RESUMO
BACKGROUND: Total gastrectomy for gastric cancer is associated with excessive weight loss and decreased calorie intake. Nutritional support using eicosapentaenoic acid modulates immune function and limits catabolism in patients with advanced cancer, but its impact in the perioperative period is unclear. METHODS: This was a randomized phase III clinical trial of addition of eicosapentaenoic acid-rich nutrition to a standard diet in patients having total gastrectomy for gastric cancer. Patients were randomized to either a standard diet or standard diet with oral supplementation of an eicosapentaenoic acid (ProSure®), comprising 600 kcal with 2·2 g eicosapentaenoic acid, for 7 days before and 21 days after surgery. The primary endpoint was percentage bodyweight loss at 1 and 3 months after surgery. RESULTS: Of 127 eligible patients, 126 were randomized; 124 patients (61 standard diet, 63 supplemented diet) were analysed for safety and 123 (60 standard diet, 63 supplemented diet) for efficacy. Across both groups, all but three patients underwent total gastrectomy with Roux-en-Y reconstruction. Background factors were well balanced between the groups. Median compliance with the supplement in the immunonutrition group was 100 per cent before and 54 per cent after surgery. The surgical morbidity rate was 13 per cent in patients who received a standard diet and 14 per cent among those with a supplemented diet. Median bodyweight loss at 1 month after gastrectomy was 8·7 per cent without dietary supplementation and 8·5 per cent with eicosapentaenoic acid enrichment (P = 0·818, adjusted P = 1·000). Similarly, there was no difference between groups in percentage bodyweight loss at 3 months (P = 0·529, adjusted P = 1·000). CONCLUSION: Immunonutrition based on an eicosapentaenoic acid-enriched oral diet did not reduce bodyweight loss after total gastrectomy for gastric cancer compared with a standard diet. Registration number: UMIN000006380 ( http://www.umin.ac.jp/).
Assuntos
Ácido Eicosapentaenoico/administração & dosagem , Gastrectomia/métodos , Neoplasias Gástricas/cirurgia , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Peso Corporal , Suplementos Nutricionais , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Apoio Nutricional/métodos , Assistência Perioperatória/métodos , Neoplasias Gástricas/dietoterapia , Adulto JovemRESUMO
OBJECTIVE: We evaluated the effect of a reduction in the systemic ratio of n-6:n-3 polyunsaturated fatty acids (PUFAs) on changes in inflammation, glucose metabolism, and the idiopathic development of knee osteoarthritis (OA) in mice. We hypothesized that a lower ratio of n-6:n-3 PUFAs would protect against OA markers in cartilage and synovium, but not bone. DESIGN: Male and female fat-1 transgenic mice (Fat-1), which convert dietary n-6 to n-3 PUFAs endogenously, and their wild-type (WT) littermates were fed an n-6 PUFA enriched diet for 9-14 months. The effect of gender and genotype on serum PUFAs, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and glucose tolerance was tested by 2-factor analysis of variance (ANOVA). Cortical and trabecular subchondral bone changes were documented by micro-focal computed tomography (CT), and knee OA was assessed by semi-quantitative histomorphometry grading. RESULTS: The n-6:n-3 ratio was reduced 12-fold and 7-fold in male and female Fat-1 mice, respectively, compared to WT littermates. IL-6 and TNF-α levels were reduced modestly in Fat-1 mice. However, these systemic changes did not reduce osteophyte development, synovial hyperplasia, or cartilage degeneration. Also the fat-1 transgene did not alter subchondral cortical or trabecular bone morphology or bone mineral density. CONCLUSIONS: Reducing the systemic n-6:n-3 ratio does not slow idiopathic changes in cartilage, synovium, or bone associated with early-stage knee OA in mice. The anti-inflammatory and anti-catabolic effects of n-3 PUFAs previously reported for cartilage may be more evident at later stages of disease or in post-traumatic and other inflammatory models of OA.
Assuntos
Artrite Experimental/prevenção & controle , Gorduras Insaturadas na Dieta/uso terapêutico , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Osteoartrite/prevenção & controle , Animais , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Biomarcadores/metabolismo , Glicemia/metabolismo , Peso Corporal , Cartilagem Articular/patologia , Citocinas/sangue , Ácidos Graxos Ômega-6/administração & dosagem , Ácidos Graxos Ômega-6/uso terapêutico , Feminino , Masculino , Camundongos Transgênicos , Osteoartrite/metabolismo , Osteoartrite/patologia , Membrana Sinovial/patologia , Tíbia/patologiaRESUMO
OBJECTIVE: Sepsis is a major cause of adult respiratory distress syndrome. In this study, we evaluated the effect of FR167653, which is a potent suppressant of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 production, on lipopolysaccharide (LPS)-induced lung injury and lethality in rats, and we examined the involvement of p38 mitogen-activated protein (MAP) kinase in the action of FR167653. DESIGN: Prospective, randomized study. SETTING: Animal research facility in a university. SUBJECTS: Male Sprague-Dawley rats weighing 200-270 g. INTERVENTIONS: All the animals were assigned to one of the following four groups: control group, FR-only group, LPS-only group, and LPS/FR group. Animals in the LPS-only and LPS/FR groups received 6 mg/kg of LPS intravenously. The animals in the FR-only and LPS/FR groups also received an infusion of FR167653 at 0.2 mg x kg(-1) x hr(-1), commencing 30 mins before the LPS (or vehicle) injection and continuing for 5.5 hrs. MEASUREMENTS AND MAIN RESULTS: LPS significantly induced the accumulation of pulmonary neutrophils and lung edema, both of which were significantly attenuated by treatment with FR167653. FR167653 also significantly decreased the LPS-induced lethality. Histologically, tissue damage was milder in the LPS/FR group than in the LPS-only group. Serum concentrations of TNF-alpha and IL-1beta and plasma concentrations of thromboxane B2 were all suppressed in the LPS/FR group compared with the LPS-only group. Western blot analysis revealed that FR167653 inhibited the phosphorylation of p38 MAP kinase in lung tissues. CONCLUSIONS: FR167653 administration decreased serum TNF-alpha and IL-1beta concentrations, which was associated with decreased lung injury and lethality. The mechanism responsible for the decreased TNF-alpha and IL-1 may be related to the inhibitory effect of FR167653 on p38 MAP kinase activation.
Assuntos
Modelos Animais de Doenças , Infecções por Escherichia coli/complicações , Escherichia coli , Imunossupressores/uso terapêutico , Interleucina-1/antagonistas & inibidores , Lipopolissacarídeos , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/microbiologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Avaliação Pré-Clínica de Medicamentos , Imunossupressores/química , Imunossupressores/imunologia , Interleucina-1/sangue , Interleucina-1/imunologia , Pulmão/química , Masculino , Proteínas Quinases Ativadas por Mitógeno/análise , Estudos Prospectivos , Pirazóis/química , Pirazóis/imunologia , Piridinas/química , Piridinas/imunologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Síndrome do Desconforto Respiratório/imunologia , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/mortalidade , Análise de Sobrevida , Tromboxano B2/sangue , Fatores de Tempo , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
Stabilization of w/o/w emulsion and its application to transcatheter arterial embolization (TAE) therapy are reviewed. W/o/w emulsion was stabilized by making inner aqueous phase hypertonic, addition of chitosan in inner phase, and techniques of phase-inversion with porous membrane. Lipiodol w/o/w emulsion for TAE therapy was prepared by using a two-step pumping emulsification procedure. The procedure is so easy that the emulsion could be prepared even during the surgical operation. The deposition after hepatic arterial administration of the emulsion was detected by an X-ray CT scanner. The concentration of epirubicin hydrochloride (EPI) in liver was increased and its residence was prolonged by encapsulating it in the w/o/w emulsion. The toxic effects of EPI and lipiodol on the normal hepatic cells were reduced. The w/o/w emulsion prepared by us is a suitable formulation for the TAE therapy.
Assuntos
Quimioembolização Terapêutica , Emulsões , Animais , Quitina/análogos & derivados , Quitina/farmacologia , Quitosana , Estabilidade de Medicamentos , Epirubicina/administração & dosagem , Artéria Hepática , Humanos , Óleo Iodado/administração & dosagem , Óleo Iodado/toxicidade , Neoplasias Hepáticas Experimentais/tratamento farmacológico , RatosRESUMO
BACKGROUND: Activated neutrophils are reported to be closely involved in ischemia-reperfusion injury after lung transplantation. We investigated the beneficial effects of a new recombinant specific neutrophil elastase inhibitor, ONO-5046.Na, and an extracorporeal-type granulotrap (G-1) column on ischemia-reperfusion lung injury, by using an in situ warm lung ischemia model in dogs. METHODS: Warm ischemia was induced for 3 hours by clamping the pulmonary arteries and veins. The left main bronchus was bisected and reanastomosed prior to reperfusion. The left lung was collapsed for 3 hours. A total of 27 adult mongrel dogs were divided into three groups: the control group (n = 9) treated with a saline vehicle; the ONO group (n = 9), in which ONO-5046.Na was continuously administrated from before induced ischemia and to ending 2 hours after reperfusion; and the G-1 group (n = 9), in which a G-1 column was applied for 90 minutes starting 30 minutes before reperfusion under passive bypass support. RESULTS: Circulating neutrophils in the G-1 group decreased significantly (p<.05) compared to preischemia, and significantly decreased compared with the other groups after reperfusion. Oxygenation was improved actually and pulmonary vascular resistance was kept lower level after the administration of ONO-5046.Na. The increase of lung weight was significantly ameliorated in both the G-1 and ONO groups. In the histopathological study, lungs from the control group demonstrated diffuse alveolar edema, neutrophil infiltration, massive alveolar exudate and hemorrhage, and thickening of the interstitium. Lungs from the G-1 group showed mild swelling of the alveolar wall and neutrophil infiltration. Lungs from the ONO group showed virtually no abnormalities. CONCLUSION: This study demonstrated that a neutrophil elastase inhibitor and neutrophil depletion prevented lung reperfusion injury. These treatments may prevent ischemia and reperfusion injury in lung transplantation.
Assuntos
Glicina/análogos & derivados , Leucaférese/instrumentação , Elastase de Leucócito/antagonistas & inibidores , Pulmão/irrigação sanguínea , Traumatismo por Reperfusão/terapia , Inibidores de Serina Proteinase/uso terapêutico , Sulfonamidas/uso terapêutico , Animais , Cães , Avaliação Pré-Clínica de Medicamentos , Glicina/farmacologia , Glicina/uso terapêutico , Hemodinâmica/efeitos dos fármacos , Leucaférese/métodos , Pulmão/patologia , Neutrófilos , Tamanho do Órgão/efeitos dos fármacos , Distribuição Aleatória , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Inibidores de Serina Proteinase/farmacologia , Sulfonamidas/farmacologia , Fatores de TempoRESUMO
sigma Receptor antagonists may be effective antipsychotic drugs that do not induce motor side effects caused by ingestion of classical drugs such as haloperidol. We obtained evidence that 1-(2-dipropylaminoethyl)-4-methoxy-6H-dibenzo[b,d]pyran hydrochloride 2a had selective affinity for sigma receptor over dopamine D2 receptor. This compound was designed to eliminate two bonds of apomorphine 1 to produce structural flexibility for the nitrogen atom and to bridge two benzene rings with a -CH2O- bond to maintain the planar structure. In light of the evidence, N, N-dipropyl-2-(4-methoxy-3-benzyloxylphenyl)ethylamine hydrochloride 10b was designed. Since compound 10b had eliminated a biphenyl bond of 6H-dibenzo[b,d]pyran derivative 2a, it might be more released from the rigid structure of apomorphine 1 than compound 2a. The chemical modification of compound 10b led to the discovery that N, N-dipropyl-2- [4-methoxy-3-(2-phenylethoxyl)phenyl]ethylamine hydrochloride 10g (NE- 100), the best compound among arylalkoxyphenylalkylamine derivatives 3, had a high and selective affinity for sigma receptor and had a potent activity in an animal model when the drug was given orally. We report here the design, synthesis, structure-activity relationships, and biological characterization of novel arylalkoxyphenylalkylamine derivatives 3.
Assuntos
Anisóis/síntese química , Antipsicóticos/síntese química , Propilaminas/síntese química , Receptores sigma/metabolismo , Animais , Anisóis/química , Anisóis/farmacologia , Antipsicóticos/química , Antipsicóticos/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Técnicas In Vitro , Ligantes , Masculino , Camundongos , Camundongos Endogâmicos ICR , Propilaminas/química , Propilaminas/farmacologia , Ensaio Radioligante , Ratos , Ratos Wistar , Receptores de Dopamina D2/metabolismo , Comportamento Estereotipado/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
We investigated the effects of bucillamine and N-acetyl-L-cysteine (NAC) on cytokine production and CIA. Bucillamine and NAC inhibited NF-kappaB activation and tumour necrosis factor-alpha (TNF-alpha) mRNA expression in human monocytic leukaemia cell line THP-1, and cytokine production from monocyte cell lines at concentrations >10-3 M. They also inhibited cytokine production and CIA in mice at a dose of 500 mg/kg. These results suggest that NF-kappaB inhibitors such as bucillamine and NAC may inhibit cytokine-related diseases, including arthritis.
Assuntos
Acetilcisteína/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Artrite Experimental/tratamento farmacológico , Colágeno , Cisteína/análogos & derivados , Animais , Anticorpos/sangue , Artrite Experimental/induzido quimicamente , Colesterol/sangue , Colágeno/imunologia , Cisteína/farmacologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos DBA , NF-kappa B/metabolismo , Fosfolipídeos/sangue , Ratos , Ratos Wistar , Triglicerídeos/sangue , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/metabolismoRESUMO
The effects of perfluorooctanoic acid (PFOA) on the levels of lipids in liver and serum were compared between mice fed a diet supplemented with soy bean oil (SO), perilla oil (PO), or fish oil (FO) for 4 weeks. Hepatic content of triglyceride (TG) was significantly lower in the mice fed the FO diet than that in the mice fed either the SO or the PO diet. The treatment with PFOA caused a marked accumulation of TG in the livers of SO-fed and PO-fed mice (seven- and twofold over their respective controls), whereas a level of TG remained low in the mice fed the FO diet. Incorporation in vivo of [3H]glycerol revealed that FO-feeding reduced synthesis of TG in the liver. The administration of PFOA increased the incorporation of [3H]glycerol into hepatic phospholipid (PL) regardless of the dietary oil, while synthesis of hepatic TG from [3H]glycerol was not altered by the treatment with PFOA. Serum level of TG was reduced by the administration of PFOA to the mice fed either the SO diet or the PO diet, while no change in the level was observed in the mice fed the FO diet. These results suggest that the accumulation of TG in the livers of PFOA-treated mice is due to the inhibition of the secretion of TG into circulation. PFOA-induced hepatic accumulation of TG is prevented by the feeding of the FO diet which inhibits TG formation. Among three dietary oils, FO-feeding alone prevented the PFOA-caused accumulation of TG in the liver. The importance of docosahexaenoic acid (22:6(n - 3)) is discussed in relation to the prevention of fatty liver induced by chemicals.
Assuntos
Caprilatos/toxicidade , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/prevenção & controle , Óleos de Peixe/uso terapêutico , Fluorocarbonos/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Ácidos Graxos/análise , Fígado Gorduroso/dietoterapia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Microcorpos/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Fosfolipídeos/biossíntese , Fosfolipídeos/sangue , Óleos de Plantas/uso terapêutico , Óleo de Soja/uso terapêutico , Triglicerídeos/biossíntese , Triglicerídeos/sangue , Ácido alfa-Linolênico/uso terapêuticoRESUMO
Eighteen patients with invasive periadventitial tissue (T4) or distant lymph node metastatic (M1,LYM) squamous cell carcinoma were entered into a pilot study of neoadjuvant chemotherapy with etoposide (50 mg/m2/day, days 1-5), leucovorin (30 mg/body/day, days 2-5), 5-fluorouracil (5-FU; 400 mg/m2/day, days 2-5) and cisplatin (100 mg/m2/day, day 1) (ELFP). The overall response rate was 56%. The response rates in the T4 tumor and M1,LYM patients were 56 and 50%, respectively. Radical esophagectomies were performed on six of 17 patients who had completely recovered from the chemotherapy, a resectability of 35%. Histologically, the primary tumor was moderately to slightly effective, and the lymph nodes markedly to moderately effective. Histologic responses in the lymph nodes were different from those in the primary tumors and in each node. There were four chemo-surgically related deaths. Median survival times in responding and non-responding patients were nine and three months, respectively. In conclusion, neoadjuvant chemotherapy with ELFP appears to be effective against esophageal squamous cell cancer with periadventitial tissue invasion or distant lymph node metastasis. Chemo-surgically related deaths were however, 22%, showing neoadjuvant chemotherapy to necessitate extremely careful attention to the medical and surgical management of patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Idoso , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Esquema de Medicação , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Esofagectomia , Etoposídeo/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Taxa de SobrevidaRESUMO
BACKGROUND: Dose and injection times have not previously been determined for subcutaneously administered recombinant human erythropoietin that would allow sufficient deposition of blood for autologous use in cardiac surgery. STUDY DESIGN AND METHODS: A double-blind, multicenter trial of placebo (Group 1) and recombinant human erythropoietin at 12,000 IU (Group 2) and at 24,000 IU (Group 3) was performed on 114 patients at 26 institutions to determine the dosage that would permit an 800-g preoperative deposit of blood for autologous use. The test drug was administered subcutaneously on Days 21, 14, and 7 prior to operation, and oral iron preparations at 200 mg per day were given for 21 days. There were 28 patients in Group 1, 28 in Group 2, and 30 in Group 3, with 28 excluded for a violation of the protocol. RESULTS: Blood was safely drawn 14 and 7 days before operation from 22 patients in Group 1 (78.6%), from 26 in Group 2 (92.9%), and from all patients in Group 3 (p = 0.018). The hemoglobin level on the day before operation decreased by 1.1 +/- 1.1 g per dL (11 +/- 11 g/L) in Group 1 and by 0.9 +/- 0.9 g per dL (9 +/- 9 g/L) in Group 2 and rose by 0.1 +/- 0.8 g per dL (1 +/- 8 g/L) in Group 3, compared to initial levels. Allogeneic blood transfusion could be avoided in 62, 89, and 90 percent of Group 1, 2, and 3 patients, respectively (p = 0.013). CONCLUSION: The present study shows that subcutaneously administered recombinant human erythropoietin at a dose of 24,000 IU per week for 3 weeks is effective and sufficient to allow the safe deposition of 800 g of blood for autologous use in cardiac surgery.
Assuntos
Transfusão de Sangue Autóloga , Procedimentos Cirúrgicos Cardíacos , Eritropoetina/uso terapêutico , Doadores de Sangue , Método Duplo-Cego , Eritropoetina/administração & dosagem , Eritropoetina/sangue , Feminino , Ferritinas/sangue , Hemoglobinas/metabolismo , Humanos , Injeções Subcutâneas , Ferro/sangue , Japão , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêuticoRESUMO
The manipulation of 20:4(n - 6) contents in phosphatidylcholine of liver and kidney of rats by dietary oils and p-chlorophenoxyisobutyric acid (clofibric acid) as well as the effects on the formation of prostaglandin E2 in kidney were studied. Three groups of rats were fed diets that contained either safflower oil (SO) or perilla oil (PO) or fish oil (FO) for 1 week. Each dietary group was divided into two groups. One group continued the same diet for another 1 week; the second group continued the same diet and received subcutaneous injections of clofibric acid once a day for 1 week. The content of 20:4(n - 6) in hepatic phosphatidylcholine was markedly lowered by feeding either FO or PO and was further decreased by the administration of clofibric acid. Feeding either FO or PO lowered the content of 20:4(n - 6) in hepatic phosphatidylethanolamine, whereas clofibric acid increased it. The decrease in the level of 20:4(n - 6) in serum phospholipid was produced by feeding either FO or PO and by the administration of clofibric acid as well. There was a high correlation for the levels of 20:4(n - 6) between hepatic phosphatidylcholine and serum phospholipid. The changes brought about by dietary oils and clofibric acid in renal phosphatidylcholine was similar to those observed in liver. The content of 20:4(n - 6) in renal phosphatidylcholine was highly correlated with the level of 20:4(n - 6) in serum phospholipid. Other phospholipids in kidney responded less sensitively to the manipulation by dietary oils and clofibric acid. These results suggest that the level of 20:4(n - 6) in renal phosphatidylcholine is regulated by the level of 20:4(n - 6) in hepatic phosphatidylcholine through the changes in serum level of 20:4(n - 6). Formation of prostaglandin E2 in kidney slices was dependent on the content of 20:4(n - 6) in renal phosphatidylcholine.
Assuntos
Ácido Araquidônico/análise , Ácido Clofíbrico/farmacologia , Dinoprostona/biossíntese , Óleos de Peixe/farmacologia , Fosfatidilcolinas/química , Óleo de Cártamo/farmacologia , Ácido alfa-Linolênico , Animais , Rim/efeitos dos fármacos , Rim/metabolismo , Ácidos Linoleicos/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Fosfatidilcolinas/sangue , Fosfolipídeos/sangue , Fosfolipídeos/química , Óleos de Plantas/farmacologia , Ratos , Ratos WistarRESUMO
Rats and mice were fed a diet, prepared with soybean oil (SO), perilla oil (PO) or fish oil (FO), for 4 weeks. Compared with the groups of SO-feeding, FO-feeding increased content of eicosapentaenoic acid (20:5 n-3), docosapentaenoic acid (22:5 n-3) and docosahexaenoic acid (22:6 n-3) and PO-feeding elevated the content of alpha-linolenic acid (18:3 n-3), 20:5 n-3 and 22:5 n-3 or hepatic lipids of both rats and mice. FO-feeding increased the activity of peroxisomal beta-oxidation in the livers of both rats and mice. The activities of peroxisomal beta-oxidation in rats and mice that were fed FO diet at a high fat (40% of energy) concentration corresponded to 20% and 30%, respectively, of the maximum activities induced by peroxisome proliferators (4-chlorophenoxyisobutyric acid or perfluorooctanoic acid). To a lesser extent, PO-feeding elevated this activity too. There were significant correlations between peroxisomal beta-oxidation activity and the content of either 20:5 n-3, 22:5 n-3 or 22:6 n-3 in hepatic lipids. FO-feeding decreased effectively serum level of cholesterol of both rats and mice. The reduction in serum cholesterol by feeding PO was less pronounced than that observed with FO-feeding. A high correlation was found between 22:6 n-3 content in hepatic lipids and serum concentration of cholesterol. Although FO-feeding lowered the level of circulating triacylglycerol, PO-feeding produced no change. No substantial correlation was observed between the hepatic content of n-3 fatty acid and the concentration of serum triacylglycerol.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Gorduras na Dieta/farmacologia , Óleos de Peixe/farmacologia , Ácidos Linoleicos/farmacologia , Metabolismo dos Lipídeos , Fígado/efeitos dos fármacos , Microcorpos/metabolismo , Óleos de Plantas/farmacologia , Ácido alfa-Linolênico , Animais , Ácidos Graxos/metabolismo , Lipídeos/sangue , Fígado/metabolismo , Masculino , Camundongos , Oxirredução , Ratos , Ratos WistarRESUMO
The thalamic zone mediating the rhythmic burst activity related to the contralateral tremor was studied by microelectrodes in clinical cases with tremor and in monkeys with experimental tremor. The rhythmic burst time-locked with the tremor was found in a restricted area of the ventrointermedius nucleus (Vim) in humans and also in VPLo nucleus in monkeys. In both cases, only the lateral and ventrocaudal part of each nucleus, which was defined as the kinesthetic zone, was involved. A possible tremor-mediating neural circuit is postulated.
Assuntos
Haplorrinos/fisiologia , Tálamo/fisiopatologia , Tremor/fisiopatologia , Animais , Potenciais Evocados/fisiologia , Humanos , MicroeletrodosRESUMO
In nine patients with central (thalamic) pain after stroke, X-CT, MRI, PET scan and intraoperative thalamic microrecordings were performed. The PET studies made use of Sokoloff's method with 18FDG and a steady-state method with C15O2-15O2. CT scan and MRI revealed definite thalamic damage (Th) in 3 cases, putaminal damage (Put) in 3 cases, combined damage (Th + Put) in one case, and cortical (parietal) damage in 2 cases. In patients with a subcortical lesion, the greater the severity of superficial pain, the higher was the relative value of regional cerebral glucose metabolism (rCMRGlu) as compared to oxygen metabolism (rCMRO2) in the cerebral cortex around the central sulcus on the damaged side. Also, in a case with combined (Th + Put) lesion, regional oxygen extraction ratio (rOEF) was increased in this area. Moreover, in another case, central pain disappeared after a small subcortical haemorrhage in the same structure. In all patients including those with a cortical lesion, rCMRGlu was decreased in the postero-lateral (sensory) thalamus on the invalued side. The possible role of the cerebral cortex around the central sulcus for the genesis of central pain is discussed.
Assuntos
Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , Glucose/metabolismo , Dor , Tálamo/fisiopatologia , Tálamo/cirurgia , Adulto , Idoso , Córtex Cerebral/diagnóstico por imagem , Estimulação Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Condução Nervosa , Oxigênio/metabolismo , Consumo de Oxigênio , Medição da Dor , Radiografia , Radiocirurgia , Tomografia Computadorizada de EmissãoRESUMO
An application of MRI in functional stereotactic thalamotomy is presented. To estimate the individual anatomic variations of the thalamus prior to stereotactic thalamotomy, a special study using a proton density image that shows myeloarchitectonic features of the thalamus was performed. The proton density MRI was demonstrated to be very useful to determine the safest trajectory and tentative target point. However, as a detailed functional localization of the thalamic subnuclei cannot be yet obtained by MRI, the final target should be decided on the basis of electrophysiological findings.
Assuntos
Doença de Parkinson/patologia , Doença de Parkinson/cirurgia , Tálamo/patologia , Tálamo/cirurgia , Tremor/patologia , Tremor/cirurgia , Adulto , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Técnicas Estereotáxicas , Tálamo/anatomia & histologiaRESUMO
A 53-year-old woman who had severe mitral regurgitation associated with moderate tricuspid regurgitation and mild aortic regurgitation underwent mitral valve replacement with a 27 mm Björk-Shiley mechanical valve, left atrial plication and tricuspid annuloplasty. She fell into low output syndrome on the first postoperative day because of persistent intractable ventricular arrhythmia and eventually required open cardiac massage. The left ventricular (LV) bypass using a centrifugal pump was initiated with cannulation to ascending aorta and left atrium. Echocardiography showed LV wall motion extremely poor with the prosthetic valve being in closed posture. For prevention from thrombus formation on the prosthetic valve and in the LV, a catheter was inserted into LV through RV to give heparin and monitor the LV pressure. As the result, activated clotting time of LV was higher (range from 280-388 sec) than that of systemic blood (range from 182-258 sec). Also, the change of LV pressure was monitored through this LV catheter. Under this monitor, IABP was smoothly applied in the presence of aortic regurgitation, and she was weaned from LV-bypass successfully after 157 hrs support. She was discharge on the 77th postoperative day without thromboembolic complication.
Assuntos
Cateterismo Cardíaco , Próteses Valvulares Cardíacas , Coração Auxiliar , Heparina/uso terapêutico , Centrifugação , Feminino , Ventrículos do Coração , Heparina/administração & dosagem , Humanos , Pessoa de Meia-Idade , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/cirurgiaRESUMO
The effects of acupuncture and tactile skin stimulation on somatosensory evoked potentials (SEPs), elicited by the median nerve stimulation, were investigated in healthy subjects. Acupuncture needles were inserted into either Hegu plus Shousanli, Hegu plus Waiguan, or Shousanli positions ipsilateral to the median nerve stimulation. Tactile skin stimulation was applied to either the ulnar side of the palm, or the dorsal surface of the hand or forearm ipsilaterally to the nerve stimulation. It was found that acupuncture significantly suppressed the amplitude of P22 and P40, and that the tactile skin stimulation of the ulnar side of the palm significantly suppressed the amplitude of P22 and P40, but that the peak latencies were not affected. Dipole tracing analysis showed that the location and vector direction of P22 were not changed but the vector moment of P22 was changed by both acupuncture and tactile stimulation. Based on these findings the suppressive effect of acupuncture and skin stimulation on P22 was proposed to be due to the afferent inhibition in the somatosensory cortex. Although the suppressive mechanism of P40 by tactile skin stimulation seemed to be similar to that of P22, the suppression of P40 by acupuncture appeared to include different mechanisms.
Assuntos
Terapia por Acupuntura , Potenciais Somatossensoriais Evocados , Fenômenos Fisiológicos da Pele , Tato/fisiologia , Adolescente , Adulto , Humanos , Pessoa de Meia-Idade , Estimulação FísicaRESUMO
The effect of diltiazem as an adjunct to cardioplegia was examined for cardiac eicosanoid release in 12 patients who received aorto-coronary bypass. The patients were divided into two groups: diltiazem group (No. = 6) (10 mg/L of diltiazem in crystalloid potassium cardioplegia) and control group (No. = 6) (same cardioplegia without diltiazem). The plasma levels of thromboxane B2 and 6 keto PGF1 alpha (metabolites of thromboxane A2 and prostacyclin) in systemic artery and coronary sinus blood were measured during early reperfusion. A significantly larger arterio-venous difference in 6 keto PGF1 alpha concentration was found immediately after aortic clamp release in the diltiazem group (124 +/- 77 vs 12 +/- 47 pg/ml, p less than 0.05). The plasma thromboxane B2/6 keto PGF1 alpha ratio in coronary sinus blood was lower in the diltiazem group immediately after aortic clamp release (0.47 +/- 0.16 vs 0.74 +/- 0.18, p less than 0.05). There was no significant difference in arterio-venous TxB2 concentration between the two groups. In terms of myocardial protective effect evaluated by CPK-MB release, there was no significant difference between the two groups. The results indicated that diltiazem used as an adjunct to cardioplegia enhanced the production of endogenous PGI2 during early reperfusion, although its beneficial effect on myocardial protection was not shown in terms of enzyme leakage.
Assuntos
Soluções Cardioplégicas , Diltiazem/uso terapêutico , Epoprostenol/metabolismo , Reperfusão Miocárdica , Miocárdio/metabolismo , Compostos de Potássio , 6-Cetoprostaglandina F1 alfa/sangue , Ponte de Artéria Coronária , Parada Cardíaca Induzida , Humanos , Pessoa de Meia-Idade , Potássio , Tromboxano B2/sangueRESUMO
In diabetic rats given ginsenoside-Rb2 for 6 days, nitrogen balance was studied. Ginsenoside-Rb2 was found to suppress the total urinary excretion of nitrogen, increase nitrogen retention in the body, and thereby improve nitrogen balance.