Svalbe B, Zvejniece L, Vavers E, Pugovichs O, Muceniece R, Liepinsh E, Dambrova M, Mildronate treatment improves functional recovery following middle cerebral artery occlusion in rats, Behavioural Brain Research, 2011, 222(1):26-32.
http://www.ncbi.nlm.nih.gov/pubmed/21420440
Kopsavilkums
Mildronate (3-(2,2,2-trimethylhydrazinium) propionate) is an inhibitor of l-carnitine biosynthesis and an anti-ischemic drug. In the present study, we investigated the effects of mildronate in rats following focal cerebral ischemia. Male Wistar rats were subjected to transient occlusion of the middle cerebral artery (MCAO) for 90min, followed by the intraperitoneal administration of mildronate at doses of 100 and 200mg/kg 2h after reperfusion and then daily for an additional 14days. The beam-walking, rota-rod and cylinder tests were used to assess sensorimotor function, and vibrissae-evoked forelimb-placing and limb-placing tests examined responses to tactile and proprioceptive stimulation. Following behavioural testing, the infarct volume was measured. The cerebellar concentrations of l-carnitine, γ-butyrobetaine (GBB) and mildronate were also measured. The results showed that saline-treated MCAO rats had minor or no spontaneous recovery in sensorimotor and proprioceptive function up to 14days post-stroke. Treatment with mildronate at a dose of 200mg/kg was found to accelerate recovery of motor and proprioceptive deficits in limb-placing, cylinder and beam-walking tests. Analysis of rat cerebellar tissue extracts revealed that l-carnitine and GBB concentrations changed with mildronate treatment; the concentration of l-carnitine was significantly decreased by mildronate treatment, whereas the concentration of GBB was significantly increased. Cerebellar concentrations of mildronate also increased in a dose-dependent manner following systemic administration. Infarct size did not differ among the experimental groups on post-stroke day 14. The present study suggests that mildronate treatment improves the functional outcome in MCAO rats without influencing infarct size.
Liepinsh E, Konrade I, Skapare E, Pugovics O, Grinberga S, Kuka J, Kalvinsh I, Dambrova M, Mildronate treatment alters gamma-butyrobetaine and L-carnitine concentrations in healthy volunteers, Journal of Pharmacy and Pharmacology, 2011, 63(9):1195-1201.
http://onlinelibrary.wiley.com/doi/10.1111/j.2042-7158.2011.01325.x/pdf
Kopsavilkums
Objectives. In this study, we aimed to investigate the effects of long-term administration of the cardioprotective drug mildronate on the concentrations of l-carnitine and g-butyrobetaine in healthy volunteers.
Methods. Mildronate was administered perorally, at a dosage of 500 mg, twice daily. Plasma and urine samples were collected weekly. Daily meat consumption within an average, non-vegetarian diet was monitored. l-Carnitine, g-butyrobetaine and mildronate concentrations were measured using the UPLC/MS/MS method.
Key findings. After 4 weeks, the average concentrations of l-carnitine in plasma significantly decreased by 18%. The plasma concentrations of g-butyrobetaine increased about two-fold, and this effect was statistically significant in both the male and female groups. In urine samples, a significant increase in l-carnitine and g-butyrobetaine levels was observed, which provides evidence for increased excretion of both substances during the mildronate treatment. At the end of the treatment period, the plasma concentration of mildronate was 20 mm on average. There were no significant differences between the effects observed in female and male volunteers. Meat consumption partially reduced the l-carnitine-lowering effects induced by mildronate.
Conclusions. Long-term administration of mildronate significantly lowers l-carnitine plasma concentrations in non-vegetarian, healthy volunteers.
Соколовска Е., Ю. Румакс, Н. Караева, Д. Гринвалде, В. Клуша. И. Калвиньш и Н. Сьяксте Влияние милдроната на зазвитие периферической невропатии и некоторые показатели обмена глюкозы у крыс со стрептозотоциновой моделью сахарного диабета. Биомедицинская химия, 2011, т.57, вып. 5, С. 490-500. (PubMed indeksēts)
http://elibrary.ru/item.asp?id=17001566
Kopsavilkums
Streptozotocin (STZ) was used to induce the diabetic rat model. STZ rats were treated with mildronate (100 mg/kg daily, per os or intraperitoneally for 6 weeks). Body weight, blood glucose, triglyceride, ketone body concentrations, glycated hemoglobin percent (HbA1c%), glucose tolerance, and the development of neuropathic pain were monitored throughout the experiment. In the STZ + mildronate group, mildronate treatment caused a significant decrease in mean blood glucose (on week 4) and triglyceride concentrations (on weeks 3-6), significantly slowed the increase in HbA1c% (on week 6) and improved glucose tolerance 120 minutes after glucose ingestion during oral glucose tolerance test versus the STZ group. Mildronate completely protected development of STZ-induced neuropathic pain from the first administration week up to end of the experiment. The obtained data indicate clinical usefulness of the drug for the treatment of diabetes mellitus and its complications.
Marina Petrova *, Ruslan Muhamadejev, Brigita Vigante, Brigita Cekavicus, Aiva Plotniece, Gunars Duburs and Edvards Liepinsh, Intramolecular C-H···O Hydrogen Bonding in 1,4-Dihydropyridine Derivatives, Molecules 2011, 16, 8041-8052; doi:10.3390/molecules16098041
http://www.ncbi.nlm.nih.gov/pubmed/21931285
Kopsavilkums
The diastereotopy of the methylene protons at positions 2 and 6 in 1,4-dihydropiridine derivatives with various substituents has been investigated. NMR spectroscopy and quantum chemistry calculations show that the CH···O intramolecular hydrogen bond is one of the factors amplifying the chemical shift differences in the 1H-NMR spectra.
Dzintare M., L. Baumane, D. Meirena, J. Šaripova, L. Ļauberte, I. Kalviņš and N. Sjakste Modifications of NO production in rat tissues by ellagic acid, ipriflavone and resveratrol: a comparative study. Proceedings of the Latvian Academy of Sciences, B, Vol. 64 (2010), No 5/6, pp.182-187. Publicēts 2011. gada septembrī.
http://versita.metapress.com/content/j03678j214k34u28/
Kopsavilkums
When administered as drugs or consumed as food components, polyphenolic compounds synthesised in plants interfere with intracellular signal transduction pathways, including pathways of nitric oxide (NO) synthase (NOS) expression. However, the effects of these compounds in vivo do not always correlate with NOS-inhibiting activities, as revealed in experiments with cultured cells. The goal of this work was to compare the effects of resveratrol, ellagic acid and ipriflavone on NO production in rat organs measured by means of ESR spectroscopy. All of the above compounds are known as inhibitors of iNOS expression. The presumed ability to decrease NO production was manifested only by ellagic acid; it decreased NO production in spleen of intact rats. Iproflavone and resveratrol even enhanced the lipopolyssacharides (LPS)-induced increase of NO production. Ipriflavone increased NO production in the brain cortex, cerebellum, liver, heart, kidneys, blood, lungs and skeletal muscles. Resveratrol produced a similar effect in all of the above organs, except kidneys, lungs and muscles. Taken together, our results suggest that modifications of NO level in tissues by a natural compound cannot be predicted from data about its effects on NOS expression or activity. This stresses the importance of direct measurements of NO in tissues.
D. Tirzīte, I. Konrāde, D. Segliņa, E. Škapare, M. Dambrova, Āboli, florizīns un cukura diabēts, Latvijas ārsts, 2011, oktobris, 59-61.
http://www.latvijasarsts.lv/index.php?option=com_content&view=article&i…
