96 research outputs found
Flaxseed oil: acute and chronic supplementation increases serum and tissue concentrations of omega fatty acids in rats
No full textWe studied the bioavailability of acute supplementation of scalar doses of flaxseed oil by analysing the level of Linolenic acid (ALA, -3) and Linoleic acid (-6) in serum and tissues (adipose, liver and brain) of rats tested at 2-4-8-16 h after the administration. The amount of flaxseed oil administered by oral rate was 1.9, 4.7, 9.5 mL/kg corresponding to 1, 2.5, 5 g ALA/kg. Two techniques of lipid extraction were investigated to achieve maximal free fatty acids recovery in a reasonably short time. The corresponding fatty acid methyl esters obtained with direct methylation with MeOH/HCl, were quantified by gas chromatography/mass spectrometry (GC/MS) technique. GC-MS analyses were performed on a Gas-Chromatograph Varian 3400 on a HP-INNOWAX column (30 m x 0.25 mm; 0.25 m film thickness). Mass spectra were acquired on a Finnigan MAT SSQ 710A mass spectrometer in the electron impact (EI) mode.Serum ALA levels at 1 g/kg after 2h in the flaxseed oil group increased by 70% from 0.067 ± 0.007 to 0.096 ± 0.008 mg/mL (P<0.001 Anova) whereas no significant increase occurred in the flaxseed oil group at 2.5 g/kg (0.142 ± 0.009) or at 5 g/kg after 2 h (0.140 ± 0.008) when compared with the value obtained after 1 g/kg. A statistically significant increase of ALA was found in adipose tissue and in liver 4 h after the administration of 1 g/kg of ALA whereas higher doses (2.5-5 g/kg) did not produce any significant changes. Concerning linoleic acid (-6) no significant increased concentrations were found in serum at the three doses studied confirming that flaxseed oil is mainly a source of -3 fatty acids
Key enabling technologies for point-of-care diagnostics
No full textA major trend in biomedical engineering is the development of reliable, self-contained point-of-care (POC) devices for diagnostics and in-field assays. The new generation of such platforms increasingly addresses the clinical and environmental needs. Moreover, they are becoming more and more integrated with everyday objects, such as smartphones, and their spread among unskilled common people, has the power to improve the quality of life, both in the developed world and in low-resource settings. The future success of these tools will depend on the integration of the relevant key enabling technologies on an industrial scale (microfluidics with microelectronics, highly sensitive detection methods and low-cost materials for easy-to-use tools). Here, recent advances and perspectives will be reviewed across the large spectrum of their applications
Flaxseed oil supplementation increases plasma and tissue concentrations of W3 fatty acids in rats.
No full text-Linolenic acid (ALA) is a major dietary (-3) fatty acid. The essential fatty acids must be absorbed by food intake and play a very important role in the coagulation (inhibition of platelets aggregation) and in the inflammatory reaction (anti-inflammatory effects). In cardiovascular diseases, particularly in coronary diseases, studies demonstrated a decreased mortality in populations who eat an omega-3 rich diet or who take an omega-3 supplement.We studied the bioavailability of acute supplementation of scalar doses of flaxseed oil (Organic Oils–Perugia) by analysing the level of ALA (-3) and Linoleic acid (-6) in serum and tissues (adipose, liver and brain) of rats tested at 2-4-8-16 h after the administration. The amount of flaxseed oil administered by oral rate was 1.9, 4.7, 9.5 mL/kg corresponding to 1, 2.5, 5 g ALA/kg. Two techniques of lipid extraction were investigated to achieve maximal free fatty acids recovery in a reasonably short time. The corresponding fatty acid methyl esters obtained with direct methylation with MeOH/HCl, were quantified by gas chromatography/mass spectrometry (GC/MS) technique. GC-MS analyses were performed on a Gas-Chromatograph Varian 3400 on a HP-INNOWAX column (30 m x 0.25 mm; 0.25 m film thickness). Mass spectra were acquired on a Finnigan MAT SSQ 710A mass spectrometer in the electron impact (EI) mode with an ionization energy of 70 eV; the ion source temperature was 250°C, the filament current was 200 A, the conversion dynode power was –15.0 kV and electron multiplier voltage was 1500 V.Serum ALA levels at 1 g/kg after 2h in the flaxseed oil group (n=25) increased by 70% from 0.067 ± 0.007 to 0.096 ± 0.082 mg/mL (P<0.001 Anova) whereas no significant increase occurred in the flaxseed oil group at 2.5 g/kg (0.142 ± 0.071) or at 5 g/kg after 2 h (0.140 ± 0.106) when compared with the value obtained with 1 g/kg. ALA (1g/kg) significantly increased after 4 h in adipose tissue and in liver but also in this case at higher doses (2.5-5 g/kg) the concentration wasn’t increased. Concerning linoleic acid (-6) no significant increased concentrations were found in serum at the three doses studied confirming that flaxseed oil is a source of -3 fatty acids. These data suggested that there is a limiting step in the adsorption of these fatty acids and that there is no advantage to take more than 1 g/kg of ALA supplementation
Genetic predisposition to atorvastatin-induced myopathy: a case report
No full textWhat is known and Objective: The major clinical complication of statins is a variety of muscle complaints ranging from myalgia to rhabdomyolysis. There is growing evidence that carriers of genetic polymorphisms in the enzymes and transporters implicated in statin disposition, particularly the SLCO1B1 gene, are at increased risk of myotoxicity. Our objective is to report on two cases of statin-induced myopathy occurring in a family with two patients who are carriers of the loss of function SLCO1B1 genetic variant and to briefly review the related literature. Case summary: Patient 1, a 48-year-old man with history of coronary artery disease, experienced rapidly evolving muscle pain and weakness of the extremities during treatment with atorvastatin 40 mg. Patient 2, a 65-year-old man, father of patient 1, had symptoms similar to those of his son after 2 weeks treatment with the same statin. Atorvastatin was stopped in both cases, and symptoms resolved. On the basis of family relationship between the two patients, it was possible to hypothesize a genetic basis for the myopathy. Genotyping showed the patients to be carriers of the rs4363657 polymorphism of SLCO1B1 gene. What is new and Conclusion: The two cases reported here and the brief literature review emphasize the impact of genetic factors on the risk of myopathy with statins. Although genotyping all patients before initiating therapy is not recommended at present, pharmacogenetic testing may be useful for new patients who have a family history of statin-induced myopathy
Familial aggregation of early-onset myocardial infarction
No full textBackground: An inherited predisposition is an important factor in the etiology of myocardial infarction (MI) at a young age. However, the extent of the risk for early-onset MI in relatives of young patients is still unclear, due to the paucity of family history data. Hence familial aggregation of early-onset MI was investigated in a cohort of relatives of Italian patients who had survived MI who occurred at the age of 45 or earlier.
Methods: In the framework of a case-control study, lifetime data and early-onset MI status for 11,696 relatives of cases and 8897 relatives of controls were collected using a standardized questionnaire.
Results: Occurrence of early-onset MI in females was very uncommon (Kaplan-Meier risk=0.6%, 95% confidence interval (CI): 0.38-0.82%, for female case relatives), and significantly lower than that for male case relatives (5.0%, 95% CI: 4.41-5.56%). The hazard ratio (HR) for case relatives was approximately 3-fold greater than that for control aunts (taken as reference category). Risk for early-onset MI to siblings (HR=1.7, 95% CI: 1.33-2.18) was significantly different from that to parents (HR=0.9, 95% CI: 0.71-1.16). The familial risk ratio lambda(R) was 2.6 (95% CI: 2.30-2.89) for case relatives, using control parents as reference population for early-onset MI risk estimates (i.e. 37 per 100,000 in fathers and 7 per 100,000 in mothers).
Conclusion: We evaluated the risk of early-onset MI by category of relatives, obtaining evidence for familial aggregation of the disease in this Italian sample and providing figures for genetic counselling and planning genetic epidemiological studies. (C) 2010 European Federation of Internal Medicine. Published by Elsevier B. V. All rights reserved
G-CSF treatment of Severe Congenital Neutropenia reverses neutropenia but does not correct the underlying functional deficiency of the neutrophil in defending against microorganisms.
No full textThe treatment of children affected by severe congenital neutropenia (SCN) with G-CSF strongly reduces the risk of sepsis by reversing neutropenia. However, SCN patients who respond to the treatment with the growth factor still have an elevated risk of succumbing to sepsis. Because the disease is usually caused by heterozygous mutations of ELA2, a gene encoding for neutrophil elastase (NE), we have investigated in G-CSF–responder and nonresponder patients affected by SCN the expression of polypeptides that constitute the antimicrobial machinery of these cells. In peripheral blood–derived neutrophils of patients with heterozygous mutations of ELA2 who were treated with G-CSF, NE was nearly absent as detected by immunofluorescence and immunoblotting, suggesting that production of the mutant protein interferes with normal gene expression. This defect was associated with abnormal expression of other granule-associated proteins such as myeloperoxidase, lactoferrin, cathepsin G, and human-neutrophil-peptide. Moreover, in one patient with partial response to G-CSF, we observed an impairment of neutrophil antimicrobial activity against Candida albicans, and, to a lower extent against Escherichia coli. Thereby, we propose that the treatment with G-CSF is not sufficient to correct all of the functional deficiency of neutrophils, and this might account for the consistent risk of infections observed in SCN patient
Restraint Stress during Pregnancy Rapidly Raises Kynurenic Acid Levels in Mouse Placenta and Fetal Brain
No full textStressful events during pregnancy adversely affect brain development and may increase the risk of psychiatric disorders later in life. Early changes in the kynurenine (KYN) pathway (KP) of tryptophan (TRP) degradation, which contains several neuroactive metabolites, including kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), and quinolinic acid (QUIN), may constitute a molecular link between prenatal stress and delayed pathological consequences. To begin testing this hypothesis experimentally, we examined the effects of a 2-h restraint stress on KP metabolism in pregnant FVB/N mice on gestational day 17. TRP, KYN, KYNA, 3-HK, and QUIN levels were measured in maternal and fetal plasma and brain, as well as in the placenta, immediately after stress termination and 2 h later. In the same animals, we determined the activity of TRP 2,3-dioxygenase (TDO) in the maternal liver and in the placenta. Compared to unstressed controls, mostly transient changes in KP metabolism were observed in all of the tissues examined. Specifically, stress caused significant elevations of KYNA levels in the maternal plasma, placenta, and fetal brain, and also resulted in increased levels of TRP and KYN in the placenta, fetal plasma, and fetal brain. In contrast, 3-HK and QUIN levels remained unchanged from control values in all tissues at any time point. In the maternal liver, TDO activity was increased 2 h after stress cessation. Taken together, these findings indicate that an acute stress during the late gestational period preferentially affects the KYNA branch of KP metabolism in the fetal brain. Possible long-term consequences for postnatal brain development and pathology remain to be examined.</jats:p
Glucose metabolism and diet-based prevention of liver dysfunction in MPV17 mutant patients.
No full textBACKGROUND/AIMS: To describe in detail the specific clinical and biological characteristics of three patients with MPV17 gene mutations, a rare hepatocerebral mitochondrial DNA depletion syndrome (MDS) and the positive effects of a novel dietetic treatment based on avoidance of fasting. METHODS: We describe the case histories of three members of the same family with MPV17 mutations. RESULTS: Two patients had a very severe and progressive liver disease: 1 died in the first year of life and the other underwent liver transplantation. The third patient, now 13 years of age, had a milder form of liver disease and developed progressive ataxia. Psychomotor involvement at onset of disease was mild or absent. No patient had severe hyperlactataemia. In vivo functional studies on two patients showed no hyperlactataemia even after intravenous and oral glucose loading, regular fasting hypoglycemia 3-4h after meals and no response to glucagon. Liver function tests improved when patients received continuous iv glucose infusion or were regularly fed every 3h. CONCLUSIONS: These clinical and biochemical features allow us to differentiate patients with MPV17 mutations from other liver MDS and suggest that regular glucose intake at short intervals may be beneficial in slowing the progression of the disease
Adipose-Derived Stromal Cell Conditioned Medium on Bone Remodeling: Insights from a 3D Osteoblast-Osteoclast Co-Culture Model
No full textThis study describes the potential of the conditioned medium (CM) from adipose-derived mesenchymal stromal cells (ASCs) to affect the response of bone cells and support bone remodeling. This was in particular assessed by an in vitro model represented by a 3D human osteoblast-osteoclast co-culture. It has been reported that the effects of ASCs are predominantly attributable to the paracrine effects of their secreted factors, that are present as soluble factors or loaded into extracellular vesicles. They may affect various biological processes, including bone turnover. Our interest was to provide further evidence to support ASC-CM as a promising cell-free therapeutic agent for the treatment of bone loss. ASC-CM was characterized using nanoparticle tracking analysis (NTA), cytofluorimetry, and proteomic analysis. Human osteoblasts (hOBs) from vertebral lamina were cultured with monocytes, as osteoclasts (hOCs) precursors, in a Rotary cell culture system for 14 days. Histochemical analysis was performed to evaluate the effect of ASC-CM on bone-specific markers such as tartrate-resistant acid phosphatase (TRAP), osteopontin (OPN), RUNX2, Collagen 1 (COL1), and mineral matrix. ASC-CM characterization confirmed the content of CD63/CD81/CD9 positive extracellular vesicles. Proteomic dataset considering bone-remodeling-related keywords identified 16 processes significantly enriched. The exposure of hOBs/hOCs aggregates to ASC-CM induced increase of OPN, COL I, and RUNX2, and significantly induced mineral matrix deposition, while significantly reducing TRAP expression. These data demonstrated that CM from ASCs contains a complex of secreted factors able to control either bone resorption or bone formation and requires further investigations to deeply analyze their potential therapeutic effects
- …
