The Effect of Conjunctiva-Müller Muscle Resection on Tear Oxidative Stress Levels in Patients with Blepharoptosis.

Objectives: To examine changes in tear oxidative stress levels and tear film functions in patients with blepharoptosis and dermatochalasis following conjunctiva-Müller muscle resection (CMMR) and blepharoplasty surgeries. Materials and Methods: This prospective study included 32 healthy controls and 62 patients with blepharoptosis or dermatochalasis. CMMR surgery was performed in 20 eyes and upper blepharoplasty was performed in 42 eyes. Tear oxidative stress markers (8-hydroxy-2'-deoxyguanosine [8-OHdG] and 4-hydroxy-2-nonenal [4-HNE]) were quantified by enzyme-linked immunosorbent assay and tear film functions were evaluated preoperatively and at 1 and 6 months postoperatively. The same assessments were performed in the control group at the same time points. Results: Preoperative tear 8-OHdG and 4-HNE levels were lower in healthy controls (52.8±13.5 ng/mL and 27.8±6.4 ng/mL, respectively) compared to patients with dermatochalasis (86.1±37.2 ng/mL and 29.8±11.1 ng/mL, respectively) and blepharoptosis (90.4±39.3 ng/mL and 43.1±4.2 ng/mL, respectively) (p<0.001). 8-OHdG levels were increased at 1 month after CMMR, while both markers were decreased 1 month postoperatively in the blepharoplasty group (p=0.034). Schirmer 1 and OSDI scores did not change throughout the visits in both patient groups, but a temporary decrease in tear break-up time (TBUT) was observed after CMMR (p=0.017). Conclusion: Dermatochalasis and blepharoptosis were associated with higher tear oxidative stress levels. CMMR surgery caused a temporary decrease in TBUT scores and an increase in oxidative stress in the first postoperative month.

5 -Alpha-dihydroxyprogesterone may contribute to perceptual processing and attention of the cases with relapsing remitting multiple sclerosis.

Neurosteroids (NSs) are endogenous steroid hormones, which are synthesised and metabolised within the central nervous system (CNS). NSs aid myelination and glial differentiation and modulate cognitive functions. Herein, we aim to investigate the relationship between NS levels, 5-alpha-dihydroxyprogesterone (5-α-DHP) and allopregnanolone (ALPG), and their relationship with cognitive changes in relapsing remitting MS patients.A total of 43 cases with well controlled, relapsing remitting MS composed the study group. The control group included 21 age and gender matched healthy controls (HC). MS patients were assessed by calculating Expanded Disability Status Scale (EDSS) scores, and the Brief Repeatable Battery of Neuropsychological Tests (BRBNT) was performed in both MS group and HC. Levels of 5-α-DHP and ALPG levels were also evaluated for each participant.The median level of 5-α-DHP was 48 [IQR: 39.2-144.2] pg/mcgL in the MS group and 68.4 [IQR: 57.1-365.9] pg/mcgL in HC (p = 0.02). The median ALPG level was found to be 56.5 [IQR: 37.7-75.4] pg/mcgL in the MS group and 43.9 [IQR: 29.4-70.2] pg/mcgL in HC (p = 0.1). In both groups 5-α-DHP levels were positively correlated with Symbol Digit Modalities Test (SDMT) scores (HC: p = 0.01, r = 0.3 and MS: p = 0.03, r = 0.3). In the MS group, higher EDSS scores were associated with lower scores on Spatial Recall Test (SPART)-Delayed (p = 0.009, r= -0.4) and SDMT (p = 0.01, r= -0.4). The disease duration was negatively correlated with the scores on SPART-Immediate, SPART-Delayed and SDMT (p = 0.02, r= -0.4; p = 0.005, r= -0.4 and p = 0.05, r= -0.3).5-α-DHP may be lower even in well-controlled cases. 5-α-DHP may contribute to better perceptual processing and attention in cases with MS.

Ghrelin hormone might have a potential role in amelogenesis.

AIMS: Amelogenesis imperfecta and generalised enamel hypoplasia are developmental dental anomalies that affect dental enamel. While amelogenesis imperfecta results from various gene mutations, the exact underlying mechanisms of the etiopathogenesis of both remain unclear. This study aims to evaluate Ghrelin hormone levels in children with generalised enamel hypoplasia to establish whether Ghrelin might have a potential role in enamel hypoplasia's etiology. The second purpose is to determine the correlations among the blood levels of Ghrelin, growth hormone (GH), insulin-like growth factor-1 (IGF-1), bone alkaline phosphatase (BALP) and osteocalcin (OC) that are vital in dental development. MATERIAL AND METHODS: Study was designed with two study groups, AI (hypoplastic amelogenesis imperfecta) (n = 15; mean-age 10.36 ± 1.90) and GEH (idiopathic generalised enamel hypoplasia) (n = 15; mean-age 10.42 ± 1.84), and a healthy control (n = 15; mean-age 10.39 ± 1.91) group. After fasting for 10-12 hours, simultaneous blood samples were collected; then, after centrifugation, serum and plasma were stored at -80°C until the day of analysis. Total Ghrelin levels of plasma and serum levels of GH, IGF-1, BALP and OC were measured using commercial ELISA kits. RESULTS: Ghrelin levels of AI and GEH groups were significantly lower (P < .01) than the control group. CONCLUSION: This is the first study to reveal the decreased levels of Ghrelin in plasma of children with generalised enamel hypoplasia, suggesting a potential role for Ghrelin in amelogenesis. In order to determine its function in enamel formation, further studies should be carried out. The result of the present study suggests that paediatricians refer children with abnormal Ghrelin levels to a paediatric dentist to contribute to appropriate prophylactic and therapeutic interventions. Generalised enamel hypoplasia may also indicate possible abnormalities in Ghrelin levels for paediatricians. Therefore, paediatricians' knowledge about the clinical appearance of generalised enamel hypoplasia should be increased.

Comparison of Ischemic Preconditioning and Systemic Piracetam for Prevention of Ischemia-Reperfusion Injury in Musculocutaneous Flaps.

BACKGROUND: Ischemia-reperfusion injury plays an important role in flap failure. Ischemic preconditioning technique is the only proven method for preventing ischemia-reperfusion injury, but it is not used widely in daily practice because of difficulties such as prolonging the operation time, need for surgical experience, and increasing the risk of complications. This study has been performed with the assumption that piracetam may be a simple and inexpensive alternative to the preconditioning technique due to its antioxidant, antiaggregant, rheological, anti-inflammatory, antiapoptotic, cytoprotective, and immune modulating effects. METHODS: Thirty-two rats were divided into four groups and latissimus dorsi musculocutaneous flaps were raised. No extra procedure was applied, and no treatment was given to the control group. Four hours of ischemia was created by clamping the thoracodorsal pedicle in the second group. The animals in the third group were treated with 10 minutes of ischemia and reperfusion periods as a preconditioning procedure before the 4 hours of ischemia. Animals in the fourth group received systemic piracetam 30 minutes before and 6 days after reperfusion. Nitric oxide and myeloperoxidase levels in serum and tissue, acute inflammatory cell response, and vascular proliferation in tissue were examined at the postoperative 24th hour and 10th day. RESULTS: Myeloperoxidase activity in both preconditioning and piracetam groups, was significantly lower than the ischemia-reperfusion group. Acute inflammatory cell response was similarly decreased in both preconditioning and piracetam groups compared with ischemia-reperfusion group. Tissue measurements of nitric oxide were also significantly higher in both preconditioning and piracetam groups than in the ischemia-reperfusion group. However, vascular proliferation increased in the preconditioning group, while it did not show any significant change in the piracetam group. CONCLUSION: This study shows that systemic piracetam treatment provides protection against ischemia-reperfusion injury in musculocutaneous flaps and can offer a simple and inexpensive alternative to the preconditioning technique.

Correlation between serum granulysin level and clinical activity in patients with alopecia areata before and after tofacitinib therapy.

BACKGROUND: Alopecia areata (AA) is a common immune-mediated disorder. Destruction of anagen hair follicles by cytotoxic T cells (CTL) plays a major role in the pathogenesis of AA. Serum granulysin has been shown to reflect overall activity of CTLs. AIMS: In this study, we aimed to compare serum granulysin levels in patients with AA before and after therapy and to analyze correlation between serum granulysin levels and disease severity. METHODS: We evaluated the Severity of Alopecia Tool (SALT) score and serum granuysin levels of 38 AA patients at baseline and at 6th month of therapy. Thirty-three patients were treated with tofacitinib 5 mg b.i.d, and five patients were treated with topical immunotherapy. Serum granulysin levels were measured by enzyme-linked immunosorbent assay. RESULTS: A moderate correlation was found between SALT scores and serum granulysin level at baseline (r = .378, P = .019). Baseline serum granulysin levels were significantly higher in patients with alopecia totalis/universalis compared with patients with patchy AA (P = .004, Z = 2.778). Serum granulysin levels significantly decreased in patients treated with tofacitinib compared to baseline (P = .001). The reduction in serum granulysin levels after tofacitinib therapy correlated with the reduction in SALT scores (P = .001). CONCLUSIONS: Our results suggest serum granulysin levels to be a good correlate of immunological activity of AA. We also assume granulysin to be a potential mediator of follicle attack, the effects of which is blocked by tofacitinib therapy. Therefore, changes in serum granulysin levels under therapy can reflect the downregulation of immunological activity of AA.

Anemia after kidney transplantation: Does its basis differ from anemia in chronic kidney disease?

BACKGROUND: Although similar factors play a role in both PTA and anemia in patients with CKD, additional risk factors exist in the pathogenesis of PTA. The present study aimed at comparing anemia and inflammation-related parameters between RTx recipients and CKD patients and elucidating the risk factors of PTA. METHODS: This single-centered, cross-sectional study consisted of 68 participants: 48 were in the RTx group and 20 were in the CKD group. The CKD patients were comparable to the RTx recipients in terms of age, gender, and eGFR. Serum levels of EPO, hepcidin, and IL-6 were measured by enzyme-linked immunosorbent assays. The ratio of EPO/Hb was calculated to estimate endogenous EPO resistance. RESULTS: The prevalence of anemia was 46% in the RTx group and 30% in the CKD group (P = .23). RTx recipients had significantly lower Hb (P = .04), higher EPO (P < .001), and ferritin levels (P = .001), and higher EPO/Hb ratios (P < .001); however, CKD patients showed a higher frequency of absolute iron deficiency (P = .008). Neither hepcidin nor IL-6 levels differed between the two groups. Hb level of RTx recipients was correlated with only eGFR (r = .437, P = .002) but not with any of the transplantation-related factors, while Fe level was the only parameter to be correlated with Hb level of CKD patients (r = .622, P = .01). CONCLUSION: In the present study comparing GFR-matched RTx and CKD patients, lower GFR level appears to be the factor most strongly associated with anemia, and endogenous EPO resistance is among the contributing factors to PTA.

Comparison of ischemic preconditioning and BotulinumA Toxin injection for the prevention of ischemia-reperfusion injury in musculocutaneous flaps

Background/aim: The aim of the study was to evaluate the protective effect of Botulinum A toxin injection against ischemia-reperfusion injury. Materials and methods: Thirty-two Sprague-Dawley rats were divided into: control, ischemia-reperfusion, ischemic preconditioning, and botulinum groups. In all groups the musculocutaneous pedicle flap was occluded for 4 h, and then reperfused to induce ischemia-reperfusion injury. Serum and tissue myeloperoxidase (MPO) and nitric oxide (NO) levels were measured at 24 h and at 10 days. Results: Tissue MPO levels did not differ significantly between the ischemic preconditioning and botulinum groups at 24 h but was significantly lower in the botulinum group at 10 days. Tissue NO levels were significantly higher in the ischemic preconditioning group compared to the botulinum group at 24 h and at 10 days. Serum MPO showed no significant difference between these two groups at 24 h but was significantly lower in the ischemic preconditioning group compared to the botulinum group at 10 days. Serum NO levels were not significantly different at 24 h but significantly higher in the botulinum group at 10 days. Conclusion: Findings show that botulinum has a protective effect against the ischemia-reperfusion injury via increased NO and decreased MPO levels in tissue. Based on tissue NO levels, ischemic preconditioning was significantly higher than botulinum.

Is there any relationship between adipocytokines and angiogenesis factors to address endothelial dysfunction and platelet aggregation in untreated patients with preeclampsia?

PURPOSE: Preeclampsia is a multisystem disorder and its etiology remains still unclear. Recent hypotheses rely on imbalance between angiogenic and antiangiogenic factors and disruption of endothelial function of spiral arteries. In addition; increased VTE (venous thromboembolism) risk is still unclear in preeclampsia. Our aim was to investigate the relationship between endothelial dysfunction, adipocytokines, platelet function, and vasculogenesis in preeclampsia. METHODS: Plasma angiogenic (PlGF, VEGF), antiangiogenic factors (sflt-1, endoglin) with adipocytokines (leptin, adiponectin, ghrelin), endothelial dysfunction markers (vWF, NO), and platelet function markers (ADP and collagen induced platelet aggregation, P-selectin) were examined in 30 early-onset, 22 late-onset preeclampsia, and 27 healthy pregnants. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum biomarker levels except NO. NO levels were determined using colorimetric method. RESULTS: Endoglin, leptin, and vWF levels were increased in preeclampsia (P < 0.001), whereas PlGF, P-selectin (P < 0.001), and col-induced platelet aggregation slope (P < 0.05) were decreased in the same counterpart as compared to healthy pregnants. Endoglin also correlated with sflt-1 in preeclamptic patients. CONCLUSION: Increase in the levels of antiangiogenic factors and leptin herewith decline in the level of other angiogenic factor PlGF, did not affect nitric oxide and platelet aggregation markers significantly. Increased levels of vWF and endoglin might be result of endothelial dysfunction, so our findings suggest that an impaired angiogenesis may address endothelial dysfunction, but not platelet aggregation for preeclampsia.

Maternal serum atrial natriuretic peptide (ANP) and brain-type natriuretic peptide (BNP) levels in gestational diabetes mellitus.

OBJECTIVE: The aim of the study is to evaluate maternal serum atrial natriuretic peptide (ANP) and brain-type natriuretic peptide (BNP) levels in patients with getational diabetes mellitus compared with a control group. METHODS: We have measured maternal serum ANP and BNP levels in 35 otherwise healthy and 45 gestational diabetic women between gestational week 24 and 28 referred to our unit in a cross-sectional study. Independent samples t-test or the Mann-Whitney U-test was used for comparison of two groups where appropriate. RESULTS: Mean maternal serum homeostasis model assessment of insulin resistance (HOMA-IR), HbA1c, fasting glucose and insulin levels in gestational diabetes mellitus (GDM) group were significantly higher than the control group (p < 0.01). Mean maternal serum ANP and BNP levels of women with GDM were significantly lower than the control group (12.9 ± 9.9 versus 34.8 ± 16.9 pg/ml, p < 0.001; 416.6 ± 209.7 versus 629.7 ± 162.2 mg/dl, p < 0.001, respectively). Maternal serum ANP and BNP levels were negatively correlated with insulin levels, HbA1c and HOMA-IR values (p < 0.05). CONCLUSIONS: Maternal serum ANP and BNP levels are significantly lower in patients with GDM. These biomarkers might be valuable in clinical setting for identifying high-risk women for developing diabetes during pregnancy.

Adrenomedullin--A New Marker in Febrile Neutropenia: Comparison With CRP and Procalcitonin.

In this study, we aimed to determine serum adrenomedullin levels and compare them with levels of C-reactive protein (CRP) and procalcitonin (PCT). Cancer patients aged 0-18 years who experienced febrile neutropenia attacks were included in the study. Adrenomedullin, CRP, and PCT were analyzed at admission, day 3, and days 7-10 later. Fifty episodes of febrile neutropenia that developed in 37 patients were analyzed in this study. The mean age of the patients was 7.5 ± 4.7 (1-18) years. The patients had leukemia (73%), solid tumors (19%), and lymphoma (8%). The percentages of the patients in the clinically documented infection (CDI), fever of unknown origin (FUO), sepsis, and microbiological documented infection (MDI) categories were 34%, 34%, 20%, and 12%, respectively. During the study period, four patients were lost. In the MDI group, adrenomedullin levels on day 3 were significantly higher than those in the CDI and FUO groups. PCT levels were significantly higher in the sepsis group than those in the CDI group at admission, day 3, and days 7-10. In the sepsis group, PCT levels on days 7-10 days were significantly higher than those in the sepsis group. PCT values from the deceased patients on days 7-10 were significantly higher than those from patients who survived. CRP levels did not differ significantly among the febrile neutropenia groups. First, in our study, adrenomedullin was used as a biomarker in the febrile neutropenia episodes of children with cancer. Among adrenomedullin, CRP, and PCT, procalcitonin demonstrates the highest correlation with the severity of infection.

Barnidipine ameliorates the vascular and renal injury in L-NAME-induced hypertensive rats.

The present study was aimed to investigate the influence of Barnidipine treatment on early stage hypertension by determining the function and morphology of the mesenteric and renal arteries as well as the kidney in N(ω)-Nitro-L-Arginine Methyl Ester (L-NAME)-induced hypertensive rats. Barnidipine (3 mg/kg/day p.o) was applied to rats after 2 weeks of L-NAME (60 mg/kg/day) administration, and continued for the next 3 weeks concomitantly with L-NAME. The systolic blood pressure (SBP) of rats was determined to decrease significantly in Barnidipine treated hypertensive group when compared to that of rats received L-NAME alone. Myograph studies demonstrated that the contractile reactivity to noradrenaline were significantly reduced in both of the resistance arteries while endothelium-dependent relaxations to acethylcholine were significantly diminished particularly in the mesenteric arteries of L-NAME-induced hypertensive rats. The impaired contractile and endothelial responses were completely restored by concomitant treatment of Barnidipine with L-NAME. Histopathological examinations verified structural alterations in the arteries as well as the kidney. Moreover, a decrease in endothelial nitric oxide synthase (eNOS) expression was presented both in the arteries and kidney of hypertensive rats which were increased following Barnidipine treatment. Elevated plasma levels of malondialdehyde (MDA) and myeloperoxidase (MPO) were also reduced in Barnidipine treated hypertensive rats. In conclusion, besides to its efficacy in reducing the elevated SBP, amelioration of vascular function, modulation of arterial and renal eNOS expressions as well as reduction of the plasma levels of oxidative and inflammatory biomarkers are possible supportive mechanisms mediating the favorable implications of Barnidipine in L-NAME-induced hypertension model.

Serum endocan concentration in women with pre-eclampsia.

PURPOSE: To investigate serum endocan levels in pregnant subjects with and without pre-eclampsia. METHODS: This cross-sectional study was conducted on 49 pregnant women with pre-eclampsia and 32 healthy pregnant women matched for gestational age. Maternal levels of serum endocan were measured with the use of an enzyme-linked immunosorbent assay kit. RESULTS: Mean endocan levels were not significantly different among groups (10.7 ± 4.5 vs. 10.3 ± 3.2 ng/mL, p 0.763). Mean uterine artery PI and RI were higher in the pre-eclampsia group (p < 0.001, p < 0.001). Mean endocan levels were negatively correlated with BMI at the time of blood sampling (r = -0.247, p = 0.044). There was no correlations between mean endocan levels and all the others parameters. CONCLUSION: These findings suggest that the role of endocan in the pathogenesis of pre-eclampsia was not related to pre-eclampsia; hence, further studies are needed to investigate the role of endocan in the pathogenesis of pre-eclampsia.

Evaluation of Lp-PLA2 mass, vitronectin and PAI-1 activity levels in patients with preeclampsia.

PURPOSE: The aim of the current study is to determine, correlate and compare the plasma lipoprotein-associated phospholipase A2 (Lp-PLA2), vitronectin (Vn), Plasminogen activator inhibitor-1 (PAI-1) activity and tissue plasminogen activator (t-PA) levels in early-onset preeclampsia, late-onset preeclampsia and in control pregnant women. METHODS: A total of 79 individuals, 30 early-onsets, and 22 late-onset preeclamptic and 27 control pregnant women were included into the scope of this study. Enzyme-linked immunosorbent assay procedure was used to determine the serum Lp-PLA2 and plasma Vn, t-PA antigen and PAI-1 activity levels. Serum C-reactive protein (CRP) levels were measured immunoturbidimetrically in routine clinical chemistry analyser. RESULTS: In patients with preeclampsia, Lp-PLA2, PAI-1, t-PA, CRP and blood pressures levels were increased (p = 0.000) and correlated with each other. Vn levels were decreased (p = 0.016) but not correlated with other parameters in preeclamptic patients. CONCLUSION: We are of the opinion that increased Lp-PLA2 levels may partially contribute to endothelial dysfunction by the progression of inflammation. In addition, increased complex formation with Vn is likely to bring about the increase of PAI-1 activity in patients with preeclampsia. Moreover, increased t-PA and decreased Vn levels may also be the consequences of compensatory mechanisms against disease progression.

Effect of laser photocoagulation on plasma levels of VEGF-A, VEGFR-2, and Tie2 in infants with retinopathy of prematurity.

PURPOSE: To report the baseline plasma levels of vascular endothelial growth factor-A (VEGF-A), soluble vascular endothelial growth factor receptor-2 (sVEGFR-2) and soluble Tie2 in infants with treatment-requiring retinopathy of prematurity (ROP) and to investigate the effect of laser treatment on the plasma levels. METHODS: Blood samples were collected from infants with prethreshold type 1 ROP before, 1 day after, and 1 week after confluent laser photocoagulation. Enzyme-linked immunosorbent assay procedure was used to determine plasma VEGF-A, sVEGFR-2, and sTie2 levels. RESULTS: A total of 48 eyes of 30 infants were included. The mean postconceptional age at which laser photocoagulation was performed was 37.5 ± 2.9 weeks. The mean number of laser spots applied to each eye was 1,480 ± 420. Regression of active retinopathy occurred within 1 week of treatment in all cases. Baseline plasma VEGF-A, sVEGFR-2, and sTie2 levels did not differ between unilateral and bilateral and also zone I and zone II disease. A significantly progressive decrease was observed in plasma VEGF-A, sVEGFR-2, and sTie2 levels at 1 day and 1 week after laser photocoagulation. CONCLUSIONS: Plasma levels of VEGF-A, sVEGFR-2, and sTie2 decreased significantly in our patients after laser treatment; however, because of the variability in the measurements, further studies evaluating the clinical value of these angiogenic factors in patients with treatment-requiring ROP are necessary.

Maternal serum apelin and YKL-40 levels in early and late-onset pre-eclampsia.

OBJECTIVE: The aim of the present study is to investigate whether alterations in the serum levels of apelin and YKL-40 differ between early and late onset pre-eclampsia and whether there is a correlation between apelin and YKL-40 in women who subsequently develop early and late pre-eclampsia. MATERIALS AND METHODS: A total number of 80 pregnant women, 40 with normal pregnancy and 40 with pre-eclampsia, were included in the present study. Both the normal pregnant and pre-eclamptic subjects were subdivided into two groups. Serum YKL-40 and apelin concentrations were measured. RESULTS: Mean maternal serum YKL-40 levels were both lower in women who subsequently developed early (87.45 ± 3.07 versus 103.40 ± 4.29) or late (96.43 ± 4.06 versus 99.87 ± 3.63) pre-eclampsia than those who remained normotensive. The difference was significant in early-onset preeclamptic women (p < 0.05) rather than late-onset pre-eclamptic ones (p > 0.05). Mean maternal serum apelin levels were both higher in women who subsequently developed early (8.6 ± 3.6 versus 5.7 ± 1.2) or late (9.6 ± 2.5 versus 8.1 ± 1.8) pre-eclampsia than those who remained normotensive. The difference was significant in early-onset preeclamptic women (p < 0.05) rather than late-onset pre-eclamptic ones (p > 0.05). There was a significant negative correlation between serum apelin and YKL-40 levels (r = -0.48, p = 0.001). CONCLUSION: Circulating levels of apelin are significantly increased in early-onset pre-eclampsia, indicating the role of apelin in the discrimination of the early-onset of pre-eclampsia. On the other hand, maternal serum YKL-40 levels are not elavated significantly, indicating that adipose-derived apelin is primarily involved in the vascular pathogenesis of early-onset pre-eclampsia than macrophage-derived YKL-40.