RESUMO
UNLABELLED: Vitamin D may affect skeletal muscle function. In a double-blind, randomised, placebo-controlled trial, we found that vitamin D3 supplementation (400 or 1,000 I.U. vs. placebo daily for 1 year with bimonthly study visits) does not improve grip strength or reduce falls. INTRODUCTION: This study aimed to test the supplementation effects of vitamin D3 on physical function and examine associations between overweight/obesity and the biochemical response to treatment. METHODS: In a parallel group double-blind RCT, healthy postmenopausal women from North East Scotland (latitude-57° N) aged 60-70 years (body mass index (BMI), 18-45 kg/m(2)) were assigned (computer randomisation) to daily vitamin D3 (400 I.U. (n = 102)/1,000 I.U. (n = 101)) or matching placebo (n = 102) (97, 96 and 100 participants analysed for outcomes, respectively) from identical coded containers for 1 year. Grip strength (primary outcome), falls, diet, physical activity and ultraviolet B radiation exposure were measured bimonthly, as were serum 25(OH)D, adjusted calcium (ACa) and phosphate. Fat/lean mass (dual energy X-ray absorptiometry), anthropometry, 1,25-dihydroxyvitamin D and parathyroid hormone were measured at baseline and 12 months. Participants and researchers were blinded throughout intervention and analysis. RESULTS: Treatment had no effect on grip strength (mean change (SD)/year = -0.5 (2.5), -0.9 (2.7) and -0.4 (3.3) kg force for 400/1,000 I.U. vitamin D3 and placebo groups, respectively (P = .10, ANOVA)) or falls (P = .65, chi-squared test). Biochemical responses were similar across BMI categories (<25.25-29.99, ≥30 kg/m(2)) with the exception of a small change at 12-months in serum ACa in overweight compared to non-overweight participants (P = .01, ANOVA; 1,000 I.U. group). In the placebo group, 25(OH)D peak concentration change (winter to summer) was negatively associated with weight (r = -.268), BMI (r = -.198), total (r = -.278) and trunk fat mass (r = -.251), with total and trunk fat mass predictive of winter to summer 25(OH)D change (P = .01/.004 respectively, linear regression). CONCLUSION: We found no evidence of an improvement in physical function following vitamin D3 supplementation for 1 year.
Assuntos
Colecalciferol/uso terapêutico , Suplementos Nutricionais , Atividade Motora/efeitos dos fármacos , Obesidade/sangue , Sobrepeso/sangue , Acidentes por Quedas/prevenção & controle , Idoso , Antropometria/métodos , Composição Corporal , Índice de Massa Corporal , Cálcio/sangue , Colecalciferol/administração & dosagem , Dieta , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Força da Mão/fisiologia , Humanos , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Fosfatos/sangue , Luz Solar , Vitamina D/análogos & derivados , Vitamina D/sangueRESUMO
OBJECTIVES: Evidence from the literature that inflammation is a systemic biological phenomenon prompted us to investigate whether inoculation of different irritants to the footpad of mice might influence the kinetics of resident peritoneal cells. METHODS: Mice were inoculated in the footpad at different time intervals with Mycobacterium bovis bacillus Calmette-Guerin (BCG), Ehrlich ascitic tumor cells or lipopolysaccharide (LPS), and resident peritoneal cells were analyzed by flow cytometry. RESULTS: The results indicate that different stimuli induced different responses in resident peritoneal cells. FoxP3 positive regulatory T cells increased drastically in number after BCG inoculation. Conversely, tumor cell inoculation induced a decrease in FoxP3-positive T cells in the peritoneal cavity, although this effect was not statistically significant. Results also show that cells from the paw migrate to the popliteal lymph node and to the peritoneal cavity. Yet, there are cells in the peritoneal cavity that migrate to the popliteal lymph node. CONCLUSION: These data show that cells from the peritoneal cavity are influenced by pathologies in remote regions of the animal. How this novel phenomenon influences overall immune responses, courses of infection and tumor growth are open to further investigation.
Assuntos
Inflamação/imunologia , Cavidade Peritoneal/citologia , Animais , Linfócitos B/imunologia , Carcinoma de Ehrlich/imunologia , Células Cultivadas , Pé , Fatores de Transcrição Forkhead/imunologia , Lipopolissacarídeos/imunologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium bovis/imunologia , Linfócitos T Reguladores/imunologiaRESUMO
OBJECTIVE: To compare differences in macrophage heterogeneity and morphological composition between atherosclerotic plaques obtained from recently symptomatic patients with carotid artery disease and femoral plaques from patients with severe limb ischemia. DESIGN: Experimental study. METHODS: Plaques were obtained from 32 patients undergoing carotid endarterectomy and 25 patients undergoing common femoral endarterectomy or lower limb bypass. Macrophages and T cell numbers were detected in plaque sections by immunohistochemistry and anti CD68 and CD3 antibodies. Dual staining for CD68 and M1- and M2-macrophage markers and morphometric analysis of hematoxylin and eosin stained plaque sections was performed. RESULTS: Carotid plaques had significantly increased percentage areas of confluent lipid and leukocytic infiltrates. In contrast, areas of fibroconnective tissue were significantly greater in femoral plaques and percentage areas of confluent calcification and collagen were elevated. Carotid artery plaques had greater numbers per plaque area of macrophages and T cells consistent with a more inflammatory phenotype. Proportions displaying M1-activation markers were significantly increased in the carotid compared to femoral plaques whereas femoral plaques displayed a greater proportion of M2-macrophages. CONCLUSION: Plaques from patients with recently symptomatic carotid disease have a predominance of M1-macrophages and higher lipid content than femoral plaques, consistent with a more unstable plaque.
Assuntos
Aterosclerose/imunologia , Artérias Carótidas/imunologia , Doenças das Artérias Carótidas/imunologia , Artéria Femoral/imunologia , Macrófagos/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Aterosclerose/patologia , Aterosclerose/cirurgia , Biomarcadores/análise , Complexo CD3/análise , Artérias Carótidas/patologia , Artérias Carótidas/cirurgia , Doenças das Artérias Carótidas/patologia , Doenças das Artérias Carótidas/cirurgia , Constrição Patológica , Feminino , Artéria Femoral/patologia , Artéria Femoral/cirurgia , Humanos , Imuno-Histoquímica , Macrófagos/classificação , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Placa Aterosclerótica , Escócia , Linfócitos T/imunologiaRESUMO
The ClpB heat-shock protein is necessary for the survival of Escherichia coli cells upon sudden increase of temperature. Using a PCR-based genomic walking method, the nucleotide sequence of a clpB homolog from Campylobacter jejuni was determined. The clpB gene encodes a protein of 857 amino acid (aa) residues, with a predicted molecular mass of 95.3kDa. Alignment of the deduced aa sequence with other known bacterial ClpB proteins revealed overall identity from 47% (E. coli) to 61% (Helicobacter pylori). Within the clpB promoter region, as indicated by primer extension analysis, we identified a sequence identical to the E. coli sigma70 consensus promoter. Northern blot analysis confirmed that clpB is heat-inducible in C. jejuni. The ClpB protein, fused to a 6xHis tag, was synthesized in E. coli and purified by metal-affinity and size exclusion chromatography. In ELISA studies, IgA levels reactive to recombinant ClpB were significantly higher in sera of patients with prior C. jejuni infections than in sera obtained from healthy control persons.
Assuntos
Campylobacter jejuni/genética , Proteínas de Escherichia coli , Proteínas de Choque Térmico/genética , Sequência de Aminoácidos , Linfócitos B/imunologia , Sequência de Bases , Infecções por Campylobacter/imunologia , Clonagem Molecular , Endopeptidase Clp , Escherichia coli/genética , Proteínas de Choque Térmico/imunologia , Humanos , Dados de Sequência Molecular , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Proteínas Recombinantes/imunologia , Mapeamento por Restrição , Alinhamento de SequênciaRESUMO
BACKGROUND: Animal studies showed that dietary flaxseed oil [rich in the n-3 polyunsaturated fatty acid alpha-linolenic acid (ALA)], evening primrose oil [rich in the n-6 polyunsaturated fatty acid gamma-linolenic acid (GLA)], and fish oil [rich in the long-chain n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] can decrease natural killer (NK) cell activity. There have been no studies of the effect on NK cell activity of adding these oils to the diet of humans. OBJECTIVE: Our objective was to determine the effect of dietary supplementation with oil blends rich in ALA, GLA, arachidonic acid (AA), DHA, or EPA plus DHA (fish oil) on the NK cell activity of human peripheral blood mononuclear cells. DESIGN: A randomized, placebo-controlled, double-blind, parallel study was conducted. Healthy subjects aged 55-75 y consumed 9 capsules/d for 12 wk; the capsules contained placebo oil (an 80:20 mix of palm and sunflower seed oils) or blends of placebo oil and oils rich in ALA, GLA, AA, DHA, or EPA plus DHA. Subjects in these groups consumed 2 g ALA, 770 mg GLA, 680 mg AA, 720 mg DHA, or 1 g EPA plus DHA (720 mg EPA + 280 mg DHA) daily, respectively. Total fat intake from the capsules was 4 g/d. RESULTS: The fatty acid composition of plasma phospholipids changed significantly in the GLA, AA, DHA, and fish oil groups. NK cell activity was not significantly affected by the placebo, ALA, GLA, AA, or DHA treatment. Fish oil caused a significant reduction (mean decline: 48%) in NK cell activity that was fully reversed by 4 wk after supplementation had ceased. CONCLUSION: A moderate amount of EPA but not of other n-6 or n-3 polyunsaturated fatty acids can decrease NK cell activity in healthy subjects.
Assuntos
Ácido Eicosapentaenoico/administração & dosagem , Células Matadoras Naturais/metabolismo , Idoso , Ácido Araquidônico/administração & dosagem , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Método Duplo-Cego , Ácido Eicosapentaenoico/farmacologia , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-6 , Ácidos Graxos Insaturados/administração & dosagem , Feminino , Óleos de Peixe/administração & dosagem , Humanos , Imunidade Celular/efeitos dos fármacos , Células Matadoras Naturais/efeitos dos fármacos , Subpopulações de Linfócitos/efeitos dos fármacos , Subpopulações de Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Ácido alfa-Linolênico/administração & dosagem , Ácido gama-Linolênico/administração & dosagemRESUMO
Fatty acid composition of lipid classes and NMR spectra of lipoproteins were compared in 6 young (24-35-year-old) and 6 elderly (79-90-year-old) women. Cholesteryl ester, triglyceride and protein content of LDL in elderly women were significantly higher (+52-57% and +20% for lipids and proteins, respectively) than those observed in young women. HDL lipid levels were similar in the two groups. The proportion of linoleic acid (mainly in cholesteryl esters and phospholipids) of each lipoprotein species was always lower in octogenarians when compared with young females (lowering of 13-28% and 27-46% for cholesteryl esters and phospholipids, respectively). Conversely, the proportions of mono-unsaturated fatty acids (mainly oleic acid) increased in all lipid classes, although this was only significant in cholesteryl esters from each lipoprotein species. NMR spectra of lipoproteins showed a restricted mobility of acyl chain terminal CH3 groups in old women which was significant only in VLDL and HDL3. This suggests that the decrease of linoleic acid could affect the lipid mobility in lipoproteins of elderly women.
Assuntos
Envelhecimento/sangue , Ácidos Graxos/análise , Lipoproteínas/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Ésteres do Colesterol/química , Feminino , Humanos , Ácido Linoleico , Ácidos Linoleicos/análise , Espectroscopia de Ressonância Magnética , Fosfolipídeos/química , Fatores Sexuais , Triglicerídeos/químicaRESUMO
The metabolic fate of docosahexaenoic acid (DHA) was evaluated from its intake as a nutrient in triglycerides and phosphatidylcholines to its uptake by target tissues, especially the brain. Several approaches were used including the kinetics and tissue distribution of ingested 13C-labeled DHA, the incorporation of radiolabeled DHA injected as its nonesterified form compared to the fatty acid esterified in lysophosphatidylcholine (lysoPC), and the capacity of the two latter forms to cross a reconstituted blood-brain barrier (BBB) consisting of cocultures of brain-capillary endothelial cells and astrocytes. The results obtained allow us to raise the hypothesis that lysoPC may represent a preferred physiological carrier of DHA to the brain.
Assuntos
Encéfalo/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Lisofosfatidilcolinas/metabolismo , Animais , Disponibilidade Biológica , Barreira Hematoencefálica , Gorduras Insaturadas na Dieta/farmacocinética , Ácidos Docosa-Hexaenoicos/farmacocinética , Óleos de Peixe/farmacocinética , Humanos , Fosfatidilcolinas/metabolismo , Ratos , Albumina Sérica/metabolismo , Triglicerídeos/metabolismoRESUMO
Resistance of Plasmodium falciparum to pyrimethamine is associated with a non-silent point mutation of the parasite dihydrofolate reductase (DHFR) gene (Ser108 --> Asn108). Wide-scale use of antimalarials is thought to contribute to the emergence of drug resistance. In 131 P. falciparum-infected children in rural Nigeria, the frequency of the resistant Asn108 genotype was assessed by enzymatic restriction digestion of polymerase chain reaction-amplified DHFR sequences and compared with residual pyrimethamine blood levels. The prevalence of the Asn108 variant was 41.2%. In 18.3% of the isolates, both the Asn108 and the wild-type alleles were present. In contrast to the high prevalence of resistant genotypes, residual pyrimethamine blood levels were detected in only 4%. Furthermore, age was found to be a determinant of the parasite genotype since the proportion of Asn108 variants decreased with age (P < 0.05). These findings indicate that additional, unidentified factors, rather than selection by residual drug levels alone, might be responsible for the emergence of pyrimethamine-resistant parasite genotypes.
Assuntos
Antimaláricos/uso terapêutico , Malária Falciparum/parasitologia , Plasmodium falciparum/genética , Mutação Puntual , Pirimetamina/uso terapêutico , Tetra-Hidrofolato Desidrogenase/genética , Distribuição por Idade , Animais , Antimaláricos/sangue , Antimaláricos/farmacologia , Criança , Pré-Escolar , Estudos Transversais , DNA de Protozoário/análise , Resistência a Medicamentos/genética , Genes de Protozoários , Genótipo , Humanos , Lactente , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Nigéria/epidemiologia , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/enzimologia , Reação em Cadeia da Polimerase/métodos , Prevalência , Pirimetamina/sangue , Pirimetamina/farmacologiaRESUMO
Fingerprinting of RNA by arbitrarily primed PCR was used to identify a heat-inducible gene in Campylobacter jejuni. Comparing RNA fingerprints from C. jejuni cells before and after 20 min of heat shock at 48 degrees C, a differentially amplified PCR product was identified which displayed a high degree of homology to bacterial lon genes. By screening C. jejuni genomic libraries, the entire lon gene was cloned and sequenced. It encodes a protein of 791 amino acids with a calculated molecular mass of 90.2 kDa. Alignment of the Lon amino acid sequence with that of other bacterial species revealed an overall identity of up to 56.6% (Helicobacter pylori). Northern and RNA dot blot experiments confirmed heat induction of the C. jejuni lon gene, revealing a maximum 6-8-fold increase in the level of specific mRNA.
Assuntos
Campylobacter jejuni/enzimologia , Genes Bacterianos , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Reação em Cadeia da Polimerase/métodos , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo , Proteases Dependentes de ATP , Sequência de Bases , Northern Blotting , Southern Blotting , Campylobacter jejuni/genética , Clonagem Molecular , Regulação Bacteriana da Expressão Gênica , Proteínas de Choque Térmico/química , Resposta ao Choque Térmico , Humanos , Dados de Sequência Molecular , Plasmídeos , RNA Bacteriano/análise , RNA Bacteriano/isolamento & purificação , Mapeamento por Restrição , Análise de Sequência de DNA , Serina Endopeptidases/química , Transcrição GênicaRESUMO
Feeding rodents a diet rich in evening primrose oil (EPO), which contains 5-10 g gamma-linolenic acid (GLA)/100 g total fatty acids, has been shown to decrease lymphocyte proliferation and natural killer cell activity. However, EPO contains a very high level of linoleic acid which itself can affect lymphocyte functions and it is not clear to what extent the effects of EPO can be attributed to GLA. The current study investigated the effect of two levels of GLA in the rat diet upon immune cell functions; the level of linoleic acid was maintained below 30 g/100 g total fatty acids. Weanling rats were fed on high fat (178 g/kg) diets which contained 4.4 g or 10 g GLA/100 g total fatty acids in place of a proportion of linoleic acid. The total polyunsaturated fatty acid content and the n-6 to n-3 polyunsaturated fatty acid ratio of the diet were maintained at 35 g/100 g total fatty acids and 7, respectively. The fatty acid compositions of the serum and of spleen leukocytes were markedly influenced by that of the diet, with an increase in the proportions of GLA and dihomo-gamma-linolenic acid when the diets containing GLA were fed; these diets also increased the proportion of arachidonic acid in spleen leukocytes. Spleen lymphocyte proliferation in response to concanavalin A was significantly reduced (by 60%) by feeding the diet containing the higher level of GLA, but not by the diet containing the lower level of GLA. Spleen natural killer cell activity and prostaglandin E (PGE) production by spleen leukocytes were not significantly affected by inclusion of GLA in the diet, although there was a tendency towards decreased natural killer cell activity by cells from rats fed the high GLA diet. Thus, this study shows that dietary GLA is capable of altering the fatty acid composition of cells of the immune system and of exerting some immunomodulatory effects, but that the level of GLA in the diet must exceed 4.4 g/100 g total fatty acids for these effects to become apparent.
Assuntos
Gorduras Insaturadas na Dieta/administração & dosagem , Linfócitos/imunologia , Baço/citologia , Ácido gama-Linolênico/administração & dosagem , Animais , Células Cultivadas , Concanavalina A/farmacologia , Relação Dose-Resposta a Droga , Ácidos Graxos/sangue , Ácidos Graxos/metabolismo , Ácidos Graxos Essenciais , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-6 , Ácidos Graxos Insaturados/administração & dosagem , Células Matadoras Naturais/imunologia , Ácidos Linoleicos , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/metabolismo , Masculino , Oenothera biennis , Óleos de Plantas , Prostaglandinas E/biossíntese , Ratos , Ratos Endogâmicos LewRESUMO
Fish oil is rich in the long chain n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); typically these fatty acids constitute 20 to 25 g/100 g total fatty acids in fish oil. Feeding rodents diets rich in fish oil has been shown to decrease lymphocyte proliferation and natural killer cell activity. It is not known what level of EPA + DHA is required in the diet to exert these effects. This question was addressed in the current study. Weanling rats were fed on high fat (178 g/kg) diets which contained 4.4 g alpha-linolenic acid (control) or 4.4 g EPA + DHA (4.4 EPA + DHA) or 6.6 g EPA + DHA (6.6 EPA + DHA)/100 g total fatty acids. The n-6 to n-3 polyunsaturated fatty acid ratio was maintained at approximately 7. The fatty acid compositions of the serum and of spleen leukocytes were markedly influenced by that of the diet. Spleen lymphocyte proliferation in response to concanavalin A, spleen natural killer cell activity and PGE2 production by spleen leukocytes were reduced by feeding the EPA + DHA diets compared with feeding the control diet; the 4.4 and 6.6 EPA + DHA diets caused very similar reductions. The 4.4 EPA + DHA diet reduced popliteal lymph node weight following a localised graft versus host response; this response was not investigated in rats fed the 6.6 EPA + DHA diet. The reductions in lymphocyte functions and in the in vivo graft versus host response caused by the EPA + DHA diets were similar to those previously reported following the feeding of diets rich in fish oil. Thus, this study shows that diets containing relatively low levels of EPA + DHA (20 to 25% of the level found in fish oil) exert immunomodulatory effects. Furthermore, this study suggests that the maximal effect of EPA + DHA is exerted when these fatty acids constitute a level of less than or equal to 4.4 g/100 g total dietary fatty acids.
Assuntos
Gorduras Insaturadas na Dieta/administração & dosagem , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/administração & dosagem , Linfócitos/fisiologia , Animais , Células Cultivadas , Dinoprostona/metabolismo , Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/sangue , Ácidos Graxos/metabolismo , Reação Enxerto-Hospedeiro/fisiologia , Células Matadoras Naturais/fisiologia , Linfonodos/imunologia , Ativação Linfocitária/fisiologia , Masculino , Ratos , Ratos Endogâmicos Lew , Baço/imunologia , Ácido alfa-Linolênico/administração & dosagemRESUMO
Weanling rats were fed on high-fat (178 g/kg) diets which contained 4.4 g alpha-linolenic (ALA), gamma-linolenic, arachidonic (ARA), eicosapentaenoic (EPA), or docosahexaenoic acid (DHA)/100 g total fatty acids. The proportions of all other fatty acids, apart from linoleic acid, and the proportion of total polyunsaturated fatty acids (PUFA) (approximately 35 g/100 g total fatty acids) were constant, and the n-6 to n-3 PUFA ratio was maintained as close to 7 as possible. The fatty acid compositions of the serum and of spleen leukocytes were markedly influenced by that of the diet. Prostaglandin E2 production was enhanced from leukocytes from rats fed the ARA-rich diet and was decreased from leukocytes from the EPA- or DHA-fed rats. Replacing dietary ALA with EPA resulted in diminished ex vivo lymphocyte proliferation and natural killer (NK) cell activity and a reduced cell-mediated immune response in vivo. In contrast, replacing ALA with DHA reduced ex vivo lymphocyte proliferation but did not affect ex vivo NK cell activity or the cell-mediated immune response in vivo. Replacement of a proportion of linoleic acid with either gamma-linolenic acid or ARA did not affect lymphocyte proliferation, NK cell activity, or the cell-mediated immune response. Thus, this study shows that different n-3 PUFA exert different immunomodulatory actions, that EPA exerts more widespread and/or stronger immunomodulatory effects than DHA, that a low level of EPA is sufficient to influence the immune response, and that the immunomodulatory effects of fish oil may be mainly due to EPA.
Assuntos
Ácidos Graxos Ômega-3/farmacologia , Imunidade Celular/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Baço/efeitos dos fármacos , Animais , Dinoprostona/biossíntese , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Ácidos Graxos/análise , Ácidos Graxos/sangue , Óleos de Peixe/farmacologia , Masculino , Óleos de Plantas/farmacologia , Ratos/crescimento & desenvolvimento , Ratos Endogâmicos LewRESUMO
Greatly increasing the amounts of flaxseed oil [rich in alpha-linolenic acid (ALNA)] or fish oil (FO); [rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in the diet can decrease inflammatory cell functions and so might impair host defense. The objective of this study was to determine the effect of dietary supplementation with moderate levels of ALNA, gamma-linolenic acid (GLA), arachidonic acid (ARA), DHA, or FO on inflammatory cell numbers and functions and on circulating levels of soluble adhesion molecules. Healthy subjects aged 55 to 75 yr consumed nine capsules per day for 12 wk. The capsules contained placebo oil (an 80:20 mix of palm and sunflowerseed oils) or blends of placebo oil with oils rich in ALNA, GLA, ARA, or DHA or FO. Subjects in these groups consumed 2 g ALNA; approximately 700 mg GLA, ARA, or DHA; or 1 g EPA plus DHA (720 mg EPA + 280 mg DHA) daily from the capsules. Total fat intake from the capsules was 4 g per day. None of the treatments affected inflammatory cell numbers in the bloodstream; neutrophil and monocyte phagocytosis or respiratory burst in response to E. coli; production of tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 in response to bacterial lipopolysaccharide; or plasma concentrations of soluble intercellular adhesion molecule-1. In contrast, the ALNA and FO treatments decreased the plasma concentrations of soluble vascular cell adhesion molecule-1 (16 and 28% decrease, respectively) and soluble E-selectin (23 and 17% decrease, respectively). It is concluded that, in contrast to previous reports using higher amounts of these fatty acids, a moderate increase in consumption of long-chain n-6 or n-3 polyunsaturated fatty acids does not significantly affect inflammatory cell numbers or neutrophil and monocyte responses in humans and so would not be expected to cause immune impairment. Furthermore, we conclude that moderate levels of ALNA and FO, which could be incorporated into the diet, can decrease some markers of endothelial activation and that this mechanism of action may contribute to the reported health benefits of n-3 fatty acids.
Assuntos
Moléculas de Adesão Celular/efeitos dos fármacos , Suplementos Nutricionais , Ácidos Eicosanoicos/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Insaturados/farmacologia , Inflamação/sangue , Idoso , Ácido Araquidônico/farmacologia , Moléculas de Adesão Celular/sangue , Citocinas/sangue , Ácidos Docosa-Hexaenoicos/farmacologia , Método Duplo-Cego , Ácidos Graxos/sangue , Ácidos Graxos/química , Ácidos Graxos Ômega-6 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Fagocitose/efeitos dos fármacos , Fosfolipídeos/sangue , Fosfolipídeos/química , Explosão Respiratória , Ácido alfa-Linolênico/farmacologia , Ácido gama-Linolênico/farmacologiaRESUMO
To investigate the immunological effect of feeding pigs different dietary lipids, 3-wk-old, weaned pigs were fed for 40 d on one of five diets, which differed only in the type of oil present (the oil contributed 5% by weight of the diet and the total fat content of the diets was 8% by weight). The oils used were soybean (control diet), high-oleic sunflower oil (HOSO), sunflower oil (SO), canola oil (CO), and fish oil (FO; rich in long-chain [n-3] polyunsaturared fatty acids). There were no significant differences in initial or final animal weights, weight gains, or health scores among the groups. There were no significant differences in the concentration of anti-Escherichia coli vaccine antibodies in the gut lumens of pigs fed the different diets. The fatty acid composition of the diet markedly affected the fatty acid composition of the plasma and of mononuclear cells (a mixture of lymphocytes, monocytes, and macrophages) prepared from the blood, lymph nodes, or thymus. The FO feeding resulted in a significant increase in the number of circulating granulocytes. The FO feeding significantly decreased the proportion of phagocytes engaged in uptake of E. coli and decreased the activity of those phagocytes that were active. The proliferation of lymphocytes in cultures of whole blood from pigs fed the HOSO, SO, or FO diets was less than in those from pigs fed the CO diet. Proliferation of lymph node lymphocytes from SO- or FO-fed pigs was less than that from control, CO-, or HOSO-fed pigs. The natural killer cell activity of blood lymphocytes from pigs fed the FO diet was significantly reduced compared with those from pigs fed the CO diet. The concentration of PGE2 in the medium of cultured blood, lymph node, or thymic mononuclear cells was lower if the cells came from pigs fed the FO diet. Thus, the type of oil included in the diet of growing pigs affects the numbers and functional activities of immune cells in different body compartments.
Assuntos
Ração Animal , Gorduras na Dieta/administração & dosagem , Ácidos Graxos/sangue , Leucócitos Mononucleares/metabolismo , Linfócitos/imunologia , Fagócitos/imunologia , Suínos/imunologia , Animais , Gorduras na Dieta/classificação , Ácidos Graxos Insaturados/administração & dosagem , Ácidos Graxos Insaturados/farmacologia , Feminino , Leucócitos Mononucleares/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Masculino , Fagócitos/efeitos dos fármacos , Suínos/sangue , Suínos/crescimento & desenvolvimento , Desmame , Aumento de PesoRESUMO
The N-demethylation of the pyridazinone pro-herbicide metflurazon into norflurazon implies a toxification in photosynthetic organisms. This is confirmed by quantitative structure activity relationships determined for two unicellular green algae, Chlorella sorokiniana and Chlorella fusca; however, the latter is 25 to 80 times more sensitive to metflurazon. This sensitivity is linked to differences in the N-demethylase activity of both algae, as determined by an optimized in vivo biotransformation assay. Apparent K(m) values of the metflurazon-N-demethylase indicate a 10-fold higher affinity for this xenobiotic substrate for Chlorella fusca. Furthermore, algal metflurazon-N-demethylation is characterized by distinct variations in activity, depending on the stage of cell development within the cell cycle. Several well-established inhibitors of cytochrome P450-mediated reactions, including piperonylbutoxide, 1-aminobenzotriazole, 1-phenoxy-3-(1H-1,2,4-triol-1yl)-4-hydroxy-5,5-dimethylhexane++ +, and tetcyclacis, as well as cinnamic acid, a potential endogenous substrate, inhibited the N-demethylation of metflurazon. The results suggest that the N-demethylation of metflurazon by both algae is mediated by a cytochrome P450 monooxygenase. The determination of antigenic cross-reactivity of algal proteins with heterologous polyclonal antibodies originally raised against plant P450s, anti-cinnamic acid 4-hydroxylase (CYP73A1), anti-ethoxycoumarin-O-dealkylase, anti-tulip allene oxidase (CYP74), and an avocado P450 (CYP71A1) or those of bacterial origin, CYP105A1 and CYP105B1, suggests the presence of distinct P450 isoforms in both algae.
Assuntos
Chlorella/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Herbicidas/metabolismo , Piridazinas/metabolismo , Xenobióticos/metabolismo , Biotransformação , Chlorella/efeitos dos fármacos , Cinética , Oxirredutases N-Desmetilantes/metabolismo , Oxigenases , Pró-Fármacos/metabolismo , Piridazinas/toxicidade , Especificidade da Espécie , Especificidade por SubstratoRESUMO
[(3)H]-Arachidonic acid-labelled rat T lymphocytes released radioactivity extracellularly when stimulated by the calcium ionophore A23187 or by monoclonal antibodies to some cell surface structures (CD2, CD5, CD11a, CD18, CD54, T-cell receptor) but not to others (CD49d, CD62L); release was greater with the calcium ionophore. Almost all of the radioactivity released from anti-CD2-stimulated lymphocytes was recovered in the free fatty acid fraction, whereas only about 50 per cent of that released after A23187 stimulation was recovered in this fraction. A23187 stimulation resulted in release of arachidonic acid from a variety of phospholipids (phosphatidylinositol, phosphatidylcholine and perhaps phosphatidylethanolamine), while the monoclonal antibody stimulation released arachidonic acid from phosphatidylinositol and perhaps phosphatidylcholine. Unstimulated lymphocytes released a range of fatty acids extracellularly, with palmitic acid accounting for 35-40 per cent and arachidonic acid for 5 per cent of released fatty acid. Stimulation of lymphocytes with either anti-CD2 or A23187 increased total fatty acid release 1.5- to 1.8-fold. In both cases palmitic acid remained the most predominant fatty acid released but the contribution of arachidonic acid increased. The type of lipid fed to the rats significantly influenced the amount and type of fatty acid released. Fish oil feeding significantly reduced extracellular fatty acid release by stimulated lymphocytes.
Assuntos
Gorduras na Dieta/farmacologia , Ácidos Graxos não Esterificados/metabolismo , Linfócitos T/metabolismo , Animais , Anticorpos Monoclonais/imunologia , Antígenos CD/imunologia , Ácido Araquidônico/metabolismo , Calcimicina/farmacologia , Óleos de Peixe/farmacologia , Ionóforos/farmacologia , Cinética , Masculino , Ácido Palmítico/metabolismo , Fosfolipídeos/metabolismo , Ratos , Ratos Endogâmicos Lew , Linfócitos T/efeitos dos fármacosRESUMO
The influence of droperidol on the pressor effect of noradrenaline was investigated in pithed rats injected with propranolol. Droperidol induced a dose-dependent shift of the noradrenaline dose-response curve to the right, but proved to be 20 times less potent than phentolamine. Droperidol produced a considerably more pronounced inhibition of the effect of tyramine than of that of noradrenaline.--The influence of droperidol on the increase in tension induced by noradrenaline was determined in isolated aortic strips of rats. The drug caused a marked parallel shift of the noradrenaline concentration-response curve to the right (pA2:7.99). In this preparation droperidol and phentolamine were equieffective.--Droperidol did not produce a significant shift of the noradrenaline concentration-response curves obtained for the positive chronotropic and inotropic effects in spontaneously beating right guinea-pig atria and in electrically driven left atria, respectively.--It is concluded that droperidol is a competitive inhibitor of the vascular alpha-adrenoceptors, leaving the beta-adrenoceptors of the heart unaffected, and that it inhibits the neuronal uptake mechanism of noradrenaline.
Assuntos
Vasos Sanguíneos/efeitos dos fármacos , Droperidol/farmacologia , Coração/efeitos dos fármacos , Receptores Adrenérgicos/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Vasos Sanguíneos/inervação , Relação Dose-Resposta a Droga , Interações Medicamentosas , Cobaias , Coração/inervação , Frequência Cardíaca/efeitos dos fármacos , Técnicas In Vitro , Masculino , Contração Miocárdica/efeitos dos fármacos , Norepinefrina/farmacologia , Fentolamina/farmacologia , Ratos , Fatores de Tempo , Tiramina/farmacologiaRESUMO
Within the framework of a multi-centre prospective randomised therapeutic trial, 150 patients with small-cell lung cancer (SCLC) were treated with cisplatin/vepesid and endoxan/vepesid. The aim of the study was to establish whether cisplatin--which although effective is commonly associated with adverse effects--can be replaced by endoxan. The sequence of treatment was oriented to the stage and course of the tumour disease. In the event of a treatment failure, cross-over to the alternative combination was effected. In terms of remission rates, the combination cisplatin/vepesid proved to be more effective than endoxan/vepesid, in particular in the case of patients with extensive disease. With respect to duration of remission and survival duration, however, no significant differences were to be seen.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Cisplatino/administração & dosagem , Ciclofosfamida/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
The uptake and metabolism of [3H]docosahexaenoic acid (DHA) esterified at the sn-2 position of lysophosphatidylcholine (lysoPC DHA) and in the unesterified form, both bound to albumin, was studied in 20-day-old rats. LysoPC DHA was preferentially recovered in the brain (4-5% of the injected radioactivity) over the unesterified form of DHA (0.3-0.4%). Conversely, the lysoPC form was taken up less than or at the same extent as the unesterified form by the liver, heart, and kidney. In the brain, DHA was mainly recovered in phosphatidylethanolamine whether the esterified or the unesterified form was used, although DHA from lysoPC was esterified at the same extent in phosphatidylcholine and phosphatidylethanolamine after 2.5 min. The uptake of labeled palmitic, oleic, linoleic, and arachidonic acids, esterified or not in lysophosphatidylcholine, was also studied in brain, liver, heart, and kidney. Only the brain preferentially incorporated unsaturated (but not saturated) lysoPC, with the uptake increasing with the degree of unsaturation of the fatty acid moiety. These results strongly suggest that the young rat brain specifically utilizes albumin-lysoPC-containing polyunsaturated fatty acids.