Wnt signaling pathway activities may be altered in primary Sjogren's syndrome

Background/aim: Sjögren's syndrome (SS) is an autoimmune disease and its pathogenesis is still not completely clear. The wingless (Wnt)/ß-catenin pathway has recently been shown to play an important role in inflammation. This study aims to determine the serum and saliva levels of Dickkopf (DKK)1 and sclerostin and to evaluate Wnt-1 and Wnt-3a expression in the salivary gland in patients with primary SS. Materials and methods: This study included 30 patients diagnosed with SS, 30 patients diagnosed with systemic lupus erythematosus (SLE), and 29 healthy controls. Serum and saliva levels of DKK1 and sclerostin were measured and the expressions of Wnt1 and Wnt3a in the salivary gland were measured immunohistochemically. Results: Serum DKK1 and sclerostin levels were lower in the SS and SLE groups compared to the control group (both p < 0.001). Saliva DKK1 levels were higher in the SS group compared to the control and SLE groups (p = 0.004 and p = 0.009, respectively). Wnt1 and Wnt3a expression were found in salivary gland tissue samples in 71.4% of primary SS patients and relatively frequent than control group. Conclusions: Serum DKK1 and sclerostin levels in primary SS and SLE were decreased. Moreover, levels of Wnt1 and Wnt3a expression in the salivary gland were also elevated in primary SS. Therefore, it can be concluded that the Wnt/ß-catenin pathway activities may be altered in case of glandular inflammation.

Investigation of plasma asprosin and saliva levels in newly diagnosed type 2 diabetes mellitus patients treated with metformin.

INTRODUCTION: Asprosin is a hormone that was first reported by Romere et al. [2016]. Its secretion is induced in the case of starvation. Asprosin promotes hepatic glucose release. There is no literature information available in humans to demonstrate how blood and saliva asprosin levels of patients with the newly identified type 2 diabetes mellitus (T2DM) changed after metformin treatment. We aim to examine these changes and contribute to the literature in this sense. MATERIAL AND METHODS: A total of 60 individuals: 30 healthy volunteers and 30 newly identified cases of T2DM whose treatment had been initiated, were included in the investigation. Blood and saliva sample specimens were carefully taken from both groups. Saliva asprosin and serum levels were tested using the ELISA method. Immunohistochemical methods were used to test asprosin formation sites in salivary gland tissues. RESULTS: Similarly increased asprosin levels were observed in patients from the newly diagnosed T2DM group compared with the healthy control group (p = 0.003). In the newly defined T2DM group, blood asprosin levels decreased significantly after three months of metformin treatment (p = 0.032). In terms of saliva asprosin levels, when the healthy control group and the newly identified T2DM group were compared, saliva asprosin levels were found to be higher in the newly identified T2DM group (p < 0.001). With immunohistochemical staining, asprosin immunoreactivity was observed in the submandibular and parotid glands. CONCLUSIONS: In our study, serum and saliva asprosin levels increased significantly in the newly identified individuals with type 2 diabetes, which suggests that asprosin could form a critical risk related to T2DM. Higher asprosin levels are an important marker for predicting diabetes development, and that this hormone can be signified as a main or target molecule in the treatment of diabetes.

Elabela levels in patients with type 2 diabetes: can it be a marker for diabetic nephropathy?

BACKGROUND: Elabela (ELA) is a hormone that is secreted at high levels in the kidneys of a healthy adult. This study aims to investigate whether serum ELA levels of patients with Type 2 Diabetes vary with the severity of renal damage. METHODS: Our study included 50 healthy control subjects and 100 diabetic patients, who were categorized into groups based on urine albumin/creatinine ratios (ACR). Patients included in the study were assigned to four groups: Group 1 (healthy control), Group 2 (ACR<29mg/g), Group 3 (ACR=30-299 mg/g), and Group 4 (ACR>300 mg/g normal or high serum creatinine). Physical examination findings, demographic characteristics of the study group were recorded, and serum ELA levels and other laboratory parameters were assessed using appropriate methods. RESULTS: The results of the study indicated that ELA levels determined in healthy individuals gradually decreased through stages of normal albuminuria, microalbuminuria, and macroalbuminuria. Moreover, ELA had a significant negative correlation with LDL-C (r=-0.201, p=0.014), glucose (r=-0.437, P<0.001), retinopathy (r=-0.222, P=0.006), serum BUN (r=-0.161, P=0.049), and a positive correlation with eGFR (r=0.250, P=0.002). CONCLUSIONS: The fact that ELA levels are higher in healthy individuals compared to diabetic patients without microalbuminuria, and higher in diabetic patients without microalbuminuria compared to patients with advanced albuminuria and kidney damage, suggests that the ELA level can be an important clinical prognostic variable and even a promising agent for the treatment of diabetic nephropathy patients.

A new inflammatory marker: elevated eosinophil-tolymphocyte ratio associated with presence and severity of isolated coronary artery ectasia.

OBJECTIVES: The pathophysiology of isolated coronary artery ectasia (CAE) involves atherosclerosis and inflammation. Eosinophils and lymphocytes have been found to play a significant role in inflammation, atherosclerosis and endothelial dysfunction. Many studies have explored the relationship between isolated CAE and systemic inflammation. However, there are no data regarding the relationship between eosinophil-to-lymphocyte ratio (ELR) and isolated CAE. Therefore, this study analysed the relationship between ELR and isolated CAE. METHODS: All patients who underwent coronary angiography between January 2009 and June 2018 were investigated retrospectively. Of 16 240 patients, 232 patients with isolated CAE (141 males) and 247 age- and gender-matched control subjects (130 males) with normal coronary angiography (NCA) were enrolled in this study. Baseline demographic and laboratory data were obtained from the hospital database. The severity of isolated CAE was determined according to the Markis classification, vessel count and diffuseness of ectasia. RESULTS: Patients with angiographic isolated CAE had significantly elevated white blood cell (WBC) and eosinophil counts and ELR values compared to patients with NCA [8.11 ± 1.75 vs 7.49 ± 1.80 × 109 cells/l, p < 0.0001; 0.22 (0.13-0.32) vs 0.19 (0.12-0.28) × 109 cells/l, p = 0.02; 0.11 (0.06-0.17) vs 0.08 (0.05-0.12), p < 0.0001. The ELR value for Markis I was significantly higher than for Markis IV (p = 0.04), and three-vessel isolated CAE was significantly higher than onevessel isolated CAE (p = 0.04). Additionally, the ELR value for diffuse ectasia (Markis class I, II and III) was significantly higher compared to focal (Markis class IV) ectasia (p = 0.02). In receiver operating characteristics (ROC) analyses, it was determined that an ELR value > 0.099, measured in isolated CAE patients at application, had a predictive specificity of 60.3% and a sensitivity of 56.5% (area under the curve: 0.604, 95% confidence interval: 0.553-0.655, p < 0.0001). CONCLUSIONS: Patients with isolated CAE had higher blood eosinophil counts and ELR. Furthermore, the ELR was significantly correlated with severity of isolated CAE. These findings demonstrate that ELR may have a significant role in the aetiopathogenesis of isolated CAE.

Spotlights on some electrocardiographic paradigms: How should we evaluate normal reference values of Tp-Te interval, Tp-Te dispersion and Tp-Te/QT ratio?

BACKGROUND: Experimental and clinical studies evaluating the Tp-Te interval and Tp-Te/QT ratio have reported conflicting data. The overlap between normal Tp-Te/QT ratios (0.17 ±0.02-0.27 ±0.06 ms) and pathological values (0.20 ±0.03-0.30 ±0.06 ms) measured in earlier studies has raised questions about this ECG measurement technique. OBJECTIVES: To analyze normal values of the Tp-Te interval, Tp-Te dispersion Tp-Te(d) and the Tp-Te/QT ratio based on electrocardiographic (ECG) assessment across sex and age groups in a healthy Turkish population. MATERIAL AND METHODS: A total of 1,485 healthy participants (723 men) were enrolled into the study. The age of the participants ranged 17-75 years and they did not have either any cardiovascular/systemic disorders or risk factors for atherosclerosis which were detected with physical examination and laboratory tests. The Tp-Te interval, Tp-Te(d) and Tp-Te/QT ratio were determined from V1-V6 derivations. RESULTS: For the entire study, the median Tp-Te interval was 66.0 (64.0-70.0) ms, the Tp-Te(d) was 15.0 (10.0-20.0) ms, and the Tp-Te/QT ratio was 0.18 (0.17-0.19). The Pearson's correlation test demonstrated that the Tp-Te/QT ratio significantly correlated with older age (r = 0.297; p < 0.0001), left ventricular (LV) end-diastolic diameter (LVEDD; r = 0.481; p < 0.0001), body mass index (BMI; r = 0.421; p < 0.0001), body surface area (BSA; r = 0.191; p < 0.0001), LV end-diastolic volume (LVEDV; r = 0.484; p < 0.0001), LVEDV index (r = 0.450; p < 0.0001), LV mass (r = 0.548; p < 0.0001), and LV mass index (r = 0.539; p < 0.0001). CONCLUSIONS: The reference values for Tp-Te interval, Tp-Te(d) and Tp-Te/QT ratio are associated with age, BMI, BSA, LVEDV, LVEDV index, LV mass, and LV mass index. These structural elements should be considered when using these ECG parameters for assessing repolarization inhomogeneity. These findings may guide further studies assessing healthy and diseased populations.

The effect of secukinumab treatment on hematological parameters in ankylosing spondylitis and psoriatic arthritis.

OBJECTIVE: Secukinumab, a new treatment agent, selectively neutralizes interleukin (IL)-17A. It is used in the treatment of ankylosing spondylitis (AS), psoriatic arthritis (PsA), and psoriasis. It is known that the agents used in the treatment of rheumatic diseases have effects on hematological parameters. In this study, we aimed to determine whether hematological parameters are affected in secukinumab therapy in patients with AS and PsA. METHODS: Thirty-six patients on secukinumab treatment were included in the study by scanning the database of our hospital. Data on patients' age, gender, complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), uric acid, aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine values, and additional drug treatments were recorded from our database. The 0- and 6-month values of patients were analyzed. RESULTS: Sixteen males (44.4%) and 20 females (55.6%) were included in our study. The average age was calculated to be 39.8±8.9 years. Of these, 30 patients receiving secukinumab treatment were diagnosed with AS, and 6 patients were diagnosed with PsA. Twenty-three patients (63.9%) were continued with secukinumab treatment at the 6th month. When CBC, glucose, urea, creatine, AST, ALT, ESR, CRP, and uric acid values of the patients at 0 and 6 months were compared, there was no significant difference. CONCLUSION: In our study, no significant difference was found between 0 and 6 months in terms of CBC, AST, ALT, urea, creatinine, uric acid, glucose, CRP, and ESR levels in patients receiving secukinumab. However, an increase in hemoglobin values was observed in patients who continued the treatment. These results may suggest that secukinumab treatment has no negative effects on hematological parameters.

Is there a relationship between epicardial fat tissue thickness and Tp-Te/QT ratio in healthy individuals?

INTRODUCTION: Epicardial fat is a tissue that releases many proinflammatory and atherogenic mediators, with endocrine and paracrine effects on the heart. In this study, the implication of the EFT thickness (EFTt) on transmural dispersion of repolarisation (TDR) was analysed utilizing the T-wave peak to end interval (Tp-Te), the Tp-Te dispersion (Tp-Te (d)), and the Tp-Te/QT ratio. MATERIAL AND METHODS: One thousand seven hundred and thirteen subjects were enrolled in the research. The subjects were chosen to be healthy individuals, without any cardiovascular/systemic disorders or risk factors for atherosclerosis. Transthoracic echocardiography (TTE) was applied to all subjects, and EFTt was measured in both diastole and systole. The ECG measurements were taken from standard 12-lead surface ECG. RESULTS: Correlation analysis revealed that the EFTt is highly associated with the Tp-Te interval, Tp-Te/QT ratio, Tp-Te (d), increasing age, body mass index (BMI), body surface area (BSA), left ventricular (LV) mass, LV mass index, plasma glucose during fasting, triglycerides, and low-density lipoprotein cholesterol. CONCLUSIONS: The study results showed that increased EFTt was associated with increased TDR values of Tp-Te, Tp-Te (d), and Tp-Te/QT ratio, even in the absence of other factors that could increase TDR and EFTt. Therefore, it can be stated that increased EFTt may cause an increase the risk for ventricular arrhythmia.

Low serum levels of meteorin-like/subfatin: an indicator of diabetes mellitus and insulin resistance?

INTRODUCTION: Meteorin-like (Metrnl), also known as subfatin, is a recently discovered adipokine with a favourable effect on insulin sensitivity. Studies have shown lower Metrnl levels in obese patients. However, data on its circulating levels in type 2 diabetes mellitus (T2DM) patients are contradictory. This study aims to evaluate serum Metrnl levels in T2DM patients and determine the relationship between serum Metrnl levels and insulin resistance in these patients. MATERIAL AND METHODS: This cross-sectional study was conducted among 150 participants. The study was carried out between June 2019 and December 2019 at the internal medicine outpatient clinic of a tertiary university hospital. The participants were divided into three groups: group 1 (control group, n = 50), group 2 (newly diagnosed T2DM, n = 50), and group 3 (long-standing diagnosed T2DM, n = 50). An enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels of Subfatin (Metrnl), and the correlations of Metrnl level with anthropometric parameters, HOMA index, and biochemical measurements were assessed. RESULTS: There was no statistically significant difference between the gender (p = 0.468) and age (p = 0.067) characteristics of the three groups. The Metrnl (subfatin) levels of the participants were as follows: control group - 20.05 (1.56-103.78); newly diagnosed T2DM group - 2.62 (1.25-103.78); and long-standing diagnosed T2DM group - 2.01 (0.80-19.84) pg/mL. The Metrnl (subfatin) levels of the participants in the control group were higher than in the participants in the newly diagnosed T2DM and long-standing diagnosed T2DM groups (p < 0.001). Subfatin demonstrated a negative correlation with insulin and HOMA-IR in the control group and long-standing diagnosed T2DM group. CONCLUSIONS: The subfatin level was found to be higher in the healthy control group than in both diabetic patient groups. Subfatin level showed negative correlation with both insulin level and HOMA index. There was a relationship between subfatin and insulin resistance. Low levels of subfatin in the diabetic patient groups may play a role in the pathogenesis of T2DM by increasing insulin resistance.

Associations of platelet indices with proteinuria and chronic kidney disease.

OBJECTIVES: Platelet (PLT) indices are predictive in many diseases and conditions. The relationships of these indices with proteinuria and progression of renal disease are not well known. This study aimed to assess PLT indices in patients with primary glomerular nephrotic range proteinuria (PGNRP), with and without chronic kidney disease (CKD), and to compare these indices with those of healthy individuals (His). METHODS: This cross-sectional study was performed from January 2015 to May 2015. HIs (n = 57) and patients with PGNRP (n = 41) were enrolled. PLT indices and blood biochemistry parameters were compared between HIs and patients with PGNRP, as well as between subgroups of patients with PGNRP who had CKD (n = 23) and those who did not have CKD (n = 18). RESULTS: There were no statistically significant differences in any PLT indices (i.e., platelet number, mean platelet volume, plateletcrit, and platelet distribution width) between HIs and patients with PGNRP, or between the subgroups of patients with PGNRP. However, patients with PGNRP who had CKD exhibited higher median C-reactive protein and mean albumin levels, compared with patients who did not have CKD. CONCLUSIONS: Pathological processes in proteinuria and CKD are not associated with PLT indices.

An investigation of saliva and plasma levels of urotensin 2 in recently diagnosed type 2 diabetes mellitus patients on metformin treatment.

INTRODUCTION: Diabetes mellitus (DM) is a primary disease of the carbohydrate metabolism that is characterised by absolute or relative insulin deficiency, or insulin resistance. Although life expectancy is low for diabetic patients, the prognosis has been improved in recent decades. Metformin is an oral antidiabetic that reduces insulin resistance and plasma glucose levels by decreasing glucose production in the liver. It can be used as a standalone treatment or in combination with other antidiabetic medications or insulin. Urotensin 2 (U-II), which is one of the most effective known vasoconstrictor peptides, was observed to act as a vasoconstrictor in diseases such as hypertension and heart failure, and to induce vasodilation in healthy volunteers. Some studies have proposed that the activation of the U-II system could lead to metabolic syndrome. Certain studies have determined a link between DM and U-II. However, there exist no studies on the effects of U-II in recently diagnosed type 2 DM patients after metformin treatment. This study aims to investigate the plasma and saliva levels of U-II at diagnosis and after a three-month metformin treatment in recently diagnosed type 2 DM patients, and to compare these levels to those of healthy volunteers. MATERIAL AND METHODS: Our study compared 30 recently diagnosed type 2 DM patients to their states after three-month metformin treatment and 30 healthy volunteers. RESULTS: When compared with the control group, there was no significant increase in the plasma and saliva U-II levels of recently diagnosed type 2 DM patients. We determined a statistically significant increase in the plasma and saliva ureotensin-2 levels of recently diagnosed type 2 DM patients after a three-month metformin treatment (p < 0.05). CONCLUSIONS: It was concluded that the patients with type 2 DM have a multifactorial aetiopathogenesis and an increase in U-II levels after metformin treatment. Metformin has no known effect on the U-II metabolism; therefore, the findings need confirmation through more clinical and experimental studies with more participants.

Effects of vitamin D on apoptosis and betatrophin in the kidney tissue of experimental diabetic rats.

The aim of this study is to investigate the effects of vitD on betatrophin and apoptosis in rat kidney tissue using an experimental diabetes model created with STZ. 41 male Wistar-albino breed rat were assigned to 5 groups, which included 3 groups consisting of 7 animals each and 2 groups consisting of 10 animals each. The control group received no treatments. Single-dose 0.1 M sodium buffer was administered ip to the Buffer group. The VitD group was orally administered 200 IU/day vitD.The Diabetes group was injected ip with single-dose 50 mg/kg STZ by dissolving the material in 0.1 M sodium buffer. Subjects with a glucose level exceeding 250 mg/dl were accepted to be diabetic. The Diabetes + VitD group was injected ip with 50 mg/kg single-dose STZ by dissolving the material in 0.1 M sodium buffer. Once diabetes was established, 200 IU/day vitamin D was administered orally. The histological and biochemical analyses of the Control, Buffer, and Vitamin D groups revealed similar serum TOS and TAS levels, and TUNEL positivity and betatrophin immunoreactivity. While the Diabetes group showed significantly higher TOS levels and TUNEL positivity compared to the Control group, their TAS levels and betatrophin immunoreactivity were significantly reduced. The Diabetes+Vitamin group demonstrated significantly lower TOS levels and TUNEL positivity compared to the Diabetic group, and their TAS levels and betatrophin immunoreactivity increased significantly.In conclusion; experimental diabetes was found to increase TOS and apoptotic cells and decrease TAS and betatrophin levels in kidney tissue in experimental diabetes, and that administering VitD as treatment caused a decrease in TOS and apoptotic cells and an increase in TAS and betatrophin levels. It was concluded that future studies needed to investigate various experimental diabetes times so that the role of diabetes in the pathophysiology of its effect on kidney tissue could be uncovered.

Increased Serum Sclerostin Levels in Patients With Active Acromegaly.

CONTEXT: Bone mineral density is normal in acromegalic patients and the cause of increased fracture risk that characterizes active acromegaly is unknown. OBJECTIVE: This study compared serum sclerostin levels between patients with active acromegaly and healthy individuals. DESIGN, SETTING, AND PARTICIPANTS: The serum sclerostin levels of patients with active acromegaly were compared with those of healthy volunteers in a cross-sectional study. The mean age of the 30 acromegaly patients (male/female: 14/16) was 47.26 ±â€…12.52 years (range, 18-64 years) and that of the healthy volunteers (male/female: 17/13) was 44.56 ±â€…10.74 years (range, 19-62 years). IGF-1 and GH levels were measured using an electrochemiluminescence method, and serum sclerostin levels using an ELISA. The Mann-Whitney U test was used to compare sclerostin levels between the 2 groups. The correlations of sclerostin level with IGF-1 and GH were determined using Spearman's test. RESULTS: The 2 groups did not differ in age or sex (P > 0.05). The median GH and IGF-1 levels in the patient group were 2.49 ng/mL (range, 0.22-70.00 ng/mL) (interquartile range [IQR], 1.3-4.52) and 338.5 ng/mL (range, 147-911 ng/mL) (IQR, 250-426), respectively. The median GH and IGF-1 levels in the control group were 0.95 ng/mL (range, 0.3-2.3) and 144 ng/mL (range, 98-198), respectively. The median sclerostin level was 29.95 ng/mL (range, 7.5-78.1 ng/mL) (IQR, 14.37-37.47) in the acromegaly group and 22.44 ng/mL (range, 8.45-36.44 ng/mL) (IQR, 13.71-27.52) in the control group (P < 0.05). There was a moderate positive correlation between the sclerostin and IGF-1 levels (rho = 0.54; P < 0.01), and between the sclerostin and GH levels (rho = 0.41; P < 0.05). CONCLUSIONS: High sclerostin levels may contribute to the increased fracture risk seen in patients with acromegaly.

Can hematological parameters in type 2 diabetes predict microvascular complication development?

OBJECTIVE: To examine potential associations between neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, mean platelet volume (MPV), HbA1c and microvascular complications in diabetic patients from a cost-effectiveness perspective. METHODS: One hundred patients with type 2 diabetes attending our outpatient unit between May 2018 and October 2018 were included, and 100 healthy individuals served as the control group. A retrospective file search was performed to collect information on hemoglobin, mean platelet volume (MPV), glycosylated haemoglobin (HbA1c), hematocrit (Hct), neutrophil and lymphocyte count, neutrophil/lymphocyte ratio (NLR), platelets (Plt), platelet/lymphocyte ratio (PLR), and microvascular complications (neuropathy, retinopathy, nephropathy). RESULTS: Demographic and laboratory data were retrospectively controlled between diabetes (n=100) and healthy control (n=100) groups. The mean age in diabetic patients and healthy controls was 56.34 and 36.68 years, respectively. The mean NLR in diabetics and healthy controls was 2.48 and 2.11, the difference in NLR being significant (p=0.002). MPV in diabetics and controls was 8.54 and 8.53, respectively, and the difference was not significant (p=0.93). PLR was also similar, i.e. 149.7 and 145.3 in diabetics and healthy controls (p=0.067). With respect to microvascular complications, retinopathy was found to be significantly associated with MPV and NLR (p=0.015, and p=0.051), and nephropathy showed a significant association with NLR (p=0.027) among diabetics. In contrast with the two other microvascular complications, no significant association between neuropathy and NLR could be detected, while PLR and neuropathy was significantly associated (p=0.003). CONCLUSION: Microvascular complications may be associated with certain hematologic parameters, as suggested by comparisons both between diabetics and healthy individuals and within the group of diabetic individuals. We believe that hematologic parameters such as hematocrit, MPV, NLR, and PLR, which can be obtained through a simple complete blood count, may be utilized as cost-effective predictors of diabetic microvascular complications. Further prospective studies with larger sample size are required to better delineate these associations.

Are There Differences in the Management of Acute Pancreatitis Cases Due to Severe Hypertriglyceridemia in Pregnant Women?

BACKGROUND The aim of this study was to determine the prognosis of severe disease and treatment approaches of both normal and pregnant, especially in patients with severe pancreatitis due to hypertriglyceridemia. MATERIAL AND METHODS We included 30 patients (20 females and 10 males) in this study whose follow-ups and treatments were performed after a diagnosis of hypertriglyceridemia-induced acute pancreatitis between January 2011 and May 2017. Patient personal information, such as age, sex, pre-treatment and post-treatment triglyceride levels, receipt of anti-hyperlipidemic treatments or plasmapheresis, and family history, were collected from hospital records and patient files. Patients with severe pancreatitis history, score, and prognosis were included to increase the value of our study. Mild and moderate cases were excluded. RESULTS The mean age of the patients was 35±6 years. Twenty-four patients (80%) received an anti-hyperlipidemic treatment before their pancreatitis attacks. Plasmapheresis was performed on 8 patients before their pancreatitis attacks. Eighteen patients (60%) had a family history suggesting familial hypertriglyceridemia. Twelve patients (40%) were pregnant. CONCLUSIONS The treatment of hypertriglyceridemia-induced acute pancreatitis was mostly confined to supportive, palliative treatments. However, plasmapheresis is a possible treatment option and should be used in the early stages of this disease. The response to medical treatment and support treatment was better in pregnant patients than in the other patient group, and pregnant patients did not require plasmapheresis.

Octreotide ameliorates dermal fibrosis in bleomycin-induced scleroderma

Background/aim: Insulin-like growth factor (IGF)-I is a differentiation and growth factor. Antifibrotic action of octreotide has been reported in pulmonary fibrosis. The present study aimed to research the prophylactic and therapeutic potential of octreotide on a bleomycin (BLM)-induced experimental scleroderma model. Materials and methods: Sixty Balb/c female mice were divided into 6 groups. Daily subcutaneous BLM (100 µg) was injected for 3 weeks in groups II and III and for 6 weeks in groups V and VI. Octreotide (100 µg/kg per day) was injected subcutaneously for the first 3 weeks in group III (prophylactic) and the second 3 weeks in group VI (therapeutic). Mice in groups I, II, and III were sacrificed at the end of the third week, while mice in groups IV, V, and VI were sacrificed at the end of the sixth week. Results: Repeated BLM applications increased dermal inflammatory cell counts and dermal thickness, and led to dermal fibrosis at both the third and sixth weeks. Moreover, mRNA expressions of TGF-ß1 and IGF binding protein (IGFBP)-3 and -5 were higher in the BLM- injected sham groups. On the other hand, IGFBP-3 and -5 mRNA expressions were significantly decreased in both the prophylactic and therapeutic octreotide groups. Similarly, octreotide decreased dermal inflammatory infiltrations and dermal thickness. Conclusion: Octreotide has antifibrotic actions on experimentally induced dermal fibrosis. It can be suggested that IGF-I plays pathogenic roles, and octreotide is a candidate for research in the treatment of scleroderma.

The effects of Mucuna pruriens on the renal oxidative stress and transcription factors in high-fructose-fed rats.

In the present study, we evaluated the effects of M. pruriens administration on metabolic parameters, oxidative stress and kidney nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathways in high-fructose fed rats. Male rats (n = 28) were divided into 4 groups as control, M. pruriens, fructose, and M. pruriens plus fructose. All rats were fed a standard diet supplemented or no supplemented with M. pruriens (200 mg/kg/d by gavage). Fructose was given in drinking water for 8 weeks. High fructose consumption led to an increase in the serum level of glucose, triglyceride, urea and renal malondialdehyde (MDA) levels. Although M. pruriens treatment reduced triglyceride and MDA levels, it did not affect other parameters. M. pruriens supplementation significantly decreased the expression of NF-Ò¡B and decreased expression of Nrf2 and HO-1 proteins in the kidney. This study showed that the adverse effects of high fructose were alleviated by M. pruriens supplementation via modulation of the expression of kidney nuclear transcription factors in rats fed high fructose diet.

Association of clinical and laboratory parameters with ambulatory arterial stiffness index in acromegaly patients.

OBJECTIVE: In this study, we determined the relationship between the ambulatory arterial stiffness index (AASI) and clinical and laboratory parameters in patients with acromegaly. METHODS: Sixty-five patients with acromegaly, who visited to Dicle University Medical Faculty Department of Endocrinology (33 females and 32 males), were included in this study. The study control group consisted of 65 subjects. Demographic and clinical data were recorded. Laboratory data (complete blood count, blood urea nitrogen, creatinine, electrolytes, albumin, lipid profile, growth hormone [GH], insulin-like growth factor-1, and the 75-g oral glucose tolerance test) performed over the last year were evaluated. The AASI was obtained from 24-hour ambulatory blood pressure monitoring records of all patients. This study was completed in 15 months from 2013 to 2015. RESULTS: Twelve patients (18.4%) had diabetes and 21 patients (32%) had hypertension. The mean AASI value was 0.41 ± 0.14. The mean AASI value in the control group was 0.25 ± 0.09. Growth hormone (GH) levels were positively correlated with the AASI values. AASI values tended to be higher in hypertensive subjects than that in normotensive individuals. CONCLUSIONS: Our results show that the AASI value increased in patients with acromegaly, independent of the increase in blood pressure. The AASI was strongly dependent on the degree of the GH increase in patients with acromegaly and may have an important role predicting cardiovascular risk in patients with acromegaly.

Paricalcitol Inhibits Wnt/ß-Catenin Signaling Pathway and Ameliorates Dermal Fibrosis in Bleomycin Induced Scleroderma Model.

OBJECTIVES: This study aims to determine the prophylactic and therapeutic efficacy of inhibition of Wnt/ß-catenin signaling pathway with paricalcitol in an experimental scleroderma model created with bleomycin (BLM). MATERIALS AND METHODS: Sixty female BALB/c mice (8-week old and weighing 25 g to 30 g) were divided into six groups as prophylactic-early [group 1 (control I)], sham I (group 2), paricalcitol I (group 3), therapeutic-late [group 4 (control II)], sham II (group 5), and paricalcitol II (group 6) groups. Subcutaneous BLM (100 µg/day) injections were used to induce dermal fibrosis and paricalcitol (0.3 µg/kg/day) was applied subcutaneously to BLM-injected mice during the first three weeks for preventive interventions and in the second three weeks for therapeutic interventions. Tissue samples were harvested for subsequent pathological and real-time polymerase chain reaction analysis. Tissue transforming growth factor-beta 1, axin-1, and Wnt-2 messenger ribonucleic acid expressions were determined by real-time polymerase chain reaction. RESULTS: Repeated BLM applications increased the dermal inflammatory cell infiltration and dermal thickness, and led to dermal fibrosis, in both early and late stages. Similarly, transforming growth factor-beta 1, axin-1, and Wnt-2 expressions were significantly increased in the sham groups compared to the own control group (p<0.05 for all). Contrarily, prophylactic and therapeutic paricalcitol applications decreased the transforming growth factor-beta 1, axin-1, and Wnt-2 messenger ribonucleic acid expressions compared to the own sham group (p<0.05 for all). In addition, the regressions in dermal necro-inflammation and dermal fibrosis on pathological views were also observed in the paricalcitol applied groups. CONCLUSION: In this model, increased axin-1 and Wnt-2 messenger ribonucleic acid expressions suggest that Wnt/ß-catenin pathway is active in dermal fibrosis.

Sorafenib Reveals Anti-Arthritic Potentials in Collagen Induced Experimental Arthritis Model.

OBJECTIVES: This study aims to examine the effects of sorafenib on a collagen-induced arthritis model. MATERIALS AND METHODS: The study included 50 randomly selected female Wistar-albino rats (8-10-week-old, weighing between 200 g to 250 g). The rats were divided into five equal groups as control, arthritis, etanercept, sorafenib high-dose, and sorafenib low-dose groups, respectively. Arthritis was induced by injecting mixed intradermal chicken type II collagen and incomplete Freund's adjuvant. Twenty-four hours after the advent of arthritis; rats in group 3 were injected subcutaneous etanercept (6 mg/kg/week), while those in groups 4 and 5 were given sorafenib (10 or 30 mg/ kg/day) orally until they were sacrificed on the 34th day. The rat claws and trunk bloods were carefully examined to note perisynovial inflammation and cartilage/bone injury through histopathology. Tissue vascular endothelial growth factor (VEGF) and VEGF receptor levels were carefully checked using western blot analysis. RESULTS: Analysis of the experimental data showed that collagen-induced arthritis decreased in treatments groups after 12-13 days and 34th day in contrast with the arthritis group. Histopathological examination revealed broad perisynovial inflammation and cartilage/bone break down in the arthritis group. Compared to the control group, tissue VEGF and VEGF receptor levels increased in the arthritis group. Sorafenib and etanercept decreased tissue VEGF and VEGF receptor levels, perisynovial inflammation, damage of cartilage/bone. CONCLUSION: Our findings indicate that sorafenib treatment ameliorates collagen-induced arthritis with anti-VEGF effectiveness.

Neutrophil gelatinase-associated lipocalin reflects the severity of anemia without iron deficiency and secondary hyperparathyroidism in hemodialysis patients.

OBJECTIVE: Secondary hyperparathyroidism (SHPT) and anemia are the primary and most common complications in patients receiving hemodialysis (HD). Neutrophil gelatinase-associated lipocalin (NGAL) is a new marker to assess iron deficiency and manage iron therapy for HD patients. The aim of this study was to determine any association between serum NGAL level and anemia without iron deficiency in patients with SHPT on chronic HD. METHODS: Total of 61 SHPT patients on chronic HD were enrolled in the study and divided into 3 groups: mild SHPT group (n=17), moderate SHPT group (n=21), and severe SHPT group (n=23). Hemogram, biochemical assays, and level of ferritin, high sensitivity C-reactive protein (hs-CRP), and NGAL were evaluated in all groups. RESULTS: Serum NGAL level was significantly higher and hemoglobin (Hb) level was significantly lower in severe SHPT patients compared with both mild and moderate SHPT patients. Furthermore, in severe SHPT group, serum NGAL level was significantly positively correlated with serum parathyroid hormone (r=0.79; p=0.00) and hs-CRP (r=0.52; p=0.01) level and negatively correlated with serum Hb (r=-0.56; p=0.00) level. CONCLUSION: SHPT was important factor affecting anemia in HD patients. Even when iron deficiency anemia is excluded in patients with SHPT, there was significant negative correlation between serum NGAL and Hb.