Dietary alpha-linolenic acid decreases C-reactive protein,serum amyloid A and interleukin-6 in dyslipidaemic patients

BACKGROUND: Inflammation plays an important role in the pathogenesis of coronary artery disease. We examined whether dietary supplementation with alpha-linolenic acid (ALA, 18:3n-3) affects the levels of inflammatory markers in dyslipidaemic patients. METHODS: We recruited 76 male dyslipidaemic patients (mean age=51+/-8 years) following a typical Greek diet. They were randomly assigned either to 15 ml of linseed oil (rich in ALA) per day (n=50) or to 15 ml of safflower oil (rich in linoleic acid (LA, 18:2n-6)) per day (n=26). The ratio of n-6:n-3 in linseed oil supplemented group was 1.3:1 and in safflower oil supplemented group 13.2:1. Dietary intervention lasted for 3 months. Blood lipids and C-reactive protein (CRP), serum amyloid A (SAA), and interleukin-6 (IL-6) levels were determined prior and after intervention. CRP and SAA were measured by nephelometry and IL-6 by immunoassay. RESULTS: Dietary supplementation with ALA decreased significantly CRP, SAA and IL-6 levels. The median decrease of CRP was 38% (1.24 vs. 0.93 mg/l, P=0.0008), of SAA 23.1% (3.24 vs. 2.39 mg/l, P=0.0001) and of IL-6 10.5% (2.18 vs. 1.7 pg/ml, P=0.01). The decrease of inflammatory markers was independent of lipid changes. Dietary supplementation with LA did not affect significantly CRP, SAA and IL-6 concentrations but decreased cholesterol levels. CONCLUSIONS: Dietary supplementation with ALA for 3 months decreases significantly CRP, SAA and IL-6 levels in dyslipidaemic patients. This anti-inflammatory effect may provide a possible additional mechanism for the beneficial effect of plant n-3 polyunsaturated fatty acids in primary and secondary prevention of coronary artery disease.     

Experimentation with aerosol bonsetan,pirfenidone, treprostinil and sidenafil

Introduction

Pulmonary hypertension (PH) has been identified either as a symptom or a primary entity. Several drugs are already on the market and other are being investigated. Idiopathic pulmonary fibrosis (IPF) is also a disease were several drugs are being investigated.

Materials and methods

Three jet nebulizers and three ultrasound nebulizers were used for our experiments with seven different residual cups and four different loadings. Bonsetan, treprostinil, sidenafil and pirfenidone were modified in order to be produced as aerosol in an effort to identify parameters which influence the droplet size production size.

Results

The four-way ANOVA on droplet size using the jet nebulizers revealed two statistically significant factors, drug (F=6.326, P=0.0007) and residual cup (F=4.419, P=0.0007), and their interaction term (F=5.829, P<0.0001). Drugs bonsetan and pirfenidone produce equally the lowest mean droplet size (2.63 and 2.80 respectively) as compared to other two drug mean sizes. The ANOVA results, concerning the ultrasound nebulizers, revealed only the nebulizers as producing significant effect on droplet size (F=4.753, P=0.037).

Discussion

Our study indicates the importance of the initial drug design formulation. Moreover, further investigation of the residual cup design is an additional parameter that can assist in the optimal droplet size production, indifferently of the drug formulation.     

Thrombosis in paroxysmal nocturnal hemoglobinuria at a glance: a clinical review

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired stem cell disorder, with its primary clinical manifestations being hemolytic anemia, marrow failure and thrombophilia. Chronic hemolysis, failures of the fibrinolytic system, increased leukocyte-derived tissue factor levels in plasma, procoagulant microparticles generated through complement-mediated damage of platelets and venous endothelium are related to the acquired hypercoagulable state. Visceral thrombosis (including hepatic veins and mesenteric veins), cerebrovascular events and pulmonary embolism predict a poor outcome. Thrombosis is also associated with significant morbidity during pregnancy. Depending on the sites of thrombosis, a score-based probability to predict outcome can be assigned. Abdominal vein thromboses account for the majority of morbidity and mortality related to thrombosis, and time-dependent trends suggest that mortality rates tend to decline, with the advent of evolution of therapeutic and diagnostic strategies. In contrast, mortality rates from cerebrovascular events display no significant decline. Prompt diagnosis requires both clinical suspicion and sophisticated imaging techniques, along with multidisciplinary therapeutic intervention. In the eculizumab era, a significant reduction of thrombotic events was observed during therapy, and long-term follow up is needed to establish any benefit in rates and pattern of this complication. However, up to now, only bone marrow transplantation permanently abolishes the coagulation defect.     

Complex preimplantation genetic diagnosis for beta-thalassaemia,sideroblastic anaemia,and human leukocyte antigen (HLA)-typing

Preimplantation genetic diagnosis (PGD) to select histocompatible siblings to facilitate curative haematopoeitic stem-cell transplantation (HSCT) is now an acceptable option in the absence of an available human leukocyte antigen (HLA) compatible donor. We describe a case where the couple who requested HLA-PGD, were both carriers of two serious haematological diseases, beta-thalassaemia and sideroblastic anaemia. Their daughter, affected with sideroblastic anaemia, was programmed to have HSCT. A multiplex-fluorescent-touchdown-PCR protocol was optimized for the simultaneous amplification of: the two HBB-gene mutated regions (c.118C?>?T, c.25-26delAA), four short tandem repeats (STRs) in chr11p15.5 linked to the HBB gene, the SLC25A38 gene mutation (c.726C?>?T), two STRs in chr3p22.1 linked to the SLC25A38 gene, plus eleven informative STRs for HLA-haplotyping (chr6p22.1-21.3). This was followed by real-time nested PCR and high-resolution melting analysis (HRMA) for the detection of HBB and SLC25A38 gene mutations, as well as the analysis of all STRs on an automatic genetic analyzer (sequencer). The couple completed four clinical in vitro fertilization (IVF)/PGD cycles. At least one matched unaffected embryo was identified and transferred in each cycle. A twin pregnancy was established in the fourth PGD cycle and genotyping results at all loci were confirmed by prenatal diagnosis. Two healthy baby girls were delivered at week 38 of pregnancy. The need to exclude two familial disorders for HLA-PGD is rarely encountered. The methodological approach described here is fast, accurate, clinically-validated, and of relatively low cost.     

Lipid abnormalities and oxidized LDL in chronic kidney disease patients on hemodialysis and peritoneal dialysis

Dyslipoproteinemia and oxidative modification of low-density lipoprotein (oxLDL) contribute to the development of oxidative stress and atherosclerosis in chronic kidney disease (CKD). On the contrary, high-density lipoprotein cholesterol (HDL-C), especially HDL3-C subtype, has protective effect against oxidative damage. There is limited evidence referring HDL-C subclass levels in patients on dialysis. This study was designed to compare lipid abnormalities and oxLDL levels in hemodialysis (HD) and peritoneal dialysis (PD) patients. Serum lipids, HDL subclasses, and oxLDL were measured in 55 patients with CKD-stage 5 (31 patients on HD and 24 patients on PD) and in 21 normal controls (NC). The results showed that in dialysis patients, triglycerides were higher than in controls (p < 0.0001) and HDL-C was significantly lower (p < 0.0001). The HDL2-C subclass concentration did not differ significantly between patients and controls, while HDL3-C was lower in patients (11 ± 0.5 mg/dL) than in NC (23 ± 1, p < 0.0001). oxLDL levels were markedly increased in patients (1.92 ± 0.29 mg/L) compared to NC (0.22 ± 0.05, p < 0.0001). Patients on PD had higher levels of cholesterol (p < 0.001) and apolipoprotein B (p < 0.05) than patients on HD. However, HDL-C, HDL-C subclasses, and oxLDL concentrations did not differ significantly between PD and HD patients. It is concluded that patients with CKD have a nearly 10-fold elevation of oxLDL compared with NC. Patients on PD have differences in the lipid profile compared with patients on HD; however, both modalities seem to possess similar potential to atherosclerosis development.     

Growth Retardation,Reduced Invasiveness,and Impaired Colistin-Mediated Cell Death Associated with Colistin Resistance Development in Acinetobacter baumannii

Two colistin-susceptible/colistin-resistant (Col^s/Col^r) pairs of Acinetobacter baumannii strains assigned to international clone 2, which is prevalent worldwide, were sequentially recovered from two patients after prolonged colistin administration. Compared with the respective Col^s isolates (Ab248 and Ab299, both having a colistin MIC of 0.5 μg/ml), both Col^r isolates (Ab249 and Ab347, with colistin MICs of 128 and 32 μg/ml, respectively) significantly overexpressed pmrCAB genes, had single-amino-acid shifts in the PmrB protein, and exhibited significantly slower growth. The Col^r isolate Ab347, tested by proteomic analysis in comparison with its Col^s counterpart Ab299, underexpressed the proteins CsuA/B and C from the csu operon (which is necessary for biofilm formation). This isolate also underexpressed aconitase B and different enzymes involved in the oxidative stress response (KatE catalase, superoxide dismutase, and alkyl hydroperoxide reductase), suggesting a reduced response to reactive oxygen species (ROS) and, consequently, impaired colistin-mediated cell death through hydroxyl radical production. Col^s isolates that were indistinguishable by macrorestriction analysis from Ab299 caused six sequential bloodstream infections, and isolates indistinguishable from Ab248 caused severe soft tissue infection, while Col^r isolates indistinguishable from Ab347 and Ab249 were mainly colonizers. In particular, a Col^s isolate identical to Ab299 was still invading the bloodstream 90 days after the colonization of this patient by Col^r isolates. These observations indicate considerably lower invasiveness of A. baumannii clinical isolates following the development of colistin resistance.     

Nocturnal oximetry parameters as predictors of sleep apnea severity in resource-limited settings

Nocturnal oximetry is an alternative modality for evaluating obstructive sleep apnea syndrome (OSAS) severity when polysomnography is not available. The Oxygen Desaturation (≥3%) Index (ODI3) and McGill Oximetry Score (MOS) are used as predictors of moderate-to-severe OSAS (apnea-hypopnea index-AHI >5 episodes/h), an indication for adenotonsillectomy. We hypothesised that ODI3 is a better predictive parameter for AHI >5 episodes/h than the MOS. All polysomnograms performed in otherwise healthy, snoring children with tonsillar hypertrophy in a tertiary hospital (November 2014 to May 2019) were analysed. The ODI3 and MOS were derived from the oximetry channel of each polysomnogram. Logistic regression was applied to assess associations of ODI3 or MOS (predictors) with an AHI >5 episodes/h (primary outcome). Receiver operating characteristic (ROC) curves and areas under ROC curves were used to compare the ODI3 and MOS as predictors of moderate-to-severe OSAS. The optimal cut-off value for each oximetry parameter was determined using Youden's index. Polysomnograms of 112 children (median [interquartile range] age 6.1 [3.9–9.1] years; 35.7% overweight) were analysed. Moderate-to-severe OSAS prevalence was 49.1%. The ODI3 and MOS were significant predictors of moderate-to-severe OSAS after adjustment for overweight, sex, and age (odds ratio [OR] 1.34, 95% confidence interval [CI] 1.19–1.51); and OR 4.10, 95% CI 2.06–8.15, respectively; p < 0.001 for both). Area under the ROC curve was higher for the ODI3 than for MOS (0.903 [95% CI 0.842–0.964] versus 0.745 [95% CI 0.668–0.821]; p < 0.001). Optimal cut-off values for the ODI3 and MOS were ≥4.3 episodes/h and ≥2, respectively. The ODI3 emerges as preferable or at least a complementary oximetry parameter to MOS for detecting moderate-to-severe OSAS in snoring children when polysomnography is not available.