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γ1- and γ2-melanocyte stimulating hormones induce central anxiogenic effects and potentiate ethanol withdrawal responses in the elevated plus-maze test in mice
(Elsevier, 2009) Jansone, Baiba; Rumaks, Juris; Dzirkale, Zane; Pupure, Jolanta; Svirskis, Šimons; Muceniece, Ruta; Klusa, Vija
Little is known about the endogenous functions of γ1- and γ2-melanocyte stimulating hormones (γ1- and γ2-MSH). Although γ-MSHs bind to melanocortin receptor subtypes 3 and 4, we have previously shown that these peptides also influence non-melanocortinergic processes, such as dopaminergic and GABAergic. The aim of this study was to determine the effects of γ1- and γ2-MSH (at doses 0.3, 1 and 2 nmol/mouse/5 μl) on the anxiety levels in mice in elevated plus maze. Three experimental paradigms were performed to assess the effects of peptides on: a) ethanol withdrawal; b) acute ethanol-induced anxiolytic action; c) peptides per se. We used ethanol as the model substance, since its action involves either dopaminergic/GABAergic or melanocortinergic processes. γ-MSHs were administered intracisternally in mice and behavioural responses were assessed in the elevated plus maze test. This study provides the first demonstration of an anxiogenic effect of γ1- and γ2-MSH, their synergistic/additive effect on ethanol withdrawal-induced anxiety behaviour, and an antagonism of peptides involved in the anxiolytic action of ethanol. Furthermore, results suggest that γ-MSHs belong to an anxiogenic peptide family that may play an important role in anxiety disorders as well as in the development of alcohol dependence and/or alcohol withdrawal-induced behaviours.
Identification of somatostatin receptor type 5 gene polymorphisms associated with acromegaly
(European Society of Endocrinology, 2011) Ciganoka, Darja; Balcere, Inga; Kapa, Ivo; Peculis, Raitis; Valtere, Andra; Nikitina-Zake, Liene; Lase, Ieva; Schiöth, Helgi B.; Pirags, Valdis; Klovins, Janis
A common promoter variant of the gene encoding cyclooxygenase-1 (PTGS1) is related to decreased incidence ofmyocardial infarction in patients with coronary artery disease
(Elsevier, 2011) Latkovskis, Gustavs; Licis, Normunds; Krivmane, Baiba; Erglis, Andrejs
Cyclooxigenase (COX)-1, formally known as prostanglandin endoperoxideH synthetase-1,mediates synthesis of prostaglandin H2,which is subsequently converted to various biologically active metabolites including thromboxane (TX) A2 [1]. TXA2 is synthesized and released by activated platelets and strongly reinforces thrombus formation, a critical pathway in the pathogenesis of myocardial infarction (MI). Inhibition of COX-1-derived TXA2 in platelets by low-dose aspirin administration reduces incidence of MI [2]. Hypothetically, MI-risk could also be modified by genetic variants that affect activity or expression of COX-1. Many single nucleotide polymorphisms (SNP) in the gene encoding COX-1 (PTGS1) have been described; including functional alterations in both coding and non-coding regions [3,4].We have evaluated if two of such variations are related to the risk ofMI in a historic cohort of patients with coronary artery disease (CAD).
Association of reduced glyoxalase 1 activity and painful peripheral diabetic neuropathy in type 1 and 2 diabetes mellitus patients
(Elsevier, 2013) Skapare, Elina; Konrade, Ilze; Liepinsh, Edgars; Strele, Ieva; Makrecka, Marina; Bierhaus, Angelika; Lejnieks, Aivars; Pirags, Valdis; Dambrova, Maija
Aims: The present study was undertaken to investigate the relationship between glyoxalase 1 (Glo1) enzyme activity and painful diabetic neuropathy (DN) in patients with diabetes mellitus. Methods: Glo1 activity and biochemical markers were determined in blood samples from 108 patients with type 1 diabetes, 109 patients with type 2 diabetes, and 132 individuals without diabetes as a control. Painful and painless peripheral DN was assessed and multivariate regression analysis was used to determine independent association of Glo1 activity with occurrence of painful DN. Results: In patients with type 1 and type 2 diabetes mellitus and painful DN compared to patients with painless DN, Glo1 activity was significantly reduced by 12 and 14%, respectively. The increase in Glo1 activity was significantly associated with reduced occurrence of painful DN after adjusting for confounders by multivariate analysis. Conclusions: Our results demonstrate for the first time that Glo1 activity is lower in patients with both types of diabetes mellitus who were diagnosed with painful DN. These data support the hypothesis that Glo1 activity modulates the phenotype of DN and warrant further investigation into the role of Glo1 in DN. © 2013 Elsevier Inc. All rights reserved.
Lunasin-induced behavioural effects in mice: Focus on the dopaminergic system
(Elsevier, 2013) Dzirkale, Zane; Rumaks, Juris; Svirskis, Simons; Mazina, Olga; Allikalt, Anni; Rinken, Ago; Jekabsons, Kaspars; Muceniece, Ruta; Klusa, Vija
The present study for the first time is devoted to identify central effects of synthetic lunasin, a 43 amino acid peptide. A markedly expressed neuroleptic/cataleptic effect was observed at low (0.1–10 nmol/mouse) centrally administered doses in male C57Bl/6 mice. Lunasin considerably reduced the amphetamine hyperlocomotion but weakly apomorphine climbing behaviour. No influence on ketamine and bicuculline effects was observed. Binding assay studies demonstrated modest affinity of lunasin for the dopamine D1 receptor (Ki = 60±15 M). In a functional assay of cAMP accumulation on live cells lunasin antagonised apomorphine effect on D1 receptor activation (pEC50 = 6.1±0.3), but had no effect in cells expressing D2 receptors. The obtained data suggest that lunasin’s action at least in part is provided via dopaminergic D1 receptor pathways. However, other non-identified mechanisms (probably intracellular) may play an important role in lunasin’s central action. Nevertheless further studies of lunasin are promising, particularly taking into account a necessity for novel type of antipsychotic drugs
DNA damage causes TP53-dependent coupling of self-renewal and senescence pathways in embryonal carcinoma cells
(Taylor&Francis, 2013) Jackson, Thomas R.; Salmina, Kristine; Huna, Anda; Inashkina, Inna; Jankevics, Eriks; Riekstina, Una; Kalnina, Zane; Ivanov, Andrey; Townsend, Paul A .; Cragg, Mark S.; Erenpreisa, Jekaterina
Carnitine congener mildronate protects against stress- and haloperidol-induced impairment in memory and brain protein expression in rats
(Elsevier, 2014) Beitnere, Ulrika; Dzirkale, Zane; Isajevs, Sergejs; Rumaks, Juris; Svirskis, Simons; Klusa, Vija
The present study investigates the efficacy of mildronate, a carnitine congener, to protect stress and haloperidol-induced impairment of memory in rats and the expression of brain protein biomarkers involved in synaptic plasticity, such as brain-derived neurotrophic factor (BDNF), acetylcholine esterase and glutamate decarboxylase 67 (GAD67). Two amnesia models were used: 2 h immobilization stress and 3-week haloperidol treatment. Stress caused memory impairment in the passive avoidance test and induced a significant 2-fold BDNF elevation in hippocampal and striatal tissues that was completely inhibited by mildronate. Mildronate decreased the level of GAD67 (but not acetylcholine esterase) expression by stress. Haloperidol decrease by a third hippocampal BDNF and acetylcholine esterase (but not GAD67) expression, which was normalized by mildronate; it also reversed the haloperidol-induced memory impairment in Barnes test. The results suggest the usefulness of mildronate as protector against neuronal disturbances caused by stress or haloperidol.
Breath testing as a method for detecting lung cancer
(Taylor&Francis, 2014) Taivans, Immanuels; Bukovskis, Maris; Strazda, Gunta; Jurka, Normunds
Early diagnosis of lung cancer is important due to high mortality in late stages of the disease. An ideal approach for population screening could be the breath analysis, due to its non-invasiveness, simplicity and cheapness. Using sensitive methods of analysis like gas chromatography/mass spectrometry in exhaled air of cancer patients were discovered some volatile organic compounds – possible candidates for cancer markers. However, these compounds were not specific for cancer cells. At the same time, integrative approaches used to analyze the exhaled breath have demonstrated high sensitivity and specificity of this method for lung cancer diagnosis. Such integrative approaches include detection of smell prints by electronic nose or integrated analysis of wide range of volatile organic compounds detected by gas chromatography/mass spectrometry or related methods. Modern statistical pattern recognition systems like logistic regression analysis, support vector machine or analysis by artificial neuronal network may improve diagnostic accuracy.
A cross-sectional survey of urinary iodine status in Latvia
(Elsevier, 2014) Konrade, Ilze; Neimane, Lolita; Makrecka, Marina; Strele, Ieva; Liepinsh, Edgars; Lejnieks, Aivars; Vevere, Parsla; Gruntmanis, Ugis; Pīrāgs, Valdis; Dambrova, Maija
Prevalence estimation of celiac disease in the general adult population of Latvia using serology and HLA genotyping
(Sage, 2015) Leja, Marcis; Shums, Zakera; Nikitina-Zake, Liene; Gavars, Mikus; Kikuste, Ilze; Milo, Jay; Pahomova, Jelena; Pirags, Valdis; Dzerve, Vilnis; Klovins, Janis; Erglis, Andrejs; Norman, Gary L.
Breath testing as potential colorectal cancer screening tool
(International Union against Cancer, Wiley, 2015) Amal, Haitham; Leja, Marcis; Funka, Konrads; Lasina, Ieva; Skapars, Roberts; Sivins, Armands; Ancans, Guntis; Kikuste, Ilze; Vanags, Aigars; Tolmanis, Ivars; Kirsners, Arnis; Kupcinskas, Limas; Haick, Hossam
Improving uptake of screening for colorectal cancer: a study on invitation strategies and different test kit use
(Kluwer, 2015) Santare, Daiga; Kojalo, Ilona; Huttunen, Teppo; Rikacovs, Sergejs; Rucevskis, Peteris; Boka, Viesturs; Leja, Marcis
Detection of precancerous gastric lesions and gastric cancer through exhaled breath
(British Society of Gastroenterology, 2015) Amal, Haitham; Leja, Marcis; Funka, Konrads; Skapars, Roberts; Sivins, Armands; Ancans, Guntis; Liepniece-Karele, Inta; Kikuste, Ilze; Lasina, Ieva; Haick, Hossam
Atherosclerotic Plaque Characteristics by CT Angiography Identify Coronary Lesions That Cause Ischemia A Direct Comparison to Fractional Flow Reserve
(Elsevier, 2015) Park, Hyung-Bok; Heo, Ran; Hartaigh, Bríain; Cho, Iksung; Gransar, Heidi; Nakazato, Ryo; Leipsic, Jonathon; Mancini, John; Koo, Bon-Kwon; Otake, Hiromasa; Budoff, Matthew J.; Berman, Daniel S.; Erglis, Andrejs; Chang, Hyuk-Jae; Min, James K.
Burnout syndrome among psychiatric trainees in 22 countries: Risk increased by long working hours, lack of supervision, and psychiatry not being first career choice
(Elsevier, 2016-02) Jovanović, N.; Podlesek, A.; Volpe, U.; Barrett, E.; Ferrari, S.; Rojnic Kuzman, M.; Wuyts, P.; Losevich, M. A.; etc
Very low doses of muscimol and baclofen ameliorate cognitive deficits and regulate protein expression in the brain of a rat model of streptozocin-induced Alzheimer's disease
(Elsevier, 2018-01-05) Pilipenko, Vladimirs; Narbute, Karina; Beitnere, Ulrika; Rumaks, Juris; Pupure, Jolanta; Jansone, Baiba; Klusa, Vija
Recent studies devoted to neuroprotection have focused on the role of the gamma-aminobutyric acid (GABA) system in regulating neuroinflammatory processes which play a key role in the neurodegenerative processes observed in Alzheimer's disease (AD) by inducing glial cell overactivation and impairing neurotransmission. Data on the efficacy of classical GABA-A and GABA-B receptor agonists (muscimol and baclofen, respectively) in animal models of AD are not available. Moreover, no published studies have examined the ability of optimal doses of these compounds to prevent neuroinflammation, the alterations in neurotransmission and cognitive deficits. In the present study, we used a non-transgenic rat model of AD obtained by intracerebroventricular streptozocin (STZ) injection and assessed the effects of muscimol and baclofen at very low doses (0.01-0.05mg/kg) on spatial memory and the expression of cortical and hippocampal proteins related to neuroinflammation, namely proteins involved in astroglial functions (glial fibrillary acidic protein, GFAP), GABA synthesis (GABA synthesizing enzyme, glutamic acid decarboxylase 67, GAD67) and acetylcholine degradation (acetylcholine esterase). The presented study demonstrated that in a rat model of STZ-induced AD both muscimol and baclofen at the tested doses exerted memory-enhancing and anti-inflammatory effects, as well as normalization of acetylcholine esterase and GABA expression. We suggested that the function of very low doses of GABA receptor agonists differs from typical GABA-related inhibition and may be mediated by the allosteric sites of GABA receptors or other non-specific cell regulatory pathways.
Intranasal Administration of Extracellular Vesicles Derived from Human Teeth Stem Cells Improves Motor Symptoms and Normalizes Tyrosine Hydroxylase Expression in the Substantia Nigra and Striatum of the 6-Hydroxydopamine-Treated Rats
(AlphaMed Press Wiley, 2019-04-22) Narbute, Karīna; Piļipenko, Vladimirs; Pupure, Jolanta; Dzirkale, Zane; Jonavičė, Ugnė; Tunaitis, Virginijus; Kriaučiūnaitė, Karolina; Jarmalavičiūtė, Akvilė; Jansone, Baiba; Kluša, Vija; Pivoriūnas, Augustas
Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting millions of people worldwide. At present, there is no effective cure for PD; treatments are symptomatic and do not halt progression of neurodegeneration. Extracellular vesicles (EVs) can cross the blood–brain barrier and represent promising alternative to the classical treatment strategies. In the present study, we examined therapeutic effects of intranasal administration of EVs derived from human exfoliated deciduous teeth stem cells (SHEDs) on unilateral 6‐hydroxydopamine (6‐OHDA) medial forebrain bundle (MFB) rat model of PD. CatWalk gait tests revealed that EVs effectively suppressed 6‐OHDA‐induced gait impairments. All tested gait parameters (stand, stride length, step cycle, and duty cycle) were significantly improved in EV‐treated animals when compared with 6‐OHDA‐lesion group rats. Furthermore, EVs slowed down numbers of 6‐OHDA‐induced contralateral rotations in apomorphine test. Improvements in motor function correlated with normalization of tyrosine hydroxylase expression in the striatum and substantia nigra. In conclusion, we demonstrated, for the first time, the therapeutic efficacy of intranasal administration of EVs derived from SHEDs in a rat model of PD induced by 6‐OHDA intra‐MFB lesion. Our findings could be potentially exploited for the development of new treatment strategies against PD.

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