Effects of Torcetrapib and Statin Treatment on ApoC-III and Apoprotein-Defined Lipoprotein Subclasses (from the ILLUMINATE Trial).

In the ILLUMINATE Trial, treatment with the cholesteryl ester transfer protein inhibitor torcetrapib resulted in a significant increase in both atherosclerotic cardiovascular disease events and total mortality which was not explained by changes in the routinely measured plasma lipids. To determine whether alterations in lipoproteins defined by their apoprotein content that are not estimated with conventional laboratory methods contributed to these unexpected events, we measured the apoB- and apoA-containing subclasses in a subgroup of ILLUMINATE participants. We find that torcetrapib treatment significantly increased the high-density lipoprotein subclasses LpA-I and LpA-I:A-II equally (p <0.0001) and the apoC-III content of high-density lipoprotein (p <0.001) without altering the apoB-containing subclasses. In conclusion, these findings provide further evidence that the untoward effects of torcetrapib were attributable to off-target effects and not related to disturbances in lipoprotein transport.

Apolipoprotein-containing lipoprotein subclasses and subclinical atherosclerosis in systemic lupus erythematosus.

OBJECTIVE: Traditional classification of hyperlipidemia using high-density lipoprotein, low-density lipoprotein (LDL), and very low-density lipoprotein does not provide information on lipoprotein function. Apolipoproteins (Apos), which are protein components of plasma lipoproteins (including A, B, C, D, E) with their different composition, metabolic, and atherogenic properties, provide insight on lipoprotein functioning. In particular, the Apo B/A-I ratio is associated with atherogenic LDL and development of cardiovascular disease. We explored the baseline association between these nontraditional risk factors with subclinical measures of atherosclerosis (coronary artery calcification [CAC] and carotid intima-media thickness [IMT]) in systemic lupus erythematosus (SLE). METHODS: A total of 58 SLE patients (97% women, 58% white, 40% African American, and 2% other, mean ± SD age 44 ± 11 years) had measurement of Apo and lipoproteins by immunoturbidimetric procedures, electroimmunoassays, and immunoprecipitation. CAC was measured by helical computed tomography and carotid IMT by carotid duplex. This study was based on the baseline assessment of subclinical atherosclerosis in the Lupus Atherosclerosis Prevention Study. The measurement of the lipoproteins was made on sera collected at the same time. RESULTS: There was no association between cardioprotective Apos (Apo A-I, LpA-I, LpA-I:A-II) and CAC (P < 0.15, P < 0.41, and P < 0.39, respectively) or carotid IMT (P < 0.97, P < 0.53, and P < 0.76, respectively). CAC and carotid IMT did not associate with atherogenic Apos either, including LpB:E+LpB:C:E, Apo B, LpB, LpB:C, Apo C-III, Apo C-III-HS, Apo C-III-HP, Apo C-III-R, LpA-II:B:C:D:E, and Apo B/Apo A-I. Measures of disease activity, including physician's global assessment and Systemic Lupus Erythematosus Disease Activity Index, were not associated with CAC or carotid IMT. CONCLUSION: Neither cardioprotective nor atherogenic lipoproteins were associated with measures of subclinical atherosclerosis in this series of SLE patients. Further studies with a larger sample size are warranted to confirm our findings.

Lipoprotein abnormalities in compound heterozygous lipoprotein lipase deficiency after treatment with a low-fat diet and orlistat.

BACKGROUND: The treatment of familial hyperchylomicronemia presenting in early childhood with episodes of pancreatitis has been ineffective, and affected patients remain at risk for pancreatitis. OBJECTIVE: To report on the effect of orlistat in siblings with severe inherited hyperchylomicronemia and to assess posttreatment lipoprotein concentrations and composition. METHODS: Serial observations of plasma lipid levels and hospitalizations after treatment with orlistat and lipoprotein studies on a single fasting posttreatment sample. RESULTS: The affected siblings inherited a lipoprotein lipase gene mutation from each of their parents: a novel mutation from their father (c.542G > C, p.G181R) and a known missense mutation from their mother (c.644G > A, p.G215E). When the boy presented to us at age 9 years of age and his sister at age 7 years, we found that addition of orlistat, a pancreatic lipase inhibitor, at a dose of 120 mg given before three low-fat meals a day was effective in reducing episodes of pancreatitis in the boy and in maintaining the triglyceride at lower levels in both children. During treatment, the children were observed to have elevations in apolipoprotein (apo)B, low-density lipoprotein particle concentration, abnormal apoB-containing subclasses, and deficiencies in apoA-I and apoA-II-containing lipoproteins, changes consistent with continuing increased cardiovascular risk. CONCLUSION: The data support the need for more effective long-term treatments that not only prevent pancreatitis but also offset cardiovascular risk. Orlistat can be considered effective in augmenting the effect of a low-fat diet and reducing risk for pancreatitis.

Apolipoprotein-defined and NMR lipoprotein subclasses in the veterans affairs diabetes trial.

AIMS: The VADT was a randomized clinical trial designed to assess the effect of intensive vs. standard glucose management on cardiovascular events in Type 2 diabetes. At the end of the study, intensive management failed to improve outcomes. We performed plasma lipoprotein subclass analyses to yield new information on the effects of study randomization on cardiovascular risk. METHODS: This is a cross-sectional study of a subset of the VADT (740 men: 368 intensive; 372 standard), conducted at least six months (mean±SD: 2.1±0.8years) post-randomization. Conventional lipids, apolipoprotein-defined (ADLS) lipoprotein subclasses, ApoCIII, ApoE, and Nuclear Magnetic Resonance (NMR) lipoprotein subclasses were determined. RESULTS: In intensive vs. standard groups, conventional lipids and ADLS did not differ significantly. However, with intensive treatment, NMR-determined large and medium VLDL subclasses and VLDL diameter were lower, LDL diameter was higher, medium HDL was higher, and small HDL was lower (all p<0.05). Also, ApoCIII levels were lower (p<0.01). CONCLUSIONS: In a subset of diabetic men from the VADT, intensive glucose management did not affect conventional lipids or ADLS, but had some beneficial effects on particle characteristics as defined by NMR and on ApoCIII.

Distribution of immunochemically defined apoB-containing lipoprotein subclasses in T1D.

OBJECTIVE: Young women with T1D develop CHD without any apparent lipid related risk factor. To determine whether abnormalities in the five immunochemically defined apoB-containing lipoprotein subclasses might influence this risk, we have measured these subclasses in T1D subjects. RESEARCH DESIGN AND METHODS: ApoA- and B-containing lipoprotein subclasses were isolated immunochemically and quantitated in 37 young (mean age 31.8+/-12.7 years) otherwise healthy subjects (16 males; 21 females) with T1D (HbA1c=8.2+/-1.7%) treated conventionally with subcutaneous insulin. RESULTS: T1D women had significantly more cholesterol-rich Lp-B particles (T1D: 55.9+/-4.5 vs. control 46.8+/-11.1mg apoB/dL; p<.01) which were over-represented in the apolipoprotein B particle pool (apoB/Lp-B: T1D: 1.49+/-.19 vs. control: 1.67+/-.22; p<.01). HbA1c correlated with Lp-B (r=0.60; p<.001) and the mass of apoB subclasses containing apoC-III (r=0.69; p<.001). CONCLUSIONS: Women with T1D have a disturbance in the transport of Lp-B particles manifested by both an absolute and relative increase in their number that may result from portal hypoinsulinemia and reduced LDL B,E receptor activity. This pathway may enhance CHD risk in T1D women when of LDL and apoB levels are normal.

Evaluación de la avifauna de la ciudad de La Paz, Bolivia / Avifauna evaluation of the La Paz City, Bolivia

Desde el año 1996 al 2003, mediante métodos de observación directa, caminatas y capturas con redes niebla, realizamos un inventario y obtuvimos datos sobre la historia natural, gremios tróficos y patrones de migración de la avifauna de la ciudad de La Paz (Bolivia). Registramos 136 especies de aves en 30 localidades de estudio. Las familias más representativas fueron Tyrannidae, Emberizidae y Furnariidae con 19, 16 y 15 especies, respectivamente. Registramos 18 especies de aves acuáticas y dos especies (Tachuris rubrigastra y Phleocryptes melanops) de passeriformes especialistas de totorales. Dos especies de furnáridos (Cranioleuca henricae y Upucerthia harterti) fueron endémicas bolivianas. Detectamos 57 especies en alguna categoría de migración. Movimientos altitudinales inusuales fueron observados para cinco especies (e.g. Pitangus sulphuratus, Pyrocephalus rubinus). Diecinueve especies fueron consideradas raras (e.g. Lesbia nuna, Poospiza boliviana). Los insectívoros y frugi-granívoros son los gremios tróficos mas representativos entre comunidades. El valle de la ciudad de La Paz es una ruta obligatoria para muchas aves migrantes latitudinales (boreales y australes) y altitudinales, que provienen del Altiplano por el oeste y las especies de Yungas por el este.

Since 1996 to 2003, we realized an inventory and obtained data on the natural history, trophic guilds and migration patterns of the avifauna of La Paz (Bolivia), based on direct observation, random walks and captures with mist nets. A total of 136 species of birds in 30 localities of study were registered. Tyrannids, Emberizids and Furnariids were the families most representatives with 19, 16 and 15 species, respectively. Eighteen species of waterbirds and two species of passerine rush (called totorales) specialists as Tachuris rubigastraand Phleocryptes melanops, were registered. Two furnariids species (Cranioleuca henricae and Upucerthia harterti) were Bolivian endemics. We detected 57 species in some category of migrants. Unusual elevational movements were observed for five species (e.g. Pitangus sulphuratus, Pyrocephalus rubinus). Nineteen species were considered rare (e.g. Lesbia nuna, Poospiza boliviana). Insectivores and frugi-granivores were the trophic guilds most representatives between communities. The La Paz City Valley is one obligatory route for many latitudinal (neartic and austral) and altitudinal migrants birds, which arise from highland by the western and species of mountain forest (called Yungas) by the eastern.

Propuesta de estrategias del marketing en la Fundacion INFOCAL / SSS

La Fundacion INFOCAL como parte de la FEPB busca formas innovadoras para renovar sistemas de formacion y redefinir roles nuevos y en complementacion al sector privado es asi que el servicio que brinda tiene enfoque de demanda articulado al sistema social y empresarial que le permite, con la interactividad del empresario, el desarrollo de programas donde prima la demanda como guia de accionar. Se propone una mescla de marketing como medio mas adecuado de organizar todas las variables controladas por INFOCAL y modelar los elementos componentes como respuesta a las circuntancias y necesidades variables del mercado...