The effects of SGLT-2 inhibitors on echocardiographic indices and antioxidative properties in patients with heart failure with reduced ejection fraction and diabetes mellitus.

OBJECTIVE: Sodium-glucose co-transporter-2 inhibitors (SGLT-2i) are a new class of drugs that lower blood glucose and reduce mortality in heart failure patients with reduced ejection fraction (HFrEF). They also have antioxidant effects. The exact mechanism of SGLT-2i is unknown. This study investigated the effects of SGLT-2i on asprosin, matrix metalloproteinase (MMP), and tissue inhibitor of MMP (TIMP-1) concentrations and echocardiographic measurements of strain in the left heart chamber. PATIENTS AND METHODS: This prospective follow-up study included 56 patients with HFrEF and diabetes mellitus (DM) who did not initially receive SGLT-2 inhibitors. The control group consisted of 30 healthy individuals. Patients with HFrEF were administered either empagliflozin (n=28) or dapagliflozin (n=28) in addition to their treatment. The patient group was evaluated for left ventricular global longitudinal strain (LVGLS), left atrial (LA) strain, and LA volumes at the beginning and third month of the study. The control group had blood collected once, while the patient group had it twice: at the start of the trial, on the same day as the echocardiographic evaluation, and at the end of the third month after starting an SGLT-2i. Serum levels of asprosin, MMP-1 and TIMP-1 were assessed. RESULTS: LVGLS increased significantly in HFrEF patients at the third-month assessment compared to baseline (-8.6±2.3% vs. -9±2.5%, respectively; p<0.001), but there was no significant difference in LVEF (p=0.593). A substantial increase was observed in the left atrial ejection fraction (LAEF) compared to baseline values (36.3±9.4% vs. 42.1±8.7%, respectively; p<0.001), driven by a reduction in minimal LA volume [32.5 (19-96) ml vs. 32 (20-86) ml, respectively; p=0.018]. Compared to baseline evaluation, LA reservoir [13 (6-25) vs. 16.5 (2-26), respectively; p<0.001] and contraction strain (7.7±4.3 vs. 9.4±5.6, respectively; p=0.014) values were also enhanced at the third month. Between the baseline and the 3rd month, the patient group's LA conduit strain (p=0.122) and LA maximum volume (p=0.716) remained unchanged. Serum asprosin significantly increased (11.7±5.1 ng/mL vs. 14±9.4 ng/mL, respectively; p=0.032); however, no statistically significant alteration was detected in MMP (p=0.278) and TIMP-1 levels (p=0.401). CONCLUSIONS: SGLT-2i are associated with elevated levels of LVGLS, LAEF, LA contraction strain, and LA reservoir strain. SGLT-2i medications may improve plasma asprosin levels to boost energy metabolism, reduce oxidative stress and reactive oxygen radicals.

Auditory changes in acromegaly.

OBJECTIVE: The aim of this study is to determine the changes involving auditory system in cases with acromegaly. MATERIALS AND METHODS: Otological examinations of 41 cases with acromegaly (uncontrolled n = 22, controlled n = 19) were compared with those of age and gender-matched 24 healthy subjects. Whereas the cases with acromegaly underwent examination with pure tone audiometry (PTA), speech audiometry for speech discrimination (SD), tympanometry, stapedius reflex evaluation and otoacoustic emission tests, the control group did only have otological examination and PTA. Additionally, previously performed paranasal sinus-computed tomography of all cases with acromegaly and control subjects were obtained to measure the length of internal acoustic canal (IAC). RESULTS: PTA values were higher (p < 0.001 for right ears and p = 0.001 for left ears), and SD scores were (p = 0.002 for right ears and p = 0.002 for left ears) lower in acromegalic patients. IAC width in acromegaly group was narrower compared to that in control group (p = 0.03 for right ears and p = 0.02 for left ears). When only cases with acromegaly were taken into consideration, PTA values in left ears had positive correlation with growth hormone and insulin-like growth factor-1 levels (r = 0.4, p = 0.02 and r = 0.3, p = 0.03). Of all cases with acromegaly 13 (32%) had hearing loss in at least one ear, 7 (54%) had sensorineural type and 6 (46%) had conductive type hearing loss. CONCLUSION: Acromegaly may cause certain changes in the auditory system in cases with acromegaly. The changes in the auditory system may be multifactorial causing both conductive and sensorioneural defects.

High Prolidase Levels may be a Marker of Irreversible Extracellular Matrix Changes in Controlled Acromegaly Patients?

The present study aimed to evaluate the activity of prolidase in controlled acromegaly patients and its association with oxidative stress. 25 acromegalic patients in remission who were followed in our outpatient clinic and 31 healthy controls were enrolled in the study. Serum growth hormone (GH), insulin-like growth factor 1 (IGF-1), total antioxidative status (TAS), total oxidative stress (TOS), total free sulfhydryl (-SH), paraoxonase (PON), arylesterase (ARE), lipid hydroperoxide (LOOH) and prolidase activity levels were measured. Percent ratio of TOS to TAS level was accepted as oxidative stress index (OSI). Serum prolidase activity, TOS, OSI, and LOOH levels were significantly higher in acromegaly patients compared to the healthy control group (p<0.001, p=0.001, p<0.001, and p<0.001, respectively). SH levels were significantly lower in the acromegaly patients compared to the healthy control group (p=0.002). Prolidase activity were positively correlated with TOS, OSI, LOOH and negatively correlated with -SH in patients with acromegaly (r=0.471, p<0.001; r=0.527, p<0.001; r=0.717, p<0.001; r=- 0.516, p<0.001, respectively). These associations were confirmed in the multiple regression analysis (R(2)=0.502, p<0.001). In conclusion, serum prolidase activity and oxidative stress levels were high in controlled acromegaly patients. These results suggest that extracellular matrix changes continue eventhough the disease is controlled, and elevated oxidative stress is involved in the increased prolidase activity in acromegaly patients.

CYTOGENETIC AND MOLECULAR RESPONSES OF AMMONIUM SULPHATE APPLICATION FOR TOLERANCE TO EXTREME TEMPERATURES IN VICIA FABA L.

Effects of ammonium sulphate [(NH4)2SO4] on mitosis, cell cycle and chromosomes in Vicia faba L. seeds exposed to extreme temperatures were investigated using flowcytometric and cytogenetic analysis. Seeds germinated at high and low temperatures showed a signiicant decrease in mitotic index as compared to those of optimum temperature conditions. Application of 50 and 1000 µM (NH4)2SO4 were successful in alleviating the negative effects of low and high temperature on mitotic activity, respectively. 50 µM (NH4)2SO4 showed the most positive effect on cell cycle at the extreme temperatures. This concentration increased the cell division removing or decreasing the negative effects of temperature stress. Namely, the highest G2/M and S phase percentages under stress conditions were obtained with application of 50 µM (NH4)2SO4. Chromosomal aberrations were not observed in cells of seeds germinated in distilled water and also at any temperatures. However, the frequency of chromosomal aberrations increased significantly by increasing (NH4)2SO4 concentration. The highest aberration frequency in all temperature degree tested was found at 1000 µM (NH4)2SO4 concentration.

The association of ICAM E469K with cardiovascular characteristics of acromegaly.

OBJECTIVE: It has been shown that genetic factors have a role in the development of acromegaly. We aimed to investigate the association between intercellular adhesion molecule (ICAM)-1 E469K polymorphism and some cardiovascular clinical parameters of acromegalic patients. PATIENTS AND METHODS: We included 41 patients with acromegaly and 65 healthy subjects with similar age and sex to the study. Fasting plasma glucose (FPG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglyceride (TG) were analyzed. Genotyping was made by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The frequency of genotype and allel ICAM-1 E469K was not significantly different between control and patients (p > 0.05). Systolic blood pressure (SBP), diastolic blood pressure (DBP) and FPG levels were significantly higher, and HDL-C was significantly lower in patients with KK genotypes compared to patients with EE genotype in acromegaly group (p < 0.05). CONCLUSIONS: This is the first study to investigate the role of ICAM gene polymorphism in acromegaly and its cardiovascular characteristics. ICAM E469K may not be a risk factor for the acromegaly in Turkish population but may be associated with hypertension, higher FPG and lower HDL-C in acromegalic patients.

Association of Rho/Rho-kinase gene polymorphisms and expressions with obesity-related metabolic syndrome.

OBJECTIVE: The metabolic syndrome (MetS) is a common multicomponent condition including abdominal obesity, dyslipidemia, hypertension and hyperglycemia. The aim of this study was to investigate the associations of Rho GTPase and Rho-kinase (ROCK) gene polymorphisms and expressions with MetS in a Turkish population. PATIENTS AND METHODS: A total of 141 obese MetS patients and 163 healthy controls with similar age and sex were included to this study. Polymorphisms were analyzed in genomic DNA using a BioMark 96.96 dynamic array system. mRNA from blood samples was extracted, and real-time polymerase chain reaction was performed for gene expressions. RESULTS: We observed that genotype (CC, 18.1%; CA, 13.4%, and AA, 68.5%) and allele (C, 24.8%; A, 75.2%) frequencies for the rs35996865 polymorphism of the ROCK1 gene in patients were markedly different from controls (CC, 84.2%; CA, 2.9%, and AA, 12.9%; C, 85.6%; A, 14.4%, p < 0.0001). In the rs2230774 (Thr431Asn) polymorphism of the ROCK2 gene, there were increases in the CC genotype (16.5%) and C allele frequencies (20.4%) in MetS patients when compared with the control group (CC, 6.0%, p = 0.0009, and C, 6.7%, p < 0.0001). However, no associations with the other 18 polymorphisms studied were found. Although there were an increase in peripheral blood mRNA RhoH expressions, marked decreases in RhoC, RhoBTB1, RhoV, Rnd1, and CDC42 gene expressions were noted in MetS patients. CONCLUSIONS: This is the first study to provide evidence that ROCK gene polymorphisms and gene expressions of the Rho GTPase proteins may modify individual susceptibility to MetS in the Turkish population.

Role of the transient receptor potential (TRP) channel gene expressions and TRP melastatin (TRPM) channel gene polymorphisms in obesity-related metabolic syndrome.

OBJECTIVE: Metabolic syndrome (MetS) is correlated with increased cardiovascular risk and characterized by several factors, including visceral obesity, hypertension, dyslipidemia, and insulin resistance. The etiology of MetS is complex, and can be influenced by genetic susceptibility. The aim of this study was to investigate a possible association of transient receptor potential (TRP) channels gene expressions and TRP melastatin (TRPM) gene polymorphisms with MetS in a Turkish population. PATIENTS AND METHODS: A total of 142 patients with obesity-related MetS and 166 healthy controls with similar age and sex were enrolled to this study. For polymorphism studies, genomic DNA from the participants was analyzed by a BioMark 96.96 dynamic array system (Fluidigm, South San Francisco, CA, USA). For gene expression studies, mRNA from blood samples was extracted, and real time polymerase chain reaction on the BioMark HD system was performed. RESULTS: There was an increase in A allele (64.6% in patients vs. 49.5% in controls) and decrease in G allele frequencies (35.4% in patients vs. 50.5% in control, p = 0.0019) of the TRPM5 gene rs4929982 (Arg578Gln) polymorphism. We also observed that the distribution of genotype and allele frequencies of the TRPM8 gene rs12472151 in MetS patients were significantly different from controls (p < 0.0001). Although there were marked decreases in TRPC1, TRPC3, TRPM2, TRPM5, TRPV4, TRPV5, TRPV6, MCOLN2 (TRPML2), and MCOLN3 (TRPML3) gene expressions, an augmentation was noted in TRPC6 gene expression. CONCLUSIONS: Genetic polymorphisms in TRPM5 and TRPM8 genes may modify individual susceptibility to MetS in the Turkish population. This study also revealed that there is a significant relationship between TRP channels gene expressions and MetS.

Serum calprotectin: a new potential biomarker for thyroid papillary carcinoma.

The aim of this study was to evaluate serum calprotectin levels and oxidative stress status in patients with papillary thyroid carcinoma (PTC) and the changes in their levels after total thyroidectomy. The study involved 30 patients with PTC and 30 healthy controls. Blood samples were obtained from the PTC patients before and 1 month after the operation. Preoperative and postoperative serum samples from PTC patients and healthy controls were analysed for calprotectin, total antioxidant status (TAS), total oxidant status (TOS) and lipid hydroperokside (LOOH). The preoperative calprotectin, TOS, OSI and LOOH levels of the patients with PTC were significantly higher compared to those of the control group (p < 0.001, for each). The levels of calprotectin decreased significantly in patients with PTC after the operation (p < 0.001), while TAS, TOS and OSI levels remained unchanged (p = 0.313, p = 0.085 and p = 0.163, respectively). Preoperative serum calprotectin levels were positively correlated with TOS, OSI and LOOH levels and negatively correlated with TAS levels in patients with PTC. In conclusion, serum calprotectin levels is increased in patients with PTC, and calprotectin is positively correlated with TOS and LOOH. Serum calprotectin levels is significantly decreased after total thyroidectomy.

Serum prolidase levels in Graves' disease without ophthalmopathy and its association with oxidative status.

OBJECTIVE: The aim of this study was to evaluate serum prolidase levels and its association with oxidative stress in autoimmune thyroid disease (AITD). MATERIALS AND METHODS: 25 with Hashimoto thyroiditis (HT) and 25 patients Graves' disease (GD), and 27 healthy controls were enrolled in the study. The patients with signs of Graves' ophthalmopathy were excluded from the study. Serum samples were obtained in euthyroid period at the third month of treatment. Serum prolidase, total antioxidant status (TAS), total oxidative stress (TOS), and total free sulfhydryl (-SH) levels were measured. RESULTS: Serum prolidase levels were significantly higher in the patients with GD compared to the HT and the healthy control group. Oxidative stress index (OSI) and TOS levels of the patients with both GD and HT were significantly higher compared to those of the control group (p < 0.001, for each), while -SH levels were significantly lower (p < 0.001, for each). There was no significant difference between the patients with HT and healthy control group in terms of prolidase levels (p = 0.580). Prolidase levels were positively correlated with TOS and OSI and negatively correlated with -SH (r = 0.565, p = 0.003; r = 0.604, p = 0.001; r = -0.532, p = 0.006). CONCLUSION: Serum prolidase activity is increased in GD patients without signs of ophthalmopathy, and showed a positive correlation with oxidative stress parameters.