Hypotensive effect of alpha-lipoic acid after a single administration in rats

Objective: The effect of alpha-lipoic acid on blood pressure was investigated many times in chronic studies, but there are no studies on the effect of this compound after a single administration. Alpha-lipoic acid is a drug used in diabetic neuropathy, often in obese patients, to treat hypertension. Therefore, knowledge of the potential antihypertensive effect of alpha-lipoic acid even after a single dose and possibly too much pressure reduction is interesting and useful. Methods: The mechanism of the hypotensive effect of alpha-lipoic acid was examined in normotensive rats in vivo after a single intraperitoneal administration, blood pressure in the left carotid artery of the rats was measured prior to the administration of the compounds (alphalipoic acid and/or glibenclamide) and 80 min thereafter. Results: Alpha-lipoic acid at a dosage of 50 mg/kg b.w. i.p. significantly decreased the blood pressure from the 50th min after drug administration. This cardiovascular effect of this compound was reversed by glibenclamide, a selective KATP blocker. Glibenclamide alone at this dose did not significantly affect the blood pressure. Statistical significance was evaluated using two-way ANOVA. Conclusion: This suggests that alpha-lipoic acid affects ATP-dependent potassium channels. It is possible that this is an indirect effect of hydrogen sulfide because alpha-lipoic acid can increase its concentration. The results obtained in this study are very important because the patients taking alpha-lipoic acid may be treated for co-existing hypertension. Therefore, the possibility of blood pressure lowering by alphalipoic acid should be taken into account, although it does not lead to excessive orthostatic hypotension. (Anatol Cardiol 2016; 16: 306-9

Lasers and ancillary treatments for scar management Part 2: Keloid, hypertrophic, pigmented and acne scars

The formation of a wide range of excessive scars following various skin injuries is a natural consequence of healing. Scars resulting from surgery or trauma affect approximately 100 million people per annum in the developed world and can have profound physical, aesthetic, psychological and social consequences. Thus, scar treatment is a priority for patient and physician alike. Laser treatment plays an important role in scar management with additional support from ancillary modalities. Subsequent to part 1: Burns scars, part 2 focuses on our strategies and literature review of treatment of keloid, hypertrophic, pigmented and acne scars where lasers are used in conjunction with other measures, and illustrated with case studies

Modulation of endothelial cell proliferation and capillary network formation by the ox-LDL component: 1-palmitoyl-2-archidonoyl-sn-glycero-3-phosphocholine (ox-PAPC)

Atherosclerotic plaque formation is often associated with pathological angiogenesis. Modified phospholipids, including oxidized lipoproteins such as LDL, are found to induce adhesion of the monocytes to the endothelial cells and to stimulate their chemotaxis. Effects of oxidized 1-palmitoyl-2-archidonoyl-sn-glycero-3-phosphocholine (ox-PAPC) mimic actions of minimally modified LDL in vivo. Interleukin-8 (IL-8) and interleukin-15 (IL-15) are known to induce both inflammation and angiogenesis. The goal of our study was to analyze a potential synergism between ox-PAPC and IL-15 in the in vitro model of angiogenesis carried out in the human endothelial cells (HUVECs). Increasing IL-15 concentrations led to formation of the tube-like structures in the matrigel 3D-model of angiogenesis (P < 0.05), in contrast to ox-PAPC that inhibited this process. HUVECs incubation with ox-PAPC led to reduced IL-15 gene basal expression (P = 0.033) along with parallel increase, however statistically insignificant, of basal gene expression of IL-8 (P = 0.086). Our findings point to the ox-PAPC opposite effects on the IL-8- and IL-15-mediated angiogenic responses that contribute to pathological angiogenesis induced by ox-LDL

Omega-3 fatty acid supplementation influences the whole blood transcriptome in women with obesity, associated with pro-resolving lipid mediator production

The n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may reduce low-grade inflammation associated with obesity. The relationship between therapeutic response to n-3 PUFAs and modification of the transcriptome in obesity or metabolic syndrome remains to be explored.Blood samples were obtained from women with obesity before and after three-months supplementation with a moderate dose of n-3 PUFAs (1.8 g EPA + DHA per day) or from controls. n-3 PUFAs (GC) and plasma concentrations of lipoxins, resolvins, protectin X (GC-MS/MS) and inflammatory markers (ELISA) were measured. Whole blood transcriptome was assayed using microarray.Women supplemented with n-3 PUFAs for 3 months had significantly higher levels of EPA and DHA in plasma phosphatidylcholine. n-3 PUFA supplementation, in contrast to placebo, significantly decreased the concentrations of several inflammatory markers (SELE, MCP-1, sVCAM-1, sPECAM-1, and hsCRP), fasting triglycerides and insulin and increased the concentrations of pro-resolving DHA derivatives in plasma. The microarray data demonstrated effects of n-3 PUFAs on PPAR-?, NRF2 and NF-?B target genes.N-3 PUFAs increased DHA-derived pro-resolving mediators in women with obesity. Elevated resolvins and up-regulation of the resolvin receptor occurred in parallel with activation of PPAR-? target genes related to lipid metabolism and of NRF2 up-regulated antioxidant enzymes

Hepatocyte RXR alpha deletion in mice leads to inhibition of angiogenesis

To investigate the effect of RXRα deficiency in liver on angiogenesis, hepatocyte RXRα-deficient and control wild-type mice were fed either standard or high-fat diet (HF) for 7 weeks. In the 6th week of feeding, Matrigel model of in vivo angiogenesis was applied. Matrigel plug infiltrating cells were then used for visualization of vessels (CD31 staining) as well as for gene expression analysis. HF diet appeared to decrease angiogenesis in hRXRα-deficient mice. Genes related to angiogenesis (Nos3, Kdr) were down-regulated, whereas genes connected with adipogenesis (Cebpb, Srebf1), apoptosis (Gzmb,Bcl2) and proinflammatory pathway (NfκB, Tnfα) were up-regulated by HF diet in hRXRα-deficient mice in the microarray study. Our results suggest that impaired fatty acid metabolism in liver (hRXRα-deficient mice) leads to impaired angiogenesis due to lipotoxicity and promotion of adipogenesis

Omics biomarkers and an approach for their practical implementation to delineate health status for personalized nutrition strategies

Personalized nutrition (PN) has gained much attention as a tool for empowerment of consumers to promote changes in dietary behavior, optimizing health status and preventing diet related diseases. Generalized implementation of PN faces different obstacles, one of the most relevant being metabolic characterization of the individual. Although omics technologies allow for assessment the dynamics of metabolism with unprecedented detail, its translatability as affordable and simple PN protocols is still difficult due to the complexity of metabolic regulation and to different technical and economical constrains. In this work, we propose a conceptual framework that considers the dysregulation of a few overarching processes, namely Carbohydrate metabolism, lipid metabolism, inflammation, oxidative stress and microbiota-derived metabolites, as the basis of the onset of several non-communicable diseases. These processes can be assessed and characterized by specific sets of proteomic, metabolomic and genetic markers that minimize operational constrains and maximize the information obtained at the individual level. Current machine learning and data analysis methodologies allow the development of algorithms to integrate omics and genetic markers. Reduction of dimensionality of variables facilitates the implementation of omics and genetic information in digital tools. This framework is exemplified by presenting the EU-Funded project PREVENTOMICS as a use case