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OBJECTIVES: Takayasu's arteritis (TAK) is a chronic inflammatory large vessel vasculitis with a grim prognosis due to the excessive risk for cardiovascular (CV) diseases. Its diagnosis relies on radiographic imaging and its differentiation particularly from atherosclerosis could be challenging. Hypothesising that vascular morphology observed in TAK would be comparable to that found in type 2 diabetes mellitus (T2DM), a prototype for advanced atherosclerosis, we compared two disease groups using carotid artery B mode US and shear wave elastography (SWE). METHODS: A total of 72 patients with TAK (63F/9M; mean age: 42.7± 10.0 years) and 74 patients with T2DM (65F/9M; mean age: 50.2± 7.1 years) were studied. Intima-media thickness (IMT), outer diameter and arterial stiffness as assessed by SWE values were measured on the common carotid artery (CCA) and atherosclerotic plaques were recorded. Clinical characteristics, CV risk factors and previous history of CV diseases were determined. Framingham risk score was calculated. RESUULTS: Patients with TAK exhibited significantly lower atherosclerotic risk but higher systolic blood pressure (BP) levels compared to those with T2DM. The mean values of CCA IMT, outer diameter, and stiffness were significantly elevated among patients with TAK compared to those with T2DM. Carotid artery plaques were evenly distributed between the study groups, but their anatomical localisation and composition differed significantly. While coronary artery disease (CAD) was more prevalent among T2DM patients, cerebrovascular diseases were more frequent among TAK patients. CONCLUSIONS: Our study revealed distinctive vascular alterations and atherosclerotic changes when compared to advanced atherosclerosis associated with T2DM. Apart from these, higher levels of systolic BP and significantly different distribution of CV diseases between TAK and T2DM also suggest that TAK should be handled with distinct assessment strategies than that employed in conventional atherosclerotic conditions.
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A series of salicylidene uracil (1-18) derived from 5-aminouracil and substituted salicylaldehydes were analyzed for cytotoxic activity and enzyme inhibitory potency. Nine out of eighteen derivatives (6-8, 10, 12-15, 18) are novel molecules synthesized for the first time in this work, and other derivatives were previously synthesized by our group. The compounds were characterized by Proton nuclear magnetic resonance, carbon nuclear magnetic resonance, fourier transform infrared spectroscopy, and elemental analysis. All compounds were tested for their in vitro cytotoxicity against PC-3 (human prostate adenocarcinoma), A549 (human alveolar adenocarcinoma), and SHSY-5Y (human neuroblastoma) cancer cell lines and the nontumorigenic HEK293 (human embryonic kidney cells) cell line. The 3,5-di-tert-butylsalicylaldehyde derived compound (8) was toxic to PC-3 human prostate adenocarcinoma cells, showing a promising IC50 value at 7.05 ± 0.76 µM. The present study also aimed to evaluate the inhibitory effects of the compounds against several key enzymes, namely carbonic anhydrase I and II (CA I and CA II), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and glutathione reductase (GR), which are implicated in various global disorders, such as Alzheimer's disease, epilepsy, cancer, malaria, diabetes, and glaucoma. The inhibitory profiles of the tested compounds were assessed by determining their Ki values, which ranged from 2.96 to 9.24 nM for AChE, 3.78 to 12.57 nM for BChE, 8.42 to 25.74 nM for CA I, 7.24 to 19.74 nM for CA II, and 0.541 to 1.124 µM for GR. Molecular docking studies were also performed for all compounds. Most derivatives exhibited much more effective inhibitory action compared with clinically used standards. Thus, our findings indicate that the salicylidene derivatives presented in this study are promising drug candidates that need further evaluation.
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Adenocarcinoma , Antineoplásicos , Humanos , Butirilcolinesterasa/metabolismo , Acetilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/química , Inhibidores de Anhidrasa Carbónica , Simulación del Acoplamiento Molecular , Células HEK293 , Relación Estructura-Actividad , Antineoplásicos/farmacología , Estructura MolecularRESUMEN
The sediment formed during erosion processes is acknowledged as one of the important contributors to environmental damage. In forest areas, sediment production occurs as a result of meteorological factors and wood harvesting, as well as forest road construction activities carried out for the continuity of forests. In this context, the aim of the study is to reveal the sediment risk in forest areas at the provincial level in Turkey by using entropy-based weighted aggregated sum product assessment (WASPAS) and fuzzy clustering methods. The results establish that the weights of the factors affecting the sediment risk are the forest road construction rate (0.3721), the wood harvesting rate (0.3463), the average precipitation (0.2227), and the average temperature (0.0587). Seven provinces were found in the highest risk class of the cluster in terms of sediment risk. Two of those (Yalova and Kocaeli) are located in the Marmara Region, while the others (Bartin, Düzce, Giresun, Ordu, and Zonguldak) are located in the Black Sea Region. Four of the provinces in the lowest risk class of the cluster (Bingöl, Bitlis, Erzincan, and Malatya) are located in the Eastern Anatolia Region, while a fifth (Siirt) is located in the Southeastern Anatolia Region. As is seen in the study, multi-criteria decision-making methods make it possible to evaluate different scenarios for sedimentation estimation and control and to select the most effective solutions. In conclusion, the use of WASPAS, entropy, and fuzzy clustering methods can provide a comprehensive and effective approach for assessing the sediment risk.
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Monitoreo del Ambiente , Agricultura Forestal , Turquía , Entropía , Análisis por Conglomerados , Conceptos MeteorológicosRESUMEN
BACKGROUND: The significance of antiphospholipid antibodies (aPL) is controversial in Takayasu arteritis (TA). This study was conducted to explore the frequency of aPL and their association with disease-related complications in TA. METHODS: : This cross-sectional study was conducted to investigate the presence of anti-cardiolipin (aCL), anti-beta 2 glycoprotein- 1(aß2G1) antibodies, and lupus anticoagulant (LA) in TA patients. TA patients admitted to the Department of Rheumatology of Hacettepe University Faculty of Medicine between December 2015 and September 2016 who fulfilled the American College of Rheumatology (ACR) classification criteria for TA were consecutively enrolled in the study. Patients were grouped according to aPL positivity and compared in terms of disease manifestations, type of vascular involvement at diagnosis, and vascular complications/interventions attributable to TA. RESULTS: Fifty-three TA (49 female) patients were enrolled in the study. We detected 9 (16.9%) patients with IgM and/or IgG aß2G1 and/or LA positivity. There were no patients with positive aCL. All aß2G1 titers were low. There were no differences in terms of symptoms, signs, type of vascular involvement, the number of patients with disease-related complications or vascular interventions/surgery between aPL (+) and aPL(-) groups (p > 0.05 for all). The number of patients with thrombotic lesions was similar between the groups (p > 0.05). There were no patients with a history of venous thrombosis or on anticoagulant treatment in the aPL(+) group. Only 1 patient with IgM aß2G1 (+) had a history of pregnancy loss. DISCUSSION: Our results indicate that aPL positivity is not rare in TA. On the other hand, all aPL titers were low and no differences were found in the frequency of disease-related complications between aPL(+) and aPL(-) patient groups. Only TA patients with atypical manifestations with high suspicion of aPL-related complications should be considered to be investigated for aPL.
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Síndrome Antifosfolípido , Arteritis de Takayasu , Embarazo , Humanos , Femenino , Arteritis de Takayasu/complicaciones , Estudios Transversales , Anticuerpos Anticardiolipina , Anticuerpos Antifosfolípidos , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico , Inhibidor de Coagulación del Lupus , beta 2 Glicoproteína I , Inmunoglobulina MRESUMEN
BACKGROUND: Tumour necrosis factor inhibitors and anti-interleukin-6 (anti-IL-6) therapies are increasingly being used in Takayasu's arteritis (TA) patients who are unresponsive to corticosteroids ± conventional immunosuppressive agents. The aim of this study is to assess the efficacy and safety of anti-IL-6 (tocilizumab) therapy in refractory TA patients in real life. METHODS: Fifteen TA patients (86.7% were female) who received at least 3 cycles of tocilizumab therapy were retrospectively assessed by clinical, laboratory, and radiological evaluations before and after tocilizumab therapy. RESULTS: The median (min-max) age of the patients at evaluation was 35 (20-58) years and the median disease duration from diagnosis was 24 (12-168) months. The median (min.-max.) duration of follow-up after tocilizumab was 15 (3-42) months. There was a significant decrease in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and patient global visual analogue scale (VAS) scores of patients after tocilizumab therapy. The median (min.-max.) ESR was 26 (5-119) vs. 3 (2-49) mm/h, P = 0.02; CRP was 39.8 (2.4-149.0) vs. 7.9 (0-92.9) mg/L, P = 0.017; and patient global VAS was 50 (0-90) vs. 30 (0-60), P = 0.027, respectively. In 8 patients, ESR and CRP levels were in the normal range in the last control. Imaging modality results after tocilizumab were available for 9 patients; 8 patients were radiologically stable and regression was seen in 1 patient. Comparable imaging modality results before and after tocilizumab were available for 5 patients; 4 patients were radiologically stable and regression was seen in 1 patient. Radiological findings were consistent with laboratory responses. Glucocorticoid dosages decreased from a mean dosage of 16.2 (9.1) mg/day at baseline to 7.1 (3.8) mg/day (P = 0.001) at the last follow-up visit. There was no increase in the steroid dosage in any of the patients. All patients tolerated tocilizumab well. DISCUSSION: Based on retrospective real life data, anti-IL-6 (tocilizumab) appears to be an effective and tolerable treatment option in refractory TA patients.
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The effects of high-intensity interval and continuous exercise on erythrocytes carbonic anhydrase (CA, EC 4.2.1.1) activity levels were scarcely investigated up until now. Here we present a study focused on the CA activity from erythrocytes of athletes experiencing interval and continuous training for 6 weeks, during cold weather and at high altitude (> 1600 m). We observed a 50% increase in the blood CA activity at the second week after initiation of the training in both interval and continuos running groups, whereas the control group did not experience any variation in the enzyme activity levels. In the trained individuals a mild decrease in their body mass, BMI and an increased [Formula: see text] were also observed. The CA activity returned at the basal values after 4-6 weeks after the training started, probably proving that a metabolic compensation occurred without the need of an enhanced enzyme activity. The unexpected 50% rise of activity for an enzyme which acts as a very efficient catalyst for CO2 hydration/bicarbonate dehydration, such as the blood CA, deserves further investigations for better understanding the physiologic basis of this phenomenon.
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Altitud , Anhidrasas Carbónicas/sangre , Frío , Eritrocitos/enzimología , Entrenamiento de Intervalos de Alta Intensidad , Acondicionamiento Físico Humano , Carrera/fisiología , Deportes , Índice de Masa Corporal , Clima , Humanos , Masculino , Consumo de Oxígeno , Distribución Aleatoria , Estudiantes , Universidades , Adulto JovenRESUMEN
Background/aim: Abnormal capillaroscopic findings have been reported in vasculitic syndromes such as Behçet's disease, HenochSchönlein purpura, and Wegener's granulomatosis. This study was conducted to define the capillaroscopic changes in patients with Takayasu arteritis (TA). Materials and methods: We studied 28 TA patients (27 females). The nail folds from the 2nd to 5th fingers on both hands were examined with video capillaroscopy for all. A patient was defined as having an abnormal capillaroscopic examination if more than 1 morphologic abnormality was present in at least 2 nail folds. Results: The median capillary density of TA patients was 9 (range: 911). There were no patients with capillary disorganization or avascular areas. Tortuous capillaries were detected in all patients. The other common morphological capillary abnormalities included enlarged/dilated capillaries (39.3%), branching capillaries (35.7%), and hemorrhages (32.1%). Only 1 patient had giant capillaries with early scleroderma-like pattern. Overall, there were 11 (39.3%) patients with abnormal capillaroscopic findings. There were more patients with abnormal capillaroscopic findings in the subgroup of TA patients whose upper extremity blood pressure could not be measured as compared to those whose blood pressure could be measured (66.7% vs. 26.3% patients; P = 0.04). Conclusion: Capillaroscopic abnormalities are frequently seen in TA patients. We consider that abnormal capillaroscopic findings in TA patients reflect the impaired blood flow due to narrowed or occluded arteries rather than the primary capillary involvement of the disease process.
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Capilares/patología , Angioscopía Microscópica , Arteritis de Takayasu/patología , Adulto , Femenino , Dedos/irrigación sanguínea , Humanos , MasculinoRESUMEN
A series of hydrazinecarbothioamide derivatives incorporating ethyl, phenyl, tolyl, benzyl, and allyl moieties were prepared and tested as possible inhibitors of three members of the pH regulatory enzyme family, carbonic anhydrase (CA; EC 4.2.1.1). The inhibitory and activatory potencies of the compounds against the cytosolic human isoforms hCA I and hCA II and the transmembrane, tumor-associated hCA IX were analyzed by a hydrase assay with CO2 as substrate, and the inhibition constants (KI) were calculated. Most compounds investigated here exhibited nanomolar or low micromolar inhibition constants against the three isoenzymes. KI values were in the range of 34.1-871 nM for hCA I and compounds 5-10 showed interesting activation of the hCA II with KA value of 0.81-12.5 µM. Compounds 11-16 exhibited moderate inhibition effects on hCA IX in the range of 0.317-1.245 µM but they were less effective for hCA II. Tested compounds were also investigated using in silico applications at the binding pockets of these three targets. The different mechanisms of inhibition by these tested compounds as compared to sulfonamides, and their diverse inhibition profile for these mammalian isozymes, makes this class of derivatives of great interest for the design of novel CA inhibitors.
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Antígenos de Neoplasias/química , Anhidrasa Carbónica II/química , Anhidrasa Carbónica I/química , Anhidrasas Carbónicas/química , Hidrazinas/química , Isoenzimas/química , Piridinas/química , Tioamidas/química , Sitios de Unión , Anhidrasa Carbónica I/antagonistas & inhibidores , Anhidrasa Carbónica II/antagonistas & inhibidores , Anhidrasa Carbónica IX , Humanos , Hidrazinas/farmacología , Isoenzimas/antagonistas & inhibidores , Estructura Molecular , Piridinas/farmacología , Tioamidas/farmacologíaRESUMEN
The inhibition of two human cytosolic carbonic anhydrase isozymes I and II, with some novel glycine and phenylalanine sulfonamide derivatives were investigated. Newly synthesized compounds G1-4 and P1-4 showed effective inhibition profiles with KI values in the range of 14.66-315µM for hCA I and of 18.31-143.8µM against hCA II, respectively. In order to investigate the binding mechanisms of these inhibitors, in silico docking studies were applied. Atomistic molecular dynamic simulations were performed for docking poses which utilize to illustrate the inhibition mechanism of used inhibitors into active site of CAII. These sulfonamide containing compounds generally were competitive inhibitors with 4-nitrophenylacetate as substrate. Some investigated compounds here showed effective hCA II inhibitory effects, in the same range as the clinically used sulfonamide, sulfanilamide or mafenide and might be used as leads for generating enzyme inhibitors possibly targeting other CA isoforms which have not been yet assayed for their interactions with such agents.
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Inhibidores de Anhidrasa Carbónica/síntesis química , Glicina/análogos & derivados , Glicina/química , Fenilalanina/análogos & derivados , Fenilalanina/química , Sulfonamidas/química , Anhidrasa Carbónica I/antagonistas & inhibidores , Anhidrasa Carbónica I/aislamiento & purificación , Anhidrasa Carbónica II/antagonistas & inhibidores , Anhidrasa Carbónica II/aislamiento & purificación , Inhibidores de Anhidrasa Carbónica/química , Pruebas de Enzimas , Eritrocitos , Glicina/síntesis química , Humanos , Modelos Moleculares , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Fenilacetatos/química , Fenilalanina/síntesis química , Relación Estructura-Actividad , Sulfonamidas/síntesis químicaRESUMEN
INTRODUCTION: The aim of this study is to examine the effects of Ramadan fasting on melatonin, cortisol, and serotonin levels. METHODS: In this study, the blood of 19 healthy male individuals between the ages of 26 and 51, registered in Agri (Turkey) Family Health Center and fasting during Ramadan, was studied. The study was carried out in 2021-2022. The SPSS-22 package program was used in the analysis of the data. Wilcoxon analysis was used in the study. RESULTS: It was determined that the pre-test-post-test melatonin and cortisol levels of the individuals were not statistically significant (p>0.05). It was determined that the pre-test-post-test serotonin difference of the individuals was statistically significant (p<0.05). CONCLUSION: It has been determined that Ramadan fasting increases the serotonin level of individuals but does not change the levels of melatonin and cortisol. It was determined that the level of happiness of individuals increased after Ramadan fasting. Longitudinal studies on the effects of Ramadan fasting are recommended.
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Melatonina , Humanos , Masculino , Adulto , Persona de Mediana Edad , Hidrocortisona , Serotonina , Turquía , Islamismo , AyunoRESUMEN
Nephrotoxicity is a very important complication of 5-fluorouracil (5-FU)-treated cancer patients. Increased oxidative stress, kidney damage, and apoptosis play an important role in the pathogenesis of nephrotoxicity caused by 5-FU. In this study, protective effects of two natural compounds, hesperidin and curcumin, on experimentally induced kidney damage in mice with 5-FU were determined. Application of 5-FU resulted in severe histopathological changes and severe renal failure with increased serum urea and creatinine levels. Also, 5-FU-induced kidney damage, increased levels of malondialdehyde (MDA), decreased superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) activity, and glutathione (GSH) level have been demonstrated. Also, where 5-FU is in the concentration of caspase-3 and 8-OHdG immune-positive cells and therefore causes apoptosis and DNA damage in kidney tissue cells. However, especially high doses of hesperidin and curcumin treatment significantly improved 5-FU-induced oxidative stress/lipid peroxidation, apoptosis/DNA damage, and renal dysfunction. Based on these data, our results suggest that hesperidin and curcumin may be used as new and promising agents against 5-FU-induced nephrotoxicity.
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Curcumina , Hesperidina , Insuficiencia Renal , Animales , Antioxidantes/metabolismo , Curcumina/metabolismo , Curcumina/farmacología , Fluorouracilo/toxicidad , Glutatión/metabolismo , Hesperidina/farmacología , Humanos , Riñón/metabolismo , Malondialdehído/metabolismo , Ratones , Estrés Oxidativo , Superóxido Dismutasa/metabolismoRESUMEN
This study aimed to investigate the effect of dietary sunflower meal (SFM) and multi-enzyme levels on performance, carcass traits, intestinal histomorphology and pancreatic enzyme production in quails. Three hundred and twenty, 1-day-old quail chicks were divided into 8 groups with 4 replicates consisting of 10 birds each in the group. The experiment was randomized design consisting of a 4 × 2 factorial arrangement, with four levels of SFM (0%, 10%, 15%, or 20%) and two levels of multi-enzyme (0.0 or 1.0 g/kg) inclusion in the diet. The body weight, body weight gain, and feed conversion ratio were negatively influenced by the 15% and 20% SFM (p < 0.01) but were not affected by the 10% SFM for 6 week age. The relative gizzard (p < 0.05) weights significantly increased with 20% SFM, but the relative breast weight decreased (p < 0.01). The relative liver weight increased by the addition of enzymes in the diet (p < 0.05). The villus width (p < 0.01) and villus surface area (p < 0.05) of ileum increased linearly with SFM, whereas the villus height (p < 0.01), villus height: crypt depth (p < 0.01) and tunica muscularis thickness (p < 0.01) decreased linearly with SFM. Consequently, it is possible to say that the birds with the least absorptive same weight are the most efficient. The addition of multi-enzyme increased villus height and crypt depth but decreased tunica muscularis thickness of ileum (p < 0.01). Chymotrypsin activity in the pancreas decreased linearly with SFM (p < 0.01). Amylase activity in the pancreas decreased significantly with the addition of the multi-enzyme (p < 0.05). As a result of the study, SFM can be used at a 10% level in growing quail diets with beneficial effects on the absorption surface area. The effects of enzyme supplementation on parameters measured were less pronounced than the SFM inclusion level that higher villus height and lower tunica muscularis thickness were determined in multi-enzyme-fed birds compared to those untreated counterparts.
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The aim of the present work was to provide information about Enterococcus strains isolated from pre-packaged chicken samples in Ankara (Turkey), focusing on their prevalence, phenotypic and genotypic characteristics, and antibiotic resistance. We report the first study on the occurrence of antibiotic resistant enterococci in pre-packaged chicken samples in Ankara. A total of 97 suspicious enterococcal isolates were identified from 122 chicken samples. All isolates were identified to species level by phenotypic and molecular methods. In the 16S rDNA sequence analysis, Enterococcus faecium (61.85%) and Enterococcus faecalis (38.15%) were found to be the most frequently detected Enterococcus spp. Of the 97 isolates tested for hemolytic activity, 12.37% enterococcal strains were ß-hemolytic. ß-Hemolysin was most prevalent among E. faecium (58.33%) compared to E. faecalis (41.66%). Disk diffusion method was used for determining of antibiotic resistance. The analysis of the antimicrobial resistance of the 97 Enterococcus isolates revealed that the resistance to kanamycin (98.96%), rifampicin (80.41%) and ampicillin (60.82%) was most frequent. Furthermore, resistance to erythromycin (38.14%) and ciprofloxacin (34.02%) was also observed. The frequencies of resistance to tetracycline (9.27%), penicillin G (8.24%), and chloramphenicol (3.09%), gentamicin (2.06%) and streptomycin (1.03%) were low. None of the isolates was resistant to vancomycin. Multi-drug resistance was found in 97.93% of Enterococcus strains. E. faecium strains showed a more resistant phenotype than E. faecalis strains according to the antibiotic resistance levels. The results of this study indicated that chicken meat is a potential reservoir for the transmission of antibiotic resistance from animals to humans.
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'Erythema Multiforme associated with Phenytoin And Cranial radiation Therapy' (EMPACT) is a very rare clinic situation and classified in EM-like drug reactions. It can be easily misdiagnosed as acute urticaria or drug eruption in ED. Initial symptoms may resemble a simple skin problem, but diagnosing and early hospitalization of the patients can be lifesaving. Here, we present a man with renal cell cancer and brain metastases who admitted to ED due to fever and generalized rash. His skin lesions beginning from his head and spreading through the torso appeared four days after the end of radiotherapy (11 days after the initial dose of both radiation and oral phenytoin). Inspection showed erythematous lesions on the scalp, neck, torso and arms. These lesions had desquomative character on the scalp. Erythematous maculopapular lesions with the tendency of fusion were also visible on the chest, abdomen, back, on the flexor areas of the arm, forearm and femoral region. Laboratory studies showed normal complete blood counts, high creatinine kinase, creatinine kinase-MB, gamma-glutamyl transpeptidase, aspartate aminotransferase, lactate dehydrogenase, albumin and total protein. After discontinuation of phenytoin and giving H1, H2 receptor blockers and steroid intravenously, he was discharged two weeks later with full recovery.