Peri-implant crevicular fluid and serum levels of soluble ST2 in peri-implant diseases: A pilot study.

BACKGROUND AND OBJECTIVE: Soluble ST2 (sST2) is a current biomarker of cardiovascular disease. It is used to predict susceptibility to cardiovascular diseases and to analyze their prognosis. Serum sST2 level increases in inflammatory diseases such as periodontitis. However, the level of sST2 in peri-implant diseases and crevicular fluid has not been investigated yet. Thus, the aim of this cross-sectional study is to analyze the level of sST2 in peri-implant health and diseases. METHODS: Sixty-nine participants were divided into 3 groups as peri-implant health (PH), peri-implant mucositis (PM), and peri-implantitis (P-I). Peri-implant crevicular fluid (PICF) and serum samples were collected from each participant. The levels of sST2 and IL-6 in PICF and sST2, IL-6, and CRP in serum were compared between the groups. Pocket depth (PD), modified bleeding index (mBI), modified plaque index (mPI), keratinized mucosa index (KTW), and gingival/mucosal recession (REC) were recorded as clinical parameters. Biomarkers in the serum and PICF were analyzed by ELISA kit. RESULTS: Sixty-nine patients were included in the study. The differences in the following parameters were statistically significant between groups: age (p = .009), implant function time (p = .027), PD (p < .001), mBI (p < .001), mPI (p < .001), and KTW (p = .043). The PICF volume of P-I and PM groups were statistically higher than PH (p < .001). The amount of sST2 in P-I and PM groups were higher than PH (p = .043). Serum CRP was higher in the P-I group than in other groups (p = .034). There were no significant differences in serum sST2 (p = .247) and IL-6 (p = .110) levels between groups. CONCLUSION: The PICF levels of sST2 were significantly higher in PM and P-I groups compared to the healthy group. However, no significant difference was observed between the groups in terms of serum sST2 level.

Searching for the urine osmolality surrogate: an automated machine learning approach.

OBJECTIVES: Automated machine learning (AutoML) tools can help clinical laboratory professionals to develop machine learning models. The objective of this study was to develop a novel formula for the estimation of urine osmolality using an AutoML tool and to determine the efficiency of AutoML tools in a clinical laboratory setting. METHODS: Three hundred routine urinalysis samples were used for reference osmolality and urine clinical chemistry analysis. The H2O AutoML engine completed the machine learning development steps with minimum human intervention. Four feature groups were created, which include different urinalysis measurements according to the Boruta feature selection algorithm. Method comparison statistics including Spearman's correlation, Passing-Bablok regression analysis were performed, and Bland Altman plots were created to compare model predictions with the reference method. The minimum allowable bias (24.17%) from biological variation data was used as the limit of agreement. RESULTS: The AutoML engine developed a total of 183 ML models. Conductivity and specific gravity had the highest variable importance. Models that include conductivity, specific gravity, and other urinalysis parameters had the highest R2 (0.70-0.83), and 70-84% of results were within the limit of agreement. CONCLUSIONS: Combining urinary conductivity with other urinalysis parameters using validated machine learning models can yield a promising surrogate. Additionally, AutoML tools facilitate the machine learning development cycle and should be considered for developing ML models in clinical laboratories.

Efficacy of Acupuncture on Pain Mechanisms, Inflammatory Responses, and Wound Healing in the Acute Phase of Major Burns: An Experimental Study on Rats.

We investigated acupuncture, a potential contributor for burn care, on physiological and pathological pain mechanisms and systemic and local inflammatory responses in a rat experimental burn model. Forty male Sprague-Dawley rats were divided into two groups. One-hour groups (five rats/group) were observed for 1 hour and included Sh1 (sham/observation), ShA1 (sham + acupuncture/observation), Brn1 (burn/observation), and BrnA1 (burn + acupuncture/observation). Seven-day groups (five rats/group) were observed for 7 days and included Sh7 (sham/observation), ShA7 (sham + acupuncture/observation), Brn7 (burn/observation), and BrnA7 (burn + acupuncture/observation). "Pain-distress scores" were noted daily, and acupuncture was repeated within every wound-dressing change on alternate days. After observation periods, blood samples for interleukin 6 and beta-endorphin and skin biopsies for inflammatory changes and immunohistochemical staining of interleukin 6 were collected for analysis(P < .05). In 1-hour groups, interleukin 6 accumulation in burn wounds of BrnA1 was less than Brn1, with Brn1 having the highest mean blood level (P < .05). Mean beta-endorphin levels were higher in ShA1, Brn1, and BrnA1 than in Sh1 (P < .05). In all 7-day groups, the agonizing period was 48 to 72 hours after burn, with Brn7 most affected (P < .05). Microvessels were multiplied in the Brn7 group, with significantly higher numbers in burn wounds of BrnA7 (P ˂ .05). Burn wounds of BrnA7 had less accumulation of interleukin 6 than Brn7 with the Brn7 group having the highest mean blood level and Sh7, ShA7, and BrnA7 having similarly low levels (P ˃ .05). Beta-endorphin levels in ShA7, Brn7, and BrnA7 were lower than in Sh7 (P < .05). Acupuncture contributed to the management of physiological and pathological pain, modulation of inflammatory responses, and associated enhancement of angiogenesis in the acute phase of burn injury in rats.

Evaluation of Dynapenia and Sarcopenia and Their Associations With Serum Insulin-Like Growth Factor-1 Levels in Renal Transplant Recipients.

OBJECTIVES: Dynapenia and sarcopenia are related to increased morbidity and mortality in the general population. Chronic kidney disease (CKD) causes sarcopenia and dynapenia with different mechanisms. The aim of this study is to compare the muscle parameters in renal transplant recipients to CKD patients and patients without kidney disease and assess their associations with serum insulin-like growth factor-1 (IGF-1) levels. METHOD: In total, 120 renal transplant recipients (mean age: 40.4 ± 10.5 years), 60 CKD patients (mean age: 41.9 ± 11.4 years), and 60 control subjects with normal kidney function (mean age: 38.8 ± 9.9 years) were enrolled. Body mass index, hand grip strength, bioelectrical impedance analysis, 6-minute walking test, and serum IGF-1 level were measured and compared between groups. Muscle parameters were evaluated according to The Foundation for the National Institutes of Health Biomarkers Consortium Sarcopenia Project criteria. RESULTS: IGF-1 levels were highest in the renal transplantation group and lowest in the control group (P = .029). In total, 12.5% of patients in the renal transplantation group (13.3% overweight, 20% obese), 11.6% in the CKD group, and 1.6% in the control group had dynapenia (P = .015). In addition, 8.3% of patients in the CKD group, 3.3% in the renal transplantation group (50% overweight), and none of the patients in the control group had sarcopenia (P = .054). In multivariate analyses, muscle strength was associated with IGF-1 levels in renal transplant recipients (beta = 2.314, t = 3.456, P = .001). CONCLUSIONS: Serum IGF-1 is closely associated with muscle strength in renal transplant recipients. The negative effects of CKD on muscle system cannot be completely resolved with renal transplantation. Sarcopenic obesity and dynapenic obesity need special attention and therefore body mass index cannot be used as the only parameter to evaluate frailty in renal transplant recipients.

Detection of COVID-19 by Machine Learning Using Routine Laboratory Tests.

OBJECTIVES: The present study aimed to develop a clinical decision support tool to assist coronavirus disease 2019 (COVID-19) diagnoses with machine learning (ML) models using routine laboratory test results. METHODS: We developed ML models using laboratory data (n = 1,391) composed of six clinical chemistry (CC) results, 14 CBC parameter results, and results of a severe acute respiratory syndrome coronavirus 2 real-time reverse transcription-polymerase chain reaction as a gold standard method. Four ML algorithms, including random forest (RF), gradient boosting (XGBoost), support vector machine (SVM), and logistic regression, were used to build eight ML models using CBC and a combination of CC and CBC parameters. Performance evaluation was conducted on the test data set and external validation data set from Brazil. RESULTS: The accuracy values of all models ranged from 74% to 91%. The RF model trained from CC and CBC analytes showed the best performance on the present study's data set (accuracy, 85.3%; sensitivity, 79.6%; specificity, 91.2%). The RF model trained from only CBC parameters detected COVID-19 cases with 82.8% accuracy. The best performance on the external validation data set belonged to the SVM model trained from CC and CBC parameters (accuracy, 91.18%; sensitivity, 100%; specificity, 84.21%). CONCLUSIONS: ML models presented in this study can be used as clinical decision support tools to contribute to physicians' clinical judgment for COVID-19 diagnoses.

Differences in Antibody Responses Between an Inactivated SARS-CoV-2 Vaccine and the BNT162b2 mRNA Vaccine in Solid-Organ Transplant Recipients.

OBJECTIVES: Vaccination against SARS-CoV-2 may reduce COVID-19 mortality and complications in solidorgan transplant recipients, and we evaluated the associated antibody responses and adverse effects in this high-risk population. MATERIALS AND METHODS: This prospective observational study (April-June 2021) included 10 liver and 38 kidney transplant recipients who received 2 vaccine doses (Sinovac, n = 31; or BioNTech, n = 17) and 56 healthy adults (Sinovac), all of whom provided 3 blood samples (prevaccination, 4 weeks after first dose, and 4-6 weeks after second dose) for quantitative tests (Abbott Quant assay forimmunoglobulin G antibodies against SARS-CoV-2 spike protein). Type I error was α = .05 in all statistical analyses (SPSS, version 25). RESULTS: We analyzed demographic data, antibody responses, and adverse events after 2 doses of SARSCoV-2 vaccine, comparedimmune responses from solidorgan transplant recipients (median age, 36.5 years) versus healthy patients (median age, 37.5 years), and observed significantly higher seropositivity in healthy versus transplant patients after Sinovac vaccination (100% vs 67.5%; P = .001). However, we observed no significant seropositive differences for Sinovac versus BioNTech second doses in transplantrecipients. Median SARS-CoV-2 immunoglobulin G level after second dose was significantly higher in BioNTech (1388.6 AU/mL) versus Sinovac patients (136.6 AU/mL) (P = .012). The seropositivity difference between the 2 vaccines was significant in participants 24 to 44 years old (P = .040). The rate of at least 1 side effect was 82.4% (n = 14) for BioNTech vaccine and 32.3% (n = 10) for Sinovac vaccine, and the difference was statistically significant.The most common side effect was arm pain (significantly higher in BioNTech group). CONCLUSIONS: Solid-organ transplant recipients demonstrated inadequate vaccine responses (higher risk of complications and mortality) versus healthy patients. Furthermore, immune responses may differ between vaccines. Therefore, additional vaccine doses and strict control measures remain crucial.

Severe chronic periodontitis is not common in Acromegaly: Potential protective role of gingival BMP-2

Background/aim: Advanced chronic periodontitis is observed rarely in acromegaly. Periodontal tissue including the alveolar bone is seemed to be spared from the systemic metabolic derangements of bone in this patient population. Chronic elevation of growth hormone, IGF-1, and bone morphogenetic proteins may play a role in periodontal tissue regeneration in acromegalics. In this study, we aimed to evaluate the potential roles of local gingival bone morphogenetic proteins (BMP) in periodontal tissue pathology in acromegaly. Materials and methods: Thirty-five patients with acromegaly and 22 healthy subjects were recruited. All the participants were examined by the same periodontologist for the diagnosis of periodontal diseases. BMP-2 and -4 were studied in gingival crevicular fluid. Results: Gingival BMP-2 and BMP-4 levels were similar in acromegaly and control groups in general, with and without chronic periodontitis. For all the participants, gingival BMP-2 levels were statistically lower in those participants with chronic periodontitis then those without periodontitis (29.4 ± 11.2 vs. 41.2 ± 23.2, respectively, p = 0.027). Causal relation between the gingival BMP levels and periodontal tissue health status was tested with one way ANOVA which revealed a significant difference between gingival BMP- 2 levels in those with different degrees of periodontal tissue pathology (p = 0.025). When analyzed separately, gingival BMP-2 levels revealed a causal relation with the degree of periodontal pathology with borderline significance only in patients with acromegaly (p = 0.057). Conclusion: Acromegaly is a disease with an unexpectedly low frequency of advanced periodontitis, irrespective of the long disease duration and pathognomonic oral manifestations. BMP-2 might have a protective role against chronic advanced periodontitis in these patients.

Maternal and cord blood homocysteine, vitamin B12, folate, and B-type natriuretic peptide levels at term for predicting congenital heart disease of the neonate: A case-control study.

Objective: To investigate the effectiveness of the metabolic markers homocysteine, vitamin B12, folate, and B-type natriuretic peptide in maternal and cord blood for detecting congenital heart disease.Methods: Homocysteine, vitamin B12, folate, and B-type natriuretic peptide concentrations in maternal and cord blood samples at term were measured in the case (n = 42) and control (n = 43) groups with and without fetal congenital heart disease, respectively. Additionally, newborns with congenital heart disease were divided into two subgroups: those with (n = 30) and without (n = 8) 6-month infant survival. The case and control groups and case subgroups were compared with each other with respect to maternal age, gravidity, parity, gestational age at delivery, birth weight, maternal and cord blood levels of homocysteine, vitamin B12, folate, and B-type natriuretic peptide, and arterial cord blood pH and base excess values. Statistical analyses were performed using SPSS for Windows, version 22.0. The Student's t-test, the Mann-Whitney U test, and the χ2 test were used where appropriate. A p value of < .05 was considered statistically significant.Results: Mean maternal age, birth weight and median gravidity, parity and gestational age at delivery were not significantly different between the case and control groups, as well as between the case subgroups (all p > .05). Concentrations of metabolic markers in maternal blood were not significantly different between the two groups (p > .05). Homocysteine and B-type natriuretic peptide levels in cord blood samples were significantly higher, whereas folate levels were significantly lower in the case group compared with the control group (all p < .05). Cord blood B-type natriuretic peptide levels were significantly higher (p < .05) and arterial cord blood pH values were significantly lower (p < .05) in the case subgroup without 6-month infant survival compared with the case subgroup with 6-month infant survival.Conclusion: High cord blood B-type natriuretic peptide and homocysteine levels and low cord blood folate levels at term may be useful for predicting congenital heart disease in the neonate. Neonates with congenital heart disease who have high cord blood B-type natriuretic peptide and low pH values may have adverse outcomes.

Phosphodiesterase 4 inhibitor plus metformin is superior to metformin alone for the treatment of polycystic ovary syndrome: A rat model study.

The role of metformin in the management of polycystic ovary syndrome (PCOS) and PCOS-related obesity remains controversial. Recent research on the treatment of PCOS-related obesity investigated novel therapeutic agents with the potential to work synergistically with metformin. The aim of the present study was to determine the synergistic effect of a phosphodiesterase 4 inhibitor (PDE4i) and metformin on weight and hormonal changes in a rat model of PCOS. A total of 40 female Sprague-Dawley rats were randomly divided into 4 groups (n=10/group): Sham; PCOS control (no medication after PCOS induction with dehydroepiandrosterone); metformin (300 mg/kg/day p.o. after PCOS induction); and metformin + PDE4i (300 mg/kg/day p.o. metformin + 0.5 mg/kg/day p.o. PDE4i after PCOS induction). The body weight was measured every 7 days, from day 1 to day 49. Vaginal smears were performed and examined daily via light microscopy for determination of the stage of each rat's estrous cycle. At the end of 21st day and at the end of the study, blood samples were collected from rats and the testosterone and insulin levels were measured. Immunohistochemical staining was performed to quantify phosphorylated cyclic AMP response element-binding protein expression in all groups. At the end of the study, the median body weight differed significantly among the groups (χ2=30.581, P<0.001), being the highest in the PCOS control group and the lowest in the metformin + PDE4i group. At the end of the study, the median testosterone level differed significantly among the groups (χ2=27.057, P<0.001), being the highest in the PCOS control group and the lowest in the metformin + PDE4i group. The cycle was restored to normal at the end of the study in all the rats in the metformin and metformin + PDE4i groups, whereas an irregular cycle persisted in all the rats in the PCOS control group. In conclusion, PDE4i + metformin was superior to metformin alone in reducing weight gain and decreasing the testosterone levels in a rat model of PCOS.

Cystatin-C and TGF-β levels in patients with diabetic nephropathy / Concentración de cistatina C y TGF-β en pacientes con nefropatía diabética

Objetivo: Evaluar la insuficiencia renal en pacientes con diabetes tipo 2 con normoalbuminuria o microalbuminuria mediante la detección de la concentración de cistatina C en suero y de TGF-β en suero y orina. Métodos: Estudio transversal realizado en el Departamento de Endocrinología de la Facultad de Medicina de la Universidad de Baskent. En el estudio, se incluyó a pacientes con diabetes mellitus tipo 2 sin nefropatía diabética manifiesta conocida. Los pacientes seleccionados se estratificaron en 4 grupos, agrupados en términos de edad, sexo, grado de microalbuminuria y filtración glomerular estimada (FGe) calculada mediante la fórmula MDRD. Resultados: Se incluyó a 78 pacientes. Se clasificaron en 4 grupos dependiendo de la excreción urinaria de albúmina y de la FGe. Se observó que la complicación macrovascular era mayor en los pacientes con microalbuminuria que en otros (p<0,01), pero no hubo diferencias con relación a otras complicaciones diabéticas. La concentración sérica de cistatina C fue significativamente mayor en los pacientes del grupo 1 con normoalbuminuria, mientras que las concentraciones de TGF-β1 en suero y orina fueron mayores en los pacientes del grupo 2 con microalbuminuria. Se observó una correlación negativa entre la concentración sérica de cistatina C y la FGe en los pacientes del grupo 2 (r=−0,892, p<0,001). Por último, se observó una correlación negativa entre la FGe y la cistatina C en todos los grupos de pacientes (r=−0,726, p=0,001). Conclusiones: Aunque se recomienda la excreción urinaria de albúmina para la detección de la nefropatía diabética tipo 2, hay un grupo de pacientes con disminución de la FGe, pero sin aumento de la excreción urinaria de albúmina, en los que estaba indicado usar la concentración de cistatina C en suero como un biomarcador temprano de nefropatía diabética (AU)

Objective: To evaluate renal impairment in type 2 diabetic patients with normoalbuminuria or microalbuminuria by detection of serum cystatin C and serum and urinary TGF-β levels. Methods: Cross-sectional study conducted at the Department of Endocrinology in Baskent University School of Medicine. Patients with type 2 diabetes mellitus without known overt diabetic nephropathy were included in the study. Recruited patients were stratified into four groups, matched in terms of age, gender, microalbuminuria level and estimated GFR calculated with MDRD. Results: 78 patients were enrolled. They were categorized into four groups depending on their urinary albumin excretion and estimated glomerular filtration rate. Macrovascular complication was found to be higher in patients with microalbuminuria than in other patients (p<0.01), but there were no differences in terms of other diabetic complications. Serum cystatin C level was significantly higher in normoalbuminuric group one patients, while serum and urinary TGF-β1 levels were higher in microalbuminuric group two patients. The serum level of cystatin C was found to negatively correlate with eGFR in group two patients (r=−0.892, p<0.001). Finally, there was a negative correlation between eGFR and cystatin C in all the patient groups (r=−0.726, p=0.001). Conclusions: Although urinary albumin excretion is recommended for the detection of type two diabetic nephropathy, there is a group of patients with decreased eGFR but without increased urinary albumin excretion, in which serum cystatin C level was indicated to be used as an early biomarker of diabetic nephropathy (AU)

Cystatin-C and TGF-ß levels in patients with diabetic nephropathy.

OBJECTIVE: To evaluate renal impairment in type 2 diabetic patients with normoalbuminuria or microalbuminuria by detection of serum cystatin C and serum and urinary TGF-ß levels. METHODS: Cross-sectional study conducted at the Department of Endocrinology in Baskent University School of Medicine. Patients with type 2 diabetes mellitus without known overt diabetic nephropathy were included in the study. Recruited patients were stratified into four groups, matched in terms of age, gender, microalbuminuria level and estimated GFR calculated with MDRD. RESULTS: 78 patients were enrolled. They were categorized into four groups depending on their urinary albumin excretion and estimated glomerular filtration rate. Macrovascular complication was found to be higher in patients with microalbuminuria than in other patients (p<0.01), but there were no differences in terms of other diabetic complications. Serum cystatin C level was significantly higher in normoalbuminuric group one patients, while serum and urinary TGF-ß1 levels were higher in microalbuminuric group two patients. The serum level of cystatin C was found to negatively correlate with eGFR in group two patients (r=-0.892, p<0.001). Finally, there was a negative correlation between eGFR and cystatin C in all the patient groups (r=-0.726, p=0.001). CONCLUSIONS: Although urinary albumin excretion is recommended for the detection of type two diabetic nephropathy, there is a group of patients with decreased eGFR but without increased urinary albumin excretion, in which serum cystatin C level was indicated to be used as an early biomarker of diabetic nephropathy.

Alternative tumor markers in the diagnosis of ovarian cancer.

OBJECTIVES: The aim of the study was to assess the usefulness of various tumor markers (CA125, HE4, bcl2) measured in serum, urine and saliva in the differential diagnosis of adnexal masses. MATERIAL AND METHODS: Our study was conducted at the Baskent University Medical School, Department of Obstetrics and Gynecology, Ankara, Turkey, between November 2010 and March 2011. Fifty patients with a suspicion of malignant adnexal mass and 30 controls were included in the study. Serum and urine CA-125, HE4, and bcl2 levels were evaluated for their role in the diagnosis of epithelial ovarian cancer (EOC). RESULTS: Serum CA-125 and HE4 levels, and urine HE4 levels were significantly higher in malignant cases as compared to controls (p < 0.05). Mean levels of bcl2 in saliva and urine were similar in malignant cases and controls (p > 0.05). CONCLUSIONS: We demonstrated that serum CA125, serum HE4 and urine HE4 levels were elevated in patients with ovarian cancer. These findings should be assessed in future studies with larger sample sizes in order to reach more definite conclusions.

The effect of adipose stromal vascular fraction on transverse rectus abdominis musculocutaneous flap: an experimental study.

BACKGROUND: Transverse rectus abdominis musculocutaneous (TRAM) flap is one of the options in reconstruction after breast cancer surgery for breast reconstruction. Tissue necrosis often occurs in the third and fourth perfusion zones of the flap. A study was planned to find out the effects of adipose stromal vascular fraction (SVF) cells on viability of TRAM flap and the experimental model was designed to be applicable in clinical practice. METHODS: Right inferior epigastric artery pedicled, 5 × 2.5 cm sized TRAM flap was used as a flap model in 30 rats in three groups (group 1: sham; group 2: phosphate-buffered saline (PBS); group 3: SVF cell injected). The viability of the flaps were assessed on the postoperative 7th day with photographs and software for the calculations. RESULTS: The mean viable flap percentage to total flap area was recorded as 51.8% ± 11.19, 49.5% ± 10.30, 82.3% ± 9.56, in group 1, group 2, and group 3, respectively (p < 0.05). The mean capillary density was noted as 5.15 ± 0.56, 4.37 ± 0.58, and 12.40 ± 1.17 in groups 1, 2, and 3, respectively (p < 0.05). The fibrosis gradient indicated no difference between the groups (p > 0.05). The in-vivo differentiation of SVF cells to endothelial cells was noted. The blood VEGF levels showed a marked increase in the experimental group (p < 0.05). CONCLUSION: The adipose SVF cells were found out to improve the TRAM flap viability and decrease necrosis, especially in zone 3 and 4.

Aspirin resistance in cerebrovascular disease and the role of glycoprotein IIIa polymorphism in Turkish stroke patients.

Aspirin resistance occurs in 5-45% of high-risk patients, with various mechanisms proposed for its development. This study aimed to determine the relationships among aspirin resistance, aspirin dosage, type of aspirin and glycoprotein IIIa P1A1/A2 polymorphism in patients with vascular risk factors. Two hundred and eight (75 symptomatic, 133 asymptomatic) patients with vascular risk factors who were using aspirin for primary or secondary prevention were prospectively included. The symptomatic group was further classified into two groups according to aspirin use at the time of stroke. Aspirin resistance was measured by the PFA-100 system (collagen/epinephrine cartridge) and glycoprotein IIIa P1A1/A2 polymorphism was determined by PCR. The overall prevalence of aspirin resistance was 32.2%. The mean age of patients with aspirin resistance was significantly higher than that in those who did not have resistance (P = 0.009). The prevalence of aspirin resistance was similar for the symptomatic and asymptomatic under aspirin therapy groups. The resistance rate was found to be highest with 100 mg enteric-coated preparation use (39.3%). Increasing the aspirin dosage and/or shifting to uncoated preparations caused a change in aspirin sensitivity of 36-60%. Repeated measurements showed development of aspirin resistance in 14% of patients who were sensitive to aspirin in previous measurements. Glycoprotein IIIaP1A1/A2 polymorphism, aspirin resistance and development of atherothrombotic stroke were not significantly related. The effect of aspirin can change by time, dosage and type of preparation used. There are no relationships among glycoprotein IIIa P1A1/A2 polymorphism, aspirin resistance and development of atherothrombotic stroke.

Is Celiac Disease an Etiological Factor in Children with Nonsyndromic Intellectual Disability?

To determine the prevalence of celiac disease in children and adolescents with nonsyndromic intellectual disability, we investigated serum levels of tissue transglutaminase antibody and total IgA from 232 children with nonsyndromic intellectual disability and in a healthy control group of 239 children. Study participants who were positive for tissue transglutaminase antibody underwent a duodenal biopsy. A total of 3 patients in the nonsyndromic intellectual disability group (5.45%) and 1 in the control group (0.41%) had positive serum tissue transglutaminase antibody (P > .05). Duodenal biopsy confirmed celiac disease in only 1 patient who had nonsyndromic intellectual disability. In this present study, children with nonsyndromic intellectual disability did not exhibit a higher celiac disease prevalence rate compared with healthy controls. Therefore, we suggest that screening test for celiac disease should not be necessary as a part of the management of mild and moderate nonsyndromic intellectual disability. However, cases of severe nonsyndromic intellectual disability could be examined for celiac disease.

Comparison of Carvedilol and Metoprolol for Preventing Contrast-Induced Nephropathy after Coronary Angiography.

AIMS: Contrast-induced nephropathy (CIN) is one of the most common causes of hospital-acquired acute renal failure. Oxidative stress and vasoconstriction might play key roles in its pathogenesis. In a few experimental models, antioxidant properties of carvedilol have been documented. The aim of this study was to analyze and compare the effects of carvedilol and metoprolol on the development of CIN in patients undergoing coronary angiography. METHODS: One hundred patients currently taking metoprolol and 100 patients currently taking carvedilol were enrolled into the study. Venous blood samples were obtained before and 48 h after contrast administration. Cystatin C and malondialdehyde values were examined and compared. CIN was defined as a creatinine increase of at least 25% or 0.5 mg/dl from the baseline value. RESULTS: Seven patients in the carvedilol group (7%) and 22 patients in the metoprolol group (22%) developed CIN (p = 0.003). In the metoprolol group, the median cystatin C concentration increased significantly from 978 to 1,086 ng/ml (p = 0.001) 48 h after radiocontrast administration. In the carvedilol group, the median cystatin C concentration did not change significantly (1,143 vs. 1,068 ng/ml; p = 0.94). In the metoprolol group, the mean malondialdehyde concentration increased significantly from 7.09 ± 1.48 to 8.38 ± 2.6 nmol/l (p < 0.001). In the carvedilol group, the mean serum malondialdehyde concentration did not change significantly (7.44 ± 1.21 vs. 7.56 ± 1.11 nmol/l; p = 0.59). CONCLUSION: When compared to metoprolol, carvedilol might decrease oxidative stress and subsequent development of CIN.

AMH levels at central precocious puberty and premature thelarche: is it a parameter?

BACKGROUND: The possible difference of antimüllerian hormone (AMH) levels at central precocious puberty (CPP) and premature thelarche (PT) has not been properly evaluated. OBJECTIVE/HYPOTHESIS: By evaluating AMH levels in girls with diagnosed CPP and PT, we aim to show the change of AMH levels at the pubertal onset. SUBJECTS: Sixty-five girls who have breast development before the age of 8 years and 25 healthy girls were enrolled in the study. METHODS: The subjects were divided into two groups as CPP and PT, according to results of GnRH test. AMH levels were determined in the two groups. RESULTS: The mean AMH levels of the CPP group were significantly lower than those in the PT group (13.57±9.85 pmol/L and 58.42±12.78 pmol/L, respectively, p=0.022). CONCLUSION: These results suggest that the AMH levels decrease in the duration of the hypothalamus-pituitary-ovarian axis activation. We thought that AMH might/may be a marker for distinguishing between CPP and PT.

The Notch pathway is a critical regulator of angiogenesis in a skin model of ischemia.

The Notch pathway is definitely required for normal vascular development. Although the contribution of Notch in postnatal angiogenesis is the focus of intense investigation, the implication of Notch in reparative neovascularization in the skin remains unexplored. In this study, we investigated Notch changes using a skin model of ischemia. Thirty Sprague-Dawley rats were divided into two groups. In the surgery group (n = 24), a caudally based dorsal skin flap was raised and sutured back into its initial position. In the control group, no surgical procedure was performed. Tissue biopsies were obtained at different time intervals. Tissue specimens were assessed for Delta-like ligand 4 (DLL4) and vascular endothelial growth factor (VEGF) gene expression by real-time polymerase chain reaction (PCR). Immunohistochemical staining was used for detection of DLL4 in tissue materials. Quantitative assessment of skin flap microvasculature was made. Compared with normoperfused tissue, VEGF and DLL4 expressions increased significantly (p < 0.01). Immunohistochemical analysis revealed weak and patchy expression of DLL4 in microvascular endothelial cells of normoperfused tissues. Conversely, DLL4 expression was upregulated in capillary endothelial cells after ischemia. In conclusion, in this study we have shown that the Notch ligand DLL4 is upregulated in skin tissue after ischemia. A deeper understanding of these fundamental principles will aid in the development of new avenues for the treatment of blood vessel-related skin pathologies.

The Effects of Niacin on Inflammation in Patients with Non-ST Elevated Acute Coronary Syndrome.

BACKGROUND: In this study, we aimed to evaluate the effects of niacin on high sensitivity C reactive protein (hs-CRP) and cholesterol levels in non-ST elevated acute coronary syndrome (NSTE-ACS) patients. METHODS: In this prospective, open label study, 48 NSTE-ACS were randomized to niacin or control group. Patients continued their optimal medical therapy in the control group. In the niacin group patients were assigned to receive extended-release niacin 500 mg/day. Patients were contacted 1 month later to assess compliance and side effects. Blood samples for hs-CRP were obtained upon admittance to the coronary care unit, in the third day and in the first month of the treatment. Fasting blood samples for cholesterol levels were obtained before and 30 days after the treatment. The primary end point of the study was to evaluate changes in hs-CRP, cholesterol levels, short-term cardiovascular events, and the safety of niacin in NSTE-ACS. RESULTS: Baseline demographic, clinical and laboratory characteristics were similar between the two groups. Logarithmic transformation of baseline and 3(rd) day hs-CRP levels were similar between the groups; but 1 month later, logarithmic transformation of hs-CRP level was significantly lower in the niacin group (0.43 ± 0.39 to 0.83 ± 0.91, p = 0.04). HDL-C level was significantly increased in the niacin group during follow-up. Drug related side effects were seen in 7 patients in the niacin group but no patients discontinued niacin. CONCLUSIONS: Our findings demonstrate that lower dose extended release niacin can be used safely and decreases hs-CRP and lipid parameters successfully in NSTE-ACS patients. KEY WORDS: Acute coronary syndrome; hs-CRP; Inflammation; Niacin.

Inhibition of the Notch Pathway Promotes Flap Survival by Inducing Functional Neoangiogenesis.

OBJECTIVE: The Notch pathway seems to function as an antiangiogenic factor, negatively regulating the sprouting effect of vascular endothelial growth factor (VEGF). This function is well defined in embryonic and tumor vasculature. However, little is known about its function in ischemia-induced angiogenesis. In the first part of this study, we investigated the role of Notch in reparative angiogenesis after ischemia. In the second part, we hypothesized that anti-Notch therapy will result in increased angiogenic sprouting. We analyzed the effect of Notch inhibition in the induction of angiogenic sprouting. METHODS: In the first part, we investigated the effect of ischemia on the Notch ligand delta-like ligand 4 (DLL4). Twenty rats were divided equally into 2 groups. In the surgery group, dorsal skin flap was used as model of ischemia. In the control group, no surgical procedure was performed. DLL4 and VEGF gene expressions were assessed. Immunohistochemical staining was used for detection of DLL4 in tissue materials. Plasma levels of VEGF and DLL4 were measured. In the second part, we investigated the effect of Notch inhibition using a gamma-secretase inhibitor (GSI) on inducing neoangiogenesis. Twenty rats were assigned to 2 equal groups. In all animals, dorsal skin flap was raised and sutured back into its bed. Animals in the GSI-treated group received GSI intravenously after surgery for 3 days. Saline was administered in the control group. Necrotic area measurements, microangiography, and histologic evaluations were performed to compare groups. RESULTS: In the first part, VEGF and DLL expressions increased in ischemic tissues (P < 0.01). Immunohistochemical analysis revealed that DLL4 expression was upregulated in capillary endothelial cells after ischemia. Plasma levels for VEGF and DLL4 were higher in the animals that underwent surgery (P < 0.01). In the second part, GSI treatment resulted in higher flap survival rates (P < 0.05). Microscopic analysis exhibited increase in the number of microvascular structures after GSI treatment (P < 0.05). Microangiographic evaluation showed that neovascularization increased in the GSI-applied flaps. CONCLUSIONS: We present an evidence for the importance of the Notch pathway in the regulation of ischemia-induced angiogenesis. Notch inhibition promotes flap survival by creating a neovasculature that has an increase in vascular density.