Comparison of serum levels of cell adhesion molecules (E-selectin, P-selectin, ICAM-1, VCAM-1, LRG-1) in placental invasion and adhesion anomalies with patients with vaginal delivery and former cesarean.

OBJECTIVE: It is aimed to be a technique that can be used for diagnosis and to prevent maternal deaths in cases where the serum levels of cell adhesion molecules are different in patients with abnormal placentation compared to healthy pregnant women. MATERIALS AND METHODS: Patients between March 2020 and September 2021 were included in the study. While 56 patients, out of 153 cases formed the placental adhesion and/or localization anomaly group, 55 cases without placental adhesion anomaly (placental invasion anomaly and/or previa pathology) constituted the cesarean section group and 42 cases constituted the vaginal birth control group. Demographic characteristics and histories of 153 patients were questioned. I-CAM-1, V-CAM-1, E-Selectin, P-Selectin, LRG-1 levels were studied. The parameters measured by the ELISA method were studied in the Thermo Fisher Scientific Multiscan Go (Finland) device at the Hatay Mustafa Kemal University Medical Faculty Medical Biochemistry USA ELISA Laboratory. Wholehouse and One Way Anova analysis methods were used to compare the results. RESULTS: There were significant differences in E-Selectin, P-Selectin, ICAM-1 and LRG-1 values between the groups (p < 0.05). There was a significant difference between the vaginal birth (VB) and previa/percreata (PP) groups in terms of E-Selectin (p = 0.038). In terms of P-Selectin, there was a significant difference between the C/S and previa/percreata (PP) groups (p < 001). P-Selectin was higher in the previa/percreata (PP) group. There was a significant difference between the Vaginally birth (VB), C/S group (p = 0.041) and the vaginal birth (VB), previa/percreata (PP) group (p = 0.013) in terms of ICAM-1, but there was no significant difference between the C/S and previa/percreata (PP) groups. In terms of LRG-1, there was a significant difference between all 3 groups (p < 0.05). DISCUSSION: A recent study investigated the potential modulatory effects of trans-resveratrol (RSV), arginase and endothelial dysfunction biomarkers in patients with PE. Another reflection of endothelial dysfunction in PE is increased endothelial activation biomarkers such as intercellular adhesion molecule-1 (ICAM-1), von Willebrand factor (vWF), and Caspase-3 (CASP-3). The study, regarding vWF expression, the preeclampsia (PE) group showed higher levels compared to endothelial cells incubated with healty pregnant (HP) plasma [Bueno-Pereira et al 2022 Antioxidants 2111]. From this and similar studies, the hypothesis that the role of cell adhesion molecules in endothelial damage may be the underlying cause of invasion and location anomalies emerges. This hypothesis is the starting point of our study. CONCLUSIONS: In our study, all adhesion molecules except V-CAM-1 were found to be significantly higher in the previa/percreata (PP) group. E-Selectin and LRG-1 adhesion molecules were found to be significantly higher even in C/S patients compared to normal delivery. As a result; these adhesion molecules can be studied as a marker in previa/percreata (PP) patients.

Evaluation of the possible effect of inspiratory muscle training on inflammation markers and oxidative stress in childhood asthma.

Airway inflammation characterized as asthma is one of the most common chronic diseases in the world. The aim of this study was to evaluate the possible effect of inspiratory muscle training on inflammation markers and oxidative stress levels in childhood asthma. A total of 105 children (age range 8-17 years), including 70 asthmatics and 35 healthy children, participated in the study. The 70 asthma patients were randomly assigned to the inspiratory muscle training (IMT) group (n = 35) and control group (n = 35), and healthy children were assigned to the healthy group (n = 35). The IMT group was treated with the threshold IMT device for 7 days/6 weeks at 30% of maximum inspiratory pressure. Respiratory muscle strength was evaluated with a mouth pressure measuring device, and respiratory function was evaluated with a spirometer. In addition, CRP, periostin, TGF-ß, and oxidative stress levels were analyzed. The evaluation was performed only once in the healthy group and twice (at the beginning and end of 6 weeks) in asthma patients. In the study, there were significant differences between asthma patients and the healthy group in terms of MIP and MEP values, respiratory function, oxidative stress level, periostin, and TGF-ß. Post-treatment, differences were observed in the oxidative stress level, periostin, and TGF-ß of the IMT group (p < .05). CONCLUSION: After 6 weeks of training, IMT positively contributed to reducing the inflammation level and oxidative stress. This suggests that IMT should be used as an alternative therapy to reduce inflammation and oxidative stress. (Trial Registration: The clinical trial protocol number is NCT05296707). WHAT IS KNOWN: • It is known that adjunctive therapies given in addition to pharmacological treatment contribute to improving symptom control and quality of life in individuals with asthma. WHAT IS NEW: • There are no studies about the effect of respiratory physiotherapy on biomarkers in asthmatic children. The sub-mechanism of improvement in individuals has not been elucidated. • In this context, inspiratory muscle training has a positive effect on inflammation and oxidative stress levels in children with asthma and IMT should be used as an alternative treatment for childhood asthma.

Endometrial Injury Upregulates Expression of Receptivity Genes in Women with Implantation Failure.

BACKGROUND: Homeobox genes A10 (HOXA10) and A11 (HOXA11), members of the abdominal B gene family, are responsible for embryonic survival and implantation. This study was planned to investigate whether endometrial injury alters the expression of both transcripts in women with implantation failure. METHODS: A total of 54 women with implantation failure were divided into two equal groups as experimental (scratching) and sham (no scratching). Participants in the scratching group were exposed to endometrial injury in the mid-luteal phase, and those in the sham group were exposed to endometrial flushing. The scratching group, but not the sham group, underwent prior endometrial sampling. A second endometrial sampling was performed on the scratching group in the mid-luteal phase of the following cycle. The mRNA and protein levels of the HOXA10 and 11 transcripts were determined in endometrial samples collected before and after injury/flushing. Participants in each group underwent IVF/ET in the cycle after the second endometrial sampling. RESULTS: Endometrial injury caused a 60.1-fold (p < 0.01) increase in HOXA10 mRNA and a 9.0-fold increase in HOXA11 mRNA (p < 0.02). Injury resulted in a significant increase in both HOXA10 (p < 0.001) and HOXA11 protein expression (p < 0.003). There was no significant change in HOXA10 and 11 mRNA expressions after flushing. Clinical pregnancy, live birth, and miscarriage rates of the both groups were similar. CONCLUSIONS: Endometrial injury increases homeobox transcript expression at both mRNA and protein levels.

The effect of continuous positive airway pressure treatment on inflammatory parameters and periostin levels in patients with obstructive sleep apnea syndrome.

BACKGROUND: The purpose of the study was to examine the effects of continuous positive airway pressure (CPAP) treatment on inflammation parameters in patients with obstructive sleep apnea syndrome (OSAS). METHODS: Patients aged 18 to 65 years who underwent polysomnography (PSG) in the sleep clinic between January 1, 2019, and December 31, 2019, were included in the study. Patients with severe OSAS initiated treatment with CPAP. Patients and control subjects were assessed for levels of periostin, TNF-alpha, TGF-beta, and IL-6. Patients were re-evaluated 3 months later. Comparisons for the serum markers were made between controls and patients of different severity of OSAS. Comparisons of serum markers were also made between baseline and 3 month follow-up.  RESULTS: A total of 92 patients were enrolled in the study, including 25 controls (apnea-hypopnea index or AHI < 5/h), 39 patents with mild to moderate OSAS who did not receive CPAP, and 28 patients with severe OSAS receiving CPAP treatment. When all three groups were compared, levels of periostin, TNF-alpha, TGF-beta, and IL-6, as inflammatory markers, were higher in the OSAS group, though not at a statistically significant level. In patients with severe OSAS, there were statistically significant decreases in the TGF-beta 1, TNF-alpha, and IL-6 values between baseline values and the same measures taken after 3 months of CPAP treatment. Periostin values also decreased after treatment, but this decrease was not at a significant level. CONCLUSION: Inflammatory parameters of patients with OSAS were significantly higher compared with healthy participants. Regression of inflammation was detected after CPAP treatment.

Designing and validating an autoverification system of biochemical test results in Hatay Mustafa Kemal University, clinical laboratory.

Introduction: Autoverification (AV) is a postanalytical tool that uses algorithms to validate test results according to specified criteria. The Clinical and Laboratory Standard Institute (CLSI) document for AV of clinical laboratory test result (AUTO-10A) includes recommendations for laboratories needing guidance on implementation of AV algorithms. The aim was to design and validate the AV algorithm for biochemical tests. Materials and methods: Criteria were defined according to AUTO-10A. Three different approaches for algorithm were used as result limit checks, which are reference range, reference range ± total allowable error, and 2nd and 98th percentile values. To validate the algorithm, 720 cases in middleware were tested. For actual cases, 3,188,095 results and 194,520 reports in laboratory information system (LIS) were evaluated using the AV system. Cohen's kappa (κ) was calculated to determine the degree of agreement between seven independent reviewers and the AV system. Results: The AV passing rate was found between 77% and 85%. The highest rates of AV were in alanine transaminase (ALT), direct bilirubin (DBIL), and magnesium (Mg), which all had AV rates exceeding 85%. The most common reason for non-validated results was the result limit check (41%). A total of 328 reports evaluated by reviewers were compared to AV system. The statistical analysis resulted in a κ value between 0.39 and 0.63 (P < 0.001) and an agreement rate between 79% and 88%. Conclusions: Our improved model can help laboratories design, build, and validate AV systems and be used as starting point for different test groups.

Evaluation of IL-23p19/Ebi3 (IL-39) gingival crevicular fluid levels in periodontal health, gingivitis, and periodontitis.

OBJECTIVES: IL-23p19/Ebi3 (IL-39) was described as a new IL-12 family member. The aim of this study is to evaluate the gingival crevicular fluid (GCF) IL-39 levels in periodontal diseases and health and to correlate them to GCF levels of IL-1ß and periostin. MATERIALS AND METHODS: Sixty-six adult patients were included in the study. The study design was comprised of three groups, each containing 22 individuals: the periodontally healthy (PH), gingivitis (G), and periodontitis (P) groups. The clinical periodontal parameters were recorded and GCF samples were collected from the participants. GCF interleukin (IL)-39, IL-1ß, and periostin levels were examined using the enzyme-linked immunosorbent assay. RESULTS: GCF IL­1ß, periostin, and IL-39 levels were higher in the P and G groups than in the PH group (p < 0.001). Positive correlations were detected between all GCF biochemical parameters and clinical periodontal parameters (p < 0.05). In the multivariate generalized linear regression analysis, the P (ß = 37.6, 95% CI = 22.9-52.4) and G (ß = 28.4, 95% CI = 15.8-41) groups were associated with GCF IL-39 levels (p < 0.001). CONCLUSION: IL-39 levels were elevated in the presence of periodontal disease paralleling the increase in IL­1ß and periostin levels. IL-39 may have a role in the periodontal inflammation process. STATEMENT OF CLINICAL RELEVANCE: IL-39, a new cytokine from the IL-12 family, can be a possible predictor marker of periodontal diseases.

Hemostatic effects of traditional Inula viscosa and Capsella bursa-pastoris plant mixture extract on rat liver parenchymal bleeding model.

BACKGROUND: Failure to achieve effective bleeding control and problems related to transfusion in liver surgery are the most common causes of post-operative mortality and morbidity. Various methods/drugs including topical hemostatic agents have been em-ployed for bleeding control in liver surgery. This study was aimed to investigate the hemostatic properties of the herb mixture extract of Inula viscosa and Capsella bursa-pastoris (IvCbp) in rat liver laceration model, which have been traditionally used as antiseptic and hemostatic agents public in Hatay/Tukey. METHODS: Thirty rats were divided into three groups equally and blood samples were taken from all rats for preoperative hemoglobin (Hb) measurements. Then, the standard liver resection model was applied to all rats. Sponge for the first rat group, Ankaferd Blood Stopper® Trend-Tech for the second rat group and IvCbp plant extract mixture for the third group were applied to resection areas for 3 minutes. Liver samples of all rats were evaluated in terms of inflammation and necrosis intensity on the 5th post-operative day. RESULTS: Post-operative Hb values were found as 11.0±1.1 g/dL in the sponge group, 11.9±2.0 g/dL in the Ankaferd group, and 14.1±1.2 g/dL in the IvCbp herb mixture group (p<0.001). In the histopathological examination, less necrosis was observed in the herb mixture group compared to the sponge and Ankaferd groups (p=0.001). In addition, no statistically significant necrosis difference was observed between sponge and Ankaferd groups. While less inflammation was observed in the herb mixture group compared to the other groups, Ankaferd group had the highest inflammation score (p<0.001). CONCLUSION: IvCbp herb mixture extract group provide effective hemostatic control, caused less Hb decrease and resulted in less inflammation and necrosis compared to Ankaferd and sponge groups in a rat liver resection model.

TNF-alpha, IL-6, IL-10 and fatty acids in rheumatoid arthritis patients receiving cDMARD and bDMARD therapy.

OBJECTIVE: The present study aimed to examine the effects of cDMARD and bDMARD therapy on both gene expressions and protein levels of TNF-α, IL-6, IL-10 and fatty acid levels in patients with RA. METHOD: Plasma TNF-α, IL-6, and IL-10 levels were examined by the ELISA method, while TNF-α, IL-6, and IL-10 gene expression levels were examined by RT-qPCR, and fatty acid levels were examined by GC/MS. RESULTS: IL-10 gene expression levels significantly increased in RA patients receiving cDMARD treatment compared to those of the control group. Also, eicosadienoic acid, myristoleic acid and capric acid levels were significantly lower in the patient groups compared to those in the control group. CONCLUSION: The drugs used in the treatment of RA had no effect on the fatty acid levels whereas had effects on the mRNA and protein levels of the target cytokines.

Possible role of endocannabinoids in olfactory and taste dysfunctions in Alzheimer's and Parkinson's patients and volumetric changes in the brain.

The purpose of this study is to determine the volumes of primary brain regions associated with smell and taste in Alzheimer's and Parkinson's patients and healthy controls using MR imaging and examine volumetric changes in comparison to smell/taste questionnaire and test results and endocannabinoid (EC) levels. The study included 15 AD patients with mild cognitive dysfunction scored as 18 ≤ MMSE ≤ 23, 15 PD patients with scores of 18 < MoCA < 26 and 18 ≤ MMSE ≤ 23, and 15 healthy controls. A taste and smell questionnaire was given to the participants, and their taste and smell statuses were examined using the Sniffin' Sticks smell identification test and Burghart Taste Strips. EC levels were analyzed in the blood serum samples of the participants using the ELISA method. The volumes of the left olfactory bulb (p = 0.001), left amygdala (p = 0.004), left hippocampus (p = 0.008), and bilateral insula (left p = 0.000, right p = 0.000) were significantly smaller in the Alzheimer's patients than the healthy controls. The volumes of the left olfactory bulb (p = 0.001) and left hippocampus (p = 0.009) were significantly smaller in the Parkinson's patients than the healthy controls. A significant correlation was determined between volume reduction in the left Rolandic operculum cortical region and taste dysfunction. EC levels were significantly higher in both AD (p = 0.000) and PD (p = 0.006) in comparison to the controls. Our results showed that volumetric changes occur in the brain regions associated with smell and taste in Alzheimer's and Parkinson's patients. It was observed that ECs played a role in these volumetric changes and the olfactory and taste dysfunctions of the patients.

Serum periostin levels in COVID-19: Is it useful as a new biomarker?

OBJECTIVES: Severe disease characterised by interstitial pneumonia may develop in some cases of coronavirus disease (COVID-19). Periostin has been associated with many respiratory diseases. In this study, we aimed to investigate whether periostin could be a useful new biomarker in the follow-up and severity assessment of the disease in patients with COVID-19 pneumonia. METHODS: In the study, 32 patients followed up during May to July 2020 because of COVID-19 and 24 healthy controls were included. The patients were divided into two groups, namely, mild/moderate and severe, according to the severity of the disease. Serum periostin and transforming growth factor beta (TGF-ß) levels were tested using an enzyme-linked immunosorbent assay (ELISA) method using commercially available ELISA kits. RESULTS: It was observed that the periostin level was significantly higher in both mild/moderate cases and severe cases compared with the control group at first presentation. However, TGF-ß levels at first presentation were similar between the groups. CONCLUSIONS: The current manuscript may be the first one performing periostin ELISA on COVID serum, and we believe that periostin can be used as a new biomarker.

Beclin-1, an autophagy-related protein, is associated with the disease severity of COVID-19.

AIMS: Coronavirus disease 2019 (COVID-19), which is a highly contagious disease, is an ongoing outbreak worldwide with high morbidity and mortality. The approaches targeting the autophagy processes might have promising diagnostic and therapeutic values against Coronavirus infection. Here, we aimed to investigate the relationship of Beclin-1 (BECN1), an autophagy-related protein, with blood parameters and the clinical severity in patients with COVID-19. MATERIALS AND METHODS: We enrolled 108 patients with COVID-19 and 21 healthy controls in this study, from September 2020 to January 2021 and divided all patients into two groups according to the severity of the disease: The non-severe group and the severe group. BECN1 levels and blood parameters were measured with Enzyme-Linked Absorbent Assay and routine techniques, respectively. KEY FINDINGS: Serum BECN1 levels were increased in patients with COVID-19 compared to the healthy controls, and its concentrations were significantly higher in the severe group than in the non-severe group (p < 0.001). BECN1 levels showed a significantly positive correlation with coagulation markers such as D-dimer and Fibrinogen (FIB) and inflammation markers such as C-reactive protein (CRP), Procalcitonin (PCT), Ferritin and biochemical markers such as Blood urea nitrogen and Lactate dehydrogenase (p < 0.001). We detected that areas under the ROC curve for BECN1, D-dimer, FIB, PCT, CRP and Ferritin were 0.8662, 0.9110, 0.8278, 0.9996 and 0.9284, respectively (p < 0.0001). SIGNIFICANCE: BECN1 may serve as a predictive biomarker in evaluating the disease severity of COVID-19. Our data suggest that BECN1 mediated-autophagy modulation might have a promising value in improving the clinical outcomes of COVID-19.

Presentation of a new mutation in FMF and evaluating the frequency of distribution of the MEFV gene mutation in our region with clinical findings.

Familial Mediterranean Fever (FMF), which is an autosomal recessive disease characterized by recurrent self-limiting fever, peritonitis, pleuritis, arthritis and erysipelas-like erythemas, has been common among ethnic groups such as Turkish, Armenian, Arabic and Jewish. The clinical presentation is caused by mutations in the MEFV gene encoding the Pyrin protein. In this study, we aimed to present a new mutation that has not been previously defined from the mutations in the MEFV gene which is responsible for the genetic pathology of familial Mediterranean fever and to evaluate the frequency of distribution of the MEFV gene mutation among different ethnic groups living in our region. In present retrospective study, a total of 2639 clinically suspected FMF patients who were referred to Hatay Mustafa Kemal University Hospital between 2010 and 2017 were recorded. MEFV gene mutations were observed using DNA sequence analysis. MEFV mutations were found in 2079 of the 2639 patients (78.7%) Among these patients 184 (6.97%) were homozygous, while 1365 (51.72%) were heterozygous. The most frequently observed mutation was R202Q (1319, 19.55%) followed by E148Q (n = 476, 7.05%), M694V (n = 439, 6.51%), V726A (n = 146, 2.16%) and M680I (n = 135, 2%). In a case clinically diagnosed as FMF, a new mutation called S145G (p. Ser145Gly, c.433A > G) was identified in exon 2 of the MEFV gene. Besides, addition of a new pathogenic MEFV variant to the literature, the relationship between the FMF clinic and homozygous form of R202Q, which was previously considered as a polymorphism, was highlighted.

Association of serum lncRNA H19 expression with inflammatory and oxidative stress markers and routine biochemical parameters in chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a disorder that affects millions worldwide, and current treatment options aiming at inhibiting the progression of kidney damage are limited. Long noncoding RNA (lncRNA) H19 is one of the first explored lncRNAs and its deregulation is associated with renal pathologies, such as renal cell injury and nephrotic syndrome. However, there is still no research investigating the connection between serum lncRNA H19 expressions and clinical outcomes in CKD patients. Therefore, we investigated the relation of serum lncRNA H19 expressions with routine biochemical parameters, inflammatory cytokines, oxidative stress and mineralization markers in advanced CKD patients. METHODS: lncRNA H19 serum levels from 56 CKD patients and 20 healthy controls were analyzed with reverse-transcription quantitative polymerase chain reaction method. Serum tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and osteocalcin (OC) levels were measured with enzyme linked-immunosorbent assay. Total antioxidant status (TAS) and total oxidative status (TOS) levels were evaluated by the routine measurement method. RESULTS: We found that lncRNA H19 expressions were upregulated in patients with CKD compared to the controls. Furthermore, lncRNA H19 relative expression levels showed a negative relationship with glomerular filtration rate (GFR) while it was positively correlated with ferritin, phosphorus, parathyroid hormone, TNF-α, IL-6, OC, TAS and TOS levels. CONCLUSION: lncRNA H19 expressions were increased in CKD stage 3-5 and HD patients, and elevated lncRNA H19 expressions were associated with decreased glomerular filtration rate, inflammation, and mineralization markers in these patients.

Associations between the expression of mucins (MUC1, MUC2, MUC5AC and MUC6) and clinicopathologic parameters of human breast carcinomas.

AIMS: The aim of this study is to evaluate the relationships between the expression of mucins in invasive breast carcinomas and clinicopathologic parameters. MATERIALS AND METHODS: We examined 150 cases of invasive breast carcinoma, using the 2012 World Health Organization (WHO) classification of the tumors of the breast. We studied the expression of MUC1, MUC2, MUC5AC, and MUC6 by immunohistochemistry. We also evaluated normal breast tissue and ductal carcinoma in situ (DCIS) lesions in nearby invasive tumor areas. RESULTS: In invasive breast carcinomas, MUC1, MUC2, MUC5AC, and MUC6 were expressed in 98.6%, 11.3%, 9.9, and 8.5% of cases, respectively. MUC2, MUC5AC, and MUC6 were overexpressed in invasive tumors and DCIS lesions were compared with normal breast tissue. The apical pattern of MUC1 was correlated with low grade and ER expression. MUC2 was correlated with mucinous carcinoma and an inverse association with invasive ductal carcinoma, not otherwise specified (NOS). MUC6 expression was associated with lymphovascular invasion. CONCLUSIONS: Most invasive breast tumors express MUC1 and the apical pattern of MUC1 is correlated with low grade and ER expression. MUC6 expression is associated with indicators of poor prognosis. Further comprehensive studies need to evaluate the role of mucins as a potential biomarker and to be used as a specific therapeutic target against breast cancer.

In vivo protective effects of upper zone of growth plate and cartilage matrix associated protein against cartilage degeneration in a monosodium iodoacetate induced osteoarthritis model.

Osteoarthritis (OA) is a degenerative disease affecting the majority of over 65 year old people and characterized by cartilage degeneration, subchondral abnormal changes, and inflammation. Despite the enormous socioeconomic burden caused by OA, currently, there is no effective therapy against it. Upper zone of growth plate and cartilage matrix associated protein (UCMA) is a vitamin K dependent protein and has a critical role in pathophysiological conditions associated with bone and cartilage. However, there is no research on the protective role of intra-articular UCMA treatment in OA pathogenesis. Therefore, we aimed to investigate the potential therapeutic role of UCMA in an in vivo model of OA. We report for the first time that intra-articular UCMA injection ameliorated cartilage degeneration in a monosodium iodoacetate induced OA rat model. Furthermore, the OA-induced activation of nuclear factor kappa B and bone morphogenetic protein 2 signals was attenuated by UCMA. Our results indicated that UCMA decreased cartilage oligomeric matrix protein levels but did not affect interleukin 6, total antioxidant status, and total oxidant status levels in the serum. In conclusion, UCMA exhibited a therapeutic potential in the treatment of OA. This protective effect of UCMA is possibly achieved by reducing the aggrecanase activity and the production of inflammatory cytokines.

Early postoperative changes of HDL subfraction profile and HDL-associated enzymes after laparoscopic sleeve gastrectomy.

This study aimed to determine early postoperative changes of LDL/HDL subfraction profile and HDL-associated enzymes following laparoscopic sleeve gastrectomy (LSG). Thirteen obese patients (mean body mass index (BMI) 52.74 ± 10.97 kg/m(2)) underwent LSG and normal weight control patients (mean BMI 23.56 ± 1.92 kg/m(2)) underwent laparoscopic abdominal surgery. Fasting blood samples were collected prior to surgery, at day 1 after surgery, and after postoperation oral feeding. LDL and HDL subfraction analysis was done by continuous disk polyacrylamide gel electrophoresis. Plasma levels of cholesteryl ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT), and apolipoprotein A-1 (apoA-I) were determined by enzyme-linked immunosorbent assay. Measurement of CETP and LCAT activity was performed via fluorometric analysis. LDL subfraction profile showed no change in both LSG and control group patients. No significant difference was observed in HDL cholesterol, HDL-subfraction distribution, and apoA-I levels in the control group. LSG patients showed a significant increase in HDL-large and a significant decrease in HDL-small fractions at postoperation day 1 compared to preoperation. HDL cholesterol significantly decreased and apoA-I significantly increased in LSG patients after postoperation oral feeding compared to both preoperation and postoperation day 1. Changes in HDL subfraction profile at postoperation day 1 after LSG were accompanied by a significant decrease in CETP protein, LCAT protein, and LCAT activity as compared to preoperation levels. Early changes in HDL subfraction profile and HDL-associated enzymes following LSG suggest that the surgical procedure, irrespective of changes in body weight, affects reverse cholesterol transport.

Oxidative stress and potential applications of free radical scavengers in glaucoma.

Glaucoma is the leading cause of irreversible blindness in industrialized countries and comprises a group of diseases characterized by progressive optic nerve degeneration. Glaucoma is commonly associated with elevated intraocular pressure due to impaired outflow of aqueous humor resulting from abnormalities within the drainage system of the anterior chamber angle (open-angle glaucoma) or impaired access of aqueous humor to the drainage system (angle-closure glaucoma). Oxidative injury and altered antioxidant defense mechanisms in glaucoma appear to play a role in the pathophysiology of glaucomatous neurodegeneration that is characterized by death of retinal ganglion cells. Oxidative protein modifications occurring in glaucoma serve as immunostimulatory signals and alter neurosupportive and immunoregulatory functions of glial cells. Initiation of the apoptotic cascade observed in glaucomatous retinopathy can involve oxidant mechanisms and different agents have been shown to be neuroprotective. This review focuses on the molecular mechanisms of oxidant injury and summarizes studies that have investigated novel free radical scavengers in the treatment of glaucomatous neurodegeneration.

Polymorphism in the TNF-alpha gene promoter at position -1031 is associated with increased circulating levels of TNF-alpha, myeloperoxidase and nitrotyrosine in primary Sjögren's syndrome.

OBJECTIVES: Tumour necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine which is associated with the pathogenesis of many inflammatory diseases. The aim of this study was to investigate the effect of TNF-alpha -1031 gene polymorphism on circulating TNF-alpha, myeloperoxidase (MPO) and nitrotyrosine (NT) levels in primary Sjögren's syndrome patients. METHODS: TNF-alpha-1031 T/C gene polymorphism was evaluated in 65 Sjögren's syndrome patients and 58 age and gender matched controls via 5' nuclease PCR analysis. Plasma TNF-alpha and NT levels were analysed by ELISA while MPO activity, total nitrate/nitrite and glutathione (GSH) levels were measured by spectral analysis. RESULTS: TNF-alpha -1031 C carrier genotype frequency was significantly higher (p=0.045) in Sjögren patients compared to controls (23.1 vs. 10.3%, 0R= 2.83, 95% CI=0.27-7.8). Plasma TNF-alpha concentration and NT levels were also significantly higher in Sjögren patients with -1031 C carrier genotype compared to patients with TT genotype. Sjögren patients showed a significant increase in plasma MPO activity which correlated with both TNF-alpha and NT levels in subjects with -1031 C carrier genotype assessed by linear regression analysis. TNF-alpha-1031 T/C gene polymorphism had no effect on plasma nitrate/nitrite and GSH levels which were significantly decreased in Sjögren's syndrome patients compared to controls. CONCLUSIONS: Polymorphism in the TNF-alpha gene promoter at position -1031 is associated with increased circulating levels of TNF-alpha which is correlated with increased plasma MPO activity and protein nitration in Sjögren's syndrome.

Measurement of intracellular biomolecular oxidation in liver ischemia-reperfusion injury via immuno-spin trapping.

Hepatic ischemia-reperfusion (I/R) can lead to liver failure in association with remote organ damage, both of which have significant rates of morbidity and mortality. In this study, novel spin trapping and histopathological techniques have been used to investigate in vivo free radical formation in a rat model of warm liver I/R injury. 5,5-Dimethyl-1-pyrroline N-oxide (DMPO) was administered to rats via intraperitoneal injection at a single dose of 1.5g of pure DMPO/kg body wt 2h before the initiation of liver ischemia. Blood vessels supplying the median and left lateral hepatic lobes were occluded with an arterial clamp for 60min, followed by 60min reperfusion. The effects of DMPO on I/R injury were evaluated by assessing the hepatic ultrastructure via transmission electron microscopy and by histopathological scoring. Immunoelectron microscopy was performed to determine the cellular localization of DMPO nitrone adducts. Levels of nitrone adducts were also measured to determine in situ scavenging of protein and DNA radicals. Total histopathological scoring of cellular damage was significantly decreased in hepatic I/R injury after DMPO treatment. DMPO treatment significantly decreased the hepatic conversion of xanthine oxidase and 4-hydroxynonenal formation in I/R injury compared to the untreated I/R group. The distribution of gold-nanoparticle-labeled DMPO nitrone adducts was observed in mitochondria, cytoplasm, and nucleus of hepatocytes. The formation of protein- and DNA-nitrone adducts was increased in DMPO-treated I/R livers compared to DMPO controls, indicating increased in situ protein and DNA radical formation and scavenging by DMPO. These results suggest that DMPO reduces I/R damage via protection against oxidative injury.

The effect of hemolysis on plasma oxidation and nitration in patients with sickle cell disease.

This study aimed to determine the effect of haemolysis on plasma oxidation and nitration in sickle cell disease (SCD) patients. Blood was collected from haemoglobin (Hb)A volunteers and homozygous HbSS patients who had not received blood transfusions in the last 3 months. Haemolysis was characterised by low levels of haemoglobin and haptoglobin and high levels of reticulocyte, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), plasma cell-free haemoglobin, bilirubin, total lactate dehydrogenase (LDH) and dominance of LDH-1 isoenzyme. Plasma 8-isoprostane, protein carbonyl and nitrotyrosine levels were measured to evaluate oxidised lipids, oxidised and nitrated proteins, respectively. Plasma nitrite-nitrate levels were also determined to assess nitric oxide (NO) production in both SCD patients and controls. Markers of haemolysis were significantly evident in SCD patients compared to controls. Plasma 8-isoprostane, protein carbonyl and nitrotyrosine levels were markedly elevated in SCD patients compared to controls. Linear regression analysis revealed a significant inverse correlation between haemoglobin and reticulocyte counts and a significant positive correlation of plasma cell-free haemoglobin with protein carbonyl and nitrotyrosine levels. The obtained data shows that increased haemolysis in SCD increases plasma protein oxidation and nitration.