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1.
Endocr J ; 70(2): 149-159, 2023 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-36198615

RESUMEN

Metformin, an oral medication, is prescribed to patients with type 2 diabetes mellitus. Although the efficacy, safety, and low economic burden of metformin on patients have long been recognized, approximately 5% of the patients treated with this drug develop severe diarrhea and discontinue the treatment. We previously reported that 1,000 mg·kg-1·day-1 of metformin induced diarrhea in diabetic obese (db/db) mice and wood creosote (traditional medication for diarrhea) ameliorated the symptoms. In this study, we attempted to elucidate the molecular mechanisms by which metformin induces diarrhea. Cystic fibrosis transmembrane conductance regulator (CFTR) is a key ion (chloride) channel in cyclic adenosine monophosphate (cAMP)-induced diarrhea. Metformin treatment increased bile flow (bile acids and bilirubin) in the ileum of mice. In addition, the treatment was accompanied by an increase in mRNA and protein levels of CFTR in the mucosa of the ileum and colon in both wild-type (C57BL/6J) and db/db mice. Glucagon-like peptide-1 (GLP-1), as well as cholic acid, induces CFTR mRNA expression in human colon carcinoma Caco-2 cells through cAMP signaling. Although wood creosote (10 mg/kg) ameliorated diarrhea symptoms, it did not alter the mRNA levels of Glp-1 or Cftr. Similar to overeating, metformin upregulated GLP-1 and CFTR expression, which may have contributed to diarrhea symptoms in mice. Although we could not identify db/db mouse-specific factors associated with metformin-induced diarrhea, these factors may modulate colon function. Wood creosote may not interact with these factors but ameliorates diarrhea symptoms.


Asunto(s)
Diabetes Mellitus Tipo 2 , Metformina , Ratones , Humanos , Animales , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Células CACO-2 , Péptido 1 Similar al Glucagón , Creosota , Ratones Endogámicos C57BL , AMP Cíclico/metabolismo , Colon/metabolismo , Diarrea/metabolismo , ARN Mensajero , Íleon/metabolismo
2.
Neurotoxicol Teratol ; 93: 107121, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36089172

RESUMEN

Polycyclic aromatic hydrocarbons (PAH) are products of incomplete combustion which are ubiquitous pollutants and constituents of harmful mixtures such as tobacco smoke, petroleum and creosote. Animal studies have shown that these compounds exert developmental toxicity in multiple organ systems, including the nervous system. The relative persistence of or recovery from these effects across the lifespan remain poorly characterized. These studies tested for persistence of neurobehavioral effects in AB* zebrafish exposed 5-120 h post-fertilization to a typical PAH, benzo[a]pyrene (BAP). Study 1 evaluated the neurobehavioral effects of a wide concentration range of BAP (0.02-10 µM) exposures from 5 to 120 hpf during larval (6 days) and adult (6 months) stages of development, while study 2 evaluated neurobehavioral effects of BAP (0.3-3 µM) from 5 to 120 hpf across four stages of development: larval (6 days), adolescence (2.5 months), adulthood (8 months) and late adulthood (14 months). Embryonic BAP exposure caused minimal effects on larval motility, but did cause neurobehavioral changes at later points in life. Embryonic BAP exposure led to nonmonotonic effects on adolescent activity (0.3 µM hyperactive, Study 2), which attenuated with age, as well as startle responses (0.2 µM enhanced, Study 1) at 6 months of age. Similar startle changes were also detected in Study 2 (1.0 µM), though it was observed that the phenotype shifted from reduced pretap activity to enhanced posttap activity from 8 to 14 months of age. Changes in the avoidance (0.02-10 µM, Study 1) and approach (reduced, 0.3 µM, Study 2) of aversive/social cues were also detected, with the latter attenuating from 8 to 14 months of age. Fish from study 2 were maintained into aging (18 months) and evaluated for overall and tissue-specific oxygen consumption to determine whether metabolic processes in the brain and other target organs show altered function in late life based on embryonic PAH toxicity. BAP reduced whole animal oxygen consumption, and overall reductions in total basal, mitochondrial basal, and mitochondrial maximum respiration in target organs, including the brain, liver and heart. The present data show that embryonic BAP exposure can lead to neurobehavioral impairment across the life-span, but that these long-term risks differentially emerge or attenuate as development progresses.


Asunto(s)
Contaminantes Ambientales , Petróleo , Hidrocarburos Policíclicos Aromáticos , Contaminación por Humo de Tabaco , Animales , Benzo(a)pireno/toxicidad , Creosota/metabolismo , Creosota/farmacología , Larva , Petróleo/metabolismo , Pez Cebra
3.
J Environ Manage ; 317: 115448, 2022 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-35660826

RESUMEN

Gas ebullition can mobilize dense non-aqueous phase liquids (DNAPLs) from sediments to the overlying water column, increasing the DNAPL-impacted area and posing serious challenges to the remediation and management of contaminated sediments. Despite this, there have been few laboratory studies focused on gas ebullition-facilitated transport of DNAPL. In this study, bubble-facilitated transport was investigated by injecting gas (air or nitrogen) at 1 mL/min through a creosote source zone (∼25% saturation) capped with sand layers of different thicknesses. Three short-term experiments (8.3-8.7 h) were capped with 11.4, 7.0 or 4.5 cm of sand to estimate DNAPL flux. One long-term experiment (30 days) was capped with 8 cm of sand to investigate DNAPL removal. Heptane placed on a layer of water above the sand was used as a solvent trap and analyzed for petroleum hydrocarbons (PHCs). Results showed that creosote travelled as thin coatings and films surrounding gas bubbles migrating out of the source zone. Gas invasion was dominated by capillarity in the 11.4 cm-thick sand layer and by fracturing in the 7.0 and 4.5 cm-thick sand layers. Migration through these fractures often led to the formation of creosote tails on mobilized bubbles that drained towards the rear end of the bubble. The mass released decreased exponentially with sand cap thickness. In the long-term experiment, images showed significant depletion of the source zone in 30 days. Linear regression analysis showed that relationships with high predictive capabilities for ebullition-facilitated fluxes of hydrophobic organic contaminants can be obtained by incorporating gas ebullition flux and source strength, based on results from this study along with others from the field and laboratory. To our knowledge, this is the first study to compile and integrate data collected from laboratory and field studies to develop an assessment tool to facilitate the management of contaminated sediments affected by gas ebullition.


Asunto(s)
Petróleo , Contaminantes Químicos del Agua , Creosota , Sedimentos Geológicos/química , Hidrocarburos , Arena , Contaminantes Químicos del Agua/análisis
4.
Environ Toxicol ; 31(1): 85-92, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25044495

RESUMEN

Coal tar is a significant product generated from coal pyrolysis. Coal tar can be utilized as raw materials for various industries. It is also a type of raw material from which phenols, naphthalenes, and anthracene can be extracted. The present study was designed to investigate the possibility of coal tar creosote to induce oxidative stress and biochemical perturbations in rat liver and the role of rosemary (Rosmarinus officinalis) in ameliorating its toxic effects. Male Wister Albino rats were randomly divided into four groups of seven each, group I served as control; group II treated with rosemary (10 mL of water extract/kg BW for 21 days), group III received coal tar creosote (200 mg/4 mL olive oil/kg BW for 3 days), and group IV treated with both rosemary and coal tar creosote. The administration of coal tar creosote significantly caused elevation in lipid peroxidation (LPO) and reduction in the activities of glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST). A significant decrease in reduced glutathione (GSH) content was also observed. Liver aminotransferases aspartate transaminase (AST) and alanine transaminase (ALT)] and alkaline phosphatase (AlP) were significantly decreased while lactate dehydrogenase (LDH) was increased. Rosemary pretreatment to coal tar creosote-treated rats decreased LPO level and normalized GPx, GR, SOD, CAT, and GST activities, while GSH content was increased. Also, liver AST, ALT, AlP, and LDH were maintained near normal level due to rosemary treatment. In conclusion, rosemary has beneficial effects and could be able to antagonize coal tar creosote toxicity.


Asunto(s)
Creosota/toxicidad , Hígado/efectos de los fármacos , Alanina Transaminasa/metabolismo , Animales , Antioxidantes/metabolismo , Aspartato Aminotransferasas/metabolismo , Catalasa/metabolismo , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Glutatión Transferasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/enzimología , Hígado/metabolismo , Masculino , Estrés Oxidativo/efectos de los fármacos , Fenoles/química , Fenoles/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , Rosmarinus/metabolismo , Superóxido Dismutasa/metabolismo
5.
Aust Dent J ; 58(4): 522-5, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24320911

RESUMEN

Local anaesthesia is used routinely throughout dentistry. Complications are, however, relatively uncommon. A unique case of superficial skin necrosis and neurological symptoms following administration of local anaesthesia for dental treatment is reported and the possible mechanisms behind this unusual presentation are discussed. Awareness of this possible complication and its mechanism helps clinicians diagnose and manage patients with similar problems appropriately.


Asunto(s)
Anestesia Dental/efectos adversos , Creosota/efectos adversos , Hidrocarburos Yodados/efectos adversos , Hipoestesia/inducido químicamente , Piel/patología , Timol/efectos adversos , Temblor/inducido químicamente , Anestesia Local , Anestésicos Locales , Combinación de Medicamentos , Femenino , Humanos , Necrosis/inducido químicamente , Adulto Joven
6.
Med Hist ; 57(2): 249-68, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24070348

RESUMEN

Seirogan, a popular anti-diarrhoeal pill, is arguably one of the most successful pharmaceutical products of modern Japan. What is less known is that the Japanese army initially developed Seirogan during the Russo-Japanese War as the 'Conquer-Russia-Pill', which was later marketed to the public by private manufacturers. Previous scholars have emphasised the top­down governmental method of mobilising private sectors to manipulate public opinion for the cause of external imperialist expansion and domestic stability during wartime Japan. But the matrix that the Conquer-Russia-Pill allows us to glimpse is an inverted power relation among the state, commercial sectors, and imperial citizens. While the Japanese government remained indifferent if not hostile to jingoistic pharmaceutical manufacturers who could easily disrupt international relations, pharmaceutical companies quickly recognised and exploited the opportunities that the Conquer-Russia-Pill and its symbolism provided under the banner of the empire. In turn, Japanese consumers reacted to commercial sermons carefully anchored in patriotic and militaristic discourses and images by opening their wallets. In other words, the popularity of the Conquer-Russia-Pill was a culmination of the convergence of a governmental initiative to enhance military capabilities, the commercial ingenuity of pharmaceutical manufacturers, and a consumer response to patriotic exhortations.


Asunto(s)
Antidiarreicos/historia , Creosota/historia , Industria Farmacéutica/historia , Extractos Vegetales/historia , Publicidad/historia , Antidiarreicos/uso terapéutico , Creosota/uso terapéutico , Disentería/tratamiento farmacológico , Disentería/historia , Historia del Siglo XX , Humanos , Internacionalidad/historia , Japón , Personal Militar/historia , Extractos Vegetales/uso terapéutico , Rusia (pre-1917) , U.R.S.S. , Guerra
7.
Hepatogastroenterology ; 58(109): 1252-4, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21937389

RESUMEN

Anisakiasis is a disease characterized by an abrupt onset of sharp epigastric pain, which occurs typically a few hours after eating raw or undercooked seafood. Anisakiasis was a Japanese localized disease in the past, however has become an illness of concern in many countries where eating Japanese style raw or undercooked seafood has become popular. At present, the only effective treatment is an endoscopic removal of the nematode. Development of an effective medicine is expected. We report two cases of Anisakiasis, the symptoms of which were ameliorated after the administration of an over-the-counter (OTC) medicine containing wood creosote (Seirogan). Also, we examined the in vitro effect of the Seirogan on the viability of the nematode. In the two cases, the strong epigastric pain was subdued promptly after oral intake of the Seirogan. The exposure of Seirogan suppressed the viability of Anisakis Larva in vitro dose dependently. The oral administration of medicine containing wood creosote might be effective as a first aid to ameliorate the symptoms of Anisakiasis.


Asunto(s)
Anisakiasis/tratamiento farmacológico , Creosota/uso terapéutico , Extractos Vegetales/uso terapéutico , Gastropatías/tratamiento farmacológico , Administración Oral , Adulto , Creosota/farmacología , Humanos , Masculino , Persona de Mediana Edad , Extractos Vegetales/farmacología
8.
Environ Pollut ; 158(2): 585-91, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19775788

RESUMEN

The impact of residual PAHs (2250 +/- 71 microg total PAHs g(-1)) following enhanced natural attenuation (ENA) of creosote-contaminated soil (7767 +/- 1286 microg total PAHs g(-1)) was assessed using a variety of ecological assays. Microtox results for aqueous soil extracts indicated that there was no significant difference in EC(50) values for uncontaminated, pre- and post-remediated soil. However, in studies conducted with Eisenia fetida, PAH bioaccumulation was reduced by up to 6.5-fold as a result of ENA. Similarly, Beta vulgaris L. biomass yields were increased 2.1-fold following ENA of creosote-contaminated soil. While earthworm and plant assays indicated that PAH bioavailability was reduced following ENA, the residual PAH fraction still exerted toxicological impacts on both receptors. Results from this study highlight that residual PAHs following ENA (presumably non-bioavailable to bioremediation) may still be bioavailable to important receptor organisms such as earthworms and plants.


Asunto(s)
Creosota/análisis , Oligoquetos/metabolismo , Hidrocarburos Policíclicos Aromáticos/análisis , Hidrocarburos Policíclicos Aromáticos/farmacocinética , Contaminantes del Suelo/análisis , Suelo/análisis , Aliivibrio fischeri/efectos de los fármacos , Animales , Beta vulgaris/efectos de los fármacos , Beta vulgaris/crecimiento & desarrollo , Biodegradación Ambiental , Cromatografía de Gases , Hidrocarburos Policíclicos Aromáticos/toxicidad , Contaminantes del Suelo/toxicidad , Australia del Sur , Pruebas de Toxicidad
9.
Auton Neurosci ; 133(2): 136-45, 2007 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-17182287

RESUMEN

Wood creosote has been used as an herbal medicine against acute diarrhea caused by food poisoning and has an inhibitory effect on colonic motility and enterotoxin-induced ion secretion. Since no previous studies have examined the effects of wood creosote on stress-induced alteration of colonic motility, we examined the effects on the colonic motility altered by intracerebroventricular (i.c.v.) injection of corticotropin-releasing factor (CRF), which is a key mediator in responses to stress. We recorded motor activity in proximal and distal colon of unrestrained conscious rats via two manometory catheters. The frequencies of phase III-like contraction and the % motor indices in both proximal and distal colon were measured. At the same time the number of fecal pellets excreted was counted. I.c.v. injection of CRF increased the motor activity in both proximal and distal colon, and these effects were completely antagonized by i.c.v. injection of a selective CRF type 1 antagonist but not by a CRF type 2 antagonist. Changes in colonic motility induced by CRF were reversed by intravenously administered wood creosote. Intraluminal administration of the 5-HT(3) receptor antagonist granisetron, or the 5-HT(4) receptor antagonist SB 204070 blocked the increase in colonic motility induced by i.c.v. injection of CRF. Wood creosote prevented the increase in colonic motility induced by the 5-HT(3) receptor agonist SR57227A in the proximal colon, while it prevented the increase in colonic motility induced by the 5-HT(4) receptor agonist RS67506 in the distal colon. These results indicate that wood creosote prevents the increase in colonic motility induced by CRF via 5-HT(3) receptors in the proximal colon, and via 5-HT(4) receptors in the distal colon, suggesting that wood creosote might be useful to treat stress-induced diarrhea.


Asunto(s)
Colon/efectos de los fármacos , Hormona Liberadora de Corticotropina/antagonistas & inhibidores , Creosota/farmacología , Sistema Nervioso Entérico/efectos de los fármacos , Motilidad Gastrointestinal/efectos de los fármacos , Receptores de Serotonina/efectos de los fármacos , Animales , Colon/inervación , Colon/fisiopatología , Diarrea/tratamiento farmacológico , Diarrea/metabolismo , Diarrea/fisiopatología , Sistema Nervioso Entérico/metabolismo , Sistema Nervioso Entérico/fisiopatología , Antagonistas de Aminoácidos Excitadores/farmacología , Motilidad Gastrointestinal/fisiología , Inyecciones Intraventriculares , Masculino , Ratas , Ratas Wistar , Receptores de Serotonina/metabolismo , Receptores de Serotonina 5-HT3/efectos de los fármacos , Receptores de Serotonina 5-HT3/metabolismo , Receptores de Serotonina 5-HT4/efectos de los fármacos , Receptores de Serotonina 5-HT4/metabolismo , Serotonina/metabolismo , Agonistas de Receptores de Serotonina/farmacología , Estrés Fisiológico/complicaciones , Estrés Fisiológico/fisiopatología , Resultado del Tratamiento
10.
Life Sci ; 79(9): 913-8, 2006 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-16643959

RESUMEN

Our previous studies demonstrated that wood creosote (Seirogan) inhibits intestinal secretion and normalizes the transport of electrolytes and water in rats subjected to restraint stress. The goal of the present study was to examine whether wood creosote has a protective effect against stress-induced breakdown of intestinal barrier function. F-344 rats were subjected to 90-min water avoidance stress (WAS) with wood creosote (30 mg/kg) or vehicle administered intragastrically 30 min prior to WAS. Sham stressed rats received wood creosote or vehicle treatment but did not experience the WAS. All rats were euthanized at the end of the WAS or sham-stress and the jejunum and colon were isolated. Epithelial transport was studied in modified Ussing chambers. Spontaneous secretion was assessed by electrophysiological measurement of the short circuit current (I(sc)) while electrical conductance (G) was calculated from the potential difference (PD) and I(sc) using Ohm's law. Intestinal permeability was defined by the mucosal-to-serosal flux of horseradish peroxidase (HRP). WAS significantly elevated basal I(sc) and G and increased epithelial permeability to HRP in the jejunum but not in the colon. Wood creosote resulted in a significant reduction of the stress-induced increase in I(sc), G and the mucosal-to-serosal flux of HRP compared to the vehicle-treated group. Wood creosote caused no significant effects in sham-stressed rats. The results suggest that oral administration of wood creosote may prevent stress-induced diarrhea by preventing aversive effects on small intestinal secretion and barrier function.


Asunto(s)
Creosota/uso terapéutico , Enfermedades Intestinales/etiología , Enfermedades Intestinales/fisiopatología , Mucosa Intestinal/fisiopatología , Estrés Fisiológico/complicaciones , Estrés Fisiológico/fisiopatología , Animales , Reacción de Prevención/fisiología , Transporte Biológico Activo/fisiología , Electrofisiología , Epitelio/efectos de los fármacos , Epitelio/fisiología , Mucosa Intestinal/efectos de los fármacos , Masculino , Permeabilidad , Ratas , Ratas Endogámicas F344 , Agua
11.
Appl Environ Microbiol ; 71(11): 7008-18, 2005 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16269736

RESUMEN

Bacterial community dynamics and biodegradation processes were examined in a highly creosote-contaminated soil undergoing a range of laboratory-based bioremediation treatments. The dynamics of the eubacterial community, the number of heterotrophs and polycyclic aromatic hydrocarbon (PAH) degraders, and the total petroleum hydrocarbon (TPH) and PAH concentrations were monitored during the bioremediation process. TPH and PAHs were significantly degraded in all treatments (72 to 79% and 83 to 87%, respectively), and the biodegradation values were higher when nutrients were not added, especially for benzo(a)anthracene and chrysene. The moisture content and aeration were determined to be the key factors associated with PAH bioremediation. Neither biosurfactant addition, bioaugmentation, nor ferric octate addition led to differences in PAH or TPH biodegradation compared to biodegradation with nutrient treatment. All treatments resulted in a high first-order degradation rate during the first 45 days, which was markedly reduced after 90 days. A sharp increase in the size of the heterotrophic and PAH-degrading microbial populations was observed, which coincided with the highest rates of TPH and PAH biodegradation. At the end of the incubation period, PAH degraders were more prevalent in samples to which nutrients had not been added. Denaturing gradient gel electrophoresis analysis and principal-component analysis confirmed that there was a remarkable shift in the composition of the bacterial community due to both the biodegradation process and the addition of nutrients. At early stages of biodegradation, the alpha-Proteobacteria group (genera Sphingomonas and Azospirillum) was the dominant group in all treatments. At later stages, the gamma-Proteobacteria group (genus Xanthomonas), the alpha-Proteobacteria group (genus Sphingomonas), and the Cytophaga-Flexibacter-Bacteroides group (Bacteroidetes) were the dominant groups in the nonnutrient treatment, while the gamma-Proteobacteria group (genus Xathomonas), the beta-Proteobacteria group (genera Alcaligenes and Achromobacter), and the alpha-Proteobacteria group (genus Sphingomonas) were the dominant groups in the nutrient treatment. This study shows that specific bacterial phylotypes are associated both with different phases of PAH degradation and with nutrient addition in a preadapted PAH-contaminated soil. Our findings also suggest that there are complex interactions between bacterial species and medium conditions that influence the biodegradation capacity of the microbial communities involved in bioremediation processes.


Asunto(s)
Bacterias/crecimiento & desarrollo , Creosota/metabolismo , Ecosistema , Hidrocarburos Policíclicos Aromáticos/metabolismo , Microbiología del Suelo , Contaminantes del Suelo/metabolismo , Bacterias/clasificación , Bacterias/genética , Bacterias/metabolismo , Biodegradación Ambiental , Recuento de Colonia Microbiana , ADN Bacteriano/análisis , Electroforesis/métodos , Datos de Secuencia Molecular , Petróleo/metabolismo , Filogenia , Reacción en Cadena de la Polimerasa , ARN Ribosómico 16S/genética
12.
Artículo en Inglés | MEDLINE | ID: mdl-15756962

RESUMEN

The influence of nutrients, Mycobacterium sp. strain CH1 and Mycobacterium sp. strain CH2 on the degradation of aged creosote hydrocarbon contaminants was investigated. The Mycobacterium sp. strain CH2 showed the highest positive influence on the degradation of three- and four-ring PAH compounds. The addition of Mycobacterium sp. strain CH1 had the second highest measured positive influence on the degradation of four-ring compounds. Soluble nitrogen and phosphorus also increased the degradation of aged creosote compounds in the contaminated soil. The addition of bacteria decreased the number of measured bacterial species, indicating competition for limited nutrients in the soil.


Asunto(s)
Creosota/metabolismo , Mycobacterium/metabolismo , Hidrocarburos Policíclicos Aromáticos/metabolismo , Microbiología del Suelo , Contaminantes del Suelo/metabolismo , Alabama , Biodegradación Ambiental , Biodiversidad , ADN Bacteriano/análisis , Genotipo , Mycobacterium/aislamiento & purificación , Nitrógeno , Plaguicidas/metabolismo , Fósforo , Hidrocarburos Policíclicos Aromáticos/análisis , Densidad de Población
13.
Clin Ther ; 26(10): 1644-51, 2004 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15598481

RESUMEN

BACKGROUND: Seirogan, an herbal medication containing wood creosote, a mixture of simple phenolic (single-ring)compounds, has been marketed in Asia for the past century as an antidiarrheal and antispasmodic medication. This was the first randomized, double-blind study of this herbal medication in patients with acute, nonspecific diarrhea. OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of wood creosote with those of loperamide hydrochloride in patients with acute, nonspecific diarrhea. METHODS: This double-blind, randomized, active-controlled study was conducted at 12 centers across the United States and Mexico. Patients aged >or=18 years with acute, nonspecific diarrhea, defined as a history of diarrhea for or=3 unformed stools in the 24 hours before the study, accompanied by >or=1 associated symptom (ie, nausea, vomiting, abdominal cramping, and/or fever [

Asunto(s)
Antidiarreicos/uso terapéutico , Creosota/uso terapéutico , Diarrea/tratamiento farmacológico , Loperamida/uso terapéutico , Fitoterapia , Extractos Vegetales/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cólico/tratamiento farmacológico , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del Tratamiento
14.
Pharmacotherapy ; 23(11): 1391-400, 2003 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-14620385

RESUMEN

STUDY OBJECTIVE: To assess the safety, tolerability and pharmacokinetics of escalating single doses of wood creosote, an herbal antidiarrheal and antispasmodic agent. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Clinical research center. SUBJECTS: Forty (32 men, 8 women) healthy volunteers aged 19-42 years. INTERVENTION: By random assignment, 22 men and 8 women received escalating single doses of wood creosote (45, 90, 135, 180, and 225 mg) and 10 men received placebo (for each of the five dose levels, 6 subjects received active substance and 2 subjects received placebo). MEASUREMENTS AND MAIN RESULTS: Vital signs, laboratory tests, and electrocardiograms were assessed; no dose-related or clinically significant changes were noted. Serial blood samples were obtained to determine the pharmacokinetics of four major active components of wood creosote: total (conjugated plus free) guaiacol, creosol, o-cresol, and 4-ethylguaiacol. The most common adverse events were mild headache and dizziness, with no dose-related trends being apparent. Area under the concentration-time curve from time zero to infinity increased in a dose-proportional manner for total guaiacol, creosol, and o-cresol and was not assessed for total 4-ethylguaiacol owing to lack of data at the low dose level. No apparent differences by sex were noted for any of the four active components. All four components were rapidly eliminated. CONCLUSION: Single oral doses of wood creosote up to 225 mg were safe and well tolerated in healthy men and women. Also, the doses of wood creosote were rapidly absorbed, conjugated, and eliminated. Such a rapid onset and short duration of action would appear desirable in the treatment of acute nonspecific diarrhea.


Asunto(s)
Antidiarreicos/farmacocinética , Creosota/farmacocinética , Extractos Vegetales/farmacocinética , Preparaciones de Plantas/farmacocinética , Madera , Adulto , Antidiarreicos/administración & dosificación , Antidiarreicos/efectos adversos , Área Bajo la Curva , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Creosota/administración & dosificación , Creosota/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Humanos , Modelos Lineales , Masculino , Extractos Vegetales/administración & dosificación , Extractos Vegetales/efectos adversos , Preparaciones de Plantas/administración & dosificación , Preparaciones de Plantas/efectos adversos
15.
Dig Dis Sci ; 48(7): 1303-9, 2003 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12870787

RESUMEN

Acute stress in often associated with abnormalities in gastrointestinal function, including enhanced secretion of water and electrolytes that leads to diarrhea. The goal of our study was to investigate whether Seirogan inhibits stress-induced intestinal secretion in Wistar-Kyoto rats. Electrogenic ion secretion was measured in modified Ussing chambers as an increase in basal short-circuit current (Isc) across isolated rat jejunal or colonic mucosal sheets. Mucosal preparations from rats exposed to cold restraint stress showed a significant increase in basal Isc compared to controls. The cumulative addition of Seirogan to the Ussing chamber caused a concentration-dependent reduction of the stress-induced increase of basal Isc to levels resembling nonstressed controls. In a separate experiment, Seirogan (15 mg/kg) administered by oral gavage inhibited stress-induced secretion and normalized basal Isc in the jejunum and colon. The results suggest that Seirogan may be an effective therapy for patients with stress-associated diarrhea.


Asunto(s)
Creosota/farmacología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/fisiopatología , Iones/metabolismo , Extractos Vegetales/farmacología , Estrés Fisiológico/fisiopatología , Administración Oral , Animales , Creosota/administración & dosificación , Diarrea/etiología , Diarrea/fisiopatología , Mucosa Intestinal/metabolismo , Masculino , Extractos Vegetales/administración & dosificación , Ratas , Ratas Endogámicas WKY , Estrés Fisiológico/complicaciones
16.
J Clin Pharmacol ; 43(3): 284-90, 2003 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-12638397

RESUMEN

Seirogan, an herbal medicine containing wood creosote (CAS 8021-39-4), a mixture of simple phenolic compounds, has been marketed for the past century in Asia for the treatment of acute diarrhea and associated symptoms, such as abdominal discomfort and cramping. The present study was designed to assess the safety and tolerability of an anticipated acute antidiarrheal dosing regimen. Sixty healthy males were randomized into five groups of 12 subjects each (9 wood creosote; 3 placebo) to receive 45-, 90-, 135-, 180-, and 225-mg tablets every 2 hours for five doses. Serial sitting and standing vital signs, ECG rhythm strips, and continuous telemetry monitoring were obtained predose and for 24 hours after the first dose. Clinical laboratory tests and 12-lead resting ECGs were obtained predose and 24 hours postdose. Of the subjects, 27% (12/45) receiving wood creosote and 27% (4/15) receiving placebo reported adverse events. The most common adverse events were altered taste and somnolence, reported more often with 180- and 225-mg doses. Wood creosote had no clinically significant effects on vital signs, ECG intervals or interpretations, or clinical laboratory tests. No clinically significant or serious dysrhythmias were reported on continuous telemetry monitoring. It was concluded that oral doses of wood creosote 45 to 225 mg every 2 hours for up to five doses were safe and well tolerated in 45 healthy subjects. Wood creosote doses ranging from 45 to 135 mg per dose, which are commonly administered antidiarrheal doses in Asia, were associated with minimal side effects.


Asunto(s)
Antidiarreicos/administración & dosificación , Creosota/administración & dosificación , Extractos Vegetales/administración & dosificación , Administración Oral , Adolescente , Adulto , Antidiarreicos/efectos adversos , Presión Sanguínea/efectos de los fármacos , Estudios de Cohortes , Creosota/efectos adversos , Relación Dosis-Respuesta a Droga , Electrocardiografía , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Extractos Vegetales/efectos adversos , Preparaciones de Plantas/administración & dosificación , Preparaciones de Plantas/efectos adversos , Telemetría
17.
Biol Pharm Bull ; 26(2): 194-8, 2003 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-12576679

RESUMEN

Wood creosote pills (P4) containing wood creosote and four herbal drugs, Gambir, Phellodendri Cortex, Glycyrrhizae Radix, and Citri Unshiu Pericarpium (CUP), have been used to treat food poisoning and diarrhea through self-medication in Japan. The mean dissolution time (MDT) of guaiacol, one of the active constituents of wood creosote, from P4 (138.3+/-3.3 min) was significantly longer than that (42.6+/-4.3 min) from pills (P0) containing only wood creosote. The MDT of the variant pills prepared from P4 without CUP (54.3+/-12.5 min) was found to be significantly shorter than that of P4. These findings suggest that CUP plays an important role in sustaining the dissolution of guaiacol from P4. The long MDT of guaiacol is considered one of the most important factors affecting the duration of efficacy after oral administration of wood creosote pills. The present findings are considered proof that CUP has been prescribed in traditional as well as new formulations of wood creosote pills.


Asunto(s)
Creosota/química , Guayacol/química , Preparaciones de Plantas/química , Tamaño de la Partícula , Solubilidad/efectos de los fármacos , Comprimidos
18.
Dig Dis Sci ; 47(12): 2651-6, 2002 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-12498280

RESUMEN

Our goal was to determine whether Seirogan, an herbal medicine used as an antidiarrheal agent, modifies colonic function, including motility. Experiments were performed on four female Yucatan mini-pigs with established permanent cecal fistulas providing direct access to the colon. Long-term recordings of proximal colonic motility were accomplished by a solid-state probe (six pressure ports 10 cm apart), and a motility index was calculated. Stool viscosity was also measured. The laxative bisacodyl (15 mg/kg) was used to induce colonic motility (increase in motility index) and stool softening, prior to investigating the effect of Seirogan (2-15 mg/kg per os twice a day) or a vehicle control. Seirogan (15 mg/kg), but not the placebo, reversed the bisacodyl-induced stool softening and restored the motility index to normal values by reducing the number of propagating contractions. Taken together the results suggest that inhibition of proximal colonic motility by Seirogan may contribute to its antidiarrheal action.


Asunto(s)
Colon/fisiología , Creosota/farmacología , Heces , Motilidad Gastrointestinal/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Colon/efectos de los fármacos , Femenino , Porcinos , Porcinos Enanos , Viscosidad
19.
J Hazard Mater ; 93(3): 285-306, 2002 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-12137990

RESUMEN

A column study was conducted to determine if a permeable barrier can be used to treat creosote-contaminated groundwater based on sorption and biodegradation, and to determine which processes remove the various creosote compounds. Creosote-contaminated water (sterile and non-sterile) was applied to sterile and non-sterile saturated columns with peat (20 vol.%) and sand (80 vol.%) for 2 months. Temperature was 9 degrees C, inlet oxygen concentration 9-10mg/l and average residence time was two days. The peat/sand barrier material removed 94-100% polycyclic aromatic hydrocarbons (PAHs), 93-98% nitrogen/sulfur/oxygen (NSO)-containing heterocyclic aromatic compounds, and 44-97% total phenols. The peat/sand material efficiently sorbed PAHs (>2 rings) and three-ring NSO-compounds, and also sorbed significant amounts of two-ring NSO-compounds and naphthalene. Naphthalene and NSO-compounds not sorbed were biological degraded. Phenol and cresols were efficiently removed by microbial degradation. The barrier material was somewhat less efficient removing dimethylphenols (DMPs) and trimethylphenols (TMPs), where DMPs were hardly sorbed and TMPs were hardly degraded. The results imply that a peat/sand barrier can treat creosote-contaminated groundwater. Modifications might be needed for enhanced removal of DMPs and TMPs, and oxygen supply might be necessary in aquifers with low oxygen content.


Asunto(s)
Creosota/química , Dióxido de Silicio , Suelo , Purificación del Agua/métodos , Abastecimiento de Agua , Adsorción , Biodegradación Ambiental , Filtración , Permeabilidad , Contaminación del Agua/prevención & control
20.
Yakushigaku Zasshi ; 36(1): 10-7, 2001.
Artículo en Japonés | MEDLINE | ID: mdl-11776992

RESUMEN

Two kinds of creosote have been found based on historical evidence of the medicinal uses and origins. One is wood creosote, and distillate of wood-tar containing guaiacol and creosol. The other type of creosote is coal-tar creosote, obtained from coal-tar, containing naphthalene and anthracene as the major constituents. Wood creosote was prepared for the first time in Germany in 1830 and was used for medicinal purposes. It had been listed officially in the German, American, and Japanese Pharmacopoeia as an antibacterial agent for the treatment of pulmonary tuberculosis, diarrhea, and external injury. In recent days, it has been deleted from the Pharmacopoeia in Western countries and not officially used for medicinal purposes. However, wood creosote is still been listed in the Japanese Pharmacopoeia and is used for the treatment of diarrhea. Since the interest of common people in herbal medicines and self-medication has been increasing, the use of wood creosote has also been modified in combination with some herbal drugs, "Seiro-gan" especially is quite popular in Japan as a self-medication for digestive trouble, including food poisoning or diarrhea.


Asunto(s)
Creosota/historia , Enfermedades del Sistema Digestivo/historia , Medicina de Hierbas , Automedicación/historia , Historia del Siglo XIX , Historia del Siglo XX , Historia Moderna 1601- , Japón , Mundo Occidental
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