Association Of Postalimentary Lipemia With Atherosclerotic Manifestations.

We identified different lipemic and metabolic responses after the ingestion of a standardized meal by healthy adults and related them to atherosclerotic markers. Samples from 60 normolipidemic adults were collected before and after a liquid meal (40 g fat/m² body surface) at 0, 2, 4, 6, and 8 h for measurements of lipids, free fatty acids (FFA), insulin, cholesteryl ester transfer protein (CETP), autoantibodies to epitopes of oxidized LDL (oxLDL Ab), lipolytic activities, and apolipoprotein E polymorphism. Mean carotid intima-media thickness (cIMT) was determined by Doppler ultrasound. The volunteers were classified into early (N = 39) and late (N = 31) triacylglycerol (TAG) responders to the test meal. Late responders showed lower HDL cholesterol concentration at fasting and in the TAG peak, lower insulin and higher FFA concentrations compared to early responders. Multivariate regression analyses showed that mean cIMT was associated with gender (male) and age in early responders and by cholesterol levels at the 6th hour in late responders. oxLDL Ab were explained by lipoprotein lipase and negatively by hepatic lipase and oxLDL Ab (fasting period) by CETP (negative) and FFA (positive). This study is the first to identify a postalimentary insulin resistance state, combined with a reduced CETP response exclusively among late responders, and the identification of the regulators of postalimentary atherogenicity. Further research is required to determine the metabolic mechanisms described in the different postalimentary phenotypes observed in this study, as well as in different pathological states, as currently investigated in our laboratory.451086-9

Reducing Brain Kynurenic Acid Synthesis Precludes Kynurenine-Induced Sleep Disturbances

Patients with neurocognitive disorders often battle sleep disturbances. Kynurenic acid is a tryptophan metabolite of the kynurenine pathway implicated in the pathology of these illnesses. Modest increases in kynurenic acid, an antagonist at glutamatergic and cholinergic receptors, result in cognitive impairments and sleep dysfunction. We explored the hypothesis that inhibition of the kynurenic acid synthesising enzyme, kynurenine aminotransferase II, may alleviate sleep disturbances. At the start of the light phase, adult male and female Wistar rats received systemic injections of either: (i) vehicle; (ii) kynurenine (100 mg kg−1; i.p.); (iii) the kynurenine aminotransferase II inhibitor, PF-04859989 (30 mg kg−1; s.c.); or (iv) PF-04859989 and kynurenine in combination. Kynurenine and kynurenic acid levels were evaluated in the plasma and brain. Separate animals were implanted with electroencephalogram and electromyogram telemetry devices to record polysomnography, and evaluate the vigilance states wake, rapid eye movement sleep and non-rapid eye movement sleep following each treatment. Kynurenine challenge increased brain kynurenic acid and resulted in reduced rapid eye movement sleep duration, non-rapid eye movement sleep delta power and sleep spindles. PF-04859989 reduced brain kynurenic acid formation when given prior to kynurenine, prevented disturbances in rapid eye movement sleep and sleep spindles, and enhanced non-rapid eye movement sleep. Our findings suggest that reducing kynurenic acid in conditions where the kynurenine pathway is activated may serve as a potential strategy for improving sleep dynamics

Association of postalimentary lipemia with atherosclerotic manifestations

We identified different lipemic and metabolic responses after the ingestion of a standardized meal by healthy adults and related them to atherosclerotic markers. Samples from 60 normolipidemic adults were collected before and after a liquid meal (40 g fat/m² body surface) at 0, 2, 4, 6, and 8 h for measurements of lipids, free fatty acids (FFA), insulin, cholesteryl ester transfer protein (CETP), autoantibodies to epitopes of oxidized LDL (oxLDL Ab), lipolytic activities, and apolipoprotein E polymorphism. Mean carotid intima-media thickness (cIMT) was determined by Doppler ultrasound. The volunteers were classified into early (N = 39) and late (N = 31) triacylglycerol (TAG) responders to the test meal. Late responders showed lower HDL cholesterol concentration at fasting and in the TAG peak, lower insulin and higher FFA concentrations compared to early responders. Multivariate regression analyses showed that mean cIMT was associated with gender (male) and age in early responders and by cholesterol levels at the 6th hour in late responders. oxLDL Ab were explained by lipoprotein lipase and negatively by hepatic lipase and oxLDL Ab (fasting period) by CETP (negative) and FFA (positive). This study is the first to identify a postalimentary insulin resistance state, combined with a reduced CETP response exclusively among late responders, and the identification of the regulators of postalimentary atherogenicity. Further research is required to determine the metabolic mechanisms described in the different postalimentary phenotypes observed in this study, as well as in different pathological states, as currently investigated in our laboratory

Sex-dependent variables in the modulation of postalimentary lipemia

Objective: To quantify in young adults the sex-dependent differences in lipemic responses to a fat meal, we measured the association of these responses with markers of atherosclerosis and determined their metabolic regulators. Methods: Forty-nine normolipidemic volunteers, 25 women and 24 men, were matched according to age, body mass index, waist circumference, diet, physical activity, and apolipoprotein-E phenotyping. After receiving a standardized fat meal (40 g of fat/m(2) of body surface area), serial blood samples were drawn for laboratory analysis. Common carotid intima-media thickness was measured. Results: The lipemic responses were much greater in men than in women for plasma triacylglycerol (TAG), cholesterol, and TAG in TAG-rich lipoproteins, non-esterified fatty acids, phospholipids, and apolipoprotein-B100. Men presented with increased blood pressure, carotid intima-media thickness, TAG, hepatic lipase, and insulin and lower high-density lipoprotein cholesterol, apoli-poprotein-AI, and non-esterified fatty acid concentrations. Only in men did carotid intima-media thickness correlate marginally with titers of autoantibodies to epitopes of oxidized low-density lipoprotein; in addition, phospholipids and cholesteryl esters were negatively related to autoantibodies. Multivariate analysis indicated that age (R-2 = 45%), waist circumference (R-2 = 19%), phospholipids (R-2 = 39%), non-esterified fatty acids (R-2 = 29%), insulin (R-2 = 17%), lipoprotein lipase activity (R-2 = 16%), and cholesteryl ester transfer protein (an exploratory variable; R-2 = 6%) are strong determinants of postalimentary lipemia in women and that only insulin (R-2 = 55%) and phospholipids (R-2 = 37%) are determinants in men. Conclusions: We have provided data explaining that postalimentary lipemia is differently regulated by sex. Several risk factors for coronary heart disease and significant associations with atherosclerosis biomarkers were found only in men. (c) 2006 Elsevier Inc. All rights reserved.22191

Association of postalimentary lipemia with atherosclerotic manifestations

We identified different lipemic and metabolic responses after the ingestion of a standardized meal by healthy adults and related them to atherosclerotic markers. Samples from 60 normolipidemic adults were collected before and after a liquid meal (40 g fat/m² body surface) at 0, 2, 4, 6, and 8 h for measurements of lipids, free fatty acids (FFA), insulin, cholesteryl ester transfer protein (CETP), autoantibodies to epitopes of oxidized LDL (oxLDL Ab), lipolytic activities, and apolipoprotein E polymorphism. Mean carotid intima-media thickness (cIMT) was determined by Doppler ultrasound. The volunteers were classified into early (N = 39) and late (N = 31) triacylglycerol (TAG) responders to the test meal. Late responders showed lower HDL cholesterol concentration at fasting and in the TAG peak, lower insulin and higher FFA concentrations compared to early responders. Multivariate regression analyses showed that mean cIMT was associated with gender (male) and age in early responders and by cholesterol levels at the 6th hour in late responders. oxLDL Ab were explained by lipoprotein lipase and negatively by hepatic lipase and oxLDL Ab (fasting period) by CETP (negative) and FFA (positive). This study is the first to identify a postalimentary insulin resistance state, combined with a reduced CETP response exclusively among late responders, and the identification of the regulators of postalimentary atherogenicity. Further research is required to determine the metabolic mechanisms described in the different postalimentary phenotypes observed in this study, as well as in different pathological states, as currently investigated in our laboratory

Cholesteryl Ester Transfer Protein Gene Mutations In Brazilian Hyperalphalipoproteinemia [8]

[No abstract available]695455457de Grooth, G.J., Klerkx, A.H., Stroes, E.S., A review of CETP and its relation to atherosclerosis (2004) J Lipid Res, 45, pp. 1967-1974Tall, A., Plasma lipid transfer proteins (1995) Annu Rev Biochem, 64, pp. 235-257Maruyama, T., Sakai, N., Ishigami, M., Prevalence and phenotypic spectrum of cholesteryl ester transfer protein gene mutations in Japanese hyperalphalipoproteinemia (2003) Atherosclerosis, 166, pp. 177-185Nagano, M., Yamashita, S., Horano, K., Molecular mechanisms of cholesteryl ester transfer protein deficiency in Japanese (2004) J Atheroscler Thromb, 11, pp. 110-121Gordon, D.J., Probstfield, J.L., Garrison, R.L., High density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies (1989) Circulation, 79, pp. 8-15Zhong, S., Sharp, D.S., Grove, J.S., Increased coronary heart disease in Japanese-American men with mutation in the cholesteryl ester transfer protein gene despite increased HDL levels (1996) J Clin Invest, 97, pp. 2917-2923Hirano, K., Yamashita, S., Kuga, Y., Atherosclerotic disease in marked hyperalphalipoproteinemia. Combined reduction of cholesteryl ester transfer protein and hepatic triglyceride lipase (1995) Arterioscler Thromb Vasc Biol, 15, pp. 1849-1856Inazu, A., Brown, M.L., Hesler, C.B., Increased high-density lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation (1990) N Engl J Med, 323, pp. 1234-1238Hill, S.A., Nazir, D.J., Jayaratne, P., Mutations in cholesteryl ester transfer protein and hepatic lipase in a North American population (1997) Clin Biochem, 30, pp. 413-418Inazu, A., Jian, X.C., Haraki, T., Genetic cholesteryl ester transfer protein deficiency caused by two prevalent mutations as a major determinant of increased levels of high density lipoprotein cholesterol (1994) J Clin Invest, 94, pp. 1872-1882Inazu, A., Koizumi, J., Haraki, T., Rapid detection and prevalence of cholesteryl ester transfer protein deficiency caused by an intron 14 splicing defect in hyperalphalipoproteinemia (1993) Hum Genet, 91, pp. 13-16Sakai, N., Yamashita, S., Hirano, K., Frequency of exon 15 missense mutation (442D: G) in cholesteryl ester transfer protein gene in hyperalphalipoproteinemic Japanese subjects (1995) Atherosclerosis, 114, pp. 139-145Takahashi, K., Jiang, X.C., Sakai, N., A missense mutation in the cholesteryl ester transfer protein gene with possible dominant effects on plasma high density lipoproteins (1993) J Clin Invest, 92, pp. 2060-2064Hirano, K., Yamashita, S., Funahashi, T., Frequency of intron 14 splicing defect of cholesteryl ester transfer protein gene in the Japanese general population: Relation between the mutation and hyperalphalipoproteinemia (1993) Atherosclerosis, 100, pp. 85-90Alarcon, S.B., Oliveira, H.C., Harada, L.M., Moderate hyperalphalipoproteinaemia in a Brazilian population is related to lipoprotein lipase activity, apolipoprotein A-I concentration, age and body mass index (2004) Clin Sci, 106, pp. 11-1

Symptomatic cardiac metastases of breast cancer 27 years after mastectomy: a case report with literature review - pathophysiology of molecular mechanisms and metastatic pathways, clinical aspects, diagnostic procedures and treatment modalities.

Metastases to the heart and pericardium are rare but more common than primary cardiac tumours and are generally associated with a rather poor prognosis. Most cases are clinically silent and are undiagnosed in vivo until the autopsy. We present a female patient with a 27-year-old history of an operated primary breast cancer who was presented with dyspnoea, paroxysmal nocturnal dyspnoea and orthopnoea. The clinical signs and symptoms aroused suspicion of congestive heart failure. However, the cardiac metastases were detected during a routine cardiologic evaluation and confirmed with computed tomography imaging. Additionally, this paper outlines the pathophysiology of molecular and clinical mechanisms involved in the metastatic spreading, clinical presentation, diagnostic procedures and treatment of heart metastases. The present case demonstrates that a complete surgical resection and systemic chemotherapy may result in a favourable outcome for many years. However, a lifelong medical follow-up, with the purpose of a detection of metastases, is highly recommended. We strongly call the attention of clinicians to the fact that during the follow-up of all cancer patients, such heart failure may be a harbinger of the secondary heart involvement