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1.
Bratisl Lek Listy ; 123(8): 585-588, 2022.
Article in English | MEDLINE | ID: mdl-35852510

ABSTRACT

BACKGROUND: Coronary slow flow (CSF) is determined by delayed opacification of the epicardial coronary arteries without obstructive disease. The triglyceride glucose index (TGI) has been suggested as a useful marker of insulin resistance. Previous studies have shown that TGI is associated with cardiovascular disease, but no study has examined the relationship between TGI and CSF. OBJECTIVES: Therefore, the primary objective of the present study was to investigate the relationship between TGI and CSF. METHODS: This study retrospectively evaluated patients who were admitted to our clinic with complaints of chest pain and underwent coronary angiography between January and December 2018. A total of 1100 coronary angiography images were assessed, and 72 patients with CSF were detected. Coronary flow was quantified objectively using the TIMI (thrombolysis in myocardial infarction) frame count (TFC) method as described by Gibson et al. TGI was calculated as follows: ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. RESULTS: The CSF group had significantly higher glucose levels (mg/dl) [ (114.92±30.92), (125.61±33.22), than the control and CSF groups, respectively, p=0.0001], TGI [ (9.02±0.56), (9.26±0.54), p=0.0001], and triglyceride levels (mg/dl) [ (170.67±110.81), (201.19±136.93), p=0.002]. There was no statistically significant correlation between TGI and left anterior descending artery TFC, circumflex artery TFC, right coronary artery TFC (r/p values; 0.24/0.06; 0.32/0.08; 0.18/0.36, respectively). TGI, HDL, HT, age, and sex were examined with a multiple logistic model, and TGI was found to be statistically significant for the risk of CSF (p=0.0001; O.R:7.459). CONCLUSION: TGI was statistically significantly higher in the CSF group than the control group. According to the multivariate logistic regression analysis, only TGI was independently associated with the risk of CSF, but higher TGI did not predict more slow coronary flow. Prospective studies are needed to clarify the prognostic relationship of TGI and CSF in terms of future cardiovascular events (Tab. 2, Fig. 1, Ref. 19).


Subject(s)
Coronary Circulation , Glucose , Blood Flow Velocity , Coronary Angiography/methods , Coronary Vessels , Humans , Retrospective Studies , Triglycerides
2.
J Med Biochem ; 41(2): 162-167, 2022 Apr 08.
Article in English | MEDLINE | ID: mdl-35510201

ABSTRACT

Background: Recent studies have shown that increased circulating concentrations of fibroblast growth factor 21 (FGF21) are associated with obesity, metabolic disorder, and atherosclerosis. However the relationship between FGF21 and coronary artery disease (CAD) is controversial This study was planned to investigate the role of FGF21 in CAD development and CAD severity. Methods: Seventy-eight patients with stable angina pectoris (SAP) (lesion positive) and 40 control patients (lesion negative) with similar cardiovascular risk factors were included in the study. Serum FGF21 levels were measured by ELISA method. CAD severity was evaluated by using SYNTAX and GENSINI risk scores. Results: FGF21 concentrations were found significantly higher in the SAP group than in the control group. [101.18 ± 141.62 vs. 47.93 ± 58.74 pg/mL; p = 0.03], no correlation was found between the SYNTAX (r = 0.146 and p = 0.134) and GENSINI (r = 0.211 and p = 0.084) scores with serum FGF21 levels. There was a negative relationship between serum FGF21 and serum HDL-C levels in correlation analysis (r = - 0.272; p = 0.026). Conclusions: The serum FGF21 levels are different between SAP and control patients. FGF21 is a marker for CAD diagnosis, but not for the evaluation of CAD severity.

3.
Cureus ; 14(4): e24078, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35573507

ABSTRACT

BACKGROUND: Pilates is a type of exercise that exerts positive effects on body composition and general health. This study set out to investigate the effects of equipment-based Pilates (reformer) exercise on body composition, some physical parameters, and blood parameters of medical interns showing a tendency toward sedentary life. MATERIALS AND METHODS: The experimental group (EG) comprising 22 healthy internship students in the medical faculty performed Pilates reformer exercises for nine weeks. The control group (CG) consisted of 18 students who did not engage in any exercise program. The baseline and final parameters of all the participants were measured. RESULTS: The mean age of the experimental group (EG) was 23.68±1.29 years, while that of the control group (CG) was 24.78±3.44 (p=0.089). A significant difference was evident between the performance pre-test and post-test scores of the EG (p<0.05). However, a significant positive difference was noted only between the waist pre-test and post-test results in the body composition measurements (p<0.05). A significant rise in HDL and fasting blood sugar levels and a decrease in insulin levels was observed in the post-exercise biochemical parameters measured in the EG (p=0.05). When the EG and CG were compared, a significant difference was found only in HDL cholesterol values in relation to the differences between the pre-test and the post-test groups (p=0.024). CONCLUSION: The positive data from performance tests, especially with its HDL-increasing and insulin-lowering effects in the EG, implicate that Pilates reformer exercises can produce a favorable effect on the healthy living standards of medical interns.

4.
J Investig Med ; 70(3): 780-785, 2022 03.
Article in English | MEDLINE | ID: mdl-34857627

ABSTRACT

The prevalence of metabolic syndrome (MetS) is more common in patients with hypertension and is associated with an increased risk of target organ damage and/or cardiovascular disease (CVD). Omentin-1 is a beneficial adipokine considered to play a role in MetS and MetS-related states such as obesity, diabetes, and coronary artery disease. The aim of this study was to determine the relationship between circulating omentin-1 levels and MetS uncomplicated by diabetes or CVD (nascent MetS) in patients with hypertension. In this study, 110 patients (54 men, 49%; average age: 49.72±11.32 years) treated for hypertension but without overt diabetes and/or CVD were enrolled. 66 patients were stratified into MetS (+) (group 1) and 44 patients into MetS (-) (group 2) according to the American Heart Association/National Heart, Lung, and Blood Institute criteria. The triglyceride glucose (TyG) index was used to assess insulin resistance. Circulating omentin-1 levels in venous blood samples were measured by an ELISA kit. Circulating omentin-1 levels in patients with MetS were significantly lower than in patients without MetS (46.35 ng/mL (42.70-57.70 ng/mL) vs 130.95 ng/mL (62.83-236.48 ng/mL), p<0.001). Omentin-1 was inversely correlated with TyG index (r=-0.204, p=0.033). In a multivariate logistic regression analysis, omentin-1, TyG index, and body mass index were independent predictors of MetS. A receiver operating characteristic curve analysis determined that the best cut-off value for omentin-1 in predicting MetS was 62.20 ng/mL and the area under the curve was 0.880 (95% CI 0.817 to 0.942, p<0.001). The findings of this study suggest that circulating omentin-1 levels are inversely related to the presence of MetS and may be a reliable marker to predict the development of MetS in patients with hypertension.


Subject(s)
Cardiovascular Diseases , Hypertension , Insulin Resistance , Metabolic Syndrome , Adult , Biomarkers , Cardiovascular Diseases/complications , Cytokines/metabolism , Female , GPI-Linked Proteins , Glucose , Humans , Hypertension/complications , Lectins , Male , Middle Aged , Triglycerides
5.
J Med Biochem ; 40(4): 384-389, 2021 Sep 03.
Article in English | MEDLINE | ID: mdl-34616228

ABSTRACT

BACKGROUND: The previous studies have showed that serum retinol binding protein 4 (RBP4) levels increase in metabolic disorders which are closely associated with cardiovascular diseases (CVD). However, the human studies investigating the role of RBP4 in CVD are conflicted. Therefore, we aimed to evaluate the relationship between RBP4 with the presence and severity of coronary artery disease (CAD) in this study. METHODS: 55 patients with presenting acute coronary syndrome (ACS) and 43 control subjects who had various cardiovascular risk factors with normal coronary artery on coronary angiography were included in this study. The serum RBP4 concentrations were measured using ELISA method, clinically and anatomically score models were used to assess the severity of coronary lesion. RESULTS: Serum RBP4 levels were significantly higher in patients with ACS compared to the without ACS (68.40 ± 47.94 mg/L vs. 49.46 ± 13.64 mg/L; p = 0.014). RBP4 was correlated with GENSINI and SYNTAX I score (r = 0.286 p = 0.034; r = 0.403 p = 0.002 respectively). However, there was no relationship between RBP4 and GRACE score. CONCLUSIONS: The serum RBP4 levels increase in patients with CAD and its increased levels may be correlated with CAD severity.

6.
Front Mol Biosci ; 8: 681550, 2021.
Article in English | MEDLINE | ID: mdl-34055891

ABSTRACT

Transcription by RNA polymerase II (Pol II) is regulated by different processes, including alterations in chromatin structure, interactions between distal regulatory elements and promoters, formation of transcription domains enriched for Pol II and co-regulators, and mechanisms involved in the initiation, elongation, and termination steps of transcription. Transcription factor TFII-I, originally identified as an initiator (INR)-binding protein, contains multiple protein-protein interaction domains and plays diverse roles in the regulation of transcription. Genome-wide analysis revealed that TFII-I associates with expressed as well as repressed genes. Consistently, TFII-I interacts with co-regulators that either positively or negatively regulate the transcription. Furthermore, TFII-I has been shown to regulate transcription pausing by interacting with proteins that promote or inhibit the elongation step of transcription. Changes in TFII-I expression in humans are associated with neurological and immunological diseases as well as cancer. Furthermore, TFII-I is essential for the development of mice and represents a barrier for the induction of pluripotency. Here, we review the known functions of TFII-I related to the regulation of Pol II transcription at the stages of initiation and elongation.

7.
Turk J Med Sci ; 51(4): 2112-2119, 2021 08 30.
Article in English | MEDLINE | ID: mdl-33957727

ABSTRACT

Background/aim: The aim of the study was to evaluate the effect of Controlling Nutritional Status (CONUT) score on the prognosis in patients with diffuse large B-cell lymphoma (DLBCL). Materials and methods: The present study was a retrospective study. The CONUT score was calculated based on serum albumin, total cholesterol and lymphocyte levels. This study included a total of 266 patients, 131 (49.2%) were female and 135 (50.8%) were male. The median follow-up period was 51 months (range: 1­190). Results: The median age was 64 years. The cut off CONUT was 1.5. There was a significant difference between patients with high (≥ 2) or low (< 2) CONUT scores in terms of overall survival (OS) and progression-free survival (PFS). The 5-year OS and PFS in patients with high CONUT score was 52.1% and 49.7%. The 5-year OS and PFS in patients with low CONUT score was 79.8% and 75.6% (p < 0.001). In the multivariate analysis for OS, age ≥ 65 years (HR = 1.80, p = 0.028), Eastern Cooperative Oncology Group (ECOG) > 1 (HR = 2.04, p = 0.006), stage IIIA­IVB disease (HR = 2.75, p = 0.001) and the CONUT score (HR = 1.15, p = 0.003) were found statistically significant. In the multivariate analysis for PFS, age ≥ 65 years (HR = 2.02, p = 0.007), stage IIIA­IVB disease (HR = 2.42, p = 0.002) and the CONUT score (HR = 1.19, p = 0.001) were found to be significant parameters. Conclusion: High CONUT score reduces OS and PFS in DLBCL. CONUT score is an independent, strong prognostic index in patients with DLBCL.


Subject(s)
Lymphoma, Large B-Cell, Diffuse/mortality , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Humans , Lymphocytes , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged , Nutritional Status , Prognosis , Retrospective Studies , Survival
9.
Am J Emerg Med ; 40: 110-114, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33309506

ABSTRACT

INTRODUCTION: In this study, we aimed to investigate and compare the prognostic impacts of C-reactive protein (CRP), white blood cell (WBC) count, neutrophil (NEU)-to-lymphocyte (LYM) ratio (NLR), platelet-to-lymphocyte ratio (PLR), Red Cell Distribution Width (RDW) biomarkers in laboratory-confirmed COVID-19 cases as well as to explore the most useful diagnostic biomarkers and optimal cutoff values in COVID-19 patients. METHODS: A total of 233 patients were admitted to Emergency Department (ED) of Pamukkale University Hospital during two months (March-April 2020) and underwent Sars CoV-2 PCR (Polymerase Chain Reaction), complete blood count (CBC), and CRP tests in sequence due to complaints of COVID-19. The laboratory results and demographic findings were collected from the public health management system retrospectively. The patients with positive Sars CoV-2 PCR test along with hospitalization data were also recorded. RESULTS: The CRP (p = 0.0001), lactate dehydrogenase (LDH) (p = 0.038), PLR (p = 0.0001) and NLR (p = 0.001) remained significantly higher in the patients with positive Sars CoV-2 PCR test result. By contrast, eosinophil (p = 0.0001), lymphocyte (p = 0.0001), platelet levels (p = 0.0001) were calculated as significantly higher in negative Sars CoV-2 patients. CONCLUSION: In the light of the obtained results, the CRP, LDH, PLR and NLR levels remained significantly higher in COVID-19 positive patients, while eosinophil, lymphocyte, and platelet levels were significantly elevated in COVID-19 negative patients.


Subject(s)
Blood Platelets , COVID-19/blood , COVID-19/diagnosis , Lymphocytes , Monocytes , Neutrophils , Adolescent , Adult , Aged , Aged, 80 and over , Blood Cell Count , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , Retrospective Studies , Severity of Illness Index , Young Adult
10.
J Hum Hypertens ; 35(3): 290-295, 2021 03.
Article in English | MEDLINE | ID: mdl-32978495

ABSTRACT

Hypertension (HT) is a disease that can cause death due to multiple target organ damage and eventually related vascular system damage. High blood pressure is known increased inflammatory activity and to cause endothelial dysfunction has been showed in HT patients. Omentin-1 is a glucoprotein of the adiponectin family released from visceral adipose tissue, endothelial cells, and visceral fat stromal-vascular cells. It has anti-inflammatory effect and circulating omentin-1 concentration correlates negatively with waist circumference, insulin resistance, and body-mass index. Serum omentin-1 is used as a biomarker of coronary artery disease, obesity, cancer, metabolic syndrome, inflammatorydisease, atherosclerosis, and diabetes mellitus. The aim of our study is to investigate circulating omentin-1 levels in HT patients compared to healthy normotensive controls. Patients diagnosed with new essential HT (n = 61) and healthy normotensive individuals (n = 60) were enrolled in this study. The HT group was separated into two subgroups. There were 30 patients in stage 2 HT group and 31 patients in stage 1 HT group. Omentin-1 levels were significantly lower both in stage 1 and 2 HT subgroup as compared with the normotensive controls (72.19 ± 54.33 ng/ml for stage 1 HT subgroup; 62.45 ± 47.01 ng/ml for stage 2 HT subgroup; and, 147.84 ± 58.55 ng/ml for healthy normotensive controls; overall P < 0.001). The present study demonstrated that serum Omentin-1 levels decreased in patients with HT compared with normotensive controls. These lower concentrations may be attributed to a combined outcome of endothelial dysfunction, renal injury, and inflammation in the setting of hypertension.


Subject(s)
Cytokines , Hypertension , Insulin Resistance , Lectins , Body Mass Index , Cytokines/blood , Endothelial Cells , GPI-Linked Proteins/blood , Humans , Lectins/blood , Obesity
11.
Front Physiol ; 11: 590180, 2020.
Article in English | MEDLINE | ID: mdl-33101065

ABSTRACT

TFII-I is a ubiquitously expressed transcription factor that positively or negatively regulates gene expression. TFII-I has been implicated in neuronal and immunologic diseases as well as in thymic epithelial cancer. Williams-Beuren Syndrome (WBS) is caused by a large hemizygous deletion on chromosome 7q11.23 which encompasses 26-28 genes, including GTF2I, the human gene encoding TFII-I. A subset of WBS patients has recently been shown to present with macrocytosis, a mild anemia characterized by enlarged erythrocytes. We conditionally deleted the TFII-I/Gtf2i gene in adult mice by tamoxifen induced Cre-recombination. Bone marrow cells revealed defects in erythro-megakaryopoiesis and an increase in expression of the adult ß-globin gene. The data show that TFII-I acts as a repressor of ß-globin gene transcription and that it is implicated in the differentiation of erythro-megakaryocytic cells.

12.
J Med Biochem ; 39(1): 100-107, 2020 Jan 10.
Article in English | MEDLINE | ID: mdl-32549783

ABSTRACT

BACKGROUND: There is increasing requests of Vitamin D test in many clinical settings in recent years. However, immunoassay performance is still a controversial topic. Several diagnostic manufacturers have launched automated 25-hydroxyvitamin D (25-OH D) immunoassays in the past decade. We compared the performance of Abbott Architect 25-OH D Vitamin immunoassay with liquid chromatography-tandem mass spectrometry systems (LCMS/MS) to evaluate immunoassay performance, especially in deficient groups. METHODS: Eighty human serum samples were analyzed with Architect 25-OH D vitamin kit (Abbott Diagnostics, Lake Forest, IL, USA) and LC-MS/MS systems (Zivak Technology, Istanbul, Turkey). The results of the immunoassay method were compared with the LC-MS/MS using Passing-Bablok regression analysis, Bland-Altman plots and correlation coefficient analysis. We also evaluated results in four levels of D vitamin as a severe deficiency, deficiency, insufficiency, and sufficiency. RESULTS: Architect showed 9.59% bias from LC-MS/MS with smaller mean. Passing-Bablok regression analysis demonstrated the value of 0.95 slope and had a constant bias with an intercept value of -4.25. Concordance correlation coefficient showed moderate agreement with the value of 0.918 (95% CI 0.878-0.945). Two methods revealed good interrater agreement (kappa = 0.738). While the smallest bias determined in deficiency (9.95%) group, the biggest was in insufficiency (15.15%). CONCLUSIONS: Architect 25-OH D vitamin immunoassay can be used in routine measurements but had potential misclassification of vitamin D status in insufficient and deficient groups. Although there are recent standardization attempts in 25-OH D measurements, clinical laboratories must be aware of this method.

13.
Arch Med Sci ; 16(3): 577-583, 2020.
Article in English | MEDLINE | ID: mdl-32399105

ABSTRACT

INTRODUCTION: Telomeres play an important role in maintaining chromosomal integrity. Functional loss of telomeres increases the risk of cancer by causing genomic instability. Telomere length abnormalities have been reported in several precancerous lesions. There is no study that evaluates telomere length in Billroth II distal gastrectomy, which is known as a risk factor for gastric stump carcinogenesis, in the literature. The aim of this study was to assess the relationship between the telomere length of residual gastric mucosal samples, peripheral blood lymphocytes, and other clinicopathological parameters of patients who had undergone Billroth II distal gastrectomy. MATERIAL AND METHODS: There were two groups: a control group (n = 15) and a patient group (n = 15). In all cases, upper gastrointestinal endoscopy was performed, and biopsies were taken during endoscopy. Telomere lengths were measured by qRT-PCR. RESULTS: It was observed that the lengths of the telomeres were shortened as the time of postoperative period increased in the patient group (r = -0.126) (p > 0.05). Also, the lengths of the telomeres were shortened in chronic inflammation, neutrophil activity, glandular atrophy, and intestinal metaplasia. CONCLUSIONS: The telomere length was shortened as the time of postoperative period increased in the patient group. The telomeres were also shorter in chronic inflammation, neutrophil activity, intestinal metaplasia, and glandular atrophy, in all of the study groups. Telomere length abnormalities in gastric stump carcinogenesis process may be a guide for early diagnosis and treatment.

15.
Angiology ; 70(7): 662-668, 2019 Aug.
Article in English | MEDLINE | ID: mdl-30630336

ABSTRACT

Endothelial dysfunction plays role in the generation of both essential hypertension (EH) and aortic stiffness. We evaluated the relationship between serum endocan level and aortic elastic properties (AEPs) assessed with the aortic strain, aortic distensibility, and aortic stiffness index by echocardiography. Newly diagnosed EH patients (n = 67) and controls (n = 70) were included in the study. The EH group was subdivided into stage 1 and 2 EH groups. A higher endocan level was found in the EH group, compared to the controls (34.2 ± 13.0 vs 24.1 ± 7.3 ng/mL, respectively, P < .001). All the AEP parameters were worse in the EH group, compared to the controls. Further, endocan levels correlated with aortic distensibility (r = -0.305, P < .001) and aortic strain (r = -0.181, P = .038), but not with aortic stiffness index (r = 0.162, P = .064) in the whole study population. Aortic elastic properties deteriorate and serum endocan level increases in patients with EH. Moreover, serum endocan level shows a correlation with deteriorated AEPs, and hence may a surrogate marker of escalating aortic stiffness in patients with newly diagnosed EH.


Subject(s)
Aorta/diagnostic imaging , Blood Pressure , Echocardiography, Doppler, Pulsed , Essential Hypertension/diagnostic imaging , Neoplasm Proteins/blood , Proteoglycans/blood , Vascular Stiffness , Adult , Aorta/physiopathology , Biomarkers/blood , Case-Control Studies , Cross-Sectional Studies , Elasticity , Essential Hypertension/blood , Essential Hypertension/physiopathology , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , Prospective Studies , Up-Regulation
16.
Mol Cell Biol ; 38(19)2018 10 01.
Article in English | MEDLINE | ID: mdl-30012865

ABSTRACT

The organization of the five ß-type globin genes on chromosome 11 reflects the timing of expression during erythroid cell development, with the embryonic ε-globin gene being located at the 5' end, followed by the two fetal γ-globin genes, and with the adult ß- and δ-globin genes being located at the 3' end. Here, we functionally characterized a DNase I-hypersensitive site (HS) located 4 kb upstream of the Gγ-globin gene (HBG-4kb HS). This site is occupied by transcription factors USF1, USF2, EGR1, MafK, and NF-E2 in the human erythroleukemia cell line K562 and exhibits histone modifications typical for enhancers. We generated a synthetic zinc finger (ZF) DNA-binding domain targeting the HBG-4kb HS (HBG-4kb ZF). The HBG-4kb ZF interacted with the target site in vitro and in the context of cells with a high affinity and specificity. Direct delivery of the HBG-4kb ZF to K562 and primary human erythroid cells caused a reduction in γ-globin gene expression which was associated with decreased binding of transcription factors and active histone marks at and downstream of the HS. The data demonstrate that the HBG-4kb HS is important for fetal globin production and suggest that it may act by opening chromatin in a directional manner.


Subject(s)
Chromatin/genetics , gamma-Globins/genetics , Deoxyribonuclease I , Enhancer Elements, Genetic , Erythropoiesis/genetics , Gene Expression Regulation, Developmental , Genes, Switch , Histone Code/genetics , Humans , K562 Cells , Models, Genetic , Polymorphism, Single Nucleotide , RNA/genetics , RNA/metabolism , gamma-Globins/metabolism
17.
J Cell Biochem ; 119(1): 712-722, 2018 01.
Article in English | MEDLINE | ID: mdl-28657656

ABSTRACT

Transcription factor TFII-I is a multifunctional protein implicated in the regulation of cell cycle and stress-response genes. Previous studies have shown that a subset of TFII-I associated genomic sites contained DNA-binding motifs for E2F family transcription factors. We analyzed the co-association of TFII-I and E2Fs in more detail using bioinformatics, chromatin immunoprecipitation, and co-immunoprecipitation experiments. The data show that TFII-I interacts with E2F transcription factors. Furthermore, TFII-I, E2F4, and E2F6 interact with DNA-regulatory elements of several genes implicated in the regulation of the cell cycle, including DNMT1, HDAC1, CDKN1C, and CDC27. Inhibition of TFII-I expression led to a decrease in gene expression and in the association of E2F4 and E2F6 with these gene loci in human erythroleukemia K562 cells. Finally, TFII-I deficiency reduced the proliferation of K562 cells and increased the sensitivity toward doxorubicin toxicity. The results uncover novel interactions between TFII-I and E2Fs and suggest that TFII-I mediates E2F function at specific cell cycle genes.


Subject(s)
Cell Cycle Proteins/genetics , E2F Transcription Factors/metabolism , Transcription Factors, TFII/metabolism , Cell Cycle , Cell Proliferation , Chromatin Immunoprecipitation , Computational Biology/methods , E2F Transcription Factors/genetics , Humans , K562 Cells , Promoter Regions, Genetic , Protein Binding , Transcription Factors, TFII/genetics
18.
J Plast Surg Hand Surg ; 51(6): 405-413, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28277073

ABSTRACT

BACKGROUND: Smoke of cigarettes, and specifically nicotine, has been shown to diminish pedicled transverse rectus abdominis musculocutaneous (TRAM) flap survival. Considering that Notch signalling through its ligand Delta-like 4 (Dll4) functions as anti-angiogenic factor by inhibiting the pro-angiogenic effects of vascular endothelial growth factor (VEGF), it is hypothesised that inhibition of the Notch would promote angiogenesis and increase TRAM flap survival in rats submitted to nicotine. METHODS: Twenty rats were treated with nicotine for 28 days preoperatively. Thereafter, a pedicled TRAM flap was created in all animals. The Notch inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine-t-butyl-ester was administered in animals of the treatment group. Animals in the control group were given the same amount of solvent. Five days after the surgery, viable flap areas were determined. Skin samples were evaluated for VEGF and Dll4 mRNA levels. Immunohistochemical analysis was used for the assessment of endothelial Dll4 expression. Vascular density was determined histologically. Plasma levels of VEGF and Dll4 were measured. RESULTS: A significant improvement in TRAM flap surviving area was observed in the treatment group (53.50 ± 14.25%) compared with the controls (32.20 ± 9.15%). Immunohistochemical analysis revealed a significant increase in the number of Dll4 stained vessels in animals of the treatment group (9.2 ± 1.6) in comparison with the controls (5.7 ± 1.9). VEGF mRNA levels (0.22 ± 0.08) in the treatment group were significantly lower than those in the control group (0.36 ± 0.09). CONCLUSION: Notch inhibition significantly improved TRAM flap survival in animals exposed to nicotine by promoting VEGF-induced angiogenesis.


Subject(s)
Endothelium, Vascular/drug effects , Graft Survival/drug effects , Neovascularization, Physiologic/drug effects , Nicotine/pharmacology , Surgical Flaps/blood supply , Animals , Endothelium, Vascular/physiology , Intracellular Signaling Peptides and Proteins/blood , Intracellular Signaling Peptides and Proteins/metabolism , Male , Membrane Proteins/blood , Membrane Proteins/metabolism , Models, Animal , Neovascularization, Physiologic/physiology , Rats , Rats, Sprague-Dawley , Receptors, Notch/drug effects , Receptors, Notch/metabolism , Surgical Flaps/pathology , Vascular Endothelial Growth Factors/blood , Vascular Endothelial Growth Factors/metabolism
19.
J Burn Care Res ; 38(6): e923-e933, 2017.
Article in English | MEDLINE | ID: mdl-28319529

ABSTRACT

The Notch pathway ligand Delta-like 4 (Dll4) functions as an antiangiogenic factor, inhibiting vascular endothelial growth factor (VEGF)-induced angiogenesis. This function is documented in tumor and embryonic vasculature. However, its implication in burn wounds remains unexplored. Our objective was to explore the involvement of the Notch in the healing of zone of stasis burns. We hypothesized that anti-Dll4 therapy would prevent progressive necrosis in the stasis zone by promoting angiogenesis. Burns were created in 21 rats using the comb burn model. The Notch inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine-t-butyl-ester was administered in the treatment group. Controls were given the same amount of solvent. Seven days after the burn, skin samples were evaluated for VEGF and Dll4 gene expressions. Immunohistochemical analysis was used for the assessment of vascular density, endothelial Dll4 expression, and apoptosis count. Histologic grading of tissue damage was performed. Circulating levels of VEGF and Dll4 were determined. VEGF and Dll4 mRNA levels were found to be simultaneously induced after the burn. In the treatment group, a significant increase in the number of vessels was observed. However, gross evaluation documented an expansion of necrosis to the zone of stasis with marked activation of apoptosis. Histologic assessment showed that the resultant vascular overgrowth was accompanied by extensive edema and abundant infiltration of leukocytes. We provide evidence for the involvement of Notch in the regulation of angiogenesis in zone of stasis burns.


Subject(s)
Burns/physiopathology , Neovascularization, Physiologic/physiology , Receptors, Notch/physiology , Signal Transduction/physiology , Wound Healing/physiology , Animals , Burns/pathology , Dipeptides/pharmacology , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Male , Membrane Proteins/antagonists & inhibitors , Neovascularization, Physiologic/drug effects , Rats , Rats, Sprague-Dawley , Wound Healing/drug effects
20.
J Med Biochem ; 36(4): 301-308, 2017 Oct.
Article in English | MEDLINE | ID: mdl-30581326

ABSTRACT

BACKGROUND: The Six-Sigma Methodology is a quality measurement method in order to evaluate the performance of the laboratory. In the present study, it is aimed to evaluate the analytical performance of our laboratory by using the internal quality control data of immunoassay tests and by calculating process sigma values. METHODS: Biological variation database (BVD) are used for Total Allowable Error (TEa). Sigma values were determined from coefficient of variation (CV) and bias resulting from Internal Quality Control (IQC) results for 3 subsequent months. If the sigma values are ≥6, between 3 and 6, and <3, they are classified as ¼world-class«, ¼good« or ¼un - acceptable«, respectively. RESULTS: A sigma value >6 was found for TPSA and TSH for the both levels of IQC for 3 months. When the sigma values were analyzed by calculating the mean of 3 months, folate, LH, PRL, TPSA, TSH and vitamin B12 were found >6. The mean sigma values of CA125, CA15-3, CA19-9, CEA, cortisol, ferritin, FSH, FT3, PTH and testosteron were >3 for 3-months. However, AFP, CA125 and FT4 produced sigma values <3 for varied months. CONCLUSION: When the analytical performance was evaluated according to Six-Sigma levels, it was generally found as good. It is possible to determine the test with high error probability by evaluating the fine sigma levels and the tests that must be quarded by a stringent quality control regime. In clinical chemistry laboratories, an appropriate quality control scheduling should be done for each test by using Six-Sigma Methodology.

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