A systematic review: the appraisal of the effects of metformin on lipoprotein modification and function.

AIMS: Metformin is a commonly prescribed anti-hyperglycaemic pharmacological agent, and it remains a staple in the management of type II diabetes. In addition to metformin's glucose lowering effects, research has indicated that metformin inhibits glycation-mediated and oxidative modification of lipoprotein residues. The purpose was to discuss the effects of metformin as it relates to high-density lipoprotein (HDL) and low-density lipoprotein (LDL) modification. MATERIALS AND METHODS: The purpose was to conduct a narrative and pragmatic review on the effects of metformin as it pertains to HDL and LDL modification. RESULTS: High-density lipoprotein (HDL) concentration is a quantitative measure and therefore does not provide insight into its function, which is a qualitative property. Dysfunctional HDLs are unable to carry out functions normally associated with HDL because they can be modified by glycating agents. Metformin may counteract HDL dysfunction by abating HDL modification. Reductions in HDL modification may improve reverse cholesterol transport ability and thus possibly diminish cardiovascular risk. Similarly, metformin-mediated attenuations in LDL modification may reduce their atherogenic potency. CONCLUSION: Metformin may partially ameliorate HDL dysfunction and reduce LDL modification by inhibiting alpha-dicarbonyl-mediated modification of apolipoprotein residues; consequently, the results are salient because cardiovascular disease incidence may be reduced given that reverse cholesterol transport activity predicts risk, and modified LDL are proatherogenic.

[Investigations into certain mechanisms of antinociceptive action of millimeter wavelengths].

Changes in skin susceptibility and afferent pulsation frequency were measured in n. saphenous of rats undergoing the action of ultrahigh frequency electromagnetic radiation (UHF EMR). The study was aimed at verifying the hypothesis of the involvement of interleukine-6 (L-6) and endocannabinoids in the realization of the antinociceptive effect of UHF EMR. It was shown that UHF EMR with a wavelength of 7.1 mm lowers tactile, temperature, and pain sensitivity of the skin. This change was shown to correlate with the decreased electrical activity of afferent conductors of n. saphenous. Moreover, the IL-6 level in rat blood sera increased within 10 minutes after the irradiation both in the case of LPS-induced polyphasic fever in intact animals and under the normal conditions. This finding can possibly point out to the participation of this cytokine in the mechanisms of the antinociceptive effect especially in the case of pain of inflammatory origin. The data obtained give evidence that UHF EMR and anandamide exert a synergistic effect which confirms the involvement of the endocannabinoid system in the mechanisms of the antinociceptive action of the physical factor under consideration.

Assay of the concentration and 13C-isotopic enrichment of malonyl-coenzyme A by gas chromatography-mass spectrometry.

We developed gas chromatography-mass spectrometry assays for the concentration and mass isotopomer distribution of malonyl-CoA in tissues. The assay involves perchloric acid extraction of the tissue, spiking the extract with [U-13C3]malonyl-CoA or dimethylmalonyl-CoA internal standard, isolation of short-chain acyl-CoA fraction on an oligonucleotide purification cartridge, alkaline hydrolysis to malonate, trimethylsilyl derivatization, and analysis of the mass isotopomer distribution of malonate. The assay was applied to labeling of malonyl-CoA from various [13C]substrates in perfused rat livers and hearts. In livers perfused with [1,2-13C2]acetate, malonyl-CoA is doubly labeled from [1,2-13C2]acetate and singly labeled from 13CO2. In livers perfused with either NaH13CO3 or [3-13C]lactate + [3-13C]pyruvate, the half-lives of singly labeled malonyl-CoA were less than 20 s and 6.95 min, respectively. In rat heart, the half-life of malonyl-CoA, traced with NaH13CO3, was about 1.25 min. Thus, our assay allows us to measure the turnover of tissue malonyl-CoA, the contribution of various [13C]substrates to its production in lipogenic and nonlipogenic organs, and the cycling between acetyl-CoA and malonyl-CoA in nonlipogenic organs.