacología , Ácidos Sulfúricos , Animales , Catálisis , Fenómenos Químicos , Química , Cromatografía por Intercambio Iónico , Calor , Estructura Molecular , Desnaturalización Proteica , Ratas , Relación Estructura-ActividadRESUMEN
The specificity of human antibodies for the two major sidechain determinants of the type II group B streptococcal (GBS) polysaccharide was examined in 90 pairs of maternal and cord sera. Using an ELISA system, total antibody was measured against the complete (sialylated) type II antigen and the proportion of antibody against the galactose determinant was estimated by inhibition with free beta-methylgalactopyranoside. Mothers colonized by type II or by other GBS types had higher levels of total specific antibody (means, 3.3 and 4.7 micrograms/ml, respectively) than those not colonized (mean, 2.2 micrograms/ml). Cord sera averaged 1-2 micrograms/ml lower than maternal sera. Colonization with GBS was also associated with higher levels against the galactose determinant (mean, 1.5 micrograms/ml, compared to 0.7 micrograms/ml for those not colonized). The distribution of specificities favoured antibodies against the sialic acid determinant in maternal but not cord sera. Specificity as well as antibody level may play a role in the epidemiology of GBS type II.