Brain Stimulation Differentially Modulates Nociception and Inflammation in Aversive and Non-aversive Behavioral Conditions.

Inflammation and pain are major clinical burdens contributing to multiple disorders and limiting the quality of life of patients. We previously reported that brain electrical stimulation can attenuate joint inflammation in experimental arthritis. Here, we report that non-aversive electrical stimulation of the locus coeruleus (LC), the paraventricular hypothalamic nucleus (PVN) or the ventrolateral column of the periaqueductal gray matter (vlPAG) decreases thermal pain sensitivity, knee inflammation and synovial neutrophilic infiltration in rats with intra-articular zymosan. We also analyzed the modulation of pain and inflammation during aversive neuronal stimulation, which produces defensive behavioral responses such as freezing immobility to avoid predator detection. Electrical stimulation with higher intensity to induce freezing immobility in rats further reduces pain but not inflammation. However, tonic immobility further reduces pain, knee inflammation and synovial neutrophilic infiltration in guinea pigs. The duration of the tonic immobility increases the control of pain and inflammation. These results reveal survival behavioral and neuromodulatory mechanisms conserved in different species to control pain and inflammation in aversive life-threatening conditions. Our results also suggest that activation of the LC, PVN, or vlPAG by non-invasive methods, such as physical exercise, meditation, psychological interventions or placebo treatments may reduce pain and joint inflammation in arthritis without inducing motor or behavioral alterations.

Thermophysiological, haematological, biochemical and behavioural stress responses of sheep transported on road.

The study was conducted to evaluate the thermophysiological, haematological, biochemical and behavioural stress responses of sheep transported on road. A total of 44 Chamarita breed adult ewes were randomly allotted to one of two groups, one control group (untransported) and transported group (journey of 4 h), and blood stress indicators were measured 1 day before transport and at four time points post-transport (0, 4 and 24 h). Thermophysiological profiles of ewes were measured by temperature buttons (iButton Thermochron® ) and placed in intravaginal sponges. Direct observations, with a combination of scan and behaviour sampling, were carried out to collect information on individual behaviour and the time it took the ewes to drink water, eat and rest after returning to their pen respectively. Transported ewes lost approximately 1 kg live weight compared to controls and had higher body temperatures until 12 h post-transport. Cortisol, glucose, non-esterified fatty acid (NEFA) concentrations as well as the neutrophil-lymphocyte ratio (N/L) and other physiological indicators were higher immediately after unloading in transported ewes but mostly returned to normal after 4 h, with complete recovery after 24 h. Behavioural analysis post-transport demonstrated that transported ewes chose to eat before drinking and spent less time resting than controls in the first 3 h after unloading. The study demonstrates that transportation even under short-journey conditions induced behavioural, physiological and thermophysiological responses indicative of the induction of significant stress, leading to live weight shrinkage that may jeopardize farmer's incomes. Finally, results of this study validated the use of iButton Thermochron® data loggers for monitoring the stress response during transport.

Effect of a screen with flaps and straw on behaviour, stress response, productive performance and meat quality in indoor feedlot lambs.

We analysed the effect of a modified pen using a wooden screen with flaps and cereal straw as forage and bedding, on behaviour, stress response, performance and meat quality variables of lambs housed in feedlots. Sixty male lambs were placed in enriched (ESF) or conventional (CO) pens (3 pens/treatment, 10 lambs/pen). The CO environment was barren. The ESF lambs showed a great preference for the provided items, which encouraged more natural and richer behaviour, reducing stereotypies and lamb aggressions, and increasing affiliations (P ≤ 0.05), which improves group cohesion. However, ESF lambs also developed a more natural coping style to the handling, evidenced by the higher cortisol levels (65.4 vs. 43.8 nmol/L) and a higher eye temperature as response to the reactivity test (38.1 vs. 37.8 °C). The ESF lambs had a higher (P ≤ 0.05) slaughter weight (27.2 vs. 26.3 kg), conformation score (7.38 vs. 6.07) and pH 24 (5.63 vs. 5.56) but lower cooking losses (12.9 vs. 14.9%) than CO lambs.

Periconceptional undernutrition increases quantity and quality of oocyte population, but not cognitive or emotional response of 60-day-old lambs.

Maternal periconceptional undernutrition is associated with altered development and increased risks of adverse outcomes in the offspring. The aim of this work was to determine the effect of periconceptional undernutrition on behavioural and reproductive aspects of the offspring. Fifty ewes were synchronized in oestrus (day 0) and allocated to two groups (n = 25) to be fed diets that provided 1.5 (C) or 0.5 (L) times the requirements for maintenance until day 15. Ewes were mated and fed the control diet from day 16 until lambing. Two months after lambing, 26 lambs were exposed to tests to determine their cognitive/emotional responses. Six ewe lambs were euthanized and in vitro oocyte maturation and fertilization procedures performed. The experimental diets produced no changes of mean live weight (LW) of C ewes, L ewes presenting a reduction in their initial LW with significant differences at day 15, in comparison with C ewes (p < 0.05). L ewes experienced a significant reduction in their body condition (BC) in comparison with C ewes (p < 0.05). Fourteen days after the onset of the experimental diets, mean LW and BC of L ewes was significantly lower than those of C ewes (p < 0.05). Undernourished ewes presented a trend to a reduction of prolificacy and fecundity (p < 0.10) in comparison with C ewes. Emotional and cognitive test revealed a similar response between groups. Ewe lambs from the undernourished ewes presented a population of oocytes 1.7 times higher than ovaries from control ewe lambs (66.0 ± 0.73 vs. 113.7 ± 15.6 oocytes; p < 0.05) and had more oocytes in the 'good' (p < 0.05) and 'healthy' (p < 0.05) categories. In conclusion, a low plane of nutrition around conception significantly increases quantity and quality of the oocyte population of 60-day-old female descendants. Modifications of the cognitive and emotional responses of the progeny have not been evidenced.

The effect of periconceptional undernutrition of sheep on the cognitive/emotional response and oocyte quality of offspring at 30 days of age.

Maternal periconceptional undernutrition is associated with altered development and increased risks of adverse outcomes in the offspring. This circumstance is normal in flocks under extensive farming systems, which depend on natural forage resources. The aim of this study was to determine the effect of periconceptional undernutrition in sheep on behavioral and reproductive aspects of the offspring. Eighty ewes were synchronized in estrus and allocated to two groups (n=40) to be fed diets that provided 1.5 (C) or 0.5 (L) times the requirements for maintenance. Ewes were mated and 7 days later fed the control diet until lambing. One month after lambing, 32 lambs were exposed to tests to determine their cognitive and emotional responses. Six ewe lambs were euthanized and in vitro maturation and fertilization procedures were performed. L ewes presented a significant reduction in prolificacy and fecundity (P<0.05) in comparison with C ewes. Mean LW at lambing of L lambs was significantly higher than C lambs (C: 3.80 ± 0.11; L: 4.24 ± 0.15 kg, P<0.05). Lambs born from C ewes spent more time walking than L lambs (P<0.05) in the isolation test, revealing a decrease in the locomotor activity of lambs born from undernourished ewes around conception. Ewe lambs from the undernourished ewes presented a total population of oocytes 2.3 times higher than ovaries from control ewe lambs (60.0 ± 7.8 v. 140.0 ± 18.5 oocytes; P<0.05). In conclusion, periconceptional undernutrition is able to produce an increment in the body weight and the oocyte population, and an alteration of the locomotor activity of the offspring.

Effects of an enriched housing environment on sensory aspects and fatty-acid composition of the longissimus muscle of light-weight finished lambs.

We analysed the effect of enriched housing on the sensory meat quality and fatty acid composition of longissimus muscle in 60 entire Rasa Aragonesa lambs, housed indoors for 5 weeks in six pens (10 lambs/pen, 0.95 m(2)/lamb, initial weight 17.13±0.18 kg and carcass mean 12.23±0.23 kg); three control pens (barren) and three enriched pens (straw, platform with ramps and a small ramp). The final weight, carcass weight, fatness scores and cooking losses of meat from enriched lambs (EG) were higher and pH 24 was lower (P ≤ 0.05). The EG lambs had more C18:0 and total SFA (P ≤ 0.05). Lamb odour and grass odour were more intense in EG (P ≤ 0.05). Overall liking was higher for EG (P ≤ 0.05) and associated with tenderness (P ≤ 0.0001). The results suggest that environmental enrichment can have effects on fatty acid composition and sensory meat quality.

Effect of enriched housing on welfare, production performance and meat quality in finishing lambs: the use of feeder ramps.

This study analyses the effect of environmental enrichment on the welfare, productive traits and meat quality of lambs housed in feedlots. Sixty lambs were placed in enriched (EE) or conventional (CO) pens (3 pens for each treatment, 10 lambs/pen) where EE had a wooden platform with ramps that provided access to a concentrate hopper, cereal straw as bedding and forage, and one play ramp. The CO pen was barren, similar to commercial feedlots. The physiological adaptation response of EE lambs was more efficient than CO, since the latter mobilised more body reserves (i.e., increased NEFA, P<0.05), and had lower levels of immunity (i.e., increased N/L, P<0.05), which indicate chronic stress, probably associated with the barren environment. The EE lambs had a higher (P<0.05) average daily gain, with heavier carcasses and higher fattening scores, as well as lower pHult, higher L and b values, and lower values of texture (P<0.05).

Enfermería quirúrgica urológica en losCampamentos de Refugiados Saharauis / No disponible

No disponible

The alpha7 nicotinic acetylcholine receptor as a pharmacological target for inflammation.

The physiological regulation of the immune system encompasses comprehensive anti-inflammatory mechanisms that can be harnessed for the treatment of infectious and inflammatory disorders. Recent studies indicate that the vagal nerve, involved in control of heart rate, hormone secretion and gastrointestinal motility, is also an immunomodulator. In experimental models of inflammatory diseases, vagal nerve stimulation attenuates the production of proinflammatory cytokines and inhibits the inflammatory process. Acetylcholine, the principal neurotransmitter of the vagal nerve, controls immune cell functions via the alpha7 nicotinic acetylcholine receptor (alpha7nAChR). From a pharmacological perspective, nicotinic agonists are more efficient than acetylcholine at inhibiting the inflammatory signaling and the production of proinflammatory cytokines. This 'nicotinic anti-inflammatory pathway' may have clinical implications as treatment with nicotinic agonists can modulate the production of proinflammatory cytokines from immune cells. Nicotine has been tested in clinical trials as a treatment for inflammatory diseases such as ulcerative colitis, but the therapeutic potential of this mechanism is limited by the collateral toxicity of nicotine. Here, we review the recent advances that support the design of more specific receptor-selective nicotinic agonists that have anti-inflammatory effects while eluding its collateral toxicity.

Chemoimmunotherapy versus chemotherapy for metastatic malignant melanoma.

BACKGROUND: Malignant melanoma, one of the most aggressive of all skin cancers, is increasing in incidence throughout the world. Surgery remains the cornerstone of curative treatment in earlier stages. Metastatic disease is incurable in most affected people, because melanoma does not respond to most systemic treatments. A number of novel approaches are under evaluation and have shown promising results, but they are usually associated with increased toxicity and cost. The combination of chemotherapy and immunotherapy has been reported to improve treatment results, but it is still unclear whether evidence exists to support this choice, compared with chemotherapy alone. No language restrictions were imposed. OBJECTIVES: To compare the effects of therapy with chemotherapy and immunotherapy (chemoimmunotherapy) versus chemotherapy alone in people with metastatic malignant melanoma. SEARCH STRATEGY: We searched the Cochrane Skin Group Specialised Register (14 February 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2005), MEDLINE (2003 to 30 January 2006 ), EMBASE (2003 to 20 July 2005) and LILACS (1982 to 20 February 2006). References, conference proceedings, and databases of ongoing trials were also used to locate trials. SELECTION CRITERIA: All randomised controlled trials that compared the use of chemotherapy versus chemoimmunotherapy on people of any age, diagnosed with metastatic melanoma. DATA COLLECTION AND ANALYSIS: Two authors independently assessed each study to determine whether it met the pre-defined selection criteria, with differences being resolved through discussion with the review team. Two authors independently extracted the data from the articles using data extraction forms. Quality assessment included an evaluation of various components associated with biased estimates of treatment effect. Whenever possible, a meta-analysis was performed on the extracted data, in order to calculate a weighed treatment effect across trials. MAIN RESULTS: Eighteen studies met our criteria and were included in the meta-analysis, with a total of 2625 participants. We found evidence of an increase of objective response rates in people treated with chemoimmunotherapy, in comparison with people treated with chemotherapy. Nevertheless, the impact of these increased response rates was not translated into a survival benefit. We found no difference in survival to support the addition of immunotherapy to chemotherapy in the systemic treatment of metastatic melanoma, with a hazard ratio of 0.89 (95% CI 0.72 to 1.11, p=0.31). Additionally, we found increased hematological and non-hematological toxicities in people treated with chemoimmunotherapy. AUTHORS' CONCLUSIONS: We failed to find any clear evidence that the addition of immunotherapy to chemotherapy increases survival of people with metastatic melanoma. Further use of combined immunotherapy and chemotherapy should only be done in the context of clinical trials.

High mobility group box chromosomal protein 1: a novel proinflammatory mediator in synovitis.

OBJECTIVE: High mobility group box chromosomal protein 1 (HMGB-1) is a ubiquitous chromatin component expressed in nucleated mammalian cells. It has recently and unexpectedly been demonstrated that stimulated live mononuclear phagocytes secrete HMGB-1, which then acts as a potent factor that causes inflammation and protease activation. Macrophages play pivotal roles in the pathogenesis of arthritis. The aim of this study was to determine whether synovial macrophage expression of HMGB-1 is altered in human and experimental synovitis. METHODS: Intraarticular tissue specimens were obtained from healthy Lewis rats, Lewis rats with Mycobacterium tuberculosis-induced adjuvant arthritis, and from patients with rheumatoid arthritis (RA). Specimens were immunohistochemically stained for cellular HMGB-1. Extracellular HMGB-1 levels were assessed in synovial fluid samples from RA patients by Western blotting. RESULTS: Immunostaining of specimens from normal rats showed that HMGB-1 was primarily confined to the nucleus of synoviocytes and chondrocytes, with occasional cytoplasmic staining and no extracellular matrix deposition. In contrast, inflammatory synovial tissue from rats with experimental arthritis as well as from humans with RA showed a distinctly different HMGB-1 staining pattern. Nuclear HMGB-1 expression was accompanied by a cytoplasmic staining in many mononuclear cells, with a macrophage-like appearance and an extracellular matrix deposition. Analysis of synovial fluid samples from RA patients further confirmed the extracellular presence of HMGB-1; 14 of 15 samples had HMGB-1 concentrations of 1.8-10.4 microg/ml. CONCLUSION: The proinflammatory mediator HMGB-1 was abundantly expressed as a nuclear, cytoplasmic, and extracellular component in synovial tissues from RA patients and from rats with experimental arthritis. These findings suggest a pathogenetic role for HMGB-1 in synovitis and indicate a new potential therapeutic target molecule.

Lefty proteins exhibit unique processing and activate the MAPK pathway.

Lefty polypeptides, novel members of the transforming growth factor-beta (TGF-beta) superfamily, are involved in the formation of embryonic lateral patterning. Members of the TGF-beta superfamily require processing for their activation, suggesting cleavage to be an essential step for lefty activation. Transfection of different cell lines with lefty resulted in expression of a 42-kDa protein, which was proteolytically processed to release two polypeptides of 34 and 28 kDa. Since members of the proprotein convertase (PC) family cleave different TGF-beta factors and are involved in the establishment of embryonic laterality, we studied their role in lefty processing. Cotransfection analysis showed that PC5A processed the lefty precursor to the 34-kDa form in vivo, whereas furin, PACE4, PC5B, and PC7 had a limited activity. None of these PCs showed activity in the processing of the lefty polypeptide to the 28-kDa lefty form. The mutation of the consensus sequences for PC cleavage in the lefty protein allowed the lefty cleavage sites to be identified. Mutations of the sequence RGKR to GGKG (amino acids 74-77) and of RHGR to GHGR (amino acids 132-135) prevented the proteolytic processing of the lefty precursor to the 34- and 28-kDa forms, respectively. To identify the biologically active form of lefty, we studied the effect of lefty treatment on pluripotent P19 cells. Lefty did not induce Smad2 or Smad5 phosphorylation, Smad2/Smad4 heterodimerization, or nuclear translocation of Smad2 or Smad4, but activated the MAPK pathway in a time- and dose-dependent fashion. Further analysis showed the 28-kDa (but not the 34-kDa) polypeptide to induce MAPK activity. Surprisingly, the 42-kDa lefty protein was also capable of inducing MAPK activity, indicating that the lefty precursor is biologically active. The data support a molecular model of processing as a mechanism for regulation of lefty signaling.

Lefty inhibits receptor-regulated Smad phosphorylation induced by the activated transforming growth factor-beta receptor.

Transforming growth factor-beta (TGF-beta) is a pleiotropic cytokine that regulates growth and differentiation of diverse types of cells. TGF-beta actions are directed by ligand-induced activation of TGF-beta receptors with intrinsic serine/threonine kinase activity that trigger phosphorylation of receptor-regulated Smad (R-Smad) protein. Phosphorylated R-Smad proteins bind to Smad4, and the complexes formed move into the nucleus, where they act as components of a transcriptional complex. Here, we show that TGF-beta signaling is inhibited by lefty, a novel member of the TGF-beta superfamily. Lefty perturbed TGF-beta signaling by inhibiting the phosphorylation of Smad2 following activation of the TGF-beta receptor. Moreover, lefty inhibited the events that lie downstream from R-Smad phosphorylation, including heterodimerization of R-Smad proteins with Smad4 and nuclear translocation of the R-Smad.Smad4 complex. Lefty repressed TGF-beta-induced expression of reporter genes for the p21, cdc25, and connective tissue growth factor promoters and of a reporter gene driven by the Smad-binding element. Similarly, lefty inhibited both BMP-mediated Smad5 phosphorylation and gene transcription. The action of lefty does not appear to depend on protein synthesis, including synthesis of inhibitory Smad proteins. Thus, lefty provides a repressed state of TGF-beta- or BMP-responsive genes and participates in negative modulation of TGF-beta and BMP signaling by inhibition of phosphorylation of R-Smad proteins.

Inhibition of transforming growth factor-beta/SMAD signalling by the interferon-gamma/STAT pathway.

Transforming growth factor-beta (TGF-beta) and interferon-gamma (IFN-gamma) have opposite effects on diverse cellular functions, but the basis for this antagonism is not known. TGF-beta signals through a receptor serine kinase that phosphorylates and activates the transcription factors Smads 2 and 3, whereas the IFN-gamma receptor and its associated protein tyrosine kinase Jak1 mediate phosphorylation and activation of the transcription factor Stat1. Here we present a basis for the integration of TGF-beta and IFN-gamma signals. IFN-gamma inhibits the TGF beta-induced phosphorylation of Smad3 and its attendant events, namely, the association of Smad3 with Smad4, the accumulation of Smad3 in the nucleus, and the activation of TGFbeta-responsive genes. Acting through Jak1 and Stat1, IFN-gamma induces the expression of Smad7, an antagonistic SMAD, which prevents the interaction of Smad3 with the TGF-beta receptor. The results indicate a mechanism of transmodulation between the STAT and SMAD signal-transduction pathways.

Interactions between cellular actin and human respiratory syncytial virus (HRSV).

Actin the main component of the cellular microfilament network, is present in human respiratory syncytial virus (HRSV) purified virions, as an internal component. This fact and the results of immunoprecipitation studies indicate that during HRSV infection in HEp-2 cells there are interactions between cellular actin and viral components, that can promote a transitory increase in the polymerization of synthetized actin, mainly of the beta isotype. This increased actin polymerization can be related with the formation of cytoplasmic extensions, that contain beta actin and viral particles observed in the HRSV infected HEp-2 cells. The formation of these structures may indicate that HRSV has developed an actin-based motility system similar to that described for other viral and bacterial systems.

The phosphorylated isoform of microtubule associated protein 1B (MAP1B) is expressed in the visual system of the tench (Tinca tinca, L) during optic nerve regeneration.

By using Western blot analysis and immunohistochemistry we have demonstrated that microtubule associated protein 1B (MAP1B)-phos is present in growing and regenerating axons of retinal ganglion cells of fish (Tinca tinca, L). We have found that the levels of MAP1B-phos substantially increase in regenerating optic nerves. Our observations suggest that MAP1 B-phos plays an important role in regeneration processes in the central nervous system (CNS) of the fish. These results are compared in the present paper with that found in the regenerating peripheral nervous system (PNS) of mammals.

NMDA-glutamate receptors regulate phosphorylation of dendritic cytoskeletal proteins in the hippocampus.

Most forms of synaptic potentiation need the activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors which generate changes in dendritic morphology of postsynaptic neurons. Since microtubule proteins have an essential role in dendritic morphology, they may be involved and regulated during the modifications of dendritic morphology associated with synaptic potentiation. The phosphorylation of the microtubule-associated proteins (MAPs) has been analyzed in situ after activation or blockade of NMDA-glutamate receptors in hippocampal slices. The phosphorylation of MAP1B and MAP2 has been studied by using several antibodies raised against phosphorylation-sensitive epitopes. Whereas antibodies 125 and 305 recognize phosphorylated epitopes on MAP1B and MAP2, respectively, Ab 842 recognizes a phosphorylatable sequence on MAP1B only when it is dephosphorylated. NMDA treatment decreased the phosphorylation state of the epitope recognized by the antibody 305 on MAP2 and caused a slight dephosphorylation of MAP1B sequences recognized by Ab 125 and 842. Moreover, exposure to APV (an antagonist of NMDA-glutamate receptors) counteracted the effect of NMDA and induced an increase in the phosphorylation state of these sequences in MAP2. Since phosphorylation regulates the interaction of MAPs with cytoskeleton, the results suggest that the modulation of the phosphorylated state of MAP2 by NMDA-glutamate receptors may be implicated in dendritic plasticity.

Analysis of the expression, distribution and function of cyclin dependent kinase 5 (cdk5) in developing cerebellar macroneurons.

Cultures of cerebellar macroneurons were used to study the expression, activity, subcellular localization, and function of cdk5 during neuronal morphogenesis. The results obtained indicate that in non-polarized neurons cdk5 is restricted to the cell body but as soon as polarity is established it becomes highly concentrated at the distal tip of growing axons where it associates with microtubules and the subcortical cytoskeleton. In addition, we show that laminin, an extracellular matrix molecule capable of stimulating axonal extension and promoting MAP1b phosphorylation (DiTella et al., 1996), accelerates the redistribution of cdk5 to the axonal tip and dramatically increases its activity. Finally, our results indicate that cdk5 suppression by antisense oligonucleotide treatment selectively reduces axonal elongation and decreases the phosphorylation status of MAP1b, as well as its binding to microtubules. Taken collectively, our observations suggest that cdk5 may serve as an important regulatory linker between environmental signals (e.g. laminin) and constituents of the intracellular machinery (e.g. MAP1b) involved in axonal formation.

Pérfil lipídico en sangre de cordón de recién nacidos normales y con alguna patología fetal y/o materna / Lipid profile in cord blood of normal newborns with some fetal and/or maternal pathology

Se realizaron determinaciones lipídicas en sangre de cordón de recién nacidos (RN) de ambos sexos, normales (n = 30) y con morbilidad neonatal o materna (n = 67), obtenida inmediatamente después del parto. Se consideró como RN sano una edad gestacional entre 38 y 41 semanas, peso > 2.500 g, Apgar > 7, así como ausencia de morbilidad perinatal, malformaciones congénitas y patología materna, como hipertensión arterial o diabetes. Las patologías consideradas fueron: grandes para edad gestacional, pretérmino, hipertensión materna, Apgar < 7, gemelos de pretérmino y otras. Al comparar los promedios de CT en los RN de pretérmino,Apgar < 7 con los RN normales (73 ñ 29; 73 ñ 24; 59 ñ 14 mg/dl) se encontró una diferencia significativa (p < 0.05). Para los promedios de los RN con HTA materna más pretérmino y gemelos de pretérmino (100 ñ 7; 104 ñ 26 mg/dl) la diferencia estadística fue mayor (p < 0,001). En estos dos últimos grupos, también se encontró diferencia significativa para el C-LDL (p < 0.001) (52 ñ 14; 64 ñ 24 mg/dl) comparado con RN normales (27 ñ 10 mg/dl). En los TG, fueron significativamente diferentes los promedios de los RN con HTA materna más pretérmino (58 ñ 51 mg/dl) y los con Apgar < 7 (45 ñ 47 mg/dl) comparados con RN normales (25 ñ 13 mg/dl) (p < 0,001 y p < 0,05 respectivamente). Siendo la hipercolesterolemia familiar el trastorno de las lipoproteínas más frecuente reconocido en la niñez,es importante su detección a edad temprana, así como saber diferenciarla de los niveles altos de colesterol, producto de alguna patología fetal o materna