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1.
Appl Opt ; 56(19): G188-G196, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29047484

RESUMO

We report a phenomenon manifesting itself as brief flashes of light on the snow's surface near a lidar beam. The flashes are imaged and interpreted as specular reflection patterns from individual ice particles. Such patterns have a two-dimensional structure and are similar to those previously observed in forward scattering. Patterns are easiest to capture from particles with well-defined horizontal facets, such as near-horizontally aligned plates. The patterns and their position can be used to determine properties such as ice particle shape, size, roughness, alignment, and altitude. Data obtained at Summit in Greenland show the presence of regular hexagonal and scalene plates, columns, and rounded plates of various sizes, among others.

2.
Fortschr Neurol Psychiatr ; 84(S 02): S74-S76, 2016 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-27806418

RESUMO

Insomnia is one of the most prevalent neuropsychiatric disorders throughout Europe. It is associated with a number of health-relevant problems including an increased risk of psychiatric and organic disorders. A variety of organic, social and psychological risk factors takes part in the genesis of these sleep disturbances. A key component of the pathophysiology is the multifaceted hyperarousal that is expressed in the cognitive, emotional, neuronal, neuroendocrine, the hypothalamo-pituitary-adrenal axis, and further neurovegetative domains. Recent studies document in addition to identified risk factors for insomnia a number of protective factors that are relevant for the individual as well as society.


Assuntos
Neurociências , Psiquiatria/métodos , Distúrbios do Início e da Manutenção do Sono/psicologia , Distúrbios do Início e da Manutenção do Sono/terapia , Ciências Sociais , Humanos , Fatores de Risco , Distúrbios do Início e da Manutenção do Sono/fisiopatologia
3.
Mol Psychiatry ; 20(5): 585-93, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25311366

RESUMO

Aerobic exercise in young adults can induce vascular plasticity in the hippocampus, a critical region for recall and recognition memory. In a mechanistic proof-of-concept intervention over 3 months, we investigated whether healthy older adults (60-77 years) also show such plasticity. Regional cerebral blood flow (rCBF) and volume (rCBV) were measured with gadolinium-based perfusion imaging (3 Tesla magnetic resonance image (MRI)). Hippocampal volumes were assessed by high-resolution 7 Tesla MRI. Fitness improvement correlated with changes in hippocampal perfusion and hippocampal head volume. Perfusion tended to increase in younger, but to decrease in older individuals. The changes in fitness, hippocampal perfusion and volume were positively related to changes in recognition memory and early recall for complex spatial objects. Path analyses indicated that fitness-related changes in complex object recognition were modulated by hippocampal perfusion. These findings indicate a preserved capacity of the aging human hippocampus for functionally relevant vascular plasticity, which decreases with progressing age.


Assuntos
Circulação Cerebrovascular/fisiologia , Exercício Físico/fisiologia , Hipocampo/fisiologia , Idoso , Análise de Variância , Cognição/fisiologia , Feminino , Gadolínio/metabolismo , Hipocampo/irrigação sanguínea , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Rememoração Mental , Pessoa de Meia-Idade , Testes Neuropsicológicos , Consumo de Oxigênio , Estatística como Assunto , Aprendizagem Verbal
4.
J Anim Physiol Anim Nutr (Berl) ; 98(6): 1154-65, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24589011

RESUMO

A total of 36 piglets with an initial body weight (BW) of 5.6 ± 0.7 kg, fitted with simple T-cannulas at the distal ileum, were used to evaluate the effect of three graded feeding levels (50, 75 or 100 g/kg BW(0.75) day) on apparent ileal digestibility (AID) and total tract digestibility (ATTD) of dry matter (DM), nitrogen (N) and energy, and on ATTD of organic matter (OM), ether extracts (EE), neutral detergent fibre (NDF), acid detergent fibre (ADF) and digestible (DE), metabolisable (ME) and net energy (NE) content in soybean meal (SBM)-casein-cornstarch-based diets. The AID of DM, N and energy and ATTD of NDF, ADF and EE in the diets were not affected (p > 0.05) by the feed intake (FI) level. There was a small decrease in ATTD of DM, N (CP), OM, ash and energy, and in DE, ME and NE content in the diets (p < 0.05) with increasing FI level. The net disappearance in the large intestine (in % of ileal recovery) decreased for DM, N and energy (p < 0.05) with increasing FI level. The design of the study allowed for estimating ileal endogenous loss of N and total tract endogenous loss of ash, N and EE, for estimating corresponding true ileal and total tract digestibility values, and for estimating urinary endogenous N loss. High variability in estimates of ileal endogenous N loss and total tract endogenous losses of N, EE and ash reflects great variation in individual endogenous losses between animals. Estimation of true total tract digestibility of N, EE and ash by regression analysis was affected by their decrease in ATTD with increasing FI level, as estimates for true digestibility were lower compared to their apparent values. The present results suggest that FI level can affect both apparent and true total tract nutrient digestibility in piglets.


Assuntos
Ração Animal/análise , Dieta/veterinária , Digestão/fisiologia , Glycine max/química , Íleo/fisiologia , Suínos/fisiologia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Metabolismo Energético/fisiologia , Masculino , Nitrogênio/metabolismo
5.
Pharmacopsychiatry ; 46(3): 108-13, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23293012

RESUMO

INTRODUCTION: Many antidepressants are associated with periodic limb movements (PLM) during sleep. Although some tricyclic antidepressants, such as amitriptyline, promote sleep and are thus often prescribed as a treatment for sleep disturbances that can accompany depression, it remains unclear whether amitriptyline is associated with PLM. METHODS: 32 healthy males (18-39 years) spent 2 consecutive nights in the sleep lab for polysomnographic recording. During the second night, they received either 75 mg amitriptyline or placebo in a randomized, double-blind, placebo-controlled manner. RESULTS: In subjects receiving amitriptyline but not in subjects receiving placebo, the number of periodic leg movements per h was significantly increased from baseline to intervention night. However, objective polysomnographic sleep parameters (such as the number of awakenings, wake after sleep onset, and sleep efficiency) and subjective sleep perception were not significantly associated with any PLM indices. DISCUSSION: Our findings indicate that amitriptyline can induce or even increase the number of PLM during sleep in healthy subjects. When treating sleep disturbances with amitriptyline, PLM should be considered as a possible cause of insufficient improvement.


Assuntos
Amitriptilina/uso terapêutico , Antidepressivos Tricíclicos/uso terapêutico , Síndrome da Mioclonia Noturna/tratamento farmacológico , Síndrome das Pernas Inquietas/tratamento farmacológico , Adolescente , Adulto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Atividade Motora/efeitos dos fármacos , Síndrome da Mioclonia Noturna/complicações , Polissonografia , Síndrome das Pernas Inquietas/complicações , Fases do Sono , Estatística como Assunto , Adulto Jovem
6.
J Anim Sci ; 90(13): 4883-95, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22829605

RESUMO

A study with 3 experiments and 3 periods each was conducted to assess the protein value of soybean meal (SBM) batches that were imported into the European Union (EU) from Argentina, Brazil, or the United States (US). Six random SBM batches from each origin were analyzed for contents of CP, AA, ether extract, crude ash, NDF, ADF, oligosaccharides, isoflavones, mycotoxins, trypsin inhibitor activity (TIA), and protein dispersibility index. Piglets were used for determination of standardized ileal digestibilities (SID) of CP and AA in these 18 SBM batches. In each experiment, 12 piglets (initial BW = 5.6 ± 0.7 kg) were surgically fitted with simple T-cannulas at the distal ileum. The piglets were randomly allotted to 18 semisynthetic assay diets, which included 1 of the 18 SBM batches from the 3 origins at an inclusion level of 250 g/kg (as-fed). Average content of CP was 480, 505, and 488 g/kg (as-fed) for Argentinean, Brazilian, and US SBM batches, respectively, and was greater for Brazilian SBM (P ≤ 0.05) compared with the other 2 origins. Contents of most AA were greater (P ≤ 0.05) in Brazilian compared with Argentinean SBM batches. Amino acid contents in US SBM batches ranged between those from Argentina and Brazil. Average TIA were 3.9, 5.1, and 3.4 mg trypsin inhibitor/g CP for Argentinean, Brazilian, and US SBM batches, and were greater (P ≤ 0.05) for Brazilian SBM compared with the other origins. Mycotoxins were detected in 8 out of 18 SBM batches, but all mycotoxin concentrations were less than their critical benchmarks. The contents of individual isoflavones varied considerably and differed (P ≤ 0.05) among SBM origins. The SID of CP, Arg, Phe, Thr, Trp, Asp, Gly, and Ser were greater (P ≤ 0.05) for US compared with Argentinean SBM batches, with intermediate values for Brazilian SBM batches. The obtained SID values were most variable within Argentinean SBM batches and most homogenous within US SBM batches, as indicated by great and small CV, respectively. However, SID of CP and AA were not affected (P > 0.05) by any of the chemical variables measured in this study, according to linear and quadratic regression analyses. Greatest SID values and good homogeneity between individual batches of the same origin were observed for US SBM. The results of this study with piglets will expand the database on SID of CP and AA in SBM from 3 of the major soybean-producing and processing countries.


Assuntos
Ração Animal/análise , Digestão , Glycine max/química , Íleo/fisiologia , Sus scrofa/fisiologia , Aminoácidos/metabolismo , Ração Animal/microbiologia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Isoflavonas/análise , Lisina/análise , Micotoxinas/análise , Proteínas/metabolismo , Desmame
7.
J Anim Physiol Anim Nutr (Berl) ; 94(5): 670-6, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20050950

RESUMO

Carbohydrates, which were not digested in the jejunum, will be fermented by micro-organisms to short chain fatty acids. These are transported by the monocarboxylate transporter 1 (MCT1) through the gut wall and serve as fuels for colonic cells. To deliver butyrate to the distal part of the intestine, inulin with a low precaecal digestibility was chosen as a coating material. Approximately 150 g of inulin-coated butyrate (containing 81 g butyrate) per day was fed to pigs (mean weight: 97 kg) over a period of 6 days after an adaptation period of 6 days with linear increasing amounts of butyrate. The following observations compared to controls were observed: (1) coating was digested microbially in the ileum; (2) MCT1-mRNA showed a higher expression in the ileum; (3) apoptosis was reduced in the ileum but mitosis was not changed; and (4) length of villi increased by approximately 25% in the ileum. Feeding inulin-coated butyrate resulted in an increased ileal surface. Delivery of butyrate to the colon requires a more resistant inulin-coating.


Assuntos
Ácido Butírico/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Íleo/metabolismo , Inulina/química , Inulina/metabolismo , Transportadores de Ácidos Monocarboxílicos/metabolismo , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Animais , Apoptose/efeitos dos fármacos , Ácido Butírico/química , Dieta/veterinária , Íleo/citologia , Mucosa Intestinal/anatomia & histologia , Mucosa Intestinal/efeitos dos fármacos , Masculino , Transportadores de Ácidos Monocarboxílicos/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Suínos
9.
J Surg Res ; 57(6): 711-7, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7996851

RESUMO

Acute hepatic injury initiates known cellular and molecular events for regeneration. In contrast, the molecular mechanisms of repair following chronic liver injuries have not been defined. Transforming growth factor alpha (TGF alpha) and hepatocyte growth factor (HGF) are hepatocyte mitogens whose in vivo expression in liver is central to the regulation of regeneration. To study the role of TGF alpha and HGF in liver injury and repair, we used a model of reversible biliary obstruction without a bilioenteric anastomosis. In rats, the common bile duct was obstructed either by a vessel loop suspended from the abdominal wall (LOOP) or by ligation and division (DLD). After 7 days of obstruction, animals were autopsied or were decompressed by subcutaneous release of the loop and then autopsied at 1, 2, 4, 7, or 10 days of postdecompression. Serum bilirubin (mg/dl) increased to 14.8 +/- 2.9 (DLD) and 10.3 +/- 3.0 (LOOP) (+/- SEM, NS, ANOVA) at 7 days of obstruction. Liver sections demonstrated equal ductal hyperplasia and collagen deposition after LOOP and DLD. Biliary decompression reversed bile duct proliferation and normalized bilirubin. Analysis of injured and repairing liver mRNA by ribonuclease protection assay showed that TGF alpha mRNA levels were not significantly altered by injury or during repair. HGF mRNA was elevated following obstruction and showed increased expression 1 day after decompression, peaking at 2 days of repair. This evidence of modulation of HGF during liver repair following chronic cholestatic injury suggests that HGF may have a role in cellular proliferation during repair or act as a compensatory growth factor during injury.


Assuntos
Fator de Crescimento de Hepatócito/fisiologia , Hepatopatias/fisiopatologia , Regeneração Hepática/fisiologia , Fator de Crescimento Transformador alfa/fisiologia , Animais , Divisão Celular/fisiologia , Doença Crônica , Colágeno/metabolismo , Fator de Crescimento de Hepatócito/análise , Fator de Crescimento de Hepatócito/genética , Fígado/química , Fígado/patologia , Fígado/fisiologia , Hepatopatias/metabolismo , Hepatopatias/patologia , Masculino , RNA Mensageiro/análise , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador alfa/análise , Fator de Crescimento Transformador alfa/genética
10.
Am J Pathol ; 143(6): 1574-8, 1993 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8256850

RESUMO

Extrahepatic biliary obstruction leads to bile duct epithelial cell proliferation. Somatostatin and its analogue, octreotide, have been shown to inhibit DNA synthesis and proliferation in hepatocytes. We investigated the effect of octreotide on the biliary epithelial cell proliferative responses to biliary obstruction. Male Sprague-Dawley rats underwent common bile duct ligation and subcutaneous injection of either saline or octreotide (6 micrograms/kg) twice daily for 7 days. Morphometric analysis of hepatocytes, bile duct epithelial cells, and periportal connective tissue was performed by computerized point counting. Hepatocyte volume was preserved with octreotide treatment, which also significantly decreased bile duct proliferation and periportal extracellular matrix deposition in response to biliary obstruction compared with saline treated, duct-ligated animals. These results indicate that octreotide prevents the morphological changes that accompany extrahepatic biliary obstruction.


Assuntos
Ductos Biliares Extra-Hepáticos/patologia , Colestase Extra-Hepática/patologia , Octreotida/farmacologia , Animais , Ductos Biliares Extra-Hepáticos/fisiopatologia , Divisão Celular/efeitos dos fármacos , Divisão Celular/fisiologia , Colestase Extra-Hepática/fisiopatologia , Matriz Extracelular/efeitos dos fármacos , Fibrose , Processamento de Imagem Assistida por Computador , Fígado/patologia , Fígado/fisiopatologia , Masculino , Ratos , Ratos Sprague-Dawley
11.
Am Heart J ; 126(4): 832-9, 1993 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8213439

RESUMO

Within 4 hours from the onset of symptoms in 61 patients with myocardial infarction and intravenous thrombolysis, ST segment elevation and creatine phosphokinase (CK) were measured every 15 minutes. Because of a premature enzyme rise, 42 patients (69%) were reperfused early (group 1). Immediately following reperfusion, eight of them (13%, group 1a) showed a marked increase of the ST elevation, in six of whom it was associated with clearly intensified chest pain. These patients exhibited a much steeper enzyme release and developed a larger enzymatic infarct size than patients (group 1b) without an additional transient ST elevation at reperfusion (CK peak 5.1 +/- 1.6 vs 9.8 +/- 4.2 hours after the start of thrombolysis; CK release 48 +/- 22 vs 19 +/- 18 IU/ml x hours, both p < 0.005). At angiography 11 days later, left ventricular function was significantly worse in group 1a than in group 1b (regional dyssynergic area 51 +/- 24 vs 21 +/- 18, global ejection fraction 39 +/- 14 vs 58 +/- 11; both p < 0.0005). During intravenous thrombolysis in acute myocardial infarction, some patients show a marked transient increase of the ST segment elevation at reperfusion. Their enzyme rise is very rapid and suggests a special reperfusion pattern. Most of these patients suffered large infarcts.


Assuntos
Anistreplase/administração & dosagem , Eletrocardiografia/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Estreptoquinase/administração & dosagem , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tipo Uroquinase/administração & dosagem , Adulto , Idoso , Cateterismo Cardíaco , Distribuição de Qui-Quadrado , Ensaios Enzimáticos Clínicos/estatística & dados numéricos , Angiografia Coronária , Diagnóstico Diferencial , Quimioterapia Combinada , Eletrocardiografia/estatística & dados numéricos , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Prognóstico , Fatores de Tempo
12.
Surgery ; 114(3): 532-7, 1993 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-7690161

RESUMO

BACKGROUND: Extrahepatic biliary obstruction initiates cholestasis, bile duct proliferation, periportal fibrosis, and, eventually, lethal biliary cirrhosis. Little is known about the genetic regulation of the cellular proliferation and differentiation that begins with the onset of bile duct obstruction. To focus this and future gene expression studies, we sought to determine the time frame for growth-related gene expression and questioned whether the in vivo expression of the protooncogenes H-ras and c-myc was altered after bile duct obstruction. METHODS: Female Fisher rats underwent ligation and division of the common bile duct or sham laparotomy. RESULTS: After obstruction, serum bilirubin and gamma-glutamyl transpeptidase rose to 24% and 30%, respectively, of maximum levels by 10 days after ligation. Morphologic evidence of proliferation of bile duct epithelial cells was first evident after 3 days. After hybridization to c-DNA probes, densitometry for H-ras and beta-actin revealed an immediate and parallel increase in steady-state levels of expression after 24 hours of cholestasis. Levels of c-myc messenger RNA were elevated during the first 3 days of cholestasis; however, at 7 and 10 days c-myc expression was depressed 16% and 60%, respectively. CONCLUSIONS: These profiles of expression show an oncogene response induced by early cholestasis. These data showed that elevations in H-ras and c-myc steady-state expression accompany the proliferative response of bile duct epithelial cells. Decreased levels of c-myc after initial elevation infer that ductal proliferation may continue independently of its steady-state expression, a response usually seen in vitro rather than in in vivo proliferation.


Assuntos
Envelhecimento/fisiologia , Colestase Extra-Hepática/fisiopatologia , Expressão Gênica , Fígado/metabolismo , Proto-Oncogenes , Actinas/genética , Animais , Bilirrubina/sangue , Northern Blotting , Colestase Extra-Hepática/patologia , Éxons , Feminino , Genes myc , Genes ras , Fígado/crescimento & desenvolvimento , Fígado/patologia , RNA/análise , RNA/isolamento & purificação , Ratos , Ratos Endogâmicos F344 , gama-Glutamiltransferase/sangue
13.
Z Kardiol ; 82(5): 271-8, 1993 May.
Artigo em Alemão | MEDLINE | ID: mdl-8328176

RESUMO

In 60 patients with acute myocardial infarction (pain < or = 4 h), we examined the value of ST segment monitoring in predicting early reperfusion, resulting left ventricular damage, and complications during hospitalization. Two criteria were determined by observation of the ST segment elevation during the first 4 h following initiation of thrombolysis. Early reperfusion was assessed by an early increase of the creatine phosphokinase (CK) with measurements taken in 15-min intervals. Cardiac catheterization was performed on days 11 +/- 5. According to the CK measurements, a reduction of the ST elevation > or = 50% within 1 h of serial ECG follow-up (ST criterion A) was the best indicator of early reperfusion (sensitivity 84%, specificity 80%, positive predictive value 93%, negative predictive value 67%). Simple comparison of the ST segment in the initial ECG and an ECG recorded 3 h later (ST criterion B) was less accurate according to the detection of early reperfusion (sensitivity 68%, specitivity 93%, positive predictive value 97%, negative predictive value 50%). However, contrary to ST criterion A, criterion B was useful in predicting subsequent left ventricular damage. Patients with a resolution of the initial ST elevation > or = 70%/3 h showed smaller regional wall motion abnormalities (dyssynergic area 21.3 +/- 20.3 vs 33.8 +/- 18.4, p < 0.01) and a better left ventricular ejection fraction (57.7 +/- 11.6 vs 50.2 +/- 12.6, p < 0.05). Patients with early reduction of the ST elevation following either criterion experienced fewer critical events (reinfarction, reischemia, death). In conclusion, the investigated criteria are useful in assessing reperfusion of the infarcted artery following thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Circulação Coronária/efeitos dos fármacos , Eletrocardiografia Ambulatorial/instrumentação , Infarto do Miocárdio/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/diagnóstico , Terapia Trombolítica , Função Ventricular Esquerda/efeitos dos fármacos , Anistreplase/administração & dosagem , Circulação Coronária/fisiologia , Creatina Quinase/sangue , Hemodinâmica/efeitos dos fármacos , Hemodinâmica/fisiologia , Humanos , Infusões Intravenosas , Infarto do Miocárdio/fisiopatologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Recidiva , Estreptoquinase/administração & dosagem , Ativador de Plasminogênio Tipo Uroquinase/administração & dosagem , Função Ventricular Esquerda/fisiologia
14.
Biol Neonate ; 64(6): 376-81, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8286563

RESUMO

The extracellular matrix is important in the cellular differentiation and morphogenesis of the lung. The basement membrane (BM), an integral part of the extracellular matrix, is composed primarily of type of IV collagen. The metabolism of type IV collagenase is important in remodeling of BM that occurs during growth. We examined the ontogeny of rat lung type IV collagenase mRNA expression, type IV collagenolytic activity and type IV collagen content during the perinatal period. In addition, the effect of prenatal glucocorticoid (GC) treatment on fetal lung type IV collagenase mRNA expression and type IV collagenolytic activity was studied. Lung polyadenylated RNA was extracted and subjected to Northern blot analysis and laser densitometry after hybridization with human type IV collagenase (approximately 72 kD) and rat actin cDNA probe. Type IV collagenolytic activity and type IV collagen concentration were quantitated by an enzymatic and a radioimmunoassay, respectively. While lung type IV collagenase mRNA to alpha-actin ratio and type IV collagenolytic activity were highest prior to birth (21-day fetus), the lung type IV collagen concentration was lowest at this time. Prenatal GC treatment did not influence type IV collagenase mRNA expression or the collagenolytic activity. A role for fetal lung type IV collagenase in preparation for the neonatal pulmonary vascular and/or alveolar adaptation is proposed.


Assuntos
Animais Recém-Nascidos/metabolismo , Colagenases/genética , Expressão Gênica , Pulmão/enzimologia , RNA Mensageiro/metabolismo , Animais , Betametasona/farmacologia , Colágeno/metabolismo , Feminino , Feto/efeitos dos fármacos , Feto/metabolismo , Pulmão/embriologia , Pulmão/crescimento & desenvolvimento , Troca Materno-Fetal , Gravidez , Ratos , Ratos Sprague-Dawley
15.
Surgery ; 110(2): 176-82; discussion 182-3, 1991 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-1858028

RESUMO

Partial hepatectomy (PH) initiates cellular signals for regeneration. Sequential expression of nuclear and cytosolic protooncogenes accompanies the restoration of normal liver function and architecture. Although cirrhosis is known to inhibit liver regeneration, the effects of noncirrhotic cholestasis on hepatocellular proliferation, differentiation, and regulatory gene expression are unknown. To examine this, 25 male Fisher rats underwent common bile duct ligation and division. A 47% +/- 5% PH was performed 10 days after common bile duct ligation and division when histologic analysis revealed cholestasis without cirrhosis. Despite early elevations of total hepatic DNA and RNA values, cholestatic livers demonstrated a significant threefold suppression of expected hepatocyte mitotic indexes 48 and 72 hours after PH, compared with livers after PH alone. Weight restoration in cholestatic livers was 11% +/- 5.2% compared with 40% +/- 4.3% in control livers (+/- SEM; p less than 0.001) 5 days after PH. Analysis of regenerating liver messenger RNA with complementary DNA probes revealed an abnormal, sustained elevation of K-ras expression in cholestatic livers through all time points. Cholestasis blunted but did not obliterate normal sequential elevations in H-ras found in control livers. The expression of c-myc was inhibited threefold with cholestasis 72 hours after PH. These results are the first indication that cholestasis alone inhibits hepatocyte proliferation and the expression of c-myc that normally precedes the first wave of mitosis. This implies that cholestasis without cirrhosis may alter programmed liver gene expression, inhibiting normal hepatic regeneration.


Assuntos
Colestase/fisiopatologia , Regulação da Expressão Gênica , Regeneração Hepática/fisiologia , Fígado/fisiopatologia , Animais , Northern Blotting , Sondas de DNA , Modelos Animais de Doenças , Eletroforese em Gel de Ágar , Genes myc , Genes ras , Hepatectomia , Cirrose Hepática/fisiopatologia , Masculino , Índice Mitótico/fisiologia , Tamanho do Órgão , RNA Mensageiro/fisiologia , Ratos , Ratos Endogâmicos F344 , Fatores de Tempo
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