RESUMEN
In this paper, the 4E assessment (Energetic, Exergetic, Exergoeconomic and Exergoenvironmental) of a low-temperature ORC activated by two different alternatives is presented. The first alternative (S1) contemplates the activation of the ORC through the recovery of waste heat from a flash-binary geothermal power plant. The second alternative (S2) contemplates the activation of the ORC using direct heat from a geothermal well. For both alternatives, the energetic and exergetic models were established. At the same time, the economic and environmental impact models were developed. Finally, based on the combination of the exergy concepts and the economic and ecological indicators, the exergoeconomic and exergoenvironmental performances of the ORC were obtained. The results show higher economic, exergoeconomic and exergoenvironmental profitability for S1. Besides, for the alternative S1, the ORC cycle has an acceptable economic profitability for a net power of 358.4 kW at a temperature of 110 °C, while for S2, this profitability starts being attractive for a power 2.65 times greater than S1 and with a temperature higher than 135 °C. In conclusion, the above represents an area of opportunity and a considerable advantage for the implementation of the ORC in the recovery of waste heat from flash-binary geothermal power plants.
RESUMEN
The oral tongue is considered the most frequently involved site in cases of oral squamous cell carcinoma (OSCC). Lymph node (LN) density, defined as the number of positive LNs divided by the total number of resected LNs, is considered an important prognostic factor in OSCC; however the cut-off point remains uncertain. A retrospective study was performed involving 104 patients who underwent a glossectomy procedure for oral tongue squamous cell carcinoma (OTSCC) between the years 2008 and 2018. LN density and other related prognostic factors, including pathological N-stage (pN), extranodal extension (ENE), perineural invasion (PNI), and depth of invasion (DOI), were investigated in relation to survival and recurrence rates. pN + stage, the presence of ENE, the presence of PNI, and increased DOI were found to be associated with increased LN density values, as well as lower patient survival and higher recurrence rates. The statistical analysis identified a cut-off point for LN density of 2.5%. In advanced stage disease, LN density values above 2.5% had a significant impact on the survival rate (P = 0.005), as well as the recurrence rate (P = 0.038). In conclusion, in addition to other previously known prognostic factors, LN density may serve as a strong prognostic factor for survival and recurrence in patients with advanced- and early-stage OTSCC.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Neoplasias de la Lengua , Carcinoma de Células Escamosas/patología , Neoplasias de Cabeza y Cuello/patología , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Neoplasias de la Boca/patología , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Lengua/patología , Neoplasias de la Lengua/patologíaRESUMEN
A mutation in the gene encoding for the liver mitochondrial aldehyde dehydrogenase (ALDH2-2), present in some Asian populations, lowers or abolishes the activity of this enzyme and results in elevations in blood acetaldehyde upon ethanol consumption, a phenotype that greatly protects against alcohol abuse and alcoholism. We have determined whether the administration of antisense phosphorothioate oligonucleotides (ASOs) can mimic the low-activity ALDH2-2 Asian phenotype. Rat hepatoma cells incubated for 24 h with an antisense oligonucleotide (ASO-9) showed reductions in ALDH2 mRNA levels of 85% and ALDH2 (half-life of 22 h) activity of 55% equivalent to a >90% inhibition in ALDH2 synthesis. Glutamate dehydrogenase mRNA and activity remained unchanged. Base mismatches in the oligonucleotide rendered ASO-9 virtually inactive, confirming an antisense effect. Administration of ASO-9 (20 mg/kg/day for 4 d) to rats resulted in a 50% reduction in liver ALDH2 mRNA, a 40% inhibition in ALDH2 activity, and a fourfold (P < 0.001) increase in circulating plasma acetaldehyde levels after ethanol (1 g/kg) administration. Administration of ASO-9 to rats by osmotic pumps led to an aversion (-61%, P < 0.02) to ethanol. These studies provide a proof of principle that specific inhibition of gene expression can be used to mimic the protective effects afforded by the ALDH2-2 phenotype.
Asunto(s)
Consumo de Bebidas Alcohólicas/genética , Aldehído Deshidrogenasa/genética , Aldehído Deshidrogenasa/metabolismo , Pueblo Asiatico/genética , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Mitocondrias Hepáticas/enzimología , Oligodesoxirribonucleótidos Antisentido/farmacología , Acetaldehído/sangre , Consumo de Bebidas Alcohólicas/sangre , Aldehído Deshidrogenasa Mitocondrial , Animales , Asia/etnología , Cicloheximida/farmacología , Glutamato Deshidrogenasa/metabolismo , Humanos , Hígado/enzimología , Neoplasias Hepáticas Experimentales , Masculino , Fenotipo , ARN Mensajero/genética , Ratas , Ratas Endogámicas Lew , Ratas Sprague-Dawley , Proteínas Recombinantes/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transcripción Genética/efectos de los fármacos , Transfección , Células Tumorales Cultivadas , Privación de AguaRESUMEN
Alveolar bone deficiency is a very common problem encountered by the practitioner when planning dental implants. The severity of the deficiency is variable. Many practitioners perform augmentation using the method they feel comfortable with and do not necessarily use the most appropriate method. This is a retrospective study on 21 patients between the ages of 25 and 63 years exhibiting moderate vertical alveolar bone deficiency and treated by the sandwich technique. Mean vertical bone gain was 7.5mm. Sixty-one dental implants were inserted showing a survival rate of 96.7% with a median of 3.1 years follow-up. Main advantages of the method include minimal relapse, single operation and preservation of the native cortical bone in the occlusal surface. We believe the surgeon should maintain the capability of using different augmentation techniques and utilize them appropriately for different severities of deficiency. We wish to establish a paradigm for using different augmentation methods We recommend using the sandwich technique in the moderate deficient cases as described in this work, using alveolar distraction osteogenesis for the severe cases as described in our previous work, where lack of soft tissue for proper closure is a major limitation, and using guided bone regeneration for minor deficiencies.
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Pérdida de Hueso Alveolar/cirugía , Aumento de la Cresta Alveolar/métodos , Implantación Dental Endoósea/métodos , Implantes Dentales , Osteotomía/métodos , Adulto , Pérdida de Hueso Alveolar/diagnóstico por imagen , Trasplante Óseo , Diagnóstico por Imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Minerales/uso terapéutico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
GABA(A) and GABA(B) receptor agonists stimulate feeding following microinjection into the nucleus accumbens shell and ventral tegmental area, effects blocked selectively and respectively by GABA(A) and GABA(B) receptor antagonists. GABA antagonists also differentially alter opioid-induced feeding responses elicited from these sites. Although GABA agonists and antagonists have been shown to modulate feeding elicited by deprivation or glucoprivation, there has been no systematic examination of feeding elicited by homeostatic challenges following GABA antagonists in these sites. Therefore, the present study examined the dose-dependent ability of GABA(A) (bicuculline, 75-150 ng) and GABA(B) (saclofen, 1.5-3 microg) antagonists administered into the nucleus accumbens shell or ventral tegmental area upon feeding responses elicited by food deprivation (24 h), 2-deoxy-D-glucose-induced glucoprivation (500 mg/kg) or mercaptoacetate-induced lipoprivation (70 mg/kg). A site-specific effect of GABA receptor antagonism was observed for deprivation-induced feeding in that both bicuculline and saclofen administered into the nucleus accumbens shell, but not the ventral tegmental area, produced short-term (1-4 h), but not long-term (24-48 h) effects upon deprivation-induced intake without meaningfully altering body weight recovery. In contrast to the relative inability of GABA receptor antagonism in both sites to alter 2-deoxy-D-glucose-induced intake, mercaptoacetate-induced intake was eliminated by saclofen and significantly reduced by bicuculline in the nucleus accumbens shell and eliminated by both bicuculline and saclofen in the ventral tegmental area. These data reinforce the findings that GABA(A) and GABA(B) receptors in the nucleus accumbens shell and ventral tegmental area are not only important in the modulation of pharmacologically induced feeding responses, but also participate in differentially mediating the short-term feeding response to food deprivation in the nucleus accumbens shell as well strongly modulating lipoprivic, but not glucoprivic feeding responses in both sites.
Asunto(s)
Baclofeno/análogos & derivados , Bicuculina/farmacología , Conducta Alimentaria/efectos de los fármacos , Privación de Alimentos/fisiología , Antagonistas del GABA/farmacología , Núcleo Accumbens/efectos de los fármacos , Área Tegmental Ventral/efectos de los fármacos , Animales , Baclofeno/farmacología , Conducta Animal , Peso Corporal/efectos de los fármacos , Desoxiglucosa/farmacología , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Ingestión de Alimentos/efectos de los fármacos , Conducta Alimentaria/fisiología , Glucosa/deficiencia , Lípidos/deficiencia , Masculino , Ratas , Ratas Sprague-Dawley , Tioglicolatos/farmacología , Factores de TiempoRESUMEN
Red cells of newborn calves contain 105-110 mmole K(+) and 1-5 mmole Na(+) per liter of cells. As the animals age the K(+) content decreases to a value of 25-30 mmole/liter of cells after about 60 days. At approximately the same time, the sodium content reaches a value of 60-70 mmole/liter. The time required for half change (t((1/2))) is 35-37 days for both Na(+) and K(+). The activity of (Na + K)-adenosine triphosphatase (ATPase) and the influx of K(42) and Rb(86) into the red cells are high at birth and are reduced to 5 and 15% of their original values, respectively, in mature animals. t((1/2)) for both is of the order of 30-35 days. The membrane Mg-ATPase activity is also high at birth and is reduced with a t((1/2)) of 28-32 days to a final value of about 20% of its activity at birth. Separation of red cells according to their age showed that, in animals at the age of transition, newly formed red cells contain a higher K/Na ratio and a higher active transport capacity than older red cells of the same animal. It is suggested that the changes observed are a reflection of the average age of the red cell population as the animal grows.
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Bovinos/fisiología , Eritrocitos/análisis , Potasio/sangre , Adenosina Trifosfatasas/sangre , Animales , Transporte Biológico Activo , Membrana Celular/enzimología , Centrifugación por Gradiente de Densidad , Eritrocitos/enzimología , Eritrocitos/metabolismo , Femenino , Hemoglobina Fetal/biosíntesis , Semivida , Hemoglobinas/biosíntesis , Técnicas In Vitro , Masculino , Péptidos/sangre , Fosfolípidos/sangre , Potasio/metabolismo , Isótopos de Potasio , Reticulocitos , Rubidio/metabolismo , Sodio/sangreRESUMEN
The ability of neuropeptide Y to potently stimulate food intake is dependent in part upon the functioning of mu and kappa opioid receptors. The combined use of selective opioid antagonists directed against mu, delta or kappa receptors and antisense probes directed against specific exons of the MOR-1, DOR-1, KOR-1 and KOR-3/ORL-1 opioid receptor genes has been successful in characterizing the precise receptor subpopulations mediating feeding elicited by opioid peptides and agonists as well as homeostatic challenges. The present study examined the dose-dependent (5-80 nmol) cerebroventricular actions of general and selective mu, delta, and kappa1 opioid receptor antagonists together with antisense probes directed against each of the four exons of the MOR-1 opioid receptor gene and each of the three exons of the DOR-1, KOR-1, and KOR-3/ORL-1 opioid receptor genes upon feeding elicited by cerebroventricular NPY (0.47 nmol, 2 ug). NPY-induced feeding was dose-dependently decreased and sometimes eliminated following pretreatment with general, mu, delta, and kappa1 opioid receptor antagonists. Moreover, NPY-induced feeding was significantly and markedly reduced by antisense probes directed against exons 1, 2, and 3 of the MOR-1 gene, exons 1 and 2 of the DOR-1 gene, exons 1, 2, and 3 of the KOR-1 gene, and exon 3 of the KOR-3/ORL-1 gene. Thus, whereas the opioid peptides, beta-endorphin and dynorphin A(1-17) elicit feeding responses that are respectively more dependent upon mu and kappa opioid receptors and their genes, the opioid mediation of NPY-induced feeding appears to involve all three major opioid receptor subtypes in a manner similar to that observed for feeding responses following glucoprivation or lipoprivation.
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Conducta Alimentaria/efectos de los fármacos , Antagonistas de Narcóticos , Antagonistas de Narcóticos/farmacología , Neuropéptido Y/antagonistas & inhibidores , Animales , Regulación del Apetito/fisiología , Conducta Animal/efectos de los fármacos , Masculino , Antagonistas de Narcóticos/administración & dosificación , Neuropéptido Y/farmacología , Oligodesoxirribonucleótidos Antisentido/genética , Oligodesoxirribonucleótidos Antisentido/farmacología , Ratas , Ratas Sprague-Dawley , Receptores Opioides/genéticaRESUMEN
Genetic factors influence alcohol consumption and alcoholism. A number of groups have bred alcohol drinker and non drinker rat strains, but genetic determinants remain unknown. The University of Chile rat lines UChA (low drinkers) and UChB (high drinkers) display differences in the relative K(m) for NAD+ of mitochondrial aldehyde dehydrogenase (ALDH2) but no V(max) differences. The relative K(m) differences may be due to mitochondrial changes or to genetic differences coding for ALDH2. We investigated whether there are differences in the coding regions of ALDH2 cDNA in these lines and whether the Aldh2 genotype predicts the phenotype of alcohol consumption and the K(m) of ALDH2 for NAD+. Liver cDNA was prepared, and the Aldh2 transcript was amplified, cloned and sequenced. Genotyping was conducted by DNA amplification and restriction enzyme digestion. When compared to Aldh21 of Sprague-Dawley, 94% of the UChA (low drinker) rats (n = 61), presented a mutation that changes Gln67 to Arg in the mature enzyme (allele referred to as Aldh22). In UChB (high drinker) rats (n = 69), 58% presented the Aldh21 allele, while 42% presented the Gln67Arg change plus a second mutation that changed Glu479 to Lys (allele Aldh23). The Aldh22 allele was absent in high drinker rats. Rats of different Aldh2 genotypes displayed marked phenotypic differences in both ethanol consumption (g/kg/day; means +/- SE): (Aldh21/Aldh21) = 5.7 +/- 0.2, (Aldh22/Aldh22) = 0.9 +/- 0.2 and (Aldh23/Aldh23) = 4.6 +/- 0.2; and K(m)s for NAD+ of 43 +/- 3 microm, 132 +/- 13 microm and 41 +/- 2 microm, respectively (Aldh22 versus Aldh21 or Aldh23; P < 0.0001 for both phenotypes). Overall, the data show that alleles of Aldh2 strongly segregate with the phenotype of ethanol consumption and the relative K(m) for NAD+ of ALDH2. Bases mutated suggest that non drinker Aldh22 is ancestral with regard to the coding changes in either Aldh21 or Aldh23, variants which would allow ethanol consumption and may provide an evolutionary advantage by promoting calorie intake from fermented products along with carbohydrates.
Asunto(s)
Aldehído Deshidrogenasa/genética , Etanol/administración & dosificación , Mitocondrias Hepáticas/enzimología , Mutación , Alelos , Animales , Secuencia de Bases , Clonación Molecular , Cartilla de ADN , RatasRESUMEN
An approach based on the polymerase chain reaction (PCR) was used to isolate additional members of the G-linked receptor family from a rat striatal lambda gtII cDNA library. Priming with one degenerate probe corresponding to highly conserved consensus sequences in the third transmembrane (TM) domain of 15 G-linked receptors and sequences in the phage vector resulted in one clone (G-13) encoding a dopamine D2 receptor variant with a 29 amino acid insert in the third cytoplasmic loop. In addition, the amino acid sequence encoded by clone G-36 contained conserved sequences characteristic of the G-linked class of receptors and displayed sequence homology in TM domains with the beta 2-adrenergic receptor (48%). Two conserved serine residues in TM5 postulated to be part of a ligand binding site in the adrenergic receptor, suggests that G-36 encodes a catecholaminergic receptor. Northern blot analysis confirmed the expression of G-36 in rat brain, but not in kidney, heart and lung. Several strong hybridizing bands to G-36 were obtained in both human and rat genomic DNA. The general PCR strategy employed here should prove to be extremely useful for the isolation of other members of the G-linked receptor family.
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Clonación Molecular , Receptores Dopaminérgicos/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Cuerpo Estriado/análisis , Humanos , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Ratas , Receptores Dopaminérgicos/análisis , Receptores de Dopamina D2RESUMEN
We have developed a rapid, safe, and reliable method to prepare emulsions of water-soluble antigens in an adjuvant oil phase for immunization purposes. The method, based on well established emulsification principles, employs a three-way 'T' connector to which three disposable syringes are attached. The system allows the stepwise addition of small volumes of the water phase, into the oil phase. We have compared the time required for emulsification, the rate of antigen release from the emulsion into a physiological phase, and the immunogenic properties of bovine serum albumin and transferrin contained in emulsions made by the new stepwise addition method, with those made by the widely used double-hubbed needle method. We report a significantly shorter (P < 0.001) and a more reproducible emulsification time for the stepwise addition method (6.1 +/- 2.1 min; mean +/- SD) than for the double-hubbed needle method (41.1 +/- 28.0 min). The stepwise addition method always yielded water-in-oil emulsions, while the double-hubbed needle method failed, about 20% of the time, to produce a water-in-oil emulsion after 120 min of mixing. Since the stepwise addition method employs a connector with a larger inner diameter (1.75 mm) than the one required for the double-hubbed needle method (0.84 mm); the pressure required for the former is markedly reduced compared with that required for the latter, thus making the new method safer and less labor-intensive. The rate of antigen release from the emulsions was significantly slower when the stepwise addition method was employed (P < 0.01). There were no differences in viscosity and stability in the emulsions prepared by the two methods. The ability of antigen-containing emulsions to elicit an immune response was found to be identical by the two methods; no significant differences were found in antibody titers as determined by enzyme-linked immunosorbent assays. These characteristics make the stepwise addition system the method of choice.
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Adyuvantes Inmunológicos/química , Antígenos/inmunología , Emulsiones , Inmunización/métodos , Animales , Formación de Anticuerpos , Femenino , Técnicas Inmunológicas/instrumentación , Ratones , Ratones Endogámicos BALB C , Aceites , Reproducibilidad de los Resultados , AguaRESUMEN
Chronic ethanol administration (4-5 weeks) to female spontaneously hypertensive (SH) rats led to a marked increase in the rate of ethanol metabolism. This was accompanied by an increase in hepatic alcohol dehydrogenase (ADH) and by an increase in the rate of oxygen consumption in perfused livers of these animals. Treatment with the antithyroid drug 6-n-propyl-2-thiouracil (PTU) during the last 9 days (40 mg/kg/day) of the chronic administration of ethanol reduced hepatic oxygen consumption, resulting in a net diminution of the metabolic tolerance to ethanol, despite a further elevation in ADH activity. In these animals, microsomal ethanol-oxidizing system (MEOS) activity was not affected by chronic ethanol administration or by treatment with PTU. Data strongly suggest that in the female SH rat all the metabolic tolerance to ethanol proceeds via the ADH pathway, and that the increase in hepatic oxygen consumption is more important in the development of metabolic tolerance to ethanol than the increased ADH levels.
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Etanol/metabolismo , Propiltiouracilo/farmacología , Alcohol Deshidrogenasa , Oxidorreductasas de Alcohol/análisis , Animales , Peso Corporal/efectos de los fármacos , Sistema Enzimático del Citocromo P-450/análisis , Tolerancia a Medicamentos , Etanol/farmacología , Femenino , Hígado/efectos de los fármacos , Hígado/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Oxidación-Reducción , Consumo de Oxígeno/efectos de los fármacos , Perfusión , Ratas , Ratas Endogámicas SHR , Glándula Tiroides/efectos de los fármacosRESUMEN
Administration of a single large dose of ethanol (5 g/kg) to rats elevates the rates of ethanol metabolism and of oxygen consumption in perfused livers in 2-3 hr. Pretreatment with the antithyroid drug propylthiouracil (PTU) for 10 days abolished both of these effects. Under all treatment conditions studied (controls; PTU-pretreatment; acute ethanol treatment; PTU-pretreated + acute ethanol treatment),, a significant correlation between ethanol metabolism and oxygen consumption was observed (r = 0.86). It is concluded that a normal thyroidal state is required to evoKe the swift increase in alcohol metabolism (SIAM) and an elevation of oxygen consumption.
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Etanol/metabolismo , Propiltiouracilo/farmacología , Animales , Interacciones Farmacológicas , Femenino , Glucólisis/efectos de los fármacos , Técnicas In Vitro , Cinética , Hígado/metabolismo , Consumo de Oxígeno/efectos de los fármacos , Ratas , Ratas EndogámicasRESUMEN
Acute oral administration of ethanol significantly increases (50-60%) portal blood flow to the liver. As earlier studies have indicated that this effect is maximal at concentrations of ethanol that saturate the alcohol dehydrogenase (ADH) system and is blocked by the ADH inhibitor 4-methylpyrazol, we investigated the possible role of acetaldehyde, a product in the ADH reaction, as a mediator of this effect. In the first series of experiments it was shown that, contrary to expectations, cyanamide administration prior to alcohol suppressed fully the effect of ethanol on portal blood flow without altering it in the absence of ethanol [ethanol = 69.5 +/- 5.6; ethanol + cyanamide 42.9 +/- 2.4; control = 43.0 +/- 3.0; cyanamide = 55.1 +/- 3.7 ml X min-1 X (kg body wt)-1]. Arterial blood concentrations of acetaldehyde were elevated from 3.6 +/- 0.3 microM in the presence of ethanol to 293 +/- 48 microM in the presence of ethanol + cyanamide. Infusion of acetaldehyde either into the left ventricle, resulting in arterial blood acetaldehyde levels of 227 +/- 77 microM, or into the portal circulation, resulting in arterial blood levels of 198 +/- 40 microM, did not modify portal blood flow or splanchnic hemodynamics, nor the effect of ethanol per se. The combination of cyanamide + ethanol significantly reduced total peripheral resistance (from 28 +/- 3 to 19 +/- 2 dyne X cm X sec-5), while neither ethanol or cyanamide per se, nor acetaldehyde affected total peripheral resistance. Data suggest that acetaldehyde is not involved in the ethanol-mediated increase in portal vein flow. Further studies indicate that the effects of cyanamide in suppressing the ethanol-induced increase in portal blood flow and increasing total peripheral resistance appear to be related to an ethanol-cyanamide interaction which is independent of the acetaldehyde levels in the circulation.
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Acetaldehído/sangre , Etanol/farmacología , Administración Oral , Animales , Gasto Cardíaco/efectos de los fármacos , Cianamida/farmacología , Etanol/administración & dosificación , Masculino , Ratas , Ratas Endogámicas , Flujo Sanguíneo Regional/efectos de los fármacos , Circulación Esplácnica/efectos de los fármacosRESUMEN
The antithyroid drug propylthiouracil (PTU) has been shown previously to reduce hepatic oxygen utilization and to protect the liver from ethanol-induced injury. The present study examined the effect of PTU on hepatic microsomal oxygen consumption and on the activities of NADPH-cytochrome P450 reductase (CYP-reductase) and cytochrome P4502E1 (CYP2E1) in rats receiving ethanol or acetone chronically. Liver microsomes from rats treated with ethanol for 29 days displayed increases in (i) O2 consumption (70%), (ii) hydroxyl radical (.OH) production (49%) and (iii) ethanol oxidation (50%). Microsomal CYP2E1 levels were increased markedly by chronic ethanol administration, while CYP-reductase was affected marginally, but not significantly (P = 0.06). Chronic treatment with acetone for 14 days, produced similar effects, except that .OH production was not enhanced. Administration of PTU (25 mg/kg/day) to ethanol- or acetone-fed rats, for 10 and 14 days, respectively, led to a marked reduction in the levels and activity of CYP-reductase, and to a decrease in the rates of microsomal O2 consumption, .OH production and ethanol oxidation, but did not lower the levels of CYP2E1 or the metabolism of the CYP2E1 substrate N,N-nitrosodimethylamine. These data suggest that the ability of PTU to protect the liver from ethanol-induced injury may be due to a reduction in the levels of CYP-reductase, thereby minimizing the enhancement of microsomal oxygen consumption and free radical generation associated with ethanol-induced CYP2E1 activity.
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Acetona/toxicidad , Sistema Enzimático del Citocromo P-450/biosíntesis , Etanol/toxicidad , Radical Hidroxilo/metabolismo , Microsomas Hepáticos/enzimología , Oxidorreductasas N-Desmetilantes/biosíntesis , Oxidorreductasas/biosíntesis , Propiltiouracilo/farmacología , Animales , Peso Corporal/efectos de los fármacos , Citocromo P-450 CYP2E1 , Inducción Enzimática , Femenino , NADPH-Ferrihemoproteína Reductasa , Consumo de Oxígeno , Ratas , Ratas Wistar , Hormonas Tiroideas/sangreRESUMEN
Stimulation of the peripheral renin-angiotensin system has been shown previously to decrease the voluntary intake of ethanol in the rat. The existence of a separate brain renin-angiotensin system, independent from that of the periphery, has been widely demonstrated. The brain renin-angiotensin system plays an important role in the regulation of water and electrolyte balance and neuroendocrine function. However, the role played by this system in the regulation of voluntary alcohol consumption has not yet been studied. The goal of the present work was to assess the feasibility of decreasing the voluntary alcohol intake in a strain of rats (Rapp SS/Jr rats) that have a genetic deficiency responsible for a low activity of the renin-angiotensin system and elevated alcohol intake. Adult Rapp SS/Jr rats received intraventricular transplants of fetal hypothalamic grafts (from normal donors), known to contain angiotensin-immunoreactive cell bodies. Our studies revealed that angiotensin-immunoreactivity in the cell bodies and fibres in the paraventricular, supraoptic and suprachiasmatic nuclei of the hypothalamus in Rapp SS/Jr rats was markedly reduced. Animals that had surviving grafts containing angiotensin-immunoreactive cell bodies in the dorsal third ventricle--but not in the ventral third ventricle, in the lateral ventricles, or sham operated animals--had a 40% decrease of their voluntary alcohol intake, when compared to their intake before surgery, or to the control group. However, water consumption was not reduced in both the sham and transplanted animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Consumo de Bebidas Alcohólicas , Angiotensina II/metabolismo , Trasplante de Tejido Encefálico , Conducta de Ingestión de Líquido , Hipotálamo/trasplante , Sistema Renina-Angiotensina/genética , Consumo de Bebidas Alcohólicas/genética , Alcoholismo/prevención & control , Angiotensina II/deficiencia , Animales , Ventrículos Cerebrales/metabolismo , Trasplante de Tejido Fetal , Masculino , Núcleo Hipotalámico Paraventricular/metabolismo , Ratas , Ratas Mutantes , Ratas Sprague-Dawley , Núcleo Supraquiasmático/metabolismo , Núcleo Supraóptico/metabolismo , AguaRESUMEN
Isolated perfused rat hearts receiving noradrenaline as a cardiostimulatory agent show the characteristic metabolic coronary dilatations which correlate with the inotropic effect elicited by noradrenaline. Addition of ethanol (20-400 mg/dl) to the perfusion fluid produced a concentration-dependent enhancement of the metabolic coronary dilatation. The latter was increased by 50% at about 125 mg ethanol/dl. Since the inotropic responses to noradrenaline were not affected by ethanol it is suggested that alcohol produces an alteration in the system that normally adapts the coronary flow to an increased cardiac performance. The effect of ethanol was fully reversible; removal of alcohol from the perfusion fluid restored the metabolic coronary dilatation in response to noradrenaline to control values. At high concentrations, 200-400 mg/dl, ethanol produced a small but significant reduction in contractility of the myocardium (11.1 +/- 2.4%). At these concentrations ethanol enhanced the noradrenaline induced metabolic coronary dilatation by about 100%. These data indicate that ethanol at concentrations that are commonly found in blood in vivo may be beneficial in facilitating the coronary reactions during cardiac exertion. However cardiodepressant effects, particularly at higher concentrations, must also be considered.
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Vasos Coronarios/efectos de los fármacos , Etanol/farmacología , Norepinefrina/farmacología , Vasodilatadores , Animales , Presión Sanguínea/efectos de los fármacos , Circulación Coronaria/efectos de los fármacos , Interacciones Farmacológicas , Técnicas In Vitro , Contracción Miocárdica/efectos de los fármacos , Ratas , Estimulación QuímicaRESUMEN
The acute administration of propranolol or phentolamine resulted in a small (16-19%) but significant reduction in the rate of ethanol disappearance in vivo in the naive Wistar rat. A reduction of essentially similar magnitude was also observed in ethanol-treated rats and pair-fed (sucrose) control animals, following the administration of these blockers.
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Etanol/metabolismo , Fentolamina/farmacología , Propranolol/farmacología , Consumo de Bebidas Alcohólicas , Animales , Masculino , Tasa de Depuración Metabólica/efectos de los fármacos , RatasRESUMEN
Chronic consumption of alcohol leads to an increase in liver weight, primarily due to an increase in hepatocyte volume. About 50-60% of such an increase is due to an increase in intracellular water. Accumulation of intracellular K+ osmotically accounts for about one half of the increase in intracellular water, while an increase in soluble proteins plays only a minor role in such an increase in cell volume. The increase in intracellular water is accompanied by a relative reduction in water in the extracellular space, probably due to compression of the extracellular volume by the enlarged hepatocytes. It is suggested that such an increase in hepatocyte size, with an attending reduction of the extracellular volume, results in an increased resistance to blood flow through the liver and thus in an increase in portal pressure. In alcoholics, portal and intrahepatic pressure correlate with cell size both in cirrhotics (r = 0.79) and in non-cirrhotics (r = 0.74), thus suggesting that cell enlargement plays a major role in the production of portal hypertension in the alcoholic.
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Alcoholismo/complicaciones , Etanol/toxicidad , Hemodinámica/efectos de los fármacos , Hepatomegalia/metabolismo , Hígado/efectos de los fármacos , Animales , Agua Corporal/metabolismo , Compartimento Celular/efectos de los fármacos , Electrólitos/metabolismo , Espacio Extracelular/efectos de los fármacos , Humanos , Hipertensión Portal/metabolismo , Circulación Hepática/efectos de los fármacos , Cirrosis Hepática Alcohólica/metabolismo , Tamaño de los Órganos/efectos de los fármacos , RatasRESUMEN
A simple technique for the measurement of intoxication induced by low doses of alcohol in the rat was developed. Rats are required to maintained their balance on a rectangular wooden bar that oscillates in a 120 degree angle in an arch-like fashion. A steady baseline can be obtained for each animal with approximately 10 min of training time. Ethanol, in a dose range from 0.5-1.5 g/kg, given orally or by IP route, impairs animal's performance in a dose-related manner. At the same blood ethanol concentration, a higher degree of impairment is observed at higher oscillating frequency. Significant impairment of performance can be detected at ethanol dose of 0.5 g/kg given IP or orally. Pentobarbital and chlordiazepoxide, in doses of comparable potencies to those of ethanol doses also produce a dose-related impairment of performance. The oscillating bar test is a simple but sensitive test that can qualitatively assess intoxication induced by low doses of ethanol or other sedative hypnotic drugs.
Asunto(s)
Intoxicación Alcohólica/psicología , Psicología Experimental/instrumentación , Administración Oral , Animales , Clordiazepóxido/farmacología , Relación Dosis-Respuesta a Droga , Etanol/administración & dosificación , Etanol/sangre , Etanol/farmacología , Hipnóticos y Sedantes/farmacología , Inyecciones Intraperitoneales , Masculino , Pentobarbital/farmacología , Equilibrio Postural/efectos de los fármacos , Desempeño Psicomotor/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
Matrix algebra has been applied to the resolution of overlapping polarographic waves and derivative curves of two- and three-component systems. Due to the complex exponential dependence of current on potential at the rising part of the waves, matrices were used to obtain the ratios of the concentrations of the components present, and the amount of each one of the components was calculated from the more reliable sum of the diffusion currents. The method proved successful for all cases of binary mixtures that were examined, but less so for the limiting case of a mixture of o-,m-, and p-nitrobenzoic acids in which all three half-wave potentials are found within 80 mV.