RESUMO
Quinolinyl chalcones were synthesized and evaluated for their inhibition of the Plasmodium falciparum cystein protease falcipain and their activity against cultured P. falciparum parasites. They were also tested for in vivo efficacy in a rodent P. berghei model. Their activity against falcipain and as antimalarials was moderate, but antimalarial activity was probably not due to the inhibition of falcipain and may follow a different mechanism. 1-(2,4-Dichlorophenyl)-3-[3-(2-chloro-6,7-dimethoxiquinolinyl)]-2-propen-1-one 3j was the most promising compound among those here reported (IC50 19.0 microM).
Assuntos
Antimaláricos/síntese química , Antimaláricos/farmacologia , Chalcona/análogos & derivados , Chalcona/farmacologia , Quinolonas/farmacologia , Animais , Antimaláricos/química , Antimaláricos/uso terapêutico , Chalcona/síntese química , Chalcona/uso terapêutico , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Endopeptidases/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Malária/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Plasmodium berghei/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Quinolonas/síntese química , Quinolonas/química , Quinolonas/uso terapêutico , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: To evaluate intrahepatic vascular and biliary anatomy of the left lateral segment (LLS) as applied to living-donor and split-liver transplantation. SUMMARY BACKGROUND DATA: Living-donor and split-liver transplantation are innovative surgical techniques that have expanded the donor pool. Fundamental to the application of these techniques is an understanding of intrahepatic vascular and biliary anatomy. METHODS: Pathologic data obtained from cadaveric liver corrosion casts and liver dissections were clinically correlated with the anatomical findings obtained during split-liver, living-donor, and reduced-liver transplants. RESULTS: The anatomical relation of the left bile duct system with respect to the left portal venous system was constant, with the left bile duct superior to the extrahepatic transverse portion of the left portal vein. Four specific patterns of left biliary anatomy and three patterns of left hepatic venous drainage were identified and described. CONCLUSIONS: Although highly variable, the biliary and hepatic venous anatomy of the LLS can be broadly categorized into distinct patterns. The identification of the LLS duct origin lateral to the umbilical fissure in segment 4 in 50% of cast specimens is significant in the performance of split-liver and living-donor transplantation, because dissection of the graft pedicle at the level of the round ligament will result in separate ducts from segments 2 and 3 in most patients, with the further possibility of an anterior segment 4 duct. A connective tissue bile duct plate, which can be clinically identified, is described to guide dissection of the segment 2 and 3 biliary radicles.
Assuntos
Sistema Biliar/anatomia & histologia , Transplante de Fígado/métodos , Fígado/irrigação sanguínea , Doadores Vivos , Adolescente , Cadáver , Criança , Pré-Escolar , Feminino , Veias Hepáticas/anatomia & histologia , Humanos , Lactente , Recém-Nascido , Masculino , Veia Porta/anatomia & histologia , Estudos RetrospectivosRESUMO
Reduced-organ liver transplantation for children is effective in lowering pretransplantation morbidity and mortality. Improvements in surgical technique have reduced vascular complications; however, biliary complications continue to account for significant posttransplantation morbidity. This investigation chronicles the incidence and type of biliary complications encountered with reduced-organ liver transplantation. Retrospective review of reduced-organ liver recipients over a 59-month period was performed, and biliary complications were classified as (1) missed biliary radicle, (2) anastomotic leak requiring revision, and (3) biliary stricture. From July 1992 to May 1997, 42 children received reduced-organ grafts: 32 living-donor, 8 cadaveric-reduced, 1 split-liver, and 1 auxiliary orthotopic liver transplant. Of the 42 grafts, 41 were Couinaud segments II/III and 1 was segments II/III/IV. Ten biliary complications were identified in 9 recipients (24%). Biliary complications included parenchymal radicle leaks, 5 (50%); biliary strictures, 3 (30%); and anastomotic leaks, 2 (20%). Although technical advances have reduced the incidence of biliary complications secondary to organ ischemia, parenchymal radicle leaks continue to be a source of morbidity for reduced-organ recipients. Planned exploration on posttransplantation day 7 was performed on the most recent 26 of the 42 total reduced-organ procedures as a mechanism to identify and treat early technical complications. Planned exploration as a routine component of reduced-organ transplantation has yielded a 15% incidence of discovered parenchymal leaks and a 5% incidence of discovered anastomotic leaks. This series underscores the necessity for improved anatomical studies to correctly identify duct territories and the development of accurate noninvasive methods to assess the biliary system preoperatively and intraoperatively in the application of reduced-organ liver transplantation.
Assuntos
Doenças Biliares/etiologia , Transplante de Fígado/efeitos adversos , Doenças Biliares/epidemiologia , Doenças Biliares/cirurgia , Criança , Pré-Escolar , Feminino , Seguimentos , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto , Humanos , Incidência , Lactente , Recém-Nascido , Transplante de Fígado/mortalidade , Masculino , Reoperação , Estudos Retrospectivos , São Francisco/epidemiologia , Taxa de SobrevidaRESUMO
Acridinediones have previously been shown to have potent antimalarial activity. A series of sulfur isosteres of acridinediones have been synthesized and evaluated for their inhibition of the Plasmodium falciparum cysteine protease falcipain and for their antimalarial activity. A number of these phenothiazines inhibited falcipain and demonstrated activity against cultured P. falciparum parasites at low micromolar concentrations. We propose that the compounds exerted their antimalarial effects by two mechanisms, one of which involves the inhibition of falcipain and a consequent block in parasite degradation of hemoglobin. These compounds and related phenothiazines are worthy of further study as potential antimalarial agents.
Assuntos
Antimaláricos/síntese química , Cisteína Endopeptidases/metabolismo , Inibidores de Cisteína Proteinase/síntese química , Fenotiazinas/química , Plasmodium falciparum/enzimologia , Animais , Antimaláricos/farmacologia , Células Cultivadas , Inibidores de Cisteína Proteinase/farmacologia , Fenotiazinas/farmacologia , Plasmodium falciparum/efeitos dos fármacosRESUMO
Seventy-three medical records of pediatric patients admitted for acetaminophen overdose were reviewed. Twenty-eight patients (39%) had severe liver toxic effects, and six of them underwent liver transplantation. Multiple miscalculated overdoses given by parents, with delay in therapy, are risk factors and the major cause of overdose in children 10 years of age or younger.
Assuntos
Acetaminofen/efeitos adversos , Analgésicos não Narcóticos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Acetaminofen/administração & dosagem , Adolescente , Analgésicos não Narcóticos/administração & dosagem , California/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/terapia , Criança , Pré-Escolar , Overdose de Drogas/epidemiologia , Overdose de Drogas/etiologia , Overdose de Drogas/terapia , Feminino , Humanos , Lactente , Transplante de Fígado , Masculino , Erros de Medicação/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
The transjugular intrahepatic portosystemic shunt procedure is an accepted treatment for adults with complications of portal hypertension. We performed a retrospective review of all pediatric TIPS placements performed at the University of California, San Francisco between 1990 and 1996. Twelve procedures were attempted in nine children, with a mean age (+/- SD) of 9.4 +/- 3.9 years (range, 5 to 15 years) and a mean weight of 31 +/- 18 kg (range, 16 to 70 kg). The indications for TIPS placement were portal hypertension complicated by chronic variceal hemorrhage not controlled with sclerotherapy (n = 7) and hypersplenism with thrombocytopenia (n = 2). TIPS placement was successfully completed initially in seven of nine (78%) patients. Unfavorable vascular anatomy was the cause of failure in two cases. The seven patients who underwent successful TIPS placement were followed up for an average of 136 days (range, 1 to 800 days); two still have patent shunts, three underwent liver transplantation, one had a splenorenal shunt after stenosis, and one died of underlying liver disease. Variceal bleeding was controlled in four of five patients who successfully underwent TIPS placement. Shunt occlusion occurred in four patients; patency was restored by transjugular shunt revision in three, and a splenorenal shunt was performed in one.
Assuntos
Hipertensão Portal/cirurgia , Derivação Portossistêmica Transjugular Intra-Hepática , Adolescente , Criança , Pré-Escolar , Doença Crônica , Desenho de Equipamento , Varizes Esofágicas e Gástricas/complicações , Feminino , Seguimentos , Hemorragia Gastrointestinal/complicações , Humanos , Hipertensão Portal/complicações , Masculino , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Derivação Portossistêmica Transjugular Intra-Hepática/instrumentação , Reoperação , Estudos Retrospectivos , Trombocitopenia/complicações , Grau de Desobstrução VascularRESUMO
An infant with intrauterine supraventricular tachycardia and fetal hydrops, successfully treated with administration of flecainide acetate to the mother had conjugated hyperbilirubinemia shortly after birth. An extensive evaluation failed to disclose a known cause. We believe that in utero exposure to flecainide acetate resulted in conjugated hyperbilirubinemia in this infant.
Assuntos
Doenças Fetais/tratamento farmacológico , Flecainida/efeitos adversos , Hidropisia Fetal/tratamento farmacológico , Icterícia Neonatal/induzido quimicamente , Taquicardia/tratamento farmacológico , Feminino , Flecainida/administração & dosagem , Humanos , Lactente , Recém-Nascido , Masculino , Troca Materno-Fetal , GravidezRESUMO
To determine whether arterial and capillary values for bilirubin agree in neonates, we analyzed 35 simultaneously sampled capillary and arterial specimens from 13 infants. We found a high correlation between arterial and capillary bilirubin values (r = 0.993). We conclude that arterial bilirubin samples may be substituted for capillary samples in newborn infants.
Assuntos
Bilirrubina/sangue , Coleta de Amostras Sanguíneas/métodos , Artérias , Capilares , Cateteres de Demora , Humanos , Recém-Nascido , Recém-Nascido PrematuroRESUMO
We used a highly specific method, alkaline methanolysis-high performance liquid chromatography, for determining the concentration and patterns of the unconjugated and esterified bilirubin fractions in the sera of pediatric patients with hepatobiliary disease. Bilirubin-protein conjugates were assayed using a new method that selectively removes bilirubin reversibly bound to protein, allowing measurement of the tightly bound bilirubin-protein conjugates by use of a diazo method. Fifty-two serum samples from children with varying bilirubin concentrations and diagnoses were studied. Whereas no conjugated pigment was detectable in the serum samples of healthy children or in individuals with Gilbert syndrome or Crigler-Najjar syndrome, bilirubin monoester and diester conjugates and bilirubin-protein conjugates were present in the sera of children with cholestatic liver disease, and accounted for 69% +/- 15% of the total bilirubin in these samples. Bilirubin fractional analysis was incapable of differentiating extrahepatic biliary obstruction from hepatocellular disease, because of overlap between the groups. The presence of bilirubin-protein conjugates in serum always coincided with detection of bilirubin monoester and diester conjugates. The distribution of bilirubin and its conjugates in sera provides a sensitive, although nonspecific, measure of hepatic disease.
Assuntos
Doenças Biliares/sangue , Bilirrubina/sangue , Hepatopatias/sangue , Adolescente , Adulto , Bilirrubina/análise , Criança , Pré-Escolar , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Hiperbilirrubinemia Hereditária/sangue , Lactente , MasculinoRESUMO
Se revisaron 50 pacientes con Miastenia Gravis que consultaron al Hospital Universitario de Caracas durante los anos 1971-1980. Se practica una revision de los sintomas y signos oculares que presentaron Se realiza un analisis fisiopatologicos