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1.
Pract Lab Med ; 39: e00386, 2024 Mar.
Article En | MEDLINE | ID: mdl-38715658

Objectives: Urinalysis is a first-line test for screening for urinary tract infection. Several devices performing strip and sediment analysis have been introduced. The aim of this study was to compare the performance of Labsan Tricell-1000 and Dirui FUS-2000 automated urine analyzers with manual microscopy. Methods: 463 urine samples were analyzed. Digital image processing and particle recognition automatically display the cells in a flowing sheath fluid mixed monolayer urine sample, take the pictures of particles via digital camera, analyse these pics with a particle recognition software, transfer images of the formed elements to the screen and allow well-trained personnel to select, reclassify or remove them. Manual microscopy was used for comparison. Results: Agreement between Tricell-100 and manual microscopy was very good for RBC (Ï° = 0.80), and WBC (Ï° = 0.83); good for CaOx (Ï° = 0.69), SEC (Ï° = 0.80), YLC (Ï° = 0.72), HC (0.69) and LC (Ï° = 0.64); moderate for BAC (Ï° = 0.51), APC (Ï° = 0.43) and MT (Ï° = 0.55); fair for GC (Ï° = 0.39) and RTEC (Ï° = 0.32). Conclusions: Labsan Trion TriCell-1000 demonstrated satisfactory performance and can be used in routine urinalysis. In the case of low counts of RBC, presence of yeast, crystal, casts or cell clumping in urine sediment, characterization of urine particles should be performed by manual microscopy.

2.
Scand J Clin Lab Invest ; : 1-10, 2024 May 03.
Article En | MEDLINE | ID: mdl-38701073

Tube manufacturers use different composition of gels and blood clot activator formulations in serum tube production. Our aim was to investigate the within-tube (repeatability) and between-tube variation, concordance between comparison results of BD and VacuSEL tubes. Blood samples were collected from control subjects (n = 20) and patients (n = 30) in accordance with the CLSI GP41-A6 and CLSI GP34-A guidelines. Twenty-three clinical chemistry parameters were analysed via Roche Cobas C702 Chemistry Analyzer on T0 (0 hour) and T24 (24 hour). Mean differences % were compared with Wilcoxon matched pair test. Clinical significance was evaluated based on desirable bias according to total allowable error (TEa). VacuSEL tubes demonstrated acceptable performance for the results of 20 parameters with regards to desirable bias % limits. Lactate dehydrogenase (LD) [mean difference % (%95 confidence intervals (CI) values of BD and VacuSEL tubes at T0 [6.41% (4.80-8.01%)]; sodium (Na) and total protein (TP) at T24 [-0.27% (-0.46 to -0.07%) and -1.39% (-1.87 to -0.91), respectively] were over the desirable bias limits (LD: 4.3%, Na: 0.23% and TP: 1.36%, respectively) but not exceeding total biological variation CV % [Na: 0.5 (0.0-1.0) % and TP: 2.6 (2.3-2.7) %). %95 confidence intervals (CI) of T0 LD values overlap with within-subject biological variation % (CI) limits (LD: 5.2 (4.9-5.4) %). The differences between two tubes were not medically significant and necessarily conclusive. VacuSEL serum tubes presented comparable performance with BD serum tubes.

3.
Indian J Clin Biochem ; 39(1): 130-135, 2024 Jan.
Article En | MEDLINE | ID: mdl-38223003

In this study, it was aimed to assess effects of subclinical hyperthyroidism (SH) on bone metabolism using osteoprotegerin (OPG), sclerostin, Dickkopf-1 (DKK1) and biochemical parameters. This cross-sectional prospective study included 40 patients with SH and 40 euthyroid controls. Serum OPG, sclerostin, DKK-1, type-1 procollagen, C-terminal polypeptide (CTx) and 24-hours urine N-terminal telopeptide (NTx) were measures using ELISA kit. Bone mineral density measurements were performed using dual energy X-ray absorptiometry (DEXA). Risk for 10-years hip and major fracture was estimated by Turkish version of FRAX. No significant difference was detected in age, gender, body mass index, smoking and menopause rates between SH and control groups. The risk for 10-years hip fracture and major osteoporotic fracture were estimated as 4.45% and 0.55% in SH group, respectively. The OPG levels were significantly lower in patients with SH than controls (P = 0.017). No significant difference was detected in other bone formation and degradation parameters. No significant correlation was detected between OPG level and risk for major osteoporotic fracture (P > 0.05); however, a negative correlation was detected between OPG level and risk for hip fracture (rho = 0.233; P = 0.038). Serum OPG is markedly affected in patients with SH. In addition, OPG seemed to be associated with osteoporotic fracture risk. Available data show that SH is significantly associated with risk for fracture; thus, it is important to assess risk for fracture in patients with SH.

4.
Clin Chem Lab Med ; 2023 Dec 14.
Article En | MEDLINE | ID: mdl-38095605

OBJECTIVES: Data generation in clinical settings is ongoing and perpetually increasing. Artificial intelligence (AI) software may help detect data-related errors or facilitate process management. The aim of the present study was to test the extent to which the frequently encountered pre-analytical, analytical, and postanalytical errors in clinical laboratories, and likely clinical diagnoses can be detected through the use of a chatbot. METHODS: A total of 20 case scenarios, 20 multiple-choice, and 20 direct questions related to errors observed in pre-analytical, analytical, and postanalytical processes were developed in English. Difficulty assessment was performed for the 60 questions. Responses by 4 chatbots to the questions were scored in a blinded manner by 3 independent laboratory experts for accuracy, usefulness, and completeness. RESULTS: According to Chi-squared test, accuracy score of ChatGPT-3.5 (54.4 %) was significantly lower than CopyAI (86.7 %) (p=0.0269) and ChatGPT v4.0. (88.9 %) (p=0.0168), respectively in cases. In direct questions, there was no significant difference between ChatGPT-3.5 (67.8 %) and WriteSonic (69.4 %), ChatGPT v4.0. (78.9 %) and CopyAI (73.9 %) (p=0.914, p=0.433 and p=0.675, respectively) accuracy scores. CopyAI (90.6 %) presented significantly better performance compared to ChatGPT-3.5 (62.2 %) (p=0.036) in multiple choice questions. CONCLUSIONS: These applications presented considerable performance to find out the cases and reply to questions. In the future, the use of AI applications is likely to increase in clinical settings if trained and validated by technical and medical experts within a structural framework.

5.
Nordisk Alkohol Nark ; 40(6): 625-645, 2023 Dec.
Article En | MEDLINE | ID: mdl-38045011

Background: In September 2021, a Finnish political party, the Greens, voted to include cannabis policy reform in their party programme, which would legalise the use, possession, manufacture and sale of cannabis. A rapid public discussion has emerged on different social media platforms, including Twitter. Methods: We downloaded 10 days of Twitter data and prepared it for further text analysis, including sentiment, topic modelling and thematic content analysis. Results: Before the proposal, the average daily number of tweets was approximately 140. However, during the week of the proposal, there was a significant increase in tweet volume, reaching a peak of 6,600 tweets on a single day, with a daily average of over 2,700 tweets. Sentiment analysis showed that during the public discussion, the sentiment scores of the tweets were more likely to be positive. Through topic modelling analysis, we obtained the weight of the topic for each tweet, which enabled us to identify the most representative tweets in our corpus. To narrow the sample size for content analysis, we selected tweets that had a topic percentage distribution of over 0.95 (N=188) for closer thematic content analysis. Several positive and negative themes emerged, which were then categorised under broader topics. Similar themes were identified in the most retweeted, liked and commented tweets, which came mainly from known public figures, including politicians, health experts and NGO leaders. Conclusion: Our results show that the discussion was not limited to cannabis legalisation, but instead covered a variety of topics related to drug policy.

6.
Amino Acids ; 55(12): 1937-1947, 2023 Dec.
Article En | MEDLINE | ID: mdl-37925676

Systemic lupus erythematosus (SLE) is an autoimmune disease accompanied by increased release of proinflammatory cytokines that are known to activate the indoleamine 2,3-dioxygenase (IDO-1) enzyme, which catalyzes the rate-limiting step of the kynurenine pathway (KP). This study aimed to measure KP metabolite levels in patients with SLE and investigate the relationship between disease activity, clinical findings, and KP. The study included 100 patients with SLE and 100 healthy controls. Serum tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxyanthranilic acid (3HAA), 3-hydroxykynurenine (3HK), quinolinic acid (QA) concentrations were measured with tandem mass spectrometry. Serum KYN, KYNA, 3HAA, 3HK, and QA levels of the patients with SLE were significantly higher than the control group. Serum QA levels were elevated in patients with neurological involvement (four patients with peripheral neuropathy and two patients with mononeuropathy), serum KYN levels and KYN/TRP ratio increased in patients with joint involvement, and serum KYN, 3HK, and 3HAA levels and the KYN/TRP ratio were increased in patients with renal involvement. Moreover, KYN and KYN/TRP ratios were positively correlated with the disease activity score. These findings indicated that imbalances in KP metabolites may be associated with the pathogenesis, activation, and clinical manifestations of SLE.


Kynurenine , Lupus Erythematosus, Systemic , Humans , Kynurenine/metabolism , Tryptophan/metabolism , Cytokines , Kynurenic Acid/metabolism , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism
7.
J Med Internet Res ; 25: e50199, 2023 10 20.
Article En | MEDLINE | ID: mdl-37862088

BACKGROUND: This research extends prior studies by the Finnish Institute for Health and Welfare on pandemic-related risk perception, concentrating on the role of trust in health authorities and its impact on public health outcomes. OBJECTIVE: The paper aims to investigate variations in trust levels over time and across social media platforms, as well as to further explore 12 subcategories of political mistrust. It seeks to understand the dynamics of political trust, including mistrust accumulation, fluctuations over time, and changes in topic relevance. Additionally, the study aims to compare qualitative research findings with those obtained through computational methods. METHODS: Data were gathered from a large-scale data set consisting of 13,629 Twitter and Facebook posts from 2020 to 2023 related to COVID-19. For analysis, a fine-tuned FinBERT model with an 80% accuracy rate was used for predicting political mistrust. The BERTopic model was also used for superior topic modeling performance. RESULTS: Our preliminary analysis identifies 43 mistrust-related topics categorized into 9 major themes. The most salient topics include COVID-19 mortality, coping strategies, polymerase chain reaction testing, and vaccine efficacy. Discourse related to mistrust in authority is associated with perceptions of disease severity, willingness to adopt health measures, and information-seeking behavior. Our findings highlight that the distinct user engagement mechanisms and platform features of Facebook and Twitter contributed to varying patterns of mistrust and susceptibility to misinformation during the pandemic. CONCLUSIONS: The study highlights the effectiveness of computational methods like natural language processing in managing large-scale engagement and misinformation. It underscores the critical role of trust in health authorities for effective risk communication and public compliance. The findings also emphasize the necessity for transparent communication from authorities, concluding that a holistic approach to public health communication is integral for managing health crises effectively.


COVID-19 , Social Media , Humans , Pandemics , Information Seeking Behavior , COVID-19/prevention & control , Data Analysis
8.
Mult Scler Relat Disord ; 77: 104898, 2023 Sep.
Article En | MEDLINE | ID: mdl-37481818

BACKGROUND: Tryptophan is an essential amino acid primarily metabolized by the kynurenine pathway in mammals. Intermediate metabolites emerging in this pathway have been associated with many neurogenerative diseases. This study aimed to compare tryptophan pathway metabolite levels in patients with multiple sclerosis (MS) and healthy controls and reveal the relationship of tryptophan metabolites with disease subtype and the Expanded Disability Status Scale (EDSS) score. METHODS: The study included a total of 80 MS cases [53 with relapsing remitting MS (RRMS) and 27 with secondary progressive MS (SPMS)] and 41 healthy volunteers. The patients with RRMS were further divided into relapse (RRMS-attack) and non-attack (RRMS-stable) groups. Using liquid chromatography mass spectrometry, tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid levels were measured. The serum metabolite levels of the patient and control groups were compared. In addition, the link and relationship between the EDSS score and disease duration of the patients and their plasma tryptophan metabolite levels were examined. RESULTS: The tryptophan level of the patient group was significantly lower than that of the healthy controls (p<0.05). The kynurenine (105.38±65.43), quinolinic acid (10.42±3.56), kynurenine/tryptophan ratio (0.0218±0.019), and quinolinic acid/kynurenic acid ratio (1.7054±0.96141) of the patients with MS were significantly higher compared to the controls (p<0.05). In the receiver operating characteristic analysis of the power of kynurenine/tryptophan and quinolinic acid/kynurenic acid ratios in predicting the disease, both ratios predicted the diagnosis of MS (area under the curve: 0.793 and 0.645, respectively; p<0.05), albeit at low sensitivity and specificity. The parameters were similar between the RRMS-attack and RRMS-stable patient groups (p>0.05). There was also no significant difference between the RRMS and SPMS patient groups in terms of tryptophan metabolites (p>0.05). Lastly, no significant relationship was observed between tryptophan metabolites and MS subtype and the EDSS score. CONCLUSION: Our findings revealed that the kynurenine pathway involved in the tryptophan metabolism differed between the patients with MS and healthy controls, and this difference may be a limited guide in the diagnosis of MS, due to major overlaps in values for MS versus Controls, and is insufficient to determine the disease subtype.


Multiple Sclerosis , Tryptophan , Animals , Humans , Kynurenine/metabolism , Kynurenic Acid/metabolism , Quinolinic Acid , Mammals/metabolism
9.
J Mass Spectrom Adv Clin Lab ; 28: 114-121, 2023 Apr.
Article En | MEDLINE | ID: mdl-37113385

Objectives: Recent studies have shown that derangements in kynurenine pathway metabolite levels are associated with various pathologies such as neurodegenerative diseases, schizophrenia, depression, bipolar disorder, rheumatoid arthritis, and cancer. Therefore, reliable, accurate, fast, and multiplex measurement methods for kynurenines have become increasingly important. This study aimed to validate a new mass spectrometric method for analyzing tryptophan metabolites. Methods: A tandem mass spectrometric method, including protein precipitation and evaporation steps, was developed to measure serum levels of tryptophan, kynurenine, kynurenic acid, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid. Samples were separated using a Phenomenex Luna C18 reversed-phase column. The kynurenine pathway metabolites were detected by tandem mass spectrometry. The developed method was validated according to Clinical & Laboratory Standards Institute (CLSI) guidelines and applied to hemodialysis samples. Results: The developed method was linear at the concentrations of 48.8 - 25,000, 0.98 - 500, 1.2-5000, 1.2-5000, and 0.98-250 ng/mL for tryptophan, kynurenic acid, kynurenine, 3-hydroxyanthranilic acid, and 3-hydroxykynurenine, respectively. The imprecisions were less than 12 %. The median serum concentrations of tryptophan, kynurenine, kynurenic acid, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid were 10530, 1100, 218, 17.6, and 25.4 ng/mL in pre-dialysis blood samples, respectively. They were 4560, 664, 135, 7.4, and 12.8 ng/mL in post-dialysis blood samples, respectively. Conclusions: A fast, simple, cost-effective, accurate, robust, and validated tandem mass spectrometric method was developed, and the method was successfully used for the quantitation of kynurenine pathway metabolite concentrations in hemodialysis patients.

10.
Clin Biochem ; 114: 1-10, 2023 Apr.
Article En | MEDLINE | ID: mdl-36681140

OBJECTIVES: Primary Sjögren's syndrome (pSS) is an autoinflammatory disease characterized by inflammation of the exocrine glands. Elevated inflammation causes an increase in kynurenine pathway (KP) metabolite levels by activating indoleamine 2,3-dioxygenase (IDO). The aim of this study was to measure serum KP metabolite concentrations in patients with pSS and to evaluate the relationship between these metabolites with disease activity score and clinical manifestations. DESIGN & METHODS: A total of 80 patients with pSS and 80 healthy controls were enrolled in this study. Serum tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxyanthranilic acid (3HAA), 3-hydroxykynurenine (3HK), quinolinic acid (QUIN) concentrations were quantified with liquid chromatography with tandem mass spectrometry (LC-MS/MS). Demographic characteristics, clinical manifestations and disease activity score (ESSDAI) of the participants were recorded. RESULTS: The serum level of KYN and QUIN were significantly higher in patients with pSS with low and moderate activity compared those healthy controls, while the serum level of TRP, KYNA/KYN and 3HK/KYN were lower. In addition, the significant difference for the serum level of KYNA was only in patients with moderate activity from healthy controls, and the difference was higher in favor of pSS patients. Moreover, the KYN/TRP levels were significantly increased with disease activity. The ESSDAI score was positively correlated with KYN/TRP ratio, but negatively correlated with KYNA/KYN ratio. CONCLUSIONS: These findings indicated that KP metabolites may play a role in the etiopathogenesis, activation and progression of pSS.


Kynurenine , Sjogren's Syndrome , Humans , Chromatography, Liquid , Tandem Mass Spectrometry , Tryptophan , Inflammation
11.
Nutr Metab Cardiovasc Dis ; 33(3): 602-609, 2023 03.
Article En | MEDLINE | ID: mdl-36710115

BACKGROUND AND AIMS: Smoking causes many diseases such as cardiovascular, lung diseases, stroke and premature aging. However, the role of smoking in the pathogenesis of these diseases is unclear. Increasing evidence suggests that methylarginine pathway metabolites and α-klotho may be strong markers for pathologies such as premature aging, endothelial dysfunction, and oxidant damage. Therefore, the study aimed to measure the serum levels of arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), N-monomethyl-l-arginine (L-NMMA), and α-klotho levels in smokers. METHODS AND RESULTS: This case-control analytical study included 65 smokers and 71 non-smokers. Sociodemographic characteristics, routine biochemistry parameters, Framingham risk scores and Fagerström Nicotine Dependence Test (FTND) were recorded. Serum methylarginine and α-klotho levels were analyzed by tandem mass spectrometry and enzyme-linked immunosorbent assay (ELISA), respectively. Serum ADMA (p < 0.001), L-NMMA (p = 0.024), SDMA (p < 0.001) levels of smokers were higher than non-smokers, and serum α-klotho (p < 0.001) and arginine levels (p < 0.001) were lower. There was a positive correlation between serum ADMA levels with FNDT, age and pack/year in smokers, while there was a negative correlation between klotho levels and age. A positive correlation was found between serum ADMA levels, Framingham risk score and age in non-smokers. CONCLUSION: Smoking is related to premature aging and is a strong risk factor for various diseases such as cardiovascular, inflammatory, and renal diseases. Elevated serum methylarginine and decreased serum klotho levels were found in smokers. Therefore, our findings suggest that smoking may be involved in the pathogenesis of these diseases by affecting α-klotho and methylarginine-related pathways.


Aging, Premature , Cardiovascular Diseases , Cardiovascular System , Cigarette Smoking , Humans , Arginine , omega-N-Methylarginine
12.
Biomark Med ; 16(13): 993-1004, 2022 09.
Article En | MEDLINE | ID: mdl-36052727

Aim: The aim of this study was to measure serum levels of methylarginine derivatives and related metabolites in patients with gout. Materials & methods: This study enrolled 100 patients with gout and 80 patients in the control group. Serum asymmetric dimethylarginine, symmetric dimethylarginine, L-N-monomethylarginine, arginine, homoarginine, citrulline and ornithine levels were measured with tandem mass spectrometry. Results: Serum ornithine, citrulline and total methylated arginine load levels were statistically significantly higher in patients with gout compared with the control group, while serum arginine and homoarginine levels and global arginine bioavailability ratio were statistically significantly lower. Conclusion: There may be an association between gout, methylarginine levels and hyperuricemia and increased risk of cardiovascular disease.


Gout , Homoarginine , Arginine/metabolism , Citrulline/metabolism , Homoarginine/metabolism , Humans , Nitric Oxide/metabolism , Ornithine
13.
J Emerg Med ; 63(1): 93-101, 2022 07.
Article En | MEDLINE | ID: mdl-35934654

BACKGROUND: Pulmonary embolism (PE) is a common disease associated with high mortality and morbidity. Diagnosing PE is challenging due to diverse clinical presentations and the lack of specific biomarkers. OBJECTIVE: We hypothesized that plasma galectin-3 (Gal-3) levels might reflect the severity of acute PE and be useful for diagnostic assessment. METHODS: In this prospective study, 150 patients (100 patients with PE and 50 control patients) were included. Patients were stratified into high-risk, medium-risk, and low-risk groups according to the Wells and revised Geneva scoring systems, and Gal-3 levels were compared among the groups. PE was diagnosed by means of computed tomography pulmonary angiography. RESULTS: In this study, of the 100 PE patients included in the study, 69 patients recovered and were discharged and 31 patients died. Median Gal-3 value in the PE group was 27.0 ng/mL (range 11.5-35.0 ng/mL), whereas the median Gal-3 value in the control group was significantly lower at 8.8 ng/mL (range 1.0-21.0 ng/mL) (p < 0.001). When the Gal-3 values of the PE group and the control group were evaluated with the receiver operator characteristic curve, the area under the curve was calculated as 0.99 (95% confidence interval 0.979-1). At a Gal-3 cutoff value of 13.55 ng/mL, which was determined to be the most appropriate value for PE diagnosis, the sensitivity was 98% and the specificity was 92%. CONCLUSIONS: A biomarker that rapidly and accurately diagnoses acute PE in the emergency department can be an extremely useful tool. We concluded that plasma Gal-3 levels can be regarded as a promising marker of acute PE.


Galectin 3 , Pulmonary Embolism , Acute Disease , Biomarkers , Blood Proteins , Emergency Service, Hospital , Fibrin Fibrinogen Degradation Products , Galectins , Humans , Predictive Value of Tests , Prospective Studies , Pulmonary Embolism/diagnosis
14.
J Obstet Gynaecol ; 42(6): 2018-2024, 2022 Aug.
Article En | MEDLINE | ID: mdl-35666949

The plasma levels of homoarginine (h-Arg) and methylated arginine have proven to be an independent cardiovascular risk factor. We aimed to determine the h-Arg and methyl arginine levels in serums of high-risk pregnancy causing potential complications. These participants were divided into four groups as the control group with quadruple test, the high-risk group quadruple test the control group with binary test, the high-risk group with quadruple test that have a positive result from second-trimester screening with a cut-off value of 1 in 300. The serum methyl arginine and homoarginine levels were analysed with liquid chromatography-tandem mass spectrometry. Serum h-Arg levels were found to be higher in high-risk groups compared to control groups and it was also detected higher in the groups with quadruple test than the groups with binary test (p < .05). H-Arg levels in the groups showed strong negative correlation with age and serum inhibin-A levels (r = -0.288, p < .001). Also, there was a strong negative correlation between serum asymmetric dimethylarginine (ADMA) and serum inhibin-A levels (r = -0.352, p < .001). H-Arg may be a new risk marker to detect high-risk pregnancies in early pregnancy. In addition to, methylated arginine such as ADMA has a key regulator in a physiological concentration of h-Arg.IMPACT STATEMENTWhat is already known on this subject? H-Arg levels decrease may be associated with preeclampsia, GDM, macrosomia, low birth weight, and preterm delivery in pregnancy.What do the results of this study add? Serum h-Arg levels were found to be higher in high-risk groups. Additionally, h-Arg levels and ADAM, one of the methylated arginines in the groups showed a strong negative correlation with serum inhibin-A levelsWhat are the implications of these findings for clinical practice and/or further research? H-Arg may be a new risk marker to detect high-risk pregnancies.


Homoarginine , Pregnancy, High-Risk , Arginine , Female , Humans , Infant, Newborn , Inhibins , Nitric Oxide , Pregnancy
15.
Nordisk Alkohol Nark ; 39(3): 205-224, 2022 Jun.
Article En | MEDLINE | ID: mdl-35720518

Background: Use of drug consumption rooms is a novel harm reduction approach to reach marginalised and isolated people who used drugs, under the high risk of overdose deaths and infectious diseases. The aim of this article was to evaluate the policy opportunities and barriers of the Helsinki City initiative for establishing the first drug consumption room (DCR) in Finland from the multiple streams framework. Method: A qualitative interview research method is used to evaluate the perspectives of stakeholders. By including 23 participants, we analysed the political, social and policy level advantages and disadvantages of the current initiative. Findings: Our results show that the cost of DCRs, the COVID-19 burdens on public resources, the requirement of legislative change, public unawareness, potential policy failure of DCRs, and its impacts on electoral votes constitute the main policy barriers. On the other hand, an increase in drug-related deaths, economic benefits of DCR for society, its effects on street safety and public order, being a local initiative, prospectus change in national drug strategy plans and motivation to catch up with EU standards were underlined as policy opportunities. Four issues, leadership, moral perspective, social change and generational differences, act as mediating factors, which are fluctuated according to public opinions and political environment. Conclusion: By applying the multiple streams framework, our results show that experts' DCR problematisation is still beyond the public and political interest, which needs additional effort around problem identification and prioritisation. Besides public unawareness, the COVID-19 situation seems to be postponing policy progress since the primary attention and available funds have already been dedicated to public health. Already having a local initiative and an upcoming drug strategy plan might be good formal leverage, but unexpected events might also trigger discussions.

16.
Amino Acids ; 54(6): 877-887, 2022 Jun.
Article En | MEDLINE | ID: mdl-35604497

Behçet disease (BD) is an inflammatory, multisystemic vasculitis of unknown etiopathogenesis. However, innate and adaptive immune system involvement and immune-mediated networks play a vital role in the inflammatory cascade. Indoleamine 2,3-dioxygenase 1 (IDO1) is activated in chronic inflammatory states and catalyzes the first and rate-limiting step of tryptophan (TRP) metabolism along the kynurenine pathway (KP). The study aimed to measure KP metabolites levels in patients with BD and investigate the relationship between disease activity and clinical findings with these metabolites. The study included 120 patients with BD and 120 healthy volunteers. Serum TRP, kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxyanthranilic acid (3HAA), 3-hydroxykynurenine (3HK), and quinolinic acid (QUIN) levels were measured with the tandem mass spectrometric method. Demographic data, clinical manifestations, and disease activity score (BDCAF) were recorded. Serum KYN, KYNA, 3HK, 3HAA, QUIN levels, and KYN/TRP ratio were higher (p < 0.05) in patients with BD compared to the control group, while TRP levels were lower (p < 0.05). KYN/TRP ratio and QUIN levels were significantly higher in the presence of neuro-Behçet, while serum KYN levels were significantly higher in the presence of arthritis (p < 0.05). In addition, serum QUIN levels were significantly higher in the presence of thrombosis (p < 0.05). BDCAF score positively correlated with KYN/TRP ratio. Our findings showed that serum KP metabolite levels were elevated in patients with BD, and there is a relationship between these metabolites with disease activity, clinical findings, and inflammatory burden.


Behcet Syndrome , Kynurenine , Humans , Kynurenic Acid/metabolism , Quinolinic Acid/metabolism , Tryptophan/metabolism
17.
Biomed Chromatogr ; 36(8): e5390, 2022 Aug.
Article En | MEDLINE | ID: mdl-35487588

Our aim in this study was to develop a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the measurement of atorvastatin, rosuvastatin and their major metabolites, and furthermore to evaluate patients' adherence to statin therapy and to investigate the effect of statin therapy on various hematological and biochemical parameters. A simple protein precipitation was performed for the extraction of analytes and the extracted samples were injected directly. The levels of drugs and their metabolites were measured by the validated method in a total of 210 patients diagnosed with unstable angina pectoris (USAP), ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI). Various biochemical and hematological parameters were measured. The linearity ranges for atorvastatin and rosuvastatin were 1.22-2,500 and 0.97-2000 ng/ml, respectively. The inter-assay coefficient of variation for all analytes was ≤ 6%. In patients diagnosed with USAP, STEMI and NSTEMI, treatment compliance rates were 22.1, 23.5 and 41.2% for atorvastatin and 36.1, 40.2 and 67.1% for rosuvastatin, respectively. An economical, simple and reliable measurement method has been developed. Our findings support the poor patient compliance with statin therapy in the included population. It was observed that 6 months of statin treatment caused slight changes in biochemical and hematological parameters.


Acute Coronary Syndrome , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Non-ST Elevated Myocardial Infarction , ST Elevation Myocardial Infarction , Acute Coronary Syndrome/drug therapy , Atorvastatin/therapeutic use , Chromatography, Liquid/methods , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypolipidemic Agents , Non-ST Elevated Myocardial Infarction/drug therapy , Rosuvastatin Calcium/therapeutic use , Tandem Mass Spectrometry/methods
18.
Ir J Med Sci ; 191(6): 2657-2662, 2022 Dec.
Article En | MEDLINE | ID: mdl-35088227

BACKGROUND: In this study, we investigated the effect of calcium and vitamin D (Ca/Vit D) supplementation on the clinical, hormonal, and metabolic profile of patients with low vitamin D levels. In addition, we investigated the effect of Ca/Vit D supplementation on asymmetric dimethylarginine (ADMA) level in patients with polycystic ovary syndrome (PCOS). METHODS: In total, 75 patients aged 19-35 years, with a normal body mass index and a diagnosis of PCOS and Vit D deficiency/insufficiency, were included in the study. Patients received 50,000 IU of vitamin D3 once a week for 8 weeks. Afterward, 2500 mg calcium carbonate equivalent to 1000 mg calcium ion and 9.68 mg cholecalciferol equivalent to 880 IU vitamin D3 were administered orally as a maintenance treatment once a day. RESULTS: The mean age of the patients was 21.7 ± 3.5. After Ca/Vit D supplementation, Vit D levels significantly increased compared to baseline (8.6 ng/ml) levels. An increase in SHBG levels (p < 0.001), a decrease in total testosterone, FAI (p = 0.042), and ADMA levels (p < 0.001) were observed in the first and third months compared to the onset. Significant improvement compared to baseline was observed in menstrual irregularity and median mFG score. CONCLUSION: Ca/Vit D supplementation can improve PCOS symptoms such as menstrual dysfunction, hirsutism, and hyperandrogenism. It may be effective in reducing the risk of cardiovascular disease in patients with PCOS later in life by decreasing ADMA levels, which is an indicator of endothelial dysfunction.


Polycystic Ovary Syndrome , Vitamin D Deficiency , Humans , Female , Polycystic Ovary Syndrome/complications , Polycystic Ovary Syndrome/drug therapy , Calcium/therapeutic use , Dietary Supplements , Vitamin D/therapeutic use , Cholecalciferol/therapeutic use , Metabolome
19.
Int J Neurosci ; 132(8): 826-834, 2022 Aug.
Article En | MEDLINE | ID: mdl-33086922

AIM: There are increasing reports about the potential role of kynurenine pathway metabolites in autism spectrum disorder (ASD). Early childhood is a very crucial period of time for the etiopathogenesis of ASD and previous studies reported an age-dependent alteration in kynurenine metabolism. However, no study specifically examined kynurenine metabolites in very young children with ASD. This study aimed to investigate kynurenine pathway metabolite levels, kynurenine pathway enzyme activities and neuroprotective index (kynurenic acid/3-hydroxykynurenine ratio) in toddlers and preschool children with ASD. MATERIALS AND METHODS: A total of 68 children with ASD and 44 healthy controls aged between 18 and 60 months were included in this study. Serum levels of kynurenine pathway metabolites were determined by liquid chromatography-mass spectrometry/mass spectrometry system. RESULTS: Serum 3-hydroxykynurenine and kynurenic acid concentrations were significantly higher in the ASD group than in the control group, whereas serum 3-hydroxyanthranilic acid concentrations were significantly lower. CONCLUSIONS: These findings showed that the kynurenine pathway may play a role in the etiopathogenesis of ASD in early childhood.


Autism Spectrum Disorder , Kynurenine , Child, Preschool , Humans , Infant , Kynurenic Acid , Kynurenine/metabolism , Tandem Mass Spectrometry , Tryptophan/metabolism
20.
Biomarkers ; 27(1): 71-78, 2022 Feb.
Article En | MEDLINE | ID: mdl-34852684

OBJECTIVE: In this study, the objective was to evaluate the cardiovascular and metabolic effects in men with male pattern alopecia beginning before 30 years of age. METHODS: Total of 81 people (41 androgenetic alopecia (AGA) and 40 healthy individuals) were included in the study. Twenty-four-hour ambulatory blood pressure (ABP) measurement, high sensitive C-reactive protein (hsCRP), galectin-3 were studied. Hamilton-Norwood scale (HNS) was used to determine the AGA types of the cases. RESULTS: The mean age in the AGA and control groups was 30.3 ± 7.5 and 30.8 ± 6.0, respectively. Twenty-four-hour ABP measurements, hsCRP, and galectin-3 were similar in both groups. There was a positive correlation between HNS grade with age, BMI, triglyceride levels and fasting blood glucose levels in individuals with AGA. Similarly, there was a positive correlation between HNS grade with daytime pulse wave velocity and night-time reflection magnitude. A significant positive correlation was determined between hsCRP with BMI and waist circumference, and between galectin-3 with BMI, waist circumference, hip circumference, HOMA-IR in individuals with AGA. CONCLUSIONS: This study shows that AGA patients are similar to the normal population in terms of insulin resistance or metabolic syndrome components. However, hsCRP and galectin-3 appear to be associated with cardiovascular disease risk factors in individuals with AGA.


C-Reactive Protein , Cardiovascular Diseases , Alopecia/complications , Alopecia/diagnosis , Alopecia/epidemiology , Blood Pressure Monitoring, Ambulatory/adverse effects , Cardiovascular Diseases/complications , Galectin 3 , Heart Disease Risk Factors , Humans , Male , Pulse Wave Analysis/adverse effects , Risk Factors
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