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1.
J Clin Lipidol ; 2024 May 06.
Article in English | MEDLINE | ID: mdl-38955587

ABSTRACT

BACKGROUND: Coronary microvascular dysfunction (CMD) is a common occurrence in individuals with insulin resistance (IR). Homeostatic model assessment for insulin resistance (HOMA-IR) is a widely used surrogate marker of IR, although recent studies suggest Triglyceride-Glucose (TyG) index is a superior marker of IR that had a better accuracy to predict Type 2 Diabetes or cardiovascular outcomes than HOMA-IR. OBJECTIVES: We aimed to assess the accuracy and usefulness of TyG index and HOMA-IR for predicting CMD as assessed with echocardiographic coronary flow reserve (CFR) measurement. METHODS: All cases included in the institutional CFR registry were retrospectively reviewed, and 656 cases without epicardial coronary artery disease and without major risk factors for atherosclerosis were included. A CFR ≤2.0 was defined as CMD. RESULTS: TyG index was available in all cases, while HOMA-IR was available in 398 cases. Both TyG index and HOMA-IR were associated with CMD on univariate analyses, while after adjustment for potential confounders HOMA-IR (OR:1.38, 95 %CI:1.14-1.67, p = 0.001) but not TyG index(OR:1.48, 95 %CI:0.82-2.67, p = 0.19) was associated with CMD. The predictive accuracy of HOMA-IR (c-statistic:0.63, 95 %CI:0.54-0.72, p = 0.003) was higher than TyG index(c-statistic:0.55, 95 %CI:0.47-0.63, p = 0.13), although the difference was not statistically significant (DeLong p = 0.23). There was strong evidence favoring a true difference between CMD vs. non-CMD groups for HOMA-IR (BF10:3507) but not for TyG index(BF10:0.66). CONCLUSIONS: HOMA-IR, but not TyG index, is closely associated with CMD.

2.
Allergy Asthma Proc ; 45(4): e46-e53, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38982601

ABSTRACT

Background: The standard therapeutic regimen for idiopathic chronic eosinophilic pneumonia (ICEP) involves the administration of oral corticosteroids (OCS). However, a notable proportion of individuals experience recurrent episodes after the tapering or cessation of OCS during the course of ICEP. There has been a growing interest in exploring alternative treatment modalities for patients with ICEP at heightened risk of relapse. Objective: The aim of this study was to assess the efficacy of mepolizumab at a dose of 100 mg administered every 4 weeks in preventing relapses of ICEP and its impact on the clinical outcomes. Methods: This retrospective clinical observational study used real-world data to assess the impact of mepolizumab on patients diagnosed with ICEP accompanied by severe asthma. Demographic information and clinical characteristics were extracted from medical records. The study examined the effect of mepolizumab on the annual relapse rate, OCS dose, eosinophil count, and respiratory function parameters. Results: All patients included in the study, with a median (range) follow-up period of 19 months (4-40 months), the annual relapse rate decreased from 0.33 to 0 after the initiation mepolizumab. In addition, the maintenance OCS dose, expressed in methylprednisolone equivalents, declined from 4 mg/day to 0 mg/day. A reduction in the blood eosinophil count was observed, alongside a partial improvement in respiratory function test results among the patients. Conclusion: A dose regimen of 100 mg of mepolizumab administered every 4 weeks emerges as a promising and well-tolerated therapeutic approach for averting relapses of ICEP.


Subject(s)
Antibodies, Monoclonal, Humanized , Pulmonary Eosinophilia , Humans , Male , Female , Middle Aged , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Pulmonary Eosinophilia/drug therapy , Pulmonary Eosinophilia/diagnosis , Retrospective Studies , Treatment Outcome , Adult , Aged , Recurrence , Anti-Asthmatic Agents/therapeutic use , Anti-Asthmatic Agents/administration & dosage , Eosinophils , Leukocyte Count , Chronic Disease , Adrenal Cortex Hormones/therapeutic use , Adrenal Cortex Hormones/administration & dosage , Follow-Up Studies
3.
Int J Dev Neurosci ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39010691

ABSTRACT

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterised by cognitive dysfunction, memory loss and mood changes. Hippocampal neurogenesis has been suggested to play a role in learning and memory. Neurokinin 3 receptor (NK3R) has been shown to be prevalent in the hippocampus region. The aim of the project was to investigate the role of hippocampal neurogenesis in the promnestic effects of NK3R agonist administration in an amyloid beta-induced AD rat model. Wistar albino rats were divided into control, Alzheimer, NK3R agonist and Alzheimer + NK3R agonist groups. The open field (OF) test and Morris water maze (MWM) test were performed for locomotor activity and memory analysis. Peptide gene expression levels (Nestin, DCX, Neuritin, MASH1, Neun, BDNF) were analysed by quantitative reverse transcription polymerase chain reaction (RT-PCR). In the OF test, the group-time relationship was found to be statistically different in the parameters of distance travelled and percentage of movement (p < 0.05). In MWM, the time to reach the platform and the time spent in the target quadrant were statistically significant between the groups (p < 0.05). Statistically significant differences were observed in gene expression levels (Nestin, DCX, Neuritin, MASH1) in the hippocampal tissue of rats between the groups (p < 0.05). NK3 receptor agonism favourably affected hippocampal neurogenesis in AD model rats. It was concluded that NK3 receptor agonism in the hippocampus, which is the first affected region in the physiopathology of AD, may be effective in both the formation of neural precursor cells and the reduction of neuronal degeneration. The positive effect of NK3R on cognitive functions may be mediated by hippocampal neurogenesis.

4.
Sci Rep ; 14(1): 15101, 2024 07 02.
Article in English | MEDLINE | ID: mdl-38956051

ABSTRACT

The etiology of tic disorders (TDs) is not precisely known, although several lines of evidence suggest involvement of the immune system in pathogenesis. Here, we aimed to determine the expression levels of pro-inflammatory and anti-inflammatory cytokines in children with TD and compare them with those of healthy controls. Furthermore, we also evaluated their association with clinical variables in the TD group. Within the study period, 88 children with tic disorders and 111 healthy control children were enrolled. Most children with tic disorders were diagnosed with Tourette's disorder (n = 47, 53.4%) or persistent motor tic disorder (n = 39, 44.3%), while the remainder (n = 2, 2.3%) were diagnosed with persistent vocal tic disorder. We found that children with tic disorders had significantly elevated levels of IL-1ß, TNF-α, IL-6 and IL-4 expression, while we detected lower expression levels of IL-17 in children with tic disorders. Our findings provide a molecular landscape of cytokine expression in children with TD, which may suggest a proinflammatory state not affected by the presence of comorbidity and symptom severity. Delineating the contribution of alterations in the immune system to the pathogenesis of tic disorders may pave the way for better therapeutic interventions.


Subject(s)
Cytokines , Tic Disorders , Humans , Child , Male , Female , Adolescent , Cytokines/metabolism , Case-Control Studies , Child, Preschool
5.
J Food Sci ; 89(6): 3506-3522, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38660924

ABSTRACT

This study was conducted to evaluate the effect of two distances: close (0-10 m) and far (60 m) from the heavy traffic roadside, at three different cultivation sites (MS: Mevlanakapi-Silivrikapi, SB: Silivrikapi-Belgradkapi, and BY: Belgradkapi-Yedikule kapi) along the road line. First, the phenolic compounds, antioxidant activity, and physicochemical properties in kale and arugula vegetables were examined. Second, heavy metal concentrations in vegetables, soil, and irrigated water were investigated. In both vegetables, the highest total phenolic content was detected in samples obtained from far distance in SB site (3880.3 mg/kg) for kale and in BY site (1459.9 mg/kg) for arugula, whereas the lowest content was found at the close distance in MS site for both kale (448.5 mg/kg) and arugula (586.4 mg/kg). The antioxidant activity values [mg Trolox/kg (dw)] ranged from 366.74 to 586.10 and 2349.00 to 3757.4 for kale and from 520.00 to 945.60 and 3323.00 to 5814.70 for arugula in 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) and 2,2-diphenyl-1-picrylhydrazyl methods, respectively. The levels of Cd and Hg in kale and arugula and Fe content in arugula exceeded FAO/WHO permissible limits, making them unsafe for human consumption. Meanwhile, the Pb content in kale and arugula and Fe content in kale were observed to be within acceptable limits set by FAO/WHO. In the irrigated water, the Pb value was below the permissible limit, whereas the Cd value was above it and no Hg and Fe were detected. In the soil samples, the Pb and Fe values were below the limit, whereas the Cd and Hg values were higher.


Subject(s)
Antioxidants , Brassica , Metals, Heavy , Phenols , Antioxidants/analysis , Brassica/chemistry , Phenols/analysis , Metals, Heavy/analysis , Turkey , Vegetables/chemistry , Gardens , Soil/chemistry , Soil Pollutants/analysis
6.
Orphanet J Rare Dis ; 19(1): 78, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38378595

ABSTRACT

BACKGROUND: The present study aimed to determine the problems, unmet needs and expectations of phenylketonuria (PKU) patients in Türkiye regarding follow-up and treatment in order to provide data for future planning and implementations on PKU. METHODS: The study included patients diagnosed with PKU and/or their parents. They were informed about the study via phone calls and their verbal consents were obtained. Questions in the data collection forms, which were established separately for pediatric, adolescent, and adult age groups, were applied during the interviews and the answers were recorded. RESULTS: Among 182 classical PKU patients, 66 (36.3%) were in the pediatric group (0-12 years old), 44 (24.2%) were in the adolescent group (13-19 years old), and 72 (39.5%) were in the adult group (≥ 20 years old). In all patient groups, phenylalanine-restricted diet and medical nutrition products were the main options for treatment. The median of the last measured blood phenylalanine concentration (patient-reported) was 290 µmol/L, 425 µmol/L, and 750 µmol/L in the pediatric, adolescent, and adult groups, respectively. The frequency of blood testing for serum phenylalanine level according to the age groups was appropriate in nearly half of the patients. While the majority of the patients have been visiting the metabolism center they have been diagnosed with PKU for control, considerable proportion of the patients would like to change the center or the doctor they visit for control if they could. It was determined that nearly half of the patients had trouble in accessing the metabolism center. Treatment options' being limited and expensive were the major problems. The main requests of the patients and patient relatives included easier access to the metabolism centers and more options for treatment and diet. CONCLUSIONS: Access to the services should be easier to improve the patients' follow-up and treatment. There is need for low-cost, easily applicable, and accessible nutrition products and effective novel pharmacological agents. Focusing on these issues in health policies by providing pedagogic/psychological support, establishing support programs also comprising the families, and increasing the awareness activities were the key outcomes.


Subject(s)
Phenylketonurias , Adult , Adolescent , Humans , Child , Infant, Newborn , Infant , Child, Preschool , Young Adult , Turkey , Diet , Phenylalanine , Data Collection
7.
Chem Commun (Camb) ; 59(83): 12447-12450, 2023 Oct 17.
Article in English | MEDLINE | ID: mdl-37779498

ABSTRACT

A cationic BODIPY-based G-quadruplex-selective stabiliser is developed and shown to decrease cancer cell migration-invasion up to 90%. The expression of critical genes (HIF1α, VIM, CDH1) related to metastasis is modulated. The stabiliser reprograms hypoxia-adaptive metabolism and an 1.82-fold increase in O2 consumption, enabling back-to-normal switching of energy metabolism, is observed. Stabilisers with a strong G-quadruplex affinity (0.38 µM Kd) significantly contribute to small molecule anti-cancer approaches.


Subject(s)
G-Quadruplexes , Neoplasms , Boron Compounds/pharmacology
8.
World Neurosurg ; 175: e1191-e1196, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37121506

ABSTRACT

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is a simple, cost-effective index of inflammation that can be measured by peripheral blood count. This study aimed to reveal that a high NLR value could be a prognostic marker for mortality risk in preterm babies born with IVH. METHODS: Preterm babies who had been followed up in the neonatal intensive care unit (ICU) between 2018 and 2020 were included in the study. These patients were examined in two groups, those who had had IVH and those who had not. The patients were evaluated by the week of birth, gender, first-minute APGAR score and NLR obtained from the first postnatal peripheral blood sample. RESULTS: A total of 113 babies had been born preterm and had been treated in the newborn intensive care unit (NICU) were included in the study. Intraventricular hemorrhage (IVH) was observed in 26 (23%) of the infants, and a total of 14 (12.4%) died, with the mortality rate being higher among those with IVH than those without (P = 0.026). There was also a statistically significant difference in the NLR between infants with IVH who died and those who did not (P < 0.001). NLR above 1.5 had 33.7 times higher risk of mortality compared to those with an NLR of 1.5 or below. CONCLUSIONS: This was the first study to examine the relationship between the NLR and mortality in preterm babies with IVH. This study showed that a high NLR was strongly associated with mortality in premature infants with low APGAR scores and having IVH.


Subject(s)
Infant, Premature , Neutrophils , Infant , Infant, Newborn , Humans , Cerebral Hemorrhage , Lymphocytes
9.
Medeni Med J ; 38(1): 32-38, 2023 Mar 28.
Article in English | MEDLINE | ID: mdl-36974457

ABSTRACT

Objective: Premature ventricular contractions (PVCs) are a common arrhythmic condition. The first approach in patients with symptomatic and frequent PVC is medical treatment, primarily beta-blockers (BB) or calcium channel blockers (CCB), but it is still unclear which of the two should be chosen. This study investigated which drug treatment would be beneficial according to patient and electrocardiography (ECG) characteristics in patients with idiopathic PVC. Methods: We retrospectively analyzed 156 patients with PVC who came to the cardiology outpatient clinic. Seventy-one patients were responsive to BB, and 85 were responsive to CCB. Their demographic and ECG characteristics were compared. Results: The male ratio was higher (p<0.001), and the left ventricular ejection fraction was lower in BB responders than in CCB responders (p<0.001). Although the mean heart rate was higher in BB responders (p<0.001), the initial PVC burden was lower in BB responders than in CCB responders (p<0.001). The PVC QRS duration was longer in BB responders than in CCB responders (p<0.001). Similarly, the coupling interval variability was higher in BB responders (p=0.006). Conclusions: The evaluation of clinical and ECG parameters in patients with frequent idiopathic PVCs may determine whether BBs or CCBs should be chosen as initial treatment. Further prospective studies are needed to verify our findings and establish their clinical applicability.

10.
Chem Commun (Camb) ; 59(16): 2247-2250, 2023 Feb 21.
Article in English | MEDLINE | ID: mdl-36723070

ABSTRACT

In the research, the modulation of gene expression with a novel G-quadruplex stabiliser was analysed. Activation by the removal of bulky hypoxia-responsive substituent enhances G-quadruplex stabilisation. Hypoxic MCF7 cells incubated with the stabiliser displayed significant downregulation of oncogenes c-myc, bcl-2, and hif-1α. This study presents the first hypoxia-activatable G-quadruplex stabilization and transcriptional regulation.


Subject(s)
Hypoxia , Neoplasms , Humans , Cell Hypoxia , Cell Line, Tumor , Down-Regulation , Gene Expression , Gene Expression Regulation , Hypoxia/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , MCF-7 Cells
11.
Immunobiology ; 228(2): 152353, 2023 03.
Article in English | MEDLINE | ID: mdl-36805859

ABSTRACT

Cancer comes after cardiovascular diseases in terms of mortality rate in the world. Chemotherapy, radiotherapy and surgical interventions are the current cancer treatment. Recently, it has been observed that immunotherapeutic approaches provide a significant improvement when used along with these interventions. The mononuclear system mainly consists of macrophages that play an active role in the pathology of many diseases because of having high plasticity capacities. Previous research suggested that they can be used as an alternative to cancer treatment. Aim was to investigate the effect of apelin on macrophage polarization in the tumor microenvironment. Mouse macrophage cell line RAW264.7 cells and head and were chosen for this study. The apelin expression was knockdown in neck cell carcinoma cell line SCCL MT1 cells using shRNA technique. SCCL MT1 cells having normal or suppressed apelin expression were co-cultured with mouse macrophage RAW264.7 cells. The effect of co-culturing on the expression of inflammatory genes in RAW264.7 cells was investigated. Suppressed apelin expression in SCCL MT1 cells resulted in elevated pro-inflammatory response in co-cultured macrophages. Expression of the IL1ß, IL6, and TNFα genes significantly increased, however anti-inflammatory cytokine levels were significantly decreased. However, in the control group, a downregulation was determined in pro-inflammatory genes, while an increase was observed in anti-inflammatory genes. The protein levels of these cytokines in concordance with the RT-PCR analysis. As a result of this study, apelin released from cancer cells was found to affect macrophage polarization. These results indicated that the apelin peptide may cause the intense presence of M2-type macrophages in the tumor niche, and the therapeutic approaches targeting of apelin in cancer cells may have a potential role in macrophage polarization.


Subject(s)
Head and Neck Neoplasms , Macrophages , Mice , Animals , Apelin/metabolism , Apelin/pharmacology , Macrophages/metabolism , Cytokines/metabolism , Anti-Inflammatory Agents/pharmacology , Tumor Microenvironment
12.
Microvasc Res ; 146: 104458, 2023 03.
Article in English | MEDLINE | ID: mdl-36471530

ABSTRACT

BACKGROUND: Inflammatory bowel disease (IBD), which is an umbrella term used for ulcerative colitis (UC) and Crohn's disease (CD), is associated with an increased risk for atherosclerotic cardiovascular disease (CVD). We aimed to investigate the association of local and systemic biomarkers of inflammation and gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) with endothelial and coronary microvascular dysfunction in IBD. METHODS: A total of 56 patients with IBD (20 with UC and 36 with CD) and 34 age and gender matched controls were included. For all participants, samples were collected to analyze faecal calprotectin, and TMAO concentrations. Ultrasound-based examinations were done to measure flow-mediated vasodilatation (FMD) and coronary flow velocity reserve (CFVR). RESULTS: Patients with IBD had lower CFVR (2.07 (1.82-2.40)) and FMD (8.7 ± 3.7) as compared to controls (2.30 (2.07-2.74), p = 0.005 and 11.9 ± 6.8, p = 0.03). In patients with IBD, TMAO concentration (r = -0.30, p = 0.03), C-reactive protein (r = -0.29, p = 0.03) and WBC count (r = -0.37, p = 0.006) had a significant negative correlation with CFVR, and TMAO (ß = -0.27, 95 % CI: -0.23 to -0.02) and WBC count (ß = -0.31, 95 % CI: -0.56 to -0.06) were significant predictors of CFVR after multivariate adjustment. None of the biomarkers of inflammation or TMAO showed significant correlations with FMD. In patients with UC, TMAO showed a significant correlation with both CFVR (r = -0.55, p = 0.01) and FMD (r = -0.60, p = 0.005) while only WBC count had a statistically significant correlation with CFVR (r = -0.49, p = 0.004) in patients with CD. CONCLUSIONS: Gut microbiota-derived metabolite TMAO and biomarkers of systemic inflammation are associated with measures of endothelial/coronary microvascular dysfunction in patients with IBD.


Subject(s)
Colitis, Ulcerative , Crohn Disease , Gastrointestinal Microbiome , Inflammatory Bowel Diseases , Humans , Inflammation/metabolism , Inflammatory Bowel Diseases/complications , Biomarkers/metabolism , Crohn Disease/diagnosis , Crohn Disease/complications , Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/complications
13.
Int J Mol Cell Med ; 12(3): 220-228, 2023.
Article in English | MEDLINE | ID: mdl-38751655

ABSTRACT

Endometrial carcinoma is one of the most common types of cancer among women. The progression of cancer occurs via the Epithelial- Mesenchymal Transition (EMT) pathway. Cells lose their epithelial properties and become mobile. For this reason, the EMT process is one of the most important step to be targeted in cancer treatment. Oleandrin is a cardiac glycoside and its use is limited due to its narrow therapeutic index. In this study, we aimed to evaluate effects of lower level Oleandrin doses on EMT process in endometrial carcinoma. Oleandrin was administrated to Ishikawa endometrial adenocarcinoma cells at different doses and times. IC50 dose was determined by XTT proliferation test. Expression analysis of EMT-related genes was then performed by qRT-PCR. Invasion and colony formation abilities of cells were examined microscopically. Finally, the migration analysis of cancer cells was determined by the Wound Healing Assay. The IC50 dose of Oleandrin applied to Ishikawa cells was determined as 75.3 nM at the 48 h. According to qRT-PCR analysis, expression levels of ZEB1, FN1, ITGB1, VIM, SMAD2, SNAI1, SNAI2, SNAI3, and TGFB3 genes significantly decreased, but TIMP2, TIMP3, ITGAV and GSK3B genes significantly increased. In addition, Oleandrin significantly reduced colony formation and invasion of Ishikawa cells. According to the Wound Healing analysis, the migratory abilities of the Oleandrin-treated cells were reduced compared to the control. Low dose Oleandrin suppresses the EMT pathway in Ishikawa cells. It has been shown that Oleandrin significantly suppresses the cell's colony formation, invasion and migration ability both in gene expression analyzes and microscopically.

14.
Turk J Pharm Sci ; 19(4): 416-421, 2022 Aug 31.
Article in English | MEDLINE | ID: mdl-36047572

ABSTRACT

Objectives: Coronavirus Disease-2019 (COVID-19) pandemic has a massive impact on human health, causing sudden lifestyle changes. As it affects health, determining the lifestyles of university students related to smoking has gained importance. This study provides evidence of change in smoking behavior among university students in Türkiye during the ongoing COVID-19 pandemic. Materials and Methods: This cross-sectional survey study was conducted via an electronic questionnaire approximately 2020-2021 among university students in Türkiye. The study comprised a structured questionnaire that inquired about demographic information; and the Fagerström Test for Nicotine Dependence. The questionnaire was distributed randomly to university students; it required 6 min to complete. Results: A total of 749 respondents were included in the study, aged between 19 and 35 years (54.8% females). Of 749 participants, 571 health science students (medicine, pharmacy, dentistry, etc.) completed the survey. The pre-pandemic and COVID-19 pandemic mean nicotine dependence scores were 3.03 and 2.97, respectively. A difference was seen pre-pandemic (p= 0.002) and during pandemic (p= 0.005) for those studying in health and other departments. Students who had middle socio-economical status had significantly higher nicotine dependence scores pre- COVID-19, compared to during the pandemic (p= 0.027). Compared to pre and during the pandemic, the mean score of dependence was significantly lower in students, whose parents were non-smokers during the pandemic. Conclusion: In this study, we have provided the first data on the Turkish university student's nicotine dependence changes during the COVID-19 lockdown. The nicotine dependence level may change based on various factors including behavioral changes. Crucial times such as pandemics can affect individuals, thus, smoking addiction can increase. Behavioral support for quitting smoking such as digital platforms, internet, and television programs should also assist to support smokers quitting successfully during this supreme time.

15.
Hypertens Res ; 45(10): 1653-1663, 2022 10.
Article in English | MEDLINE | ID: mdl-35986188

ABSTRACT

Coronary artery disease and cardiovascular mortality are increased in patients with an exaggerated blood pressure response to exercise. The exact cause of this increase remains unknown, but previous studies have indicated the presence of endothelial dysfunction in peripheral arteries and subclinical atherosclerosis in these patients. The present study aimed to clarify whether coronary microvascular dysfunction is also present in patients with exaggerated blood pressure response to exercise. A total of 95 patients undergoing exercise testing were consecutively enrolled. Flow-mediated vasodilatation and carotid intima-media thickness were measured using standardized methods. A transthoracic echocardiography examination was performed to measure coronary flow velocity reserve. Patients with an exaggerated blood pressure response to exercise had significantly lower coronary flow velocity reserve than the controls (2.06 (1.91-2.36) vs. 2.27 (2.08-2.72), p = 0.004), and this difference was caused by a reduction in hyperemic flow velocity (57.5 (51.3-61.5) vs. 62.0 (56.0-73.0), p = 0.004) rather than a difference in basal flow (26.5 (22.3-29.8) vs. 26.0 (24.0-28.8), p = 0.95). Patients with an exaggerated blood pressure response to exercise also had a significantly greater carotid intima-media thickness and significantly lower flow-mediated vasodilatation than controls. However, an exaggerated blood pressure response to exercise remained a significant predictor of coronary microvascular dysfunction after adjusting for confounders (OR: 3.60, 95% CI: 1.23-10.54, p = 0.02). Patients with an exaggerated blood pressure response to exercise show signs of coronary microvascular dysfunction, in addition to endothelial dysfunction and subclinical atherosclerosis. This finding might explain the increased risk of coronary artery disease and cardiovascular mortality in these patients.


Subject(s)
Atherosclerosis , Blood Flow Velocity , Blood Pressure , Exercise , Blood Flow Velocity/physiology , Blood Pressure/physiology , Carotid Intima-Media Thickness , Coronary Artery Disease , Coronary Circulation/physiology , Coronary Vessels/diagnostic imaging , Echocardiography , Humans , Hypertension
16.
Gene ; 843: 146805, 2022 Nov 15.
Article in English | MEDLINE | ID: mdl-35964872

ABSTRACT

Melanoma accounts for the majority of skin cancer-related deaths. Nerium oleander is a plant known to be toxic and consumed due to the cardiac glycosides it contains. Oleandrin is a cardiac glycoside obtained from of N. oleander. Beside capable of inhibiting proliferation and metastasis of cancer cells, cardiac glycoside derivative compounds cause cardiovascular side effects. Because of cardiovascular toxicity of clinically used cardiac glycosides, it is necessary to investigate cardiac glycoside derivative compounds capable of inhibiting proliferation and metastasis of cancer cells. It is known that oleandrin has anticarcinogenic effects in other cancers. Previous studies have shown that toll-like receptors (TLRs) and their related microRNAs (miRNAs) are associated with cancer. Therefore, aim was to investigate the effect of oleandrin on genes and miRNAs associated with TLRs in A375 melanoma cells in this study. The effects of oleandrin on cell viability, cytokines, apoptosis were evaluated using XTT, ELISA and TUNEL analyses, respectively. The effect of oleandrin on expression of TLR genes and 5 associated miRNAs in A375 cells has been determined by qRT-PCR. In addition, the levels of MyD88, TLR2 and TLR4 proteins were analyzed by western blot method. ELISA indicated that oleandrin treatment (47 nM at 48 h) reduced the level of proinflammatory cytokine IFNG. TUNEL analysis showed that apoptosis rate was significantly increased in the oleandrin dose group. According to qRT-PCR results, there was a significant decrease in IRAK1, IRAK4, MyD88, TLR2-TLR7 and TRAF3 expressions in the oleandrin treated group compared to the control (untreated cell). Also, a significant decrease in TLR4 protein expression has been observed. In addition, oleandrin significantly downregulated the levels of hsa-miRNA-146a-5p and hsa-miRNA-21-5p. In conclusion, it has been observed that oleandrin has an effect on TLR pathway-related genes and miRNAs in melanoma cells. We show that TLRs pathways and hsa-miR-146a-5p and hsa-miR-21-5p can participate in the oleandrin molecular mechanism of action.


Subject(s)
Cardiac Glycosides , Melanoma , MicroRNAs , Cardenolides , Cardiac Glycosides/pharmacology , Glycosides , Humans , Melanoma/drug therapy , Melanoma/genetics , MicroRNAs/genetics , Myeloid Differentiation Factor 88/genetics , Toll-Like Receptor 2 , Toll-Like Receptor 4/genetics , Toll-Like Receptors/genetics
17.
J Clin Ultrasound ; 50(6): 759-768, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35675314

ABSTRACT

PURPOSE: The association between hypertensive retinopathy and left atrial (LA) impairment is unknown. Accordingly, it was aimed to investigate the possible relationship between hypertensive retinopathy and LA phasic functions by means of two-dimensional speckle-tracking echocardiography (2D-STE). METHODS: A total of 124 hypertensive patients and 27 control subjects were included in the study. LA reservoir strain (LAS-S ), LA conduit strain (LAS-E ), and LA booster strain (LAS-A ) parameters were used to evaluate LA myocardial functions. RESULTS: Hypertensive patients (with and without retinopathy) displayed an obvious reduction in the LA reservoir strain (LAS-S ), and LA conduit strain (LAS-E ). Moreover, further impairment in LA reservoir and conduit strain was found in patients with hypertensive retinopathy than in the isolated hypertensive patients. There were no significant differences in LA booster strain (LAS-A ) among the three groups. Impaired LAS-S (OR: 0.764, CI: 0.657-0.888, and p < 0.001), LAS-E (OR: 0.754, CI: 0.634-0.897, and p = 0.001), and hypertension (HT) duration (OR: 2.345, CI: 1.568-3.507, and p < 0.001) were shown to be independent predictors of hypertensive retinopathy. CONCLUSION: Impaired LA reservoir and conduit strain may be used to predict hypertensive patients at higher risk of developing hypertensive retinopathy, and to determine which patients should be followed more closely for hypertensive retinopathy.


Subject(s)
Hypertension , Hypertensive Retinopathy , Retinal Diseases , Atrial Function, Left , Echocardiography/methods , Heart Atria/diagnostic imaging , Humans , Hypertension/complications , Hypertensive Retinopathy/complications , Hypertensive Retinopathy/diagnostic imaging
18.
Psychiatr Danub ; 34(1): 57-63, 2022.
Article in English | MEDLINE | ID: mdl-35467611

ABSTRACT

BACKGROUND: Traumatic experiences in the first years of life have an important role in the occurrence of major depression as well as many psychiatric diseases. The aim of this study is to investigate the relationship between childhood trauma (CT), suicidal behavior and deliberate self-harm (DSH) behavior in patients who are diagnosed with major depressive disorder (MDD). SUBJECTS AND METHODS: 106 patients who were admitted with depressive complaints to the psychiatry outpatient clinic of Recep Tayyip Erdogan University Training and Research Hospital in Turkey were included in the study. Sociodemographic and clinical features data form, Hamilton Depression Rating Scale (HAD-D), Childhood Trauma Questionnaire (CTQ-28) and Intentional Self-harm Questionnaire (DSHI) were applied to all of the cases. RESULTS: 86 (81.1%) of the cases were female and 20 (18.9%) were male. It was determined that 68.9% of the patients had CT, 49.1% had a history of DSH, and 52.1% had a suicide attempt history. It was determined that 75% of those with DSH behavior had a history of suicide attempt. There was a significant difference between the groups (p˂0.001). When the subtypes of CT, suicide ideation, suicide attempt and DSH behavior, were compared to each other, a significant relationship was found for all of the subtypes. A significant correlation was found between the number of CT and suicide attempts and DSH (p˂0.001). CONCLUSIONS: In this study, high levels of CT and its subtypes were found in patients with MDD. In the presence of CT and all of its subtypes, suicide attempt and DSH were significantly higher. In the follow-up of cases diagnosed with MDD, questioning CT is important in terms of suicide attempt and prevention of DSH.


Subject(s)
Adverse Childhood Experiences , Depressive Disorder, Major , Self-Injurious Behavior , Depressive Disorder, Major/epidemiology , Female , Humans , Male , Risk Factors , Self-Injurious Behavior/epidemiology , Self-Injurious Behavior/psychology , Suicidal Ideation
19.
Microcirculation ; 29(4-5): e12757, 2022 07.
Article in English | MEDLINE | ID: mdl-35437863

ABSTRACT

BACKGROUND AND AIMS: Microvascular disease is considered as one of the main drivers of morbidity and mortality in severe COVID-19, and microvascular dysfunction has been demonstrated in the subcutaneous and sublingual tissues in COVID-19 patients. The presence of coronary microvascular dysfunction (CMD) has also been hypothesized, but direct evidence demonstrating CMD in COVID-19 patients is missing. In the present study, we aimed to investigate CMD in patients hospitalized with COVID-19, and to understand whether there is a relationship between biomarkers of myocardial injury, myocardial strain and inflammation and CMD. METHODS: 39 patients that were hospitalized with COVID-19 and 40 control subjects were included to the present study. Biomarkers for myocardial injury, myocardial strain, inflammation, and fibrin turnover were obtained at admission. A comprehensive echocardiographic examination, including measurement of coronary flow velocity reserve (CFVR), was done after the patient was stabilized. RESULTS: Patients with COVID-19 infection had a significantly lower hyperemic coronary flow velocity, resulting in a significantly lower CFVR (2.0 ± 0.3 vs. 2.4 ± 0.5, p < .001). Patients with severe COVID-19 had a lower CFVR compared to those with moderate COVID-19 (1.8 ± 0.2 vs. 2.2 ± 0.2, p < .001) driven by a trend toward higher basal flow velocity. CFVR correlated with troponin (p = .003, r: -.470), B-type natriuretic peptide (p < .001, r: -.580), C-reactive protein (p < .001, r: -.369), interleukin-6 (p < .001, r: -.597), and d-dimer (p < .001, r: -.561), with the three latter biomarkers having the highest areas-under-curve for predicting CMD. CONCLUSIONS: Coronary microvascular dysfunction is common in patients with COVID-19 and is related to the severity of the infection. CMD may also explain the "cryptic" myocardial injury seen in patients with severe COVID-19 infection.


Subject(s)
COVID-19 , Myocardial Ischemia , Biomarkers , Blood Flow Velocity , Coronary Circulation , Coronary Vessels/diagnostic imaging , Humans , Inflammation , Microcirculation
20.
Int J Cardiovasc Imaging ; 38(1): 5-13, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34453654

ABSTRACT

In this study, we aimed to investigate the relationship between high triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio and coronary slow flow phenomenon (CSFP) in patients undergoing elective coronary angiography for suspected coronary artery disease. This prospective study included a total of 84 CSFP patients and 83 controls with normal coronary flow, as evidenced by coronary angiography. The Thrombolysis in Myocardial Infarction (TIMI) frame count (TFC) was used to measure the coronary blood flow velocity. The lipid profiles were analyzed and TG/HDL-C ratio were calculated dividing absolute TG levels by absolute HDL-C levels in peripheral blood. The median TG/HDL-C ratio was higher in the CSFP group than the control group (3.4 [2.6 to 4.9] vs. 2.3 [1.8 to 3], respectively; p < 0.001). The multivariate logistic regression analysis revealed that TG/HDL-C ratio was an independent predictor of CSFP (odds ratio [OR] 1.78, 95% confidence interval [CI] 1.59-2.32; p = 0.001) and TG/HDL-C ratio was positively correlated with the TFC in the CSFP group (r = 0.311, p < 0.001). The area under the receiver operating characteristic curve of TG/HDL-C for the diagnosis of CSFP was 0.73 (95% CI 0.65-0.81; p < 0.001). If a cut-off value of 2.75 was used, higher levels of TG/HDL-C ratio could predict the presence of CSFP with 72% sensitivity and 71% specificity. Our study results suggest that TG/HDL-C ratio is associated with CSFP and may be a useful biomarker for predicting CSFP and its severity.


Subject(s)
Cholesterol, HDL/blood , Coronary Artery Disease/diagnostic imaging , No-Reflow Phenomenon , Triglycerides/blood , Coronary Angiography , Humans , No-Reflow Phenomenon/diagnostic imaging , Predictive Value of Tests , Prospective Studies
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