Differential leucocyte RNA expression in the coronary arteries compared to systemic circulation discriminates between patients with and those without coronary artery disease / La expresión diferencial de ARN en leucocitos en las arterias coronarias comparada con la de leucocitos de circulación sistémica discrimina a pacientes con y sin enfermedad arterial coronaria

Aims: To test the hypothesis that the pattern of gene expression in circulating leukocytes may differ between vascular compartments, depending on the presence or absence of atherosclerosis, we evaluated the regional vascular differences in patterns of inflammatory cell activation. Methods: Patients (n = 8) with angiographically-established coronary artery disease (CAD+) and 8 without (CAD-) had blood samples taken from a peripheral vein as well as from left and right coronary arteries. Samples were pooled resulting in 4 CAD+ samples versus 4 CAD- samples and hybridised to a Whole Human Genome Microarray 4×44K. Results: CAD- patients had a similar gene expression profile across the different sites. CAD+ patients had statistically significant different gene expression patterns in venous vs. right and left coronary artery compartments. The expression pattern observed in the right coronary was where the most differences in gene expression were observed in CAD+ vs. CAD- patients. Overall, 1964 genes were differentially expressed between CAD+ and CAD−. Of these, 1052 were less expressed in CAD+ and 912 were more expressed in CAD+. Up to 12 of the 20 most differentially expressed genes appeared to reflect different phases of the atherosclerosis process: endothelial dysfunction, lipid accumulation, and smooth muscle cell proliferation. Conclusions: Gene expression of circulating leukocytes differentiates CAD+ from CAD- patients. Gene expression is significantly different between coronary arteries and the systemic circulation in CAD+ patients, but not in CAD- patients. Gene expression is significantly different between CAD+ and CAD- subjects, and appears to reflect the atherosclerosis process. These intra-individual differences may be an additional feature of established coronary artery disease

Objetivo: Para comprobar la hipótesis de que los patrones de expresión génica de leucocitos en circulación pueden ser diferentes entre los compartimentos vasculares dependiendo de la presencia o ausencia de arteriosclerosis, hemos evaluado en distintas regiones vasculares las diferencias entre los patrones de expresión y la activación de células inflamatorias. Métodos: Se extrajeron muestras de sangre de venas periféricas y de las arterias coronarias (derecha e izquierda) de pacientes con (n=8; CAD+) y sin (n=8; CAD−) enfermedad arterial coronaria establecida angiográficamente. Las muestras fueron hibridadas en dos pooles de 4 muestras (CAD+ vs CAD−) mediante el kit Whole Human Genome Microarray 4×44K. Resultados: Los pacientes CAD- tenían un perfil de expresión génica similar entre los distintos compartimentos vasculares. Los pacientes CAD+ tenían patrones de expresión génica significativamente diferentes entre los compartimentos venosos y las arterias coronarias derecha e izquierda. El patrón de expresión observado en la arteria coronaria derecha fue el que presentó más diferencias entre los pacientes CAD+ vs. CAD-. En conjunto, 1.964 genes estaban expresados diferencialmente entre CAD+ y CAD-. De estos, 1.052 estaban menos expresados en CAD+ i 912 estaban más expresados en CAD+. Hasta 12 de los 20 genes más diferencialmente expresados estaban relacionados con las diferentes fases del proceso arteriosclerótico: disfunción endotelial, acumulación lipídica y proliferación de células musculares lisas. Conclusiones: La expresión génica de leucocitos circulantes diferencia pacientes CAD+ de CAD-. La expresión genética es significativamente diferente entre arterias coronarias y circulación sistémica en pacientes CAD+, pero no en pacientes CAD-. Estas diferencias intraindividuales podrían ser una característica adicional en el diagnóstico de la enfermedad arterial coronaria

Hepatic Phospholipidosis Is Associated with Altered Hepatobiliary Function as Assessed by Gadoxetate Dynamic Contrast-enhanced Magnetic Resonance Imaging.

To determine if amiodarone induces hepatic phospholipidosis (PLD) sufficient to detect changes in hepatobiliary transporter function as assessed by gadoxetate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), rats were orally dosed with vehicle (1% methyl cellulose) or amiodarone (300 mg/kg/day) for 7 consecutive days. Gadoxetate DCE-MRI occurred at baseline, day 7, and following a 2-week washout of amiodarone. At day 7, the gadoxetate washout rate was significantly decreased compared to the vehicle group. Blood chemistry analysis revealed no significant changes in liver enzymes (alanine aminotransferase [ALT]/aspartate aminotransferase [AST]/alkaline phosphatase [ALP]), bilirubin, or bile acids between vehicle or amiodarone groups. Hepatic PLD was confirmed in all rats treated with amiodarone at day 7 by transmission electron microscopy. Following the 2-week washout, there was no ultrastructural evidence of hepatic PLD in rats and the gadoxetate washout rate returned to baseline levels. This is the first study to show the application of gadoxetate DCE-MRI to detect hepatobiliary functional changes associated with PLD and offer a potential new technique with clinical utility in patients suspected of having PLD. These results also suggest PLD itself has functional consequences on hepatobiliary function in the absence of biomarkers of toxicity, given the cause/effect relationship between PLD and function has not been fully established.

Pathological changes associated with white striping in broiler breast muscles.

White striping is a condition in broiler chickens characterized grossly by the occurrence of white striations, seen parallel to the direction of muscle fibers, on broiler breast fillets and thighs. Based on visual evaluation of the intensity of white striping, breast fillets can be categorized into normal (NORM), moderate (MOD), and severe (SEV) categories. This study was undertaken to evaluate the details of changes in histology as well as proximate composition occurring in the fillets with respect to the 3 degrees of white striping. In experiment 1, representative breast fillets for each degree of white striping (n = 20) were collected from 45-d-old broilers, approximately 2 h postmortem. From each fillet, 2 skeletal muscle samples were obtained and fixed in 10% neutral buffered formalin. To identify and differentiate the histological changes, slides were prepared and stained using hematoxylin and eosin, Masson's Trichrome, and Oil Red O stains. In experiment 2, samples with 3 degrees of white striping were collected from 57-d-old birds for conducting proximate analysis. Major histopathological changes observed in the MOD and SEV samples consisted of loss of cross striations, variability in fiber size, floccular/vacuolar degeneration and lysis of fibers, mild mineralization, occasional regeneration (nuclear rowing and multinucleated cells), mononuclear cell infiltration, lipidosis, and interstitial inflammation and fibrosis. Microscopic lesions were visually scored for degeneration and necrosis, fibrosis, and lipidosis. The scale used to score the samples ranged from 0 (normal) to 3 (severe). There was an increase (P < 0.05) in mean scores for degenerative or necrotic lesions, fibrosis, and lipidosis as the degree of white striping increased from NORM to SEV. The results from the histopathological study were supported by the findings from proximate analysis confirming that the fat and protein contents of muscle increased (P < 0.05) and decreased (P < 0.05), respectively, as the degree of white striping increased. In conclusion, the histopathological changes occurring in white striping indicate a degenerative myopathy that could be associated with increased growth rate in birds.

Lipoedema: presentation and management.

Lipoedema is a distinct clinical condition characterized by bilateral, symmetrical enlargement of the buttocks and lower limbs owing to excess deposition of subcutaneous fat. It is found almost exclusively in women. The common features associated with this condition are 'column- shaped' legs with sparing of the feet, bruising, sensitivity to pressure, and orthostatic oedema. The progression to lipo-lymphoedema or morbid obesity is possible. Conservative measures used in the management of lymphoedema can prevent progression/limit the orthostatic oedema. Surgical procedures may also play a part in the management of lipoedema.

Bis(monoacylglycerol)phosphate as a non-invasive biomarker to monitor the onset and time-course of phospholipidosis with drug-induced toxicities.

IMPORTANCE TO THE FIELD: Drug-induced phospholipidosis (PL) is a phospholipid storage disorder characterized by the accumulation of multi-lamellar bodies (myeloid bodies) in tissues. A major unanswered question is whether PL represents a benign adaptive response, symptom or early event in drug toxicity. The absence of a non-invasive biomarker to monitor tissue PL has made it difficult to determine the prevalence and implications of PL in the clinic. As a result, the interpretation of PL in risk assessment remains uncertain in preclinical and clinical drug development. AREAS COVERED IN THIS REVIEW: This review describes the rationale for bis(monoacylglycerol)phosphate (BMP) as a biomarker of PL and explores the potential links between PL and the toxicities of drugs. WHAT THE READER WILL GAIN: The similarities between the hypothesized roles of BMP in PL and Niemann-Pick type C disease are discussed. The potential implications of PL for cellular function are described in the context of drug-induced QT prolongation, myopathy and renal toxicity. TAKE HOME MESSAGE: A specific species of BMP, di-docosahexaenoyl-BMP, should be investigated further as a non-invasive biomarker to monitor the onset and time course of PL and to better understand the functional consequences which could contribute to the toxicities of drugs.

Phospholipidosis as a function of basicity, lipophilicity, and volume of distribution of compounds.

Drug-induced phospholipidosis (PLD) is an adaptive histologic alteration that is seen with various marketed drugs and often encountered during drug development. Various in silico and in vitro cell-based methods have been developed to predict the PLD-inducing potential of compounds. These methods rely on the inherent physicochemical properties of the molecule and, as such, tend to overpredict compounds as PLD inducers. Recognizing that the distribution of compounds into tissues or tissue accumulation is likely a key factor in PLD induction, in addition to key physicochemical properties, we developed a model to predict PLD in vivo using the measures of basicity (pK(a)), lipophilicity (ClogP), and volume of distribution (V(d)). Using sets of PLD inducers and noninducers, we demonstrate improved concordance with this method. Furthermore, we propose a screening paradigm that includes a combination of various methods to predict the in vivo PLD-inducing potential of compounds, which may be especially useful in lead identification and optimization processes in drug discovery.

Early signs of neurolipidosis-related behavioural alterations in a murine model of metachromatic leukodystrophy.

Arylsulfatase A (ASA)-deficient mice represent an animal model for the lysosomal storage disorder metachromatic leukodystrophy (MLD). Although the model has been applied in pathophysiological and therapeutic studies, the behavioural phenotype of ASA(-/-) mice is only partially characterized, and the most decisive outcome measures for therapy evaluation only emerge beyond 1 year of age. Presently, ASA(-/-) mice and ASA(+/-) control mice were studied at 6 and 12 months of age on an extensive battery including tests of neuromotor ability, exploratory behaviour, and learning and memory. Overt signs of ataxia were not observed in 6-month-old ASA(-/-) mice, but quantitative gait analysis during open-field exploration revealed that ASA(-/-) mice displayed increased hind base width and increased stride lengths for all paws. Their covert motor incoordination was evident in a correlation analysis which unveiled decreased harmonisation of concurrent gait parameters. For example, while ASA(+/-) controls demonstrated substantial convergence of front and hind base width (r=0.54), these variables actually diverged in ASA(-/-) mice (r=-0.37). Furthermore, various behavioural observations indicated emotional alterations in ASA(-/-) mice. Six-month-old ASA(-/-) mice also showed decreased response rates in scheduled operant responding. The present findings could provide relevant behavioural outcome measures for further use of this murine MLD model in preclinical studies.

Neuronal and glial accumulation of alpha- and beta-synucleins in human lipidoses.

A number of the lysosomal storage diseases that have now been characterized are associated with intra-lysosomal accumulation of lipids, caused by defective lysosomal enzymes. We have previously reported neuronal accumulation of both alpha- and beta-synucleins in brain tissue of a GM2 gangliosidosis mouse model. Although alpha-synuclein has been implicated in several neurodegenerative disorders including Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, its functions remain largely unclear. In our present study, we have examined a cohort of human lipidosis cases, including Sandhoff disease, Tay-Sachs disease, metachromatic leukodystrophy, beta-galactosialidosis and adrenoleukodystrophy, for the expression of alpha- and beta-synucleins and the associated lipid storage levels. The accumulation of alpha-synuclein was found in brain tissue in not only cases of lysosomal storage diseases, but also in instances of adrenoleukodystrophy, which is a peroxisomal disease. alpha-synuclein was detected in both neurons and glial cells of patients with these two disorders, although its distribution was found to be disease-dependent. In addition, alpha-synuclein-positive neurons were also found to be NeuN-positive, whereas NeuN-negative neurons did not show any accumulation of this protein. By comparison, the accumulation of beta-synuclein was detectable only in the pons of Sandhoff disease cases. This differential accumulation of alpha- and beta-synucleins in human lipidoses may be related to functional differences between these two proteins. In addition, the accumulation of alpha-synuclein may also be a condition that is common to lysosomal storage diseases and adrenoleukodystrophies that show an enhanced expression of this protein upon the elevation of stored lipids.

A role for lysosomal phospholipase A2 in drug induced phospholipidosis.

Many therapeutic drugs currently in use are cationic amphiphiles. These cationic amphiphilic drugs (CADs) induce phospholipidosis in humans and experimental animals. The recent study shows that CAD-induced cellular phospholipidosis is linked to the impairment of phospholipid catabolism by inhibition of lysosomal phospholipase A2 activity.

Clinical variant of Tangier disease in Japan: mutation of the ABCA1 gene in hypoalphalipoproteinemia with corneal lipidosis.

Despite progress in molecular characterization, specific diagnoses of disorders belonging to a group of inherited hypoalphalipoproteinemias, i.e., apolipoprotein AI deficiency, lecithin-cholesterol acyltransferase deficiency, Tangier disease (TD), and familial high-density lipoprotein (HDL) deficiency, remain difficult on a purely clinical basis. Several TD patients were recently found to be homozygous for mutations in the ABCA1 gene. We have documented here a clinical variant of TD in a Japanese patient who manifested corneal lipidosis and premature coronary artery disease as well as an almost complete absence of HDL-cholesterol, by identifying a novel homozygous ABCA1 mutation (R1680W). We propose that patients with apparently isolated HDL deficiency who are found to carry ABCA1 mutations may in fact belong to a category of TD patients whose phenotypic features are only partially expressed, and that a number of hidden clinical variants of TD might exist among other HDL deficiency patients who have escaped correct clinical diagnosis.

Diabetic ketosis and ketoacidosis in cats: 42 cases (1980-1995).

OBJECTIVE: To determine clinical signs, clinicopathologic abnormalities, prevalence of concurrent disease, treatment, complications of treatment, and outcome in cats with diabetic ketosis (DK) or diabetic ketoacidosis (DKA). DESIGN: Retrospective study. ANIMALS: 42 cats with DK or DKA. PROCEDURE: Medical records of diabetic cats with ketonuria were reviewed. RESULTS: In 26 cats, diabetes was newly diagnosed; in 16, diabetes had been diagnosed previously and cats had been treated with insulin (n = 14) or sulfonylurea drugs (2). Common clinical findings were lethargy, anorexia, polyuria, polydipsia, and weight loss. Common laboratory findings were hyperglycemia, hyponatremia, hypochloremia, hypokalemia, hypocalcemia, hypophosphatemia, low total CO2 content, hyperosmolality, high serum alanine transaminase activity, azotemia, glycosuria, and ketonuria. Concurrent disorders were identified in 39 cats and included hepatic lipidosis, cholangiohepatitis, pancreatitis, chronic renal failure, urinary tract infection, and neoplasia. Treatment of DK and DKA included administration of regular crystalline (34 cats), NPH (6), or ultralente (2) insulin, intravenous (38) or subcutaneous (4) administration of fluids, and enterall parenteral or administration of antibiotics (42). Complications during treatment included abnormalities in serum electrolyte concentrations (27 cats), hemolytic anemia (4), hypoglycemia (3), and neurologic abnormalities unrelated to hypoglycemia (2). Eleven cats died or were euthanatized during the initial hospitalization period for treatment of DK or DKA. Azotemia, metabolic acidosis, and hyperosmolality were more severe in cats that died than in cats that survived. Differences in regard to treatment or complications were not apparent between cats that died and cats that survived. The 31 cats that survived were discharged 1 to 16 days (median, 5 days) after initiation of insulin treatment. Diabetic ketosis or ketoacidosis recurred in 13 (42%) of these cats. CLINICAL IMPLICATIONS: A thorough diagnostic evaluation should be performed on cats with DK or DKA to identify concurrent disorders, formulate an appropriate treatment plan, and provide prognostic information to the owner.

Hepatic lipidosis in anorectic, lactating holstein cattle: a retrospective study of serum biochemical abnormalities.

The association between hepatic lipidosis (HL) and disease in 59 anorectic, ketotic, lactating Holstein heifers and cows was investigated. Severe HL, as determined by histologic evaluation of liver tissue, was present in 46 animals; only half of these animals required intensive treatment for ketosis, and only half had serum biochemical evidence of liver disease, as determined by the presence of a last value of 2-fold or greater than the upper limit of the reference ranges for at least 2 of the 4 serum tests: gamma-glutamyl transferase, aspartate aminotransferase, and sorbitol dehydrogenase activities and bile acid concentrations. Most cattle with biochemical evidence of liver disease and severe HL had been lactating for 14 or more days. Cows that required intensive treatment inconsistently had serum biochemical evidence of liver disease. Although cattle with severe HL had significantly higher serum bilirubin concentrations and aspartate aminotransferase and sorbitol dehydrogenase activities than cattle with less severe lipidosis, the specificity of abnormally high serum sorbitol dehydrogenase activity or bilirubin concentration for severe lipidosis was only 8%. Abnormally high serum aspartate aminotransferase activity was 83% sensitive and 62% specific for severe lipidosis. Serum glucose and total carbon dioxide concentrations were significantly lower in cattle with severe lipidosis than in those with mild or moderate lipidosis, and low serum glucose or total carbon dioxide concentrations were rare in cattle without severe lipidosis. From these data, we conclude that the use of a single biochemical or histopathologic criterion to define severity of disease or degree of liver compromise in anorectic, ketotic cows results in the misidentification of many animals.

Feline hepatic lipidosis.

Hepatic lipidosis occurs when lipid mobilized to the liver exceeds lipid leaving the liver via formation of very-low-density lipoproteins or by oxidation. Hepatic lipidosis in cats is associated with overt liver dysfunction. In affected cats, excess lipid is mobilized to the liver because of starvation. Removal of hepatic lipid may be impaired because of protein malnutrition, a relative carnitine deficiency, or oxidative damage to peroxisomes and other hepatic organelles. Hepatic lipidosis occurs in adult cats, and is manifest by signs of weight loss, depression, vomiting, and icterus. Diagnosis is achieved by evaluating laboratory and diagnostic imaging data, in conjunction with a liver biopsy. Aggressive tube feeding is the treatment of choice. With this treatment, survival rates are 60% to 80%.

Chloroquine-induced lipidosis in the rat retina: functional and morphological changes after withdrawal of the drug.

BACKGROUND: The antimalarial and antirheumatic drug chloroquine is one of the most infamous amphiphilic cationic drugs in clinical ophthalmology. It is known to cause lipidosis and photoreceptor degeneration in the human and the rat retina. METHODS: We treated female albino Wistar rats (mean weight 200 g) orally with chloroquine (95 mg/kg body weight) for 12 weeks, followed by a period of 4 months with normal feed. After initial electroretinography in all rats, measurements were made after 4 and 12 weeks of treatment and 16 weeks after withdrawal. The rats were prepared for histological examination. RESULTS: Treatment of rats with chloroquine caused severe lipidosis in the neuroretina; photoreceptor cell degeneration was slight. After 12 weeks of treatment, the b-wave amplitude was reduced to 30% of the initial value; the a-wave amplitude was reduced, but remained within the range of normal values. After withdrawal of chloroquine the lipidosis remitted, but the degeneration of the photoreceptor cell layer continued to progress. Despite remission of lipidosis, electroretinography demonstrated functional disturbances, marked by reduction of the a- and b-wave amplitudes to 25% and 16% of initial values, respectively. CONCLUSIONS: Seen from the point of view of function, it is doubtful whether lipidosis is the primary cause of changes in the electroretinogram or of receptor cell degeneration.

Clinical and pathological studies in horses with hepatic disease.

In horses with hepatic necrosis, lipidosis, neoplasia and cirrhosis, progression of the disease was studied by serial measurements of total serum bile acid concentrations and of plasma glutamate dehydrogenase (GD) and gamma glutamyl transferase (gamma GT) and by liver biopsy. Plasma ammonia concentrations were significantly elevated compared to clinically normal horses, but such changes were not always accompanied by a decline in plasma urea concentration. A fall in plasma glucose concentration carried a guarded prognosis. These were all invaluable aids in early diagnosis and throughout the disease course. The study suggests that other factors, such as hypokalaemia, alkalosis, short chain volatile fatty acids, false and true neurotransmitters, may be important in the pathogenesis of hepatic coma in the horse.

Chloroquine-induced lipidosis in the rat retina: a functional and morphological study.

Corneal opacity, reversible retinal lipidosis and irreversible receptor cell degeneration are known to occur after long-term treatment with chloroquine. Female albino Wistar rats (initial age 6 weeks, weight between 100 and 150 g) were treated orally with chloroquine (40-60 mg/kg body weight) for 4 weeks and with 70-80 mg/kg body weight for the following 4 (group A) and 8 weeks (group B). The animals were submitted to electroretinography ERG, and the retinas were prepared for histological investigation. After treatment with chloroquine for 8 weeks, lipidosis-like inclusions could be seen in the rat retina. A deformation of the receptor cell layer was not observed by light microscopy. The a-wave amplitude decreased to 33% and the b-wave amplitude to 40% of the values before treatment. In contrast to group A, we found receptor cell degeneration and macrophage-like cells in the peripheral and central retina in rats treated for 12 weeks. These changes were probably responsible for a-wave and b-wave reductions of 50 and 79% of values before treatment, respectively. It can be assumed that changes in ERG parameters in the first period are caused by lipidosis. Later extremer deformation is induced by receptor cell degeneration and accompanying lipidosis.

Stroke-prone SHR and arteriolipidosis-prone SHR as models for atherosclerosis: their mechanisms and application for nutritional and pharmacological studies.

1. Peritoneal macrophages (Mphi) were harvested from non-stimulated 2 month old SHRSP and WKY, and incubated with acetyl LDL or [14C]-oleate-albumin complex to check total, free and esterified cholesterol (Cho) accumulation as well as acy coenzyme A-cholesterol acyltransferase (ACAT) activity and its activation by hyperlipidaemic serum. 2. Total and esterified Cho accumulation as well as ACAT activity were enhanced in Mphi from SHRSP compared with those from WKY. 3. To observe the dietary or pharmacological influence on atherogenesis, arteriolipidosis-prone SHR (ALR) were given a high fat cholesterol diet with 3% taurine or a Ca blocker (Nilvadipine, N; 30 mg/kg), both of which significantly decreased serum Cho level and clearly attenuated arterial fat deposition.

Experimental induction of hepatic lipidosis in cats.

The effect of long-term voluntary fasting on hematologic variables, biochemical profiles, and liver histologic findings was assessed in 15 obese cats (> 40% overweight). Clinical signs and laboratory results consistent with hepatic lipidosis were observed in 12 of 15 cats after 5 to 7 weeks of fasting, and were associated with 30 to 35% reduction of initial body weight. Histologic examination of successive liver biopsy specimens revealed that obesity was not associated with liver parenchymal lipid accumulation, but that fasting resulted in lipidosis in all 15 cats. The long-term fast was associated with an early (after 2 to 4 weeks of fasting) and significant (P < 0.05) reduction in serum urea, glucose, and albumin concentrations, and RBC mass. Fasting for 5 to 7 weeks was associated with a significant (P < 0.05) increase in hepatic-associated enzyme activities and in total and direct serum bilirubin concentrations. Significant (P < 0.05) changes in serum alkaline phosphatase developed as early as 3 weeks before the onset of hyperbilirubinemia. Except for development of hepatic lipidosis, cats appeared to tolerate the fast without other adverse effect. This study confirmed that long-term fasting may induce clinical hepatic lipidosis in obese cats. Fasting appears to induce a syndrome of hepatic lipidosis that is indistinguishable from feline idiopathic hepatic lipidosis and may be an appropriate model to study the pathophysiologic features and treatment of hepatic lipidosis.

Chlorphentermine-induced lipidosis in the rat retina: a functional and morphological study.

Chronic administration of the cationic amphiphilic anorexigenic drug chlorphentermine to rats has previously been shown to induce extraocular and ocular lipidosis: large numbers of lipidosis-related cytoplasmic inclusions can be found in the pigment epithelium and smaller numbers in the neuroretina. In the present study, female albino Wistar rats were treated orally with chlorphentermine (30-45 mg/kg body weight) for 4-16 weeks. The animals were submitted to electroretinography, and the retinae were prepared for histological investigations. Our histological findings corresponded to previous reports. The changes in electroretinographic parameters were low. The clearest change was a reduction of the b-wave amplitude of 20% after 12 and 16 weeks of treatment compared with the values before drug treatment. The a-wave amplitude did not differ from that in the control group. Lipidosis in the neuroretina may be the reason for functional influences on the b-wave amplitude. The function of the receptor cells, which is represented by the a-wave, appeared unaffected by chlorphentermine.

Xantomas: marcadores cutáneos de hiperlipidemias / Xanthomas: Cutaneous markers of hyperlipidemias

Se presenta una revisión sobre los xantomas cutáneos enfatizando su importancia como marcadores de padecimientos sistémicos principalmente de la hiperlipoproteinemias primarias y secundarias. Existe una estrecha relación entre el trastorno metabólico y tipo de lípido sérico elevado con las diferentes variedades de xantomas. Se destaca la necesidad del diagnóstico temprano de la dislipidemias por el riesgo de la enfermedad coronaria aterosclerosa en pacientes jóvenes