Familial chylomicronemia syndrome (FCS) is an extremely rare lipoprotein disorder caused by mutations in at least 5 genes of the lipoprotein lipase (LPL) complex.
This work shows the molecular ...analysis of patients diagnosed with FCS, who attended the Spanish Arteriosclerosis Society lipid units and were included in the National Dyslipidemia Registry.
Among the 238 patients registered with severe hypertriglyceridemia (fasting triglycerides >1000 mg/dL), 26 were diagnosed with FCS as they had confirmed postheparin plasma LPL activity deficiency and/or homozygosity for loss-of-function mutations in LPL, GPIHBP1, APOC2, LMF1, or Apolipoprotein A5 (APOA5).
Among the 26 FCS cases, 23 had mutations in the homozygous state: 19 in LPL and 4 in the GPIHBP1 gene. The molecular analysis revealed 3 novel mutations: 2 in LPL, in 2 unrelated patients (c.312delA; p.Asp105Thrfs*66 and c.629A>G; p.His210Arg), and 1 in GPHIBP1 in a third patient (c.502delC; p.Leu168Serfs*83). These 3 patients had confirmed lack of LPL activity. Three additional patients with confirmed LPL activity deficiency were heterozygous carriers of mutations in the genes analyzed. Among these, we found 2 novel mutations in APOA5 (c.50-1G>A and c.326_327insC; p.Tyr110Leufs*158).
We have identified 5 novel pathogenic mutations: 2 in LPL, 1 in GPIHBP1, and 2 in the APOA5 gene. The genetic defaults accounting for the LPL activity deficiency of 23 of them have been clearly identified and 3 patients, who harbored mutations in heterozygosity, were diagnosed based on LPL activity deficiency, which raises the question of the involvement of new genes in the manifestation of FCS.
•We studied data from the Spanish Atherosclerosis Society Dyslipidemia Registry.•We diagnosed 26 patients with familial chylomicronemia syndrome.•We identified 5 novel mutations in LPL (2), GPIHBP1 (1), and APOA5 (2).•Twenty-three patients were homozygous for mutations in LPL (19) and GPIHBP1 (4).•Three patients heterozygous for mutations in LPL or APOA5 had LPL activity deficiency.
The effect of reaction parameters on lipase‐mediated chemo‐enzymatic epoxidation of linoleic acid was investigated. Hydrogen peroxide was found to have the most significant effect on the reaction ...rate and degree of epoxidation. Excess of hydrogen peroxide with respect to the amount of double bonds was necessary in order to yield total conversion within a short time period, as well as at temperatures above 50 °C to compensate for hydrogen peroxide decomposition. However, prolonged incubation with high excess of hydrogen peroxide leads to the accumulation of peracids in the final product. The reaction rate increased also with increasing hydrogen peroxide concentration (between 10 and 50 wt‐%); however, at the expense of enzyme inactivation. Linoleic acid was completely epoxidized when used at a concentration of 0.5–2 M in toluene at 30 °C, while in a solvent‐free medium, the reaction was not complete due to the formation of a solid or a highly viscous oily phase, creating mass transfer limitations. Increasing the temperature up to 60 °C also improved the rate of epoxide formation.
A prototype of a luminometer, designed for a future
e
+
e
-
collider detector, and consisting at present of a four-plane module, was tested in the CERN PS accelerator T9 beam. The objective of this ...beam test was to demonstrate a multi-plane tungsten/silicon operation, to study the development of the electromagnetic shower and to compare it with MC simulations. The Molière radius has been determined to be 24.0 ± 0.6 (stat.) ± 1.5 (syst.) mm using a parametrization of the shower shape. Very good agreement was found between data and a detailed Geant4 simulation.
Jugular venous catheter lodged in intercostal vein López-Millán, J.M.; Coca Gamito, C.
Revista española de anestesiología y reanimación (English ed.),
December 2020, 2020-12-00, Letnik:
67, Številka:
10
Journal Article
The prognostic value of preoperative serum levels of carcinoembryonic antigen (CEA), CA 19-9 and CA 72-4 tumor markers was investigated in patients with gastric cancer. Eighty-two patients who ...underwent surgical resection of gastric cancer were entered in the study. Correlation analyses showed that CA 72-4 was more frequently positive in patients with advanced tumors (p = 0.04), lymph node invasion (p = 0.02), liver metastasis (p = 0.02) and peritoneal involvement (p = 0.03). CA 19-9 was more frequently positive in patients with advanced tumors (p = 0.01) and with serosal (p = 0.04), lymph node (p = 0.008) and peritoneal involvement (p = 0.02). CEA was more frequently positive in patients with liver metastasis (p = 0.03). Low 3-year cumulative survival was significantly associated with elevated serum levels of CA 72-4 (p = 0.004), CA 19-9 (p = 0.001) and CEA (p < 0.001). Age, tumor stage and CA 72-4 provided prognostic information in the multivariate analysis. Patients with elevated serum levels of CA 72-4 showed a 4.2 times higher risk of death than patients with low levels of the marker. Our results suggest that CA 72-4 has prognostic value in gastric cancer, and patients with a high preoperative serum level of CA 72-4 have a greater risk of death due to gastric cancer.
Conventionally, epoxidation of unsaturated fatty acids has been studied either with titrimetric methods or in a lengthy procedure involving derivatization followed by gas chromatography (GC). We have ...developed a more rapid and descriptive analysis procedure for the substances using high performance liquid chromatography (HPLC) with evaporative light scattering detection (ELSD). Chemo-enzymatic epoxidation of unsaturated fatty acids (oleic, linoleic and linolenic acid, respectively) has been performed using hydrogen peroxide and immobilized lipase from
Candida antarctica (Novozym 435). The fatty acids and their epoxidation products were separated by HPLC on a C-18 reversed-phase column using methanol–water containing 0.05% acetic acid as mobile phase. The method facilitated the simultaneous determination of fatty acids and epoxides differing from each other in the number of epoxide rings, the degree of unsaturation and the position of the epoxide rings and double bonds. An important aspect of the method development was the use of electrospray ionization and tandem mass spectrometry to confirm the structure of the epoxide products. It is suggested that the HPLC method, providing more information about the kind and concentration of fatty acids and their epoxides, represents a powerful complement to the existing methods for monitoring epoxidation processes on fatty acids.
Concentrations of polycyclic aromatic hydrocarbons (PAHs) were determined in a sediment core collected from the Barigui River, in Curitiba, South Brazil. The USEPA's 16 priority PAH concentrations ...ranged from 39ngg−1 to 2350ngg−1 of dry sediment over a period that corresponds temporally to between ca. 1855 and 2011. The concentrations and patterns of PAH distribution changed over this time period and may be associated with several episodes in the Curitiba's history. Two major PAHs concentration peaks occurred in approximately 1910 and 1970, which might reflect population increases due to immigration programs in the 1890s and the sudden economic development that occurred in Brazil from 1960 to 1980, “The Economic Miracle Period”, respectively. Isomeric ratios revealed that the PAHs had predominantly pyrolytic sources. The population, number of highways and electric energy consumption of Curitiba, as indices of socioeconomic development, were positively correlated with PAH deposition in the sediment core from 1855 to 1970, indicating the influence of socioeconomic development on the environmental load of sedimentary PAHs.
•The changing concentration and patterns of PAHs distribution over the past 150years have been recorded.•Sources of PAHs might be associated with several historical episodes.•Indices of socio-economic development are positively correlated with PAH inputs to the sediments from the 1855 to 1970.
PDF
