RESUMO
We consider a fluid adsorbed in a wedge made from walls that exhibit a first-order wetting transition and revisit the argument as to why and how the pre-filling and pre-wetting coexistence lines merge when the opening angle is increased approaching the planar geometry. We clarify the nature of the possible surface phase diagrams, pointing out the connection with complete pre-wetting, and show that the merging of the coexistence lines lead to new interfacial transitions. These occur along the side walls and are associated with the unbinding of the thin-thick interface, rather than the liquid-gas interface (meniscus), from the wedge apex. When fluctuation effects, together with the influence of dispersion forces are included, these transitions display strong non-universal critical singularities that depend on the opening angle itself. Similar phenomena are also shown to occur for adsorption near an apex tip.
RESUMO
The inhibitory effect of 5-diazouracil on the catabolism of circulating uracil and 5-fluorouracil was examined in the rat in vivo. Measurements of the activity of the entire enzymatic pathway of uracil catabolism in the cytosolic supernatant of different rat organs as well as the determination of the total amount of 5-fluorouracil catabolites, accumulated in these tissues, served to clarify their role in the complete systemic breakdown of uracil or 5-fluorouracil. The activity of the enzymatic pathway involved in uracil catabolism was estimated from the 14CO2 produced from [2-14C]uracil in the cytosolic supernatants. Complete degradation of uracil was detected only in the liver and, at a much lower rate, in the kidneys. Fifteen min after the i.p. injection of a tracer dose of 5-fluoro[6-14C]-uracil, more than 90% of the total radioactivity in blood plasma was associated with 5-fluorouracil catabolites. The relative amount of the major catabolite alpha-fluoro-beta-alanine and of dihydrofluorouracil in blood plasma was considerably suppressed after a pretreatment with 5-diazouracil inversely correlated with a 27-fold increase in the absolute amount of unchanged 5-fluorouracil. Control animals accumulated by far the highest amount of total acid-soluble radioactivity from 5-fluoro[6-14C]uracil in liver and kidneys. Total radioactivity in all other organs was much lower and was comparable to the amount of label in blood plasma. In liver and kidneys, the sum of total acid-soluble catabolites including dihydrofluorouracil, alpha-fluoro-beta-ureidopropionic acid, and alpha-fluoro-beta-alanine made up more than 98% of the label correlating with minimal salvage utilization of the base analogue in both organs. Injection of 5-diazouracil 2 h before a tracer dose of 5-fluoro[6-14C]uracil strongly inhibited the accumulation of labeled catabolites in liver and kidneys causing a fall in total acid-soluble radioactivity in both tissues by 75 and 66%, respectively. In blood plasma and all other organs, however, pretreatment with 5-diazouracil was followed by a 2-fold enhancement of the radioactivity contents, mostly due to the appearance of unchanged 5-fluorouracil. Under these conditions, there was a 2.6- to 4-fold increase in the relative proportion of cis-diol group-containing anabolites of 5-fluorouracil in liver and in kidneys. Within 2 h, 12.7% of the administered radioactivity from 5-fluorouracil was excreted into bile. 5-Diazouracil lowered the biliary excretion of radioactivity to 2% of the injected dose.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Fluoruracila/metabolismo , Rim/metabolismo , Fígado/metabolismo , Uracila/análogos & derivados , Animais , Bile/metabolismo , Citosol/metabolismo , Mucosa Intestinal/metabolismo , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Taxa de Depuração Metabólica/efeitos dos fármacos , Ratos , Distribuição Tecidual/efeitos dos fármacos , Uracila/metabolismo , Uracila/farmacologiaRESUMO
The inhibition of cytosolic carbamoyl-phosphate synthetase II by acivicin was used to study the role of the cytosolic carbamoyl phosphate pool as the exclusive substrate source for de novo pyrimidine synthesis in rat hepatocytes. De novo pyrimidine synthesis was stimulated: 1. by uridine triphosphate deficiency (incubation with D-galactosamine) leading to a stimulation of cytosolic carbamoyl phosphate synthesis, and 2. by accumulation and efflux of mitochondrial carbamoyl phosphate (incubation with ammonium ions and L-norvaline). The stimulated orotate formation from cytosolic carbamoyl phosphate in UTP depleted cells was completely blocked by acivicin. It was not influenced by an inhibition of mitochondrial carbamoyl phosphate synthesis mediated by 4-pentenoate, since mitochondrial carbamoyl phosphate did not participate in cytosolic pyrimidine synthesis even in the presence of ammonium ion concentrations maintaining physiological rates of urea synthesis. An excess of ammonium ions led to an artificial accumulation and efflux of mitochondrial carbamoyl phosphate, which could be avoided by 4-pentenoate. The non-regulated stimulation of pyrimidine synthesis from surplus mitochondrial carbamoyl phosphate was not inhibited by acivicin. Utilization of mitochondrial carbamoyl phosphate for de novo pyrimidine synthesis presumably does not occur under physiological conditions because mitochondrial CP efflux depends on the accumulation of this metabolite in the mitochondria under experimental or pathological circumstances. Acivicin inhibition of CPS II thus cannot be bypassed by mitochondrial CP. It is suitable as inhibitor of the physiological de novo pyrimidine synthesis.
Assuntos
Antibióticos Antineoplásicos/farmacologia , Isoxazóis/farmacologia , Fígado/metabolismo , Oxazóis/farmacologia , Pirimidinas/antagonistas & inibidores , Ureia/biossíntese , Animais , Carbamoil-Fosfato/metabolismo , Citosol/metabolismo , Feminino , Fígado/citologia , Fígado/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Ácido Orótico/metabolismo , Ratos , Ratos EndogâmicosRESUMO
Sixteen unselected patients with non-resectable hepatocellular carcinoma were treated in a phase I study with 261 cycles of D-galactosamine and 6-azauridine prior to 5-fluorouridine. Thirty % of the patients survived for more than one year without signs of tumor progression and with an unchanged performance status. The compatibility of this chemotherapeutical method was quite satisfactory. The only extrahepatic side effect was a leucopenia and/or thrombocytopenia which was reversible upon reduction of the 5-fluorouridine dose. The heterogeneity of the 16 patients treated to date does not allow a definite statistical evaluation of the reported clinical observations and results. A final decision about the clinical applicability of this concept of a selective chemotherapy of hepatocellular carcinoma requires further experience.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Uridina/análogos & derivados , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Azauridina/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Feminino , Galactosamina/uso terapêutico , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Uridina/efeitos adversos , Uridina/uso terapêuticoRESUMO
BACKGROUND: A high incidence of hepatic haematomas detected at sonography following percutaneous liver biopsy and laparoscopy-guided liver biopsy has recently been reported. PATIENTS AND METHODS: Prompted by this report, we carried out a prospective study on 71 patients aged between 20 and 79 years (median age: 51 years). The patients were examined by ultrasound prior to and following laparoscopy-guided biopsy with the Silverman needle. RESULTS: Only two of the 71 patients (3%) had a hepatic haematoma after biopsy. The haemangiomas had a maximum diameter of 2.6 cm, caused no pain, and disappeared again within ten days at the latest. No therapeutic measures were required. CONCLUSION: The results of this study indicate that laparoscopy-guided liver biopsy with the Silverman needle is associated with relatively few complications.
Assuntos
Biópsia por Agulha/instrumentação , Hematoma/diagnóstico por imagem , Laparoscópios , Cirrose Hepática/patologia , Hepatopatias/diagnóstico por imagem , Fígado/patologia , Adulto , Idoso , Segurança de Equipamentos , Feminino , Humanos , Fígado/diagnóstico por imagem , Cirrose Hepática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , UltrassonografiaRESUMO
BACKGROUND: Recently, a high incidence of ultrasound-detected hepatic hematomas due to percutaneous liver biopsy has been reported. Until yet, little is known about the incidence of asymptomatic hepatic hematomas following sonographically guided fine-needle biopsy. PATIENTS AND METHODS: For that reason, we carried out a prospective study with sonographic examinations before and after liver biopsy in 160 patients. 51 patients, aged 50 to 83, median 67 years, with focal liver lesions had ultrasound-guided liver biopsy using the 0.95 mm-cut biopsy-needle, in 109 patients (17 to 80, median 49 years) with diffuse liver disease percutaneous liver biopsy with the 1.4 mm-needle of Menghini was performed. RESULT: After fine-needle biopsy none of the 51 patients with focal liver lesions displayed liver hematoma on ultrasonography. In the group of patients who underwent percutaneous Menghini biopsy a liver hematoma, sized up to 12 x 5 cm in diameter, occurred four times (3.7%). CONCLUSION: The results of this study indicate that fine-needle biopsy of the liver is a particularly safe diagnostic procedure, when compared with percutaneous Menghini biopsy.
Assuntos
Biópsia por Agulha/instrumentação , Hematoma/diagnóstico por imagem , Hepatopatias/diagnóstico por imagem , Fígado/patologia , Ultrassonografia/instrumentação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Desenho de Equipamento , Feminino , Humanos , Fígado/diagnóstico por imagem , Hepatopatias/patologia , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosAssuntos
Carboxiliases/metabolismo , Pentosiltransferases/metabolismo , Fatores Etários , Animais , Peso Corporal , Encéfalo/enzimologia , Dióxido de Carbono/metabolismo , Isótopos de Carbono , Fracionamento Celular , Galinhas , Feminino , Cobaias , Concentração de Íons de Hidrogênio , Intestinos/enzimologia , Rim/enzimologia , Fígado/enzimologia , Regeneração Hepática , Masculino , Camundongos , Músculos/enzimologia , Nucleotídeos , Ácido Orótico , Nucleotídeos de Pirimidina , Ratos , Especificidade da EspécieAssuntos
Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Nucleotídeos de Pirimidina/metabolismo , Animais , Carboxiliases/metabolismo , Nucleotídeos de Citosina/metabolismo , Galactosamina , Galactose , Glucose-6-Fosfatase/metabolismo , Guanosina/metabolismo , Hexosaminas/metabolismo , Hexosefosfatos , Fígado/metabolismo , Nucleotidiltransferases/metabolismo , Pentosiltransferases/metabolismo , Fosfotransferases/metabolismo , DNA Polimerase Dirigida por RNA/metabolismo , Ratos , Ribonucleotídeos , Açúcares de Uridina DifosfatoRESUMO
The clinical-biochemical syndrome of cholestasis is characterized by an alteration in bile constituents. As a consequence, the concentrations of bilirubin, bile acids, phospholipids and cholesterol are elevated. The main clinical symptoms of cholestasis are icterus and pruritus, and in severe cases xanthelasma and xanthoma. Primary intrahepatic cholestasis, caused by impaired bile secretion in the liver, should be separated from the extrahepatic secondary cholestasis which is a consequence of a biliary obstruction. This paper evaluates the therapy of liver diseases which developed as consequence of a primary disturbance in bile secretion.
Assuntos
Cirrose Hepática Biliar/tratamento farmacológico , Ácido Ursodesoxicólico/administração & dosagem , Adulto , Fatores Etários , Ácidos e Sais Biliares/metabolismo , Neoplasias dos Ductos Biliares/etiologia , Neoplasias dos Ductos Biliares/prevenção & controle , Colangiocarcinoma/etiologia , Colangiocarcinoma/prevenção & controle , Neoplasias do Colo/etiologia , Neoplasias do Colo/prevenção & controle , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Lactente , Recém-Nascido , Cirrose Hepática Biliar/etiologia , Assistência de Longa Duração , Pessoa de Meia-Idade , Gravidez , Fatores de RiscoRESUMO
The aim of the study was to find whether the c.I. test is useful for the exclusion and the demonstration of acquired cognitive deficits. In all, 195 patients with brain damage and 68 neurotic patients were examined with the c.I. test and with a comprehensive number of neuropsychological tests. The hit rate of the c.I.-test for the whole group was 67% and lay lower than the base rate of 74% brain damaged patients respectively only unessentially higher than the base rate of 64% patients with unambiguous acquired cognitive deficits. There were very low hit rates especially in patients with absent (46%) or low-grade cognitive deficit (54%) and with low (55%) or with high premorbid mental abilities (55%). Both the low correlations between the c.I. test and the validity criterion as well as the considerable overlapping of the c.I. test raw score distributions, grouped by grades of cognitive deficits, indicate serious deficiencies in the test. The extremely brief c.I. test possesses an inadequate grade of difficulty and cannot detect low- and medium-grade acquired cognitive deficits, and its orientation to ability-related global syndromes means that partial, multifactorial and general cognitive deficits are neglected. The c.I. test is therefore not useful as a screening method for the diagnosis of acquired cognitive deficits.
Assuntos
Dano Encefálico Crônico/diagnóstico , Transtornos Cognitivos/diagnóstico , Demência/diagnóstico , Transtornos Neurocognitivos/diagnóstico , Testes Neuropsicológicos/estatística & dados numéricos , Adulto , Dano Encefálico Crônico/classificação , Dano Encefálico Crônico/psicologia , Isquemia Encefálica/classificação , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/psicologia , Transtornos Cognitivos/classificação , Transtornos Cognitivos/psicologia , Demência/classificação , Demência/psicologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Neurocognitivos/classificação , Transtornos Neurocognitivos/psicologia , Transtornos Neuróticos/classificação , Transtornos Neuróticos/diagnóstico , Transtornos Neuróticos/psicologia , Psicometria , Reprodutibilidade dos TestesRESUMO
Several cognitive impairment/dementia diagnostic methods were examined concerning their results: (a) in the differentiation of accidental and pathological ability changes; (b) in the demonstration/exclusion of cognitive impairment; and (c) the degree of dementia. Sixty-five patients suffering from brain damage were examined with five accepted methods of diagnosing dementia (Syndrom-kurztest, KAI-MWT-Methode, Demenz-Test, Mini-Mental-Status-Test, Wurzer-Methode) and a comprehensive performance test battery as an external criterion for valid determination of the degree of dementia and definite differentiation of accidental and pathological performance changes. The five methods of diagnosing dementia differ appreciably in determining the degree of severity (r = 0.44). They are effective in registering accidental performance changes in comparison with the outer criterion, but pathological changes are inaccurately registered (hit rate 88%/53%); the results concerning the degree of cognitive impairment are identical: between 25 and 43% (r = 0.43). High rates (58%) of false-negative diagnoses are especially apparent in the range of slight and intermediate cognitive impairment. The methods examined are only useful for the demonstration and not for the exclusion of severe cognitive impairment (dementia) and in no circumstances for the registration of slight/intermediate cognitive impairment. Valid diagnosis of cognitive impairment/dementia necessitates the use of test batteries that differentiate functions including the premorbid performance level.
Assuntos
Dano Encefálico Crônico/diagnóstico , Transtornos Cognitivos/diagnóstico , Demência/diagnóstico , Testes Neuropsicológicos/estatística & dados numéricos , Adulto , Idoso , Feminino , Humanos , Testes de Inteligência/estatística & dados numéricos , Masculino , Entrevista Psiquiátrica Padronizada/estatística & dados numéricos , Pessoa de Meia-Idade , Variações Dependentes do Observador , Psicometria , Reprodutibilidade dos TestesRESUMO
Complications have been reported to occur in 0.14 through 0.29% of all patients undergoing liver biopsy. The total incidence of complications is lower in laparoscopically guided biopsy when compared with percutaneous liver biopsy. On the other hand fatal complications appear to be more frequent with laparoscopy (0.038%) than with percutaneous biopsy (0.009-0.017%). Nevertheless, laparoscopic biopsy should be preferred particularly in patients with suspected liver cirrhosis, since laparoscopy is more sensitive for this diagnosis. Until now, the significance of the type of biopsy needle used has not definitively been clarified. The results that are available however indicate, that biopsy with the Tru-cut needle is accompanied by a particularly high bleeding risk. Regarding the results of retrospective studies concerning needle diameter, less serious complications appear to occur after fine needle biopsy when compared with standard needles. Thus, fine needle biopsy should be preferred in patients with focal liver lesions, since the bleeding risk is assumed to be higher in these cases.
Assuntos
Biópsia por Agulha/instrumentação , Hepatopatias/patologia , Fígado/patologia , Humanos , Laparoscópios , Cirrose Hepática/patologia , Fatores de RiscoRESUMO
1. Ammonia liberated continuously in large amounts in muscle, kidney and brain is used immediately for the synthesis of mainly glutamine because of the toxic effects of elevated ammonia concentrations. After glutamine hydrolysis in the liver ammonia serves as substrate for the urea biosynthesis. In ureotelic animals urea is the quantitatively most important product for the elimination of surplus nitrogen. 2. The rate of urea biosynthesis depends on the amount of surplus nitrogen and acts as regulatory factor for the nitrogen balance of the adult organism. 3. Urea cycle abnormalities in liver diseases or inborn enzymatic defects are important factors leading to hyperammonaemia in patients. 4. The hyperammonaemia induces an increase of the rate of hepatic pyrimidine nucleotide biosynthesis as a consequence of an ineffective feedback inhibition of the glutamine-dependent carbamoyl phosphate synthetase. 5. The distribution of ammonia between intra- and extracellular space and the amount of ammonium ions excreted in the urine depend on the pH value. An alkalosis induces an intracellular ammonia load and inhibits the urinary ammonium ion excretion, which is increased in acidosis as one mechanism of protein elimination. 6. The ammonia-induced inhibition of the citric acid cycle by an alpha-ketoglutarate deficiency is one important reason for the neurotoxicity of ammonia, which is the main point in the pathogenesis of hepatic coma.
Assuntos
Amônia/sangue , Amônia/metabolismo , Encéfalo/metabolismo , Encefalopatia Hepática/metabolismo , Humanos , Fígado/metabolismo , Nucleotídeos de Uracila/biossíntese , Ureia/biossínteseRESUMO
Non-cardiac chest pain is caused in 50% by esophageal disorders. About 30% of such esophageal chest pain is induced by gastroesophageal reflux. 2/3 of esophageal chest pain is related to various esophageal motility disorders, which can be differentiated by manometry. Diagnostic procedures for esophageal dysfunction (endoscopy, radiology, long-term pH-metry) have been evaluated. Therapy of gastroesophageal reflux disease has been proven effective; maintenance therapy should be evaluated in further controlled randomized trials. Treatment of esophageal motility disorders, unsatisfactory so far, needs to be improved and standardized.
Assuntos
Angina Pectoris/diagnóstico , Dor no Peito/diagnóstico , Diagnóstico Diferencial , Refluxo Gastroesofágico/diagnóstico , HumanosRESUMO
Quantitative aspects of de novo pyrimidine biosynthesis in rat hepatocytes were monitored. A reduction of intracellular UTP contents by different concentrations of D-galactosamine led to a dose-dependent increase of 14CO2 incorporation into the sum of all acid-soluble uracil nucleotides. In controls the rate of de novo synthesis which was calculated from the incorporation rate of 14CO2 into the sum of all acid-soluble uracil nucleotides was 0.014 mumol X h-1 X g-1 compared to 0.056 mumol X h-1 X g-1 wet weight of liver in situations of a maximally stimulated de novo synthesis. Incubation of hepatocytes with uridine led to a dose-dependent reduction of 14CO2 incorporation to less than 25% of the amount incorporated in the controls. Alterations of the CTP content had no influence on the 14CO2 incorporation. In the presence of high D-galactosamine concentrations the increase of the total amount of acid-soluble uracil nucleotides exceeded the rate of the de novo synthesis derived from the incorporation of 14CO2 into the sum of the acid-soluble uracil nucleotide pool. It was also greater than the increase of the total amount of intra- and extracellular orotate after acidic hydrolysis--even in the presence of 6-azauridine, which stimulated de novo pyrimidine biosynthesis by itself.