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Browsing by Author "Romanovs, Mihails"

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    Case Report : Micro-RNAs in Plasma From Bilateral Inferior Petrosal Sinus Sampling and Peripheral Blood From Corticotroph Pituitary Neuroendocrine Tumors
    (2022-04-22) Niedra, Helvijs; Peculis, Raitis; Konrade, Ilze; Balcere, Inga; Romanovs, Mihails; Steina, Liva; Stukens, Janis; Sokolovska, Jelizaveta; Klovins, Janis; Rovite, Vita; Department of Internal Diseases
    Objective: Circulating miRNAs are found in bodily fluids including plasma and can serve as biomarkers for diseases. The aim of this study was to provide the first insight into the landscape of circulating miRNAs in close proximity to the adrenocorticotropic hormone (ACTH) secreting PitNET. To achieve this objective next-generation sequencing of miRNAs in plasma from bilateral inferior petrosal sinus sampling (BIPSS) - a gold standard in diagnosing ACTH-secreting PitNETs was carried out and selected miRNA candidates were further tested by RT-qPCR in independent patient cohorts. Methods: Sinistral (left) and dextral (right) BIPSS blood samples of the patient were collected in three time points: before the administration of corticotropin-releasing hormone, 5 and 15 minutes after stimulation. In differential expression analysis, sinistral plasma was compared with dextral. The selected miRNA candidates were tested in plasma by RT-qPCR in two patient groups: 1) in five ACTH secreting PitNET patients with plasma samples taken before and 24 hours after surgery, 2) in 12 ACTH secreting PitNET patients vs. 9 non-functioning PitNET patients. Results: BIPSS concluded that the highest amount of ACTH was released in the sinistral side at the 5th minute mark indicating a presence of a tumor. The highest amount of differentially expressed miRNAs was observed 5 minutes after stimulation (20 upregulated, 14 downregulated). At the 5th minute mark in sinistral plasma, two miRNAs were identified: hsa-miR-7-5p and hsa-miR-375-3p that were highly upregulated compared to other BIPSS samples and peripheral plasma samples. Further testing by qPCR revealed significant reduction of miR-7-5p in plasma 24 hours after surgery and upregulation in plasma of ACTH secreting PitNET patients compared to non-functioning PitNET patients (P =0.0013). Conclusions: By stimulating the ACTH secreting PitNET with CRH a rapid increase of two miRNAs (hsa-mir-7-5p, hsa-mir-375-3p) and ACTH can be observed in sinistral inferior petrosal (tumor side). A decrease of miR-7-5p in plasma after surgery and upregulation in plasma of ACTH secreting PitNET patients was discovered implying that further studies of this miRNA as diagnostic marker is needed.
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    Consumption of thyroid medications as an indicator of increase of thyroid morbidity in Latvia from 2011 to 2014
    (2019-08-01) Kalere, Ieva; Strele, Ieva; Miglinieks, Martiņš; Repša, Ilze; Pildava, Santa; Romanovs, Mihails; Pirags, Valdis; Konrade, Ilze; Rīga Stradiņš University
    The most common autoimmune disorders with clinically opposite manifestations are hypothyroidism in Hashimoto's thyroiditis and hyperthyroidism in Graves' disease. The healthcare burden of thyroid disease is substantial, resulting in substantial health care costs. The aim of the present analysis is to assess the use of thyroid medications in Latvia from 2011 to 2014 by age and gender. Our study used reimbursed medication prescriptions data, collected by the National Health Service of Latvia. The main indicator was the number of prevalent users of thyroid medications each year from 2011 to 2014, stratified by age and gender. From 2011 to 2014, the number of thyroxine users per 100 000 revealed a statistically significant increase in all age and gender groups, except in 0- to 9-year-old girls. The number of Thiamazole users among men increased in the age group from 40 to 89 years and in women age groups above 49 years. Increasing sales of both thyroid hormones and antithyroid medications are also observed in Estonia and Lithuania, indicating that growing thyroid morbidity is an issue in the whole region. The substantial increase in number of patients highlights the necessity for national guidelines on the use of thyroid function tests and standards of medical care.
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    Genome wide analysis of circulating miRNAs in growth hormone secreting pituitary neuroendocrine tumor patients’ plasma
    (2022-09-09) Niedra, Helvijs; Peculis, Raitis; Litvina, Helena Daiga; Megnis, Kaspars; Madrika, Ilona; Balcere, Inga; Romanovs, Mihails; Steina, Liva; Stukens, Janis; Breiksa, Austra; Nazarovs, Jurijs; Sokolovska, Jelizaveta; Liutkeviciene, Rasa; Vilkevicute, Alvita; Konrade, Ilze; Rovite, Vita; Department of Internal Diseases
    Background: Circulating plasma miRNAs have been increasingly studied in the field of pituitary neuroendocrine tumor (PitNET) research. Our aim was to discover circulating plasma miRNAs species associated with growth hormone (GH) secreting PitNETs versus assess how the plasma levels of discovered miRNA candidates are impacted by SSA therapy and whether there is a difference in their levels between GH secreting PitNETs versus other PitNET types and healthy individuals. Design: We compared plasma miRNA content and levels before and after surgery focusing on GH secreting PitNET patients. Selected miRNA candidates from our data and literature were then tested in a longitudinal manner in somatostatin analogues (SSA) treatment group. Additionally, we validated selected targets in an independent GH secreting PitNET group. Methods: miRNA candidates were discovered using the whole miRNA sequencing approach and differential expression analysis. Selected miRNAs were then analyzed using real-time polymerase chain reaction (qPCR). Results: Whole miRNA sequencing discovered a total of 16 differentially expressed miRNAs (DEMs) in GH secreting PitNET patients’ plasma 24 hours after surgery and 19 DEMs between GH secreting PitNET patients’ plasma and non-functioning (NF) PitNET patients’ plasma. Seven miRNAs were selected for further testing of which miR-625-5p, miR-503-5p miR-181a-2-3p and miR-130b-3p showed a significant downregulation in plasma after 1 month of SSA treatment. mir-625-5p was found to be significantly downregulated in plasma of GH secreting PitNET patients vs. NF PitNET patients. miR-625-5p alongside miR-130b-3p were also found to be downregulated in GH PitNETs compared to healthy individuals. Conclusions: Our study suggests that expression of plasma miRNAs miR-625-5p, miR-503-5p miR-181a-2-3p and miR-130b-3p in GH secreting PitNETs is affected by SSA treatment. Additionally, miR-625-5p can distinguish GH secreting PitNETs from other PitNET types and healthy controls warranting further research on these miRNAs for treatment efficacy.

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