ISSN:0002-9629    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Myocardial ATP production is dependent chiefly on the oxidative decarboxylation of glucose and fatty acids. The co-utilization of these and other substrates is determined by both the amount of any given substrate supplied to the heart as well as by complex intracellular regulatory mechanisms. This regulated balance is altered during and after ischemia. During aerobic reperfusion of ischemic myocardium, a rapid recovery of energy production is desirable for the complete recovery of muscle contractile function. It is now clear that the type of energy substrate used by the heart during reperfusion will directly influence this contractile recovery. By increasing the relative proportion of glucose oxidized to that of fatty acids, the mechanical function of the reperfused heart can be improved. However, fatty acid oxidation recovers quickly during reperfusion and dominates as a source of oxygen consumption. These high rates of fatty acid oxidation occur at the expense of glucose oxidation, resulting in a decreased recovery of both cardiac function and efficiency during reperfusion. One contributory factor to these high rates of fatty acid oxidation is a decrease in myocardial malonyl-coenzyme A (CoA) levels. Malonyl-CoA, which is synthesized by acetyl-CoA carboxylase, is an essential metabolic intermediary in the regulation of fatty acid oxidation. A decrease in malonyl-CoA level results in an increase of carnitine palmitoyl transferase-1 mediated fatty acid uptake into the mitochondria. This mechanism seems important in the regulation of fatty acid oxidation in the postischemic heart and is discussed in detail in this review, with reference to specific clinical scenarios of ischemia and reperfusion and options for modulating cardiac energy metabolism.

ISSN:0002-9629    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Fatty acids are the primary source of energy in the adult heart. Recently, however, it was discovered that certain saturated fatty acids, such as palmitate and stearate, cause cardiac and other types of cells to undergo programmed cell death (apoptosis). In cardiac ischemia/reperfusion injury, where blood flow is blocked and then restored to the heart, recovery of cardiac cells is inversely proportional to the concentration of fatty acids (largely composed of palmitate and stearate) in the reperfusate. The aim of this review is to summarize what is known about fatty acid induction of heart disease, the role of fatty acids in apoptosis, and apoptosis in the heart, including the role that mitochondria play in this process.

ISSN:0002-9629    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Carnitine-acylcarnitine translocase deficiency, like other defects of mitochondrial fatty acid oxidation, is an autosomal, recessively inherited disorder. When the deficiency is near total, it is usually fatal, affects life soon after birth, and constitutes one of the causes of skeletal muscle myopathy, cardiac and liver abnormalities, and childhood sudden death. The presenting features have included neonatal distress, convulsions, hypoglycemia, hyperammonemia, hypoketonemia, intermittent dicarboxyluria, hypothermia, apnea, neurological deterioration, and hypocarnitinemia with grossly elevated acylcarnitines. Two cases of partial translocase deficiency (4–6% residual activity) with milder symptoms and without cardiac involvement have also been identified. Evidence so far indicates that the translocase protein is the product of a single gene. In two cases of translocase deficiency, the accompanying mutations have been identified. The benefits of prenatal diagnosis have been provided to the affected families by assays of the translocase and/or fatty acid oxidation in cultured amniotic/villous cells. In one such case genetic counseling was made possible even when the only specimen available from a deceased sibling was the Guthrie card.

ISSN:0002-9629    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Peroxisomes are small, subcellular organelles that play a major role in lipid metabolism. Inherited disorders of peroxisomal structure and metabolism can result from defective assembly, missing protein import transporters, or individual enzyme deficiencies. Molecular studies helped by the range of disorders have now elucidated many of the pathways, including the paths of &agr;-oxidation for phytanic acid and &bgr;-oxidation for very-long-chain and branched-chain fatty acids and for bile acid synthesis. The mechanism of the transfer of substrates, intermediates, and products across the membrane is poorly understood. The carnitine system, known to transport activated acyl groups between localized coenzyme A pools, is presented. The evidence for the involvement of carnitine in the transfer of activated acyl groups to and from the peroxisomes is reviewed.

ISSN:0002-9629    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

During the development of cardiac hypertrophy and in the failing heart, the chief myocardial energy source switches from fatty acid &bgr;-oxidation to glycolysis: a reversion to the fetal energy substrate preference pattern. This review describes recent molecular studies aimed at delineating the gene regulatory pathway involved in the energy metabolic switch in the hypertrophied heart and the potential role of the attendant metabolic consequences in the pathogenesis of heart failure. Studies have been performed with the ‘spontaneous hypertensive and heart failure’ rat strain and with human cardiomyopathic tissue. These studies have demonstrated that expression of the gene that encodes medium-chain acyl-coenzyme A dehydrogenase (MCAD), a key fatty acid &bgr;-oxidation enzyme, is down-regulated during the progression from cardiac hypertrophy to ventricular dysfunction. A series of studies performed in mice transgenic for the human MCAD gene promoter have identified a transcriptional regulatory pathway involved in the repression of MCAD gene expression in the hypertrophied mouse heart. Two categories of transcription factors, nuclear hormone receptors and Sp factors, bind MCAD gene promoter regulatory elements in response to pressure overload to reactivate a fetal metabolic gene program. Studies are under way to manipulate this transcriptional regulatory pathway in mice using genetic engineering strategies to determine whether this energy metabolic derangement plays a primary role in the development of cardiac hypertrophy and heart failure.

ISSN:0002-9629    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Two genes control expression of mitochondrial carnitine palmitoyltransferase-I (CPT-I), the enzyme that catalyzes the primary rate-controlling step in fatty acid oxidation. Two CPT-I isoforms have been found—a “liver” isoform (CPT-I&agr;) expressed in most tissues, but not in skeletal muscles, and a “muscle” isoform (CPT-I&bgr;) expressed in muscles and adipocytes. Liver CPT-I&agr; increases dramatically at birth, but heart CPT-I&agr; is abundant in the fetus and diminishes at birth. Insulin, thyroid hormone, and fatty acids regulate expression of CPT-I&agr; in liver, whereas electrical stimulation increases CPT-I&bgr; and decreases CPT-I&agr; in cardiac myocytes. Both genes are TATA-less and contain Sp1 transcription factor binding sites upstream of the start site of transcription. Multiple transcripts of both CPT-I&agr; and CPT-I&bgr; exist, some of which may have roles in regulating fatty acid oxidation.

ISSN:0002-9629    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundAlthough many studies have reported the effects of dietary vitamin E on the immune response, none so far has assessed its role in nasal allergy.MethodsFemale BALB/c mice were randomized into two groups and fed a 20% casein diet (control group, 50 mg vitamin E/kg diet) or this diet supplemented with 535 mg vitamin E/kg diet (vitamin E group, 585 mg vitamin E/kg diet) for 4 weeks. During the fifth week, the mice in each group were divided into two subgroups to form a total of four treatment groups: group A (control), group B [control + toluene diisocyanate (TDI) sensitization], group C (vitamin E supplementation), and group D (vitamin E supplementation + TDI sensitization). Groups B and D were treated with two courses of intranasal application of 5% TDI in ethyl acetate, whereas groups A and C were treated with ethyl acetate alone. A week after second sensitization all groups were provoked by applying 2.5% of TDI in the vehicle and nasal allergic responses were observed for 10 minutes. Splenic lymphoproliferation, splenic cell cytokines, and the total serum IgE were measured.ResultsMembers of group D had lower (P< 0.01) scores of nasal response and sneezed less frequently (P< 0.01) than those of group B. Similarly, splenic lymphoproliferation and production of IL-4 and IL-5 as well as the total serum IgE levels were lower (P< 0.01) in group D than in group B.ConclusionsThe results indicate that higher doses of vitamin E supplementation may suppress nasal allergic responses.

ISSN:0002-9629    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundEthnicity plays a role in the prevalence, isotype distribution, and clinical significance of anticardiolipin (aCL) and anti-&bgr;2-glycoprotein I (anti-&bgr;2-GPI) antibodies in patients with systemic lupus erythematosus (SLE). Few studies have been done in the African American population.MethodsSerum samples from 100 African American patients with SLE were tested for IgG, IgM, and IgA aCL and anti-&bgr;2-GPI antibodies by enzyme-linked immunosorbent assay (ELISA). Computerized clinical data on these patients were reviewed with a specific focus on clinical manifestations of antiphospholipid syndrome (APS).ResultsPositivity for at least one isotype of aCL antibodies was found in 33% of the patients, whereas 28% were positive for at least one isotype of anti-&bgr;2-GPI antibodies. IgA was the most prevalent isotype for both antibodies; 24% of the patients in the aCL ELISA and 19% in the anti-&bgr;2-GPI ELISA were positive for IgA. Positivity for both aCL and anti-&bgr;2-GPI in the same patient was seen more frequently with the IgA isotype. Fewer than half of the patients positive for aCL antibodies had medium-to-high levels of antibodies. A few patients had presented thrombotic manifestations, and these patients were positive for aCL (P= 0.01) and anti-&bgr;2-GPI antibodies (P= 0.02). No other manifestations of APS could be significantly correlated with the presence of these antibodies.ConclusionsOur results show that IgA is the most prevalent isotype among the African American patients with SLE studied. The predominance of the IgA isotype and the low prevalence of medium-to-high levels of aCL antibodies may account for the low frequency of clinical manifestations of APS in these patients.

ISSN:0002-9629    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Addition of bisphosphonates to standard treatment of multiple myeloma (MM) decreases bone pain and skeletal events without influencing bone healing. Calcitriol, besides its established effects on bone remodeling and calcium metabolism, has both immunoregulatory and cell differentiating effects in vitro and in vivo. Moreover, low serum calcitriol has been reported in MM. We tested the effects of supportive treatment with calcitriol and pamidronate on bone disease in two stage-III-B MM patients with diffuse bone involvement, normal serum calcium, and low serum calcitriol. Complete blood counts, serum calcium, creatinine, quantitative serum and urine immunoglobulins, and biochemical indices of bone turnover, serum calcidiol, calcitriol, parathyroid hormone, skeletal radiographs, and bone mineral density by dual x-ray absorbtiometry were measured every 1–6 months for 16 months in the first patient and 7 months in the second patient. Both patients showed a dramatic improvement of MM activity and in bone disease documented by serial radiographs in the first patient and by increased bone mineral density (approximately 15%) in the second. The reduced serum calcitriol in both patients and the elevated parathyroid hormone observed in the first patient before treatment returned to normal. Supportive treatment with pamidronate does not induce bone healing in MM. Therefore, the results observed with the addition of calcitriol suggest that this hormone may have contributed to the apparent arrest of the progression of MM and caused stimulation of bone healing.

ISSN:0002-9629    

出版商:OVID    

年代:1999

数据来源: OVID