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1.
Soft Matter ; 13(39): 6969-6980, 2017 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-28920986

RESUMEN

When films are deposited from mixtures of colloidal particles of two different sizes, a diverse range of functional structures can result. One structure of particular interest is a stratified film in which the top surface layer has a composition different than in the interior. Here, we explore the conditions under which a stratified layer of small particles develops spontaneously in a colloidal film that is cast from a binary mixture of small and large polymer particles that are suspended in water. A recent model, which considers the cross-interaction between the large and small particles (Zhou et al., Phys. Rev. Lett., 2017, 118, 108002), predicts that stratification will develop from dilute binary mixtures when the particle size ratio (α), initial volume fraction of small particles (ϕS), and Péclet number are high. In experiments and Langevin dynamics simulations, we systematically vary α and ϕS in both dilute and concentrated suspensions. We find that stratified films develop when ϕS is increased, which is in agreement with the model. In dilute suspensions, there is reasonable agreement between the experiments and the Zhou et al. MODEL: In concentrated suspensions, stratification occurs in experiments only for the higher size ratio α = 7. Simulations using a high Péclet number, additionally find stratification with α = 2, when ϕS is high enough. Our results provide a quantitative understanding of the conditions under which stratified colloidal films assemble. Our research has relevance for the design of coatings with targeted optical and mechanical properties at their surface.

3.
Aliment Pharmacol Ther ; 31(10): 1112-22, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20163379

RESUMEN

BACKGROUND: An association between atopic disease and gastrointestinal complaints has been suggested. AIM: To explore the association between atopic disease, gastrointestinal symptoms, and possible gastrointestinal manifestations of atopic disease in patients with self-reported food hypersensitivity. METHODS: Symptoms, skin prick tests, serum markers of allergy and intestinal permeability were recorded in 71 adult patients. Eosinophils, tryptase- and IgE-positive cells were counted in duodenal biopsies. RESULTS: Sixty-six (93%) patients had irritable bowel syndrome (IBS) and 43 (61%) had atopic disease, predominantly rhinoconjunctivitis. All 43 were sensitized to inhalant allergens, 29 (41%) to food allergens, but food challenges were negative. Serum total IgE and duodenal IgE-positive cell counts were significantly correlated (P < 0.0001) and both were significantly higher in atopic than in non-atopic patients (P < 0.0001 and P = 0.003 respectively). IgE-positive cells appeared to be 'armed' mast cells. Intestinal permeability was significantly elevated in atopic compared with non-atopic patients (P = 0.02). Gastrointestinal symptoms and numbers of tryptase-positive mast cells and eosinophils did not differ between groups. CONCLUSIONS: Patients with self-reported food hypersensitivity had a high prevalence of IBS and atopic disease. Atopic patients had increased intestinal permeability and density of IgE-bearing cells compared with non-atopic patients, but gastrointestinal symptoms did not differ between groups.


Asunto(s)
Enfermedades Gastrointestinales/complicaciones , Inmunoglobulina E/inmunología , Enfermedades Inflamatorias del Intestino/complicaciones , Adolescente , Adulto , Anciano , Alérgenos/inmunología , Biomarcadores/sangre , Femenino , Hipersensibilidad a los Alimentos/complicaciones , Hipersensibilidad a los Alimentos/epidemiología , Hipersensibilidad a los Alimentos/patología , Enfermedades Gastrointestinales/epidemiología , Enfermedades Gastrointestinales/patología , Humanos , Inmunoglobulina E/metabolismo , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/patología , Masculino , Persona de Mediana Edad , Prevalencia , Pruebas Cutáneas/métodos , Adulto Joven
5.
Scand J Psychol ; 51(2): 179-84, 2010 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-19961557

RESUMEN

Psychological distress may be causally related to multiple, unexplained somatic symptoms. We have investigated job stress, coping strategies and subjective health complaints in patients with subjective food hypersensitivity. Sixty-four patients were compared with 65 controls. All participants filled in questionnaires focusing on job stress, job demands and control, work environment, coping strategies and subjective health complaints. Compared with controls, patients scored significantly lower on job stress and job demands, and significantly higher on authority over job decisions. Coping strategies and satisfaction with work environment did not differ significantly between the two groups, but the patients reported significantly more subjective health complaints than the controls. Scores on job stress and job demands were generally low in patients with subjective food hypersensitivity. It is unlikely, therefore, that the patients' high scores on subjective health complaints are causally related to the work situation.


Asunto(s)
Hipersensibilidad a los Alimentos/psicología , Satisfacción en el Trabajo , Enfermedades Profesionales/psicología , Trastornos Somatomorfos/psicología , Estrés Psicológico/complicaciones , Adaptación Psicológica , Adulto , Medicina Familiar y Comunitaria , Femenino , Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad a los Alimentos/inmunología , Humanos , Conducta de Enfermedad , Inmunoglobulina E/sangre , Control Interno-Externo , Pruebas Intradérmicas , Masculino , Persona de Mediana Edad , Inventario de Personalidad/estadística & datos numéricos , Psicometría , Medio Social , Carga de Trabajo/psicología
6.
J Insect Physiol ; 55(8): 758-65, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19482292

RESUMEN

The active ingestion of xylem sap by aphids is hypothesised to be an important mechanism for rehydration. When starved bird cherry-oat aphids (Rhopalosiphum padi) were allowed to feed on wheat (Triticum aestivum) treated with a sublethal dose of the xylem-mobile neonicotinoid thiamethoxam, analysis of feeding behaviours using the electrical penetration graph revealed a reduction in xylem feeding that was reversed on removal of the toxin. To test the importance of xylem-feeding behaviour as a rehydration mechanism, the effects of the sublethal dose of thiamethoxam on aphid water content, honeydew excretion, growth and fecundity were investigated. Body water contents of starved R. padi feeding on wheat treated with thiamethoxam were significantly reduced compared to aphids feeding on wheat treated with distilled water (74.5+/-0.23 and 75.6+/-0.18%, respectively). In addition, the sublethal dose of thiamethoxam had detrimental effects on aphid performance. At reproductive maturity, aphids that had been born on wheat treated with thiamethoxam were significantly smaller (as measured by body plan area; 1.07+/-0.03mm(2)), lighter (0.31+/-0.04mg) and less fecund (2.85+/-0.36nymphs/day) than aphids born on wheat treated with distilled water (1.87+/-0.02mm(2), 0.72+/-0.03mg, 11.28+/-0.58nymphs/day, respectively). Regardless of whether the observed impairment of xylem feeding is due to a neurotoxic or an antifeedant effect, these results have important implications for commercial crop protection as the behaviour-modifying effects of the sublethal dose of thiamethoxam may change the efficacy of this pesticide throughout the growing season.


Asunto(s)
Áfidos/efectos de los fármacos , Áfidos/fisiología , Conducta Alimentaria/efectos de los fármacos , Nitrocompuestos/farmacología , Oxazinas/farmacología , Tiazoles/farmacología , Agua/metabolismo , Xilema/metabolismo , Animales , Áfidos/crecimiento & desarrollo , Neonicotinoides , Tiametoxam , Triticum/metabolismo
7.
Cytotherapy ; 10(6): 543-50, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18836914

RESUMEN

The use of cellular therapy in the treatment of dermal wounds is currently an active area of investigation. Multipotent adult progenitor cells (MAPC) are an attractive choice for cytotherapy because they have a large proliferative potential, the ability to differentiate into different cell types and produce a variety of cytokines and growth factors important to wound healing. Whole bone marrow (BM) was one of the initial attempts to treat impaired wounds. While it has shown some promise, the low frequency of progenitor cell populations in BM and the large number of inflammatory cells make it less attractive. Multipotent mesenchymal stromal cells (MSC) and endothelial progenitor cells are populations of BM-derived progenitor cells that have been isolated and used to treat chronic wounds with some success. Skin-derived MAPC are another heterogeneous population of progenitor cells present in the skin with the potential to differentiate into skin elements and participate in wound healing. All of these progenitor cell populations are potential sources for cytotherapy of wounds. This review focused on the contribution of adult progenitor cell populations to dermal wound healing and their potential for use in cytotherapy.


Asunto(s)
Dermis/lesiones , Células Madre Multipotentes/fisiología , Piel/lesiones , Cicatrización de Heridas/fisiología , Células Madre Adultas/fisiología , Animales , Médula Ósea/fisiología , Células Endoteliales/fisiología , Terapia Genética , Humanos , Células Madre Mesenquimatosas/fisiología , Trasplante de Células Madre , Células del Estroma/fisiología
8.
J Sports Med Phys Fitness ; 46(1): 158-62, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16596116

RESUMEN

AIM: The relationship between salivary IgA secretion rate and upper respiratory tract infection (URTI) was studied in 155 ultramarathoners (126 males, 29 females, mean age 46.5+/-0.7 y) who had qualified to run the 160-km 2003 Western States Endurance Run. METHODS: Subjects provided saliva samples during registration, held the morning before the race, and within 5-10 minutes postrace (mean race time, 26.2+/-0.3 h). Unstimulated saliva was collected by expectoration for 4 minutes into 15-mL plastic, sterilized vials. Runners finishing the race and providing pre- and postrace saliva samples (n=106) turned in a health log specifying URTI episodes and severity of symptoms for the 2-week period following the race. RESULTS: The total volume of saliva that the runners was able to expectorate during sample collection decreased 51% postrace compared to prerace values (P<0.001). Saliva protein concentration increased 20% (P<0.001) while the saliva protein IgA concentration decreased 10% (P<0.05). Salivary IgA secretion rate decreased 46% when comparing pre- to postrace values (P<0.001). Twenty-four percent of the runners finishing the race and providing salivary samples reported an URTI episode lasting 2 days or longer during the 2-week period following the race (mean number of days with symptoms was 5.4+/-0.6 days). The decrease in salivary IgA secretion rate (pre- to postrace) was 53% greater in the 25 runners reporting URTI (-355+/-45 microg/min) compared to the 81 runners not reporting URTI (-232+/-37 microg/min), (P=0.04). CONCLUSIONS: In summary, nearly 1 in 4 runners reported an URTI episode during the 2-week period following a 160-km race, and the decrease in salivary IgA secretion rate was significantly greater in these runners compared to those not reporting URTI.


Asunto(s)
Inmunoglobulina A/metabolismo , Infecciones del Sistema Respiratorio/inmunología , Carrera/fisiología , Saliva/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad
9.
Scand J Gastroenterol ; 39(11): 1088-94, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15545167

RESUMEN

BACKGROUND: Rheumatic joint pain is a common extra-intestinal complication of inflammatory bowel disease (IBD). Because the high ratio of n-6 to n-3 fatty acids (FAs) of the Western diet might promote rheumatic disorders, we sought to compare the effects of short-term duodenal administration of n-3-rich seal oil and n-6-rich soy oil on IBD-related joint pain. METHODS: Nineteen patients with IBD-related joint pain were included in the study; 9 had Crohn disease and 10 had ulcerative colitis. Ten millilitres seal oil (n = 10) or soy oil (n = 9) was self-administered through a nasoduodenal feeding tube 3 times daily for 10 days. RESULTS: Compared with soy oil treatment, seal oil significantly reduced the duration of morning stiffness (P = 0.024), number of tender joints (P = 0.035), intensity of pain (P = 0.025) and the doctor's scoring of rheumatic disease activity (P = 0.025) at the end of the 10-day treatment period. Analysis of the effects as area under the curve (area between the curve and baseline, zero) for the entire period from start of treatment until 6 months' post-treatment suggested a long-lasting beneficial effect of seal oil administration on joint pain, whereas soy oil tended (not significantly) to aggravate the condition. Consistently, the serum ratios of n-6 to n-3 FAs (P < 0.01) and arachidonic acid to eicosapentaenoic acid (P < 0.01) were reduced after treatment with seal oil. CONCLUSION: The results suggest distinctive, differential prolonged effects on IBD-related joint pain of short-term duodenal administration of n-3-rich seal oil (significant improvement) and n-6-rich soy oil (tendency to exacerbation).


Asunto(s)
Artralgia/terapia , Ácidos Grasos Omega-3/administración & dosificación , Enfermedades Inflamatorias del Intestino/complicaciones , Aceite de Soja/administración & dosificación , Adolescente , Adulto , Animales , Artralgia/sangre , Artralgia/etiología , Duodeno , Ácidos Grasos/sangre , Ácidos Grasos Omega-6/administración & dosificación , Femenino , Lobos Marinos , Humanos , Enfermedades Inflamatorias del Intestino/sangre , Intubación Gastrointestinal , Masculino , Persona de Mediana Edad
10.
Int J Sports Med ; 24(7): 541-7, 2003 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-12968214

RESUMEN

Changes in immune and oxidative stress parameters were measured in ultramarathon runners competing in the 160-km Western States Endurance Run. Forty-five runners agreed to provide blood and saliva samples the morning before the race event, at the 90-km aid station, and 5 - 10 min post-race. Upper respiratory tract infection (URTI) during the two-week period post-race was assessed retrospectively by telephone interviews. Forty subjects completed 90-km (race time, 13.1 +/- 0.3 h), and 31 completed the 160-km race event (27.0 +/- 0.4 h). The blood neutrophil and monocyte counts rose 249 % and 214 %, respectively, in the 31 finishers. Salivary IgA (sIgA) secretion rate decreased significantly from 508 +/- 40 micro g/min pre-race, to 287 +/- 39 micro g/min at 90-km, and 254 +/- 30 micro g/min post-race (50 % decrease). Significant increases were measured in cytokines at 90-km and post-race, with post-race IL-10 increasing 9.5-fold, IL-1ra 6.1-fold, IL-6 50.2-fold, and IL-8 2.5-fold over pre-race levels. Post-race indicators of oxidative stress, F (2)-isoprostane and lipid hydroperoxides, increased 33 % and 88 %, respectively. Pearson product-moment correlations revealed positive correlations at 90-km between F (2)-isoprostane and IL-6 (r = 0.31, p = 0.048), IL-10 (r = 0.31, p = 0.050), and IL-8 (r = 0.43, p = 0.005), but no other significant relationships between immune and oxidative stress indicators at 90-km and post-race. In the group of runners completing at least 90 km of the race, 26 % reported an URTI episode during the two-week period post-race. A low sIgA secretion rate at 90-km was the best predictor of post-race URTI (173 +/- 34 micro g/min in those who later acquired URTI compared to 325 +/- 40 micro g/min in those without URTI, p = 0.007). In conclusion, a modest correlation was found between cytokines and F (2)-isoprostane at 90-km when the greatest oxidative stress occurred, but no other significant correlations in immune and oxidative stress indicators during and following a 160-km ultramarathon race event were noted. About one in four ultramarathoners reported URTI during the two-week period post-race, and a low sIgA secretion rate mid-race best predicted URTI occurrence.


Asunto(s)
Resistencia Física/inmunología , Resistencia Física/fisiología , Carrera/fisiología , Adulto , Citocinas/sangre , Femenino , Humanos , Peróxido de Hidrógeno/sangre , Inmunoglobulina A Secretora/análisis , Incidencia , Masculino , Persona de Mediana Edad , Estrés Oxidativo , Infecciones del Sistema Respiratorio/epidemiología , Saliva , Caracteres Sexuales
11.
Insect Biochem Mol Biol ; 33(7): 701-8, 2003 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12826097

RESUMEN

Insecticide resistance in laboratory selected Drosophila strains has been associated with upregulation of a range of different cytochrome P450s, however in recent field isolates of D. melanogaster resistance to DDT and other compounds is conferred by one P450 gene, Cyp6g1. Using microarray analysis of all Drosophila P450 genes, here we show that different P450 genes such as Cyp12d1 and Cyp6a8 can also be selected using DDT in the laboratory. We also show, however, that a homolog of Cyp6g1 is over-expressed in a field resistant strain of D. simulans. In order to determine why Cyp6g1 is so widely selected in the field we examine the pattern of cross-resistance of both resistant strains and transgenic flies over-expressing Cyp6g1 alone. We show that all three DDT selected P450s can confer resistance to the neonicotinoid imidacloprid but that Cyp6a8 confers no cross-resistance to malathion. Transgenic flies over-expressing Cyp6g1 also show cross-resistance to other neonicotinoids such as acetamiprid and nitenpyram. We suggest that the broad level of cross-resistance shown by Cyp6g1 may have facilitated its selection as a resistance gene in natural Drosophila populations.


Asunto(s)
Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/farmacología , Proteínas de Drosophila/genética , Proteínas de Drosophila/farmacología , Drosophila/genética , Perfilación de la Expresión Génica , Resistencia a los Insecticidas/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Animales , Animales Modificados Genéticamente , Drosophila/fisiología , Regulación de la Expresión Génica , Reacción en Cadena de la Polimerasa , Regulación hacia Arriba
12.
Vopr Pitan ; 70(5): 35-8, 2001.
Artículo en Ruso | MEDLINE | ID: mdl-11715697

RESUMEN

The use of "SGOL-1-40" milk whey in complex therapy of patients with acute chemical poisonings and their complications has been investigated. "SGOL-1-40" was prescribed twice per day with the dose of 1.5 g/kg of patient weight. On the 5th-6th day after therapy start the general state of patients improved; in the control group it happened on the 10th-12th day. It is ascertained that the ceasing of pneumonia takes place average 3 days earlier than usual. The lessening of endotoxicosis symptoms and the improvement of the patients state with chemical burns of gastrointestinal system went on more quickly.


Asunto(s)
Quemaduras Químicas/dietoterapia , Productos Lácteos , Enfermedades Gastrointestinales/dietoterapia , Intoxicación/dietoterapia , Adulto , Estudios de Casos y Controles , Humanos , Persona de Mediana Edad , Neumonía/dietoterapia
13.
Drug Chem Toxicol ; 24(4): 339-46, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11665647

RESUMEN

Compound A (2-fluoromethoxy-1,1,3,3,3-pentafluoro-1-propene) is produced by reaction of the inhalation anesthetic, sevoflurane, with CO2 absorbents. Compound A has been reported to directly react with protein. Since adduction of proteins can transform them into antigenic material, Compound A was assessed for its ability to produce a humoral immune response. Male outbred Hartley guinea pigs (500-600 g, N = 7) were exposed via inhalation for 4 h to a subtoxic level (100 ppm) of Compound A, 3 times, at 42 day intervals. Blood samples obtained at 2, 14, 28 and 40 days after each exposure were measured for ALT, creatinine, and urea nitrogen and for the presence of antibodies to trifluoroacetylated guinea pig albumin (TFA-GSA). All indicators of liver and kidney injury remained within normal range throughout the course of the study. A humoral immune response to TFA-GSA was observed following each exposure to Compound A with a titer appearing by day 14 after exposure, peaking near day 28, and resolving to normal levels by day 40. The titer levels were approximately equivalent after each exposure and about one-third that previously seen in guinea pigs after multiple exposures to halothane. Compound A would appear to have the ability to form antigenic adducts during inhalation exposure. These findings are similar to those observed for halogenated inhalation anesthetics that have been linked to cases of immune-medicated idiosyncratic hepatitis and indicate that Compound A exposure may pose the same hazard.


Asunto(s)
Anestésicos por Inhalación/toxicidad , Formación de Anticuerpos/efectos de los fármacos , Éteres/toxicidad , Hidrocarburos Fluorados/toxicidad , Éteres Metílicos/toxicidad , Alanina Transaminasa/sangre , Anestésicos por Inhalación/química , Animales , Ensayo de Inmunoadsorción Enzimática , Éteres/química , Cobayas , Hidrocarburos Fluorados/química , Hígado/efectos de los fármacos , Masculino , Éteres Metílicos/química , Sevoflurano
14.
Insect Biochem Mol Biol ; 31(6-7): 533-42, 2001 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-11267892

RESUMEN

Nicotinic acetylcholine receptors (nAChR) of insect and other invertebrates are heterogeneous and new tools are needed to dissect their multiplicity. [(3)H]-Methyllycaconitine ([(3)H]-MLA) is a novel radioligand which is a potent antagonist at vertebrate alpha7-type nAChR. Putative invertebrate nAChR of the aphid Myzus persicae, the moths Heliothis virescens and Manduca sexta, the fly Lucilia sericata, and the squid Loligo vulgaris were investigated in radioligand binding studies with [(3)H]-MLA. Saturable binding was consistent with a single class of high affinity binding sites for each of these invertebrates, characterised by a dissociation constant, K(d), of approximately 1 nM and maximal binding capacities, B(max), between 749 and 1689 fmol/mg protein for the insects and 14,111 fmol/mg protein for squid. [(3)H]-MLA binding to M. persicae membranes was characterised in more detail. Kinetic analysis demonstrated rapid association in a biphasic manner and slow, monophasic dissociation. Displacement studies demonstrate the nicotinic character of [(3)H]-MLA binding sites. Data for all nicotinic ligands, except MLA itself, are consistent with displacement from a high and a low affinity site, indicating that displacement is occurring from two or more classes of nicotinic binding site that are not distinguished by MLA itself. Autoradiographic analysis of the distribution of [(3)H]-MLA binding sites in Manduca sexta shows discrete labelling of neuropil areas of the optic and antennal lobes.


Asunto(s)
Aconitina/análogos & derivados , Aconitina/metabolismo , Receptores Nicotínicos/metabolismo , Animales , Áfidos , Unión Competitiva , Decapodiformes , Dípteros , Manduca , Mariposas Nocturnas , Ensayo de Unión Radioligante , Tritio
15.
Vopr Pitan ; 69(1-2): 50-2, 2000.
Artículo en Ruso | MEDLINE | ID: mdl-10943008

RESUMEN

The effect of enzymolic whey SGOL 1-40 ("Sgidolac") and sterilized milk mixture on experimental tuberculosis process with mice has been investigated. The mice of CBA line infected with tuberculosis (Type H37Rv) and been given this mixture (rate SGOL 1-40 to milk 1:5) per os immediately after the infection at the amount of 0.5 g/Kg body weight per day every day, perished on 42-nd day, meanwhile the mice that had received the mixture 3 weeks before the infection and all the period after it, died on 46-th day he mice in the control group (infected and untreated) died on the 38-th day. The positive treatment and prophylactic effect of the SGOL 1-40 and milk mixture on the tuberculosis process has been stated and morphologically proved.


Asunto(s)
Proteínas de la Leche/administración & dosificación , Leche , Tuberculosis/prevención & control , Animales , Fermentación , Lactalbúmina/administración & dosificación , Lactoglobulinas/administración & dosificación , Hígado/patología , Pulmón/patología , Ratones , Ratones Endogámicos CBA , Esterilización , Factores de Tiempo , Tuberculosis/patología , Tuberculosis/terapia , Tuberculosis Hepática/patología , Tuberculosis Hepática/prevención & control , Tuberculosis Pulmonar/patología , Tuberculosis Pulmonar/prevención & control
16.
Toxicol Appl Pharmacol ; 166(2): 145-50, 2000 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-10896856

RESUMEN

Dimethyl sulfoxide (DMSO) has previously been shown to have the ability to attenuate chloroform (CHCl(3))-induced liver injury in the naive rat even when administered 24 h after the toxicant. These studies were undertaken to determine if the protective action by late administration of DMSO is due to an inhibition of the bioactivation of CHCl(3). This was done by comparing the cytochrome P450 inhibitors, diallyl sulfide (DAS), and aminobenzotriazole (ABT) to DMSO for their protective efficacy when administered 24 h after CHCl(3) exposure. In addition, (14)CHCl(3) was utilized to measure the effect of DMSO and ABT on the covalent binding of CHCl(3) in the liver following their late administration. Male Sprague-Dawley rats (300-350 g) received 0.75 ml/kg CHCl(3) po. Twenty-four hours later, they received ip injection of 2 ml/kg DMSO, 100 mg/kg DAS, or 30 mg/kg ABT. Plasma ALT activities and quantitation of liver injury by light microscopy at 48 h after CHCl(3) dosing indicated that all three treatments were equally effective at protecting the liver. A detailed study of the time course of injury development indicated that the protective action of DMSO was occurring within 10 h of its administration. Therefore, in the radiolabel studies, rats were killed 24-34 h after receiving 0.75 ml/kg CHCl(3) (30 microCi/kg (14)CHCl(3)) po. Treatment with ABT at 24 h after (14)CHCl(3) dosing decreased the covalent binding of (14)C to hepatic protein by 35% and reduced the amount of (14)C in the blood by 50% by 10 h after its administration. DMSO treatment did not significantly affect any of these parameters. The lack of effect by late administration of DMSO on the covalent binding of CHCl(3) would indicate that DMSO may offer protection by mechanisms other than inhibition of the bioactivation of CHCl(3). These studies also indicate that specific cytochrome P450 inhibitors may be of benefit in clinical situations to help treat the delayed onset hepatitis that can result following poisoning with an organohalogen, even if the antidotes are administered a number of hours after the initial exposure.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Cloroformo/metabolismo , Dimetilsulfóxido/farmacología , Depuradores de Radicales Libres/farmacología , Hígado/efectos de los fármacos , Alanina Transaminasa/sangre , Compuestos Alílicos/farmacología , Animales , Sitios de Unión/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Cloroformo/toxicidad , Inhibidores del Citocromo P-450 CYP2E1 , Inhibidores Enzimáticos/farmacología , Hígado/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Sulfuros/farmacología , Factores de Tiempo , Triazoles/farmacología
17.
Toxicol Pathol ; 27(3): 342-7, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10356711

RESUMEN

Dimethyl sulfoxide (DMSO) has previously been reported to protect against hepatotoxicity resulting from chloroform (CHCl3) or bromobenzene (BB) when given 10 hr after the toxicant. The object of these studies was to further demonstrate the latent protective ability of DMSO by administering it at a much later time (24 hr) following toxicant exposure. In addition, a more detailed evaluation of the lesions was performed to better characterize the lesion progression and resolution. Male Sprague-Dawley rats received a hepatotoxic oral dose of either CHCl3 (1.0 ml/kg) or BB (0.5 ml/kg) and then received 2 ml/kg DMSO intraperitoneally 24 hr later. With both toxicants, limited centrilobular lesions were already present by the time DMSO was administered. Without treatment, liver injury rapidly progressed so that by 48 hr it occupied 40-50% of the liver, with accompanying large increases in plasma alanine aminotransferase (ALT) activity. Administration of DMSO greatly attenuated lesion development for both toxicants; the area injured was reduced by more than 4-fold, accompanied by a decrease in 48 hr ALT activity of 8-16-fold. The ability of DMSO to intervene in the development of liver injury at such a late time appears to be unique and may provide insight into therapies for acute xenobiotic-induced hepatitis.


Asunto(s)
Bromobencenos/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Cloroformo/toxicidad , Dimetilsulfóxido/uso terapéutico , Hígado/efectos de los fármacos , Enfermedad Aguda , Alanina Transaminasa/sangre , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Procesamiento de Imagen Asistido por Computador , Hígado/patología , Masculino , Ratas , Ratas Sprague-Dawley , Factores de Tiempo
18.
Exp Toxicol Pathol ; 51(6): 537-43, 1999 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-10661812

RESUMEN

Dimethyl sulfoxide (DMSO) has previously been shown to attenuate chloroform (CHCl3) and bromobenzene (BB) induced hepatotoxicity in the rat when a dose of 2.0 ml/kg is given 24 hr after the toxicants. However, the optimal dose of DMSO and the latest time at which DMSO can be administered and still provide effective protection have not been determined. In order to determine the latest time at which DMSO can interrupt the development of necrosis, male Sprague Dawley rats received either 0.75 ml/kg CHCl3 or 0.5 ml/kg BB, 20% in corn oil, p.o., followed by single dose of 2 ml/kg DMSO, 50% in saline, i.p., at 24, 26, 28 or 30 hr later. Positive control groups received either CHCl3 or BB and then 4.0 ml/kg saline, i.p., 24 hr later. All of the animals were then killed 48 hr after toxicant dosing. The extent of liver injury present when DMSO was administered was examined by killing animals at 24, 26, 28 or 30 hr after toxicant dosing. The optimal dose of DMSO for providing protection was estimated by administering either 0, 1.0, 2.0, 3.0 or 4.0 ml/kg DMSO at 24 hr after toxicant dosing and then killing the animals at 48 hr. Delaying DMSO administration to times later than 24 hr after toxicant dosing led to a loss of protection as indicated by both plasma ALT activity and the light microscopic appearance of liver tissue. The distinctive liver lesions present at 24 hr after CHCl3 or BB dosing rapidly expanded from being limited around central veins to bridging between centrilobular areas in only a few hours. This was accompanied by large increases in plasma ALT. With both toxicants, doses of DMSO greater than 2 ml/kg did not enhance its protective action while the lower dose of 1 ml/kg DMSO was not as effective. The loss of DMSO's antidotal action when given at times later than 24 hr after the toxicants indicates irreversible changes were underway as the centrilobular lesions progressed from being limited to more bridging in nature. Hopefully, further elucidation of the mechanism(s) by which DMSO interrupts the rapid progression of injury will both help to understand the steps involved in lesion development and provide insights into therapeutic interventions for drug and chemical induced hepatitis.


Asunto(s)
Bromobencenos/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas , Cloroformo/toxicidad , Dimetilsulfóxido/administración & dosificación , Depuradores de Radicales Libres/administración & dosificación , Hepatopatías/prevención & control , Animales , Dimetilsulfóxido/farmacología , Relación Dosis-Respuesta a Droga , Depuradores de Radicales Libres/farmacología , Masculino , Ratas , Ratas Sprague-Dawley , Factores de Tiempo
19.
Eur J Neurosci ; 10(3): 879-89, 1998 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9753155

RESUMEN

Manduca sexta is a nicotine-insensitive insect, the larval form of which feeds on tobacco. It has been postulated that its nicotine insensitivity may reflect the presence of a modified nicotinic acetylcholine receptor whose alpha subunits lack the amino acid residues necessary for binding nicotine: we have performed ligand binding assays and molecular cloning to examine this hypothesis. [125I]alpha-bungarotoxin bound specifically to both larval and adult membranes, with Kd values of 7.6 and 6.5 nM and Bmax values of 119 and 815 fmol/mg protein, respectively. The pharmacological profile of [1251]alpha-bungarotoxin binding was similar in both tissues. In particular, nicotine (Ki values: 1.6 microM and 2 microM for larvae and adults, respectively) competed with an affinity similar to that found for nicotine-sensitive insects. No alpha-bungarotoxin-insensitive binding sites labelled by [3H]epibatidine could be detected. Using the alpha-like subunit from the locust Schistocerca gregaria to probe two cDNA libraries, and by inverse PCR on circularized genomic DNA from Manduca sexta, we have obtained overlapping cDNA clones that contain the complete coding sequence of a putative nicotinic subunit from Manduca sexta (MARA1). No other alpha-subunit cDNAs were isolated using this probe, although it hybridized to multiple bands on Southern blots. The sequence of MARA1 is consistent with an alpha-like subunit capable of binding alpha-bungarotoxin, and it retains all those amino acids implicated in nicotine binding to vertebrate nicotinic receptors. Taken together, these findings provide no support for the hypothesis that the nicotine insensitivity of Manduca sexta is the result of a nicotinic receptor with diminished nicotine binding.


Asunto(s)
Manduca/metabolismo , Receptores Nicotínicos/metabolismo , Envejecimiento/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Southern Blotting , Compuestos Bicíclicos Heterocíclicos con Puentes/metabolismo , Bungarotoxinas/farmacología , Membrana Celular/metabolismo , Colinérgicos/metabolismo , Clonación Molecular , ADN/biosíntesis , ADN/genética , Larva/metabolismo , Datos de Secuencia Molecular , Neuronas Motoras/metabolismo , Reacción en Cadena de la Polimerasa , Piridinas/metabolismo , Receptores Nicotínicos/biosíntesis
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