Suprachoroidal Adipose Tissue-Derived Mesenchymal Stem Cell Implantation in Patients with Dry-Type Age-Related Macular Degeneration and Stargardt's Macular Dystrophy: 6-Month Follow-Up Results of a Phase 2 Study

This prospective clinical case series aimed to investigate the safety and efficacy of suprachoroidal adipose tissue-derived mesenchymal stem cell (ADMSC) implantation in patients with dry-type age-related macular degeneration (AMD) and Stargardt's macular dystrophy (SMD). This study included four patients with advanced-stage dry-type AMD and four patients with SMD who underwent suprachoroidal implantation of ADMSCs. The best-corrected visual acuity (BCVA) in the study was 20/200. The worse eye of the patient was operated on. Patients were evaluated on the first day, first week, and first, third, and sixth months postopera-tively. BCVA, anterior segment and fundus examination, color photography, fundus autofluorescence, optical coherence tomography, and visual field examination were carried out at each visit. Fundus fluorescein angiography and multifocal electroretinography (mf-ERG) recordings were performed at the end of the first, third, and sixth months and anytime if necessary during the follow-up. All eight patients completed the sixth month follow-up. None of them had any systemic or ocular complications. All of the eight patients experienced visual acuity improvement, visual field improvement, and improvement in mf-ERG recordings. Stem cell treatment with suprachoroidal implantation of ADMSCs seems to be safe and effective in the treatment of dry-type AMD and SMD

Role of transforming growth factor-β2 in, and apossible transforming growth factor-β2 gene polymorphism as a marker of, renal dysfunction in essential hypertension: A study in Turkish patients

AbstractBackground:Many studies have shown that transforming growth factor(TGF)-β has a major role in renal scarring in many renal diseases and hypertension.Objectives:The primary aim of this study was to investigate both the relationship between hypertension and serum and urinary levels of TGF-β2 (a more sensitive isoform for glomeruli than TGF-β1), and the effects of combination therapy with perindopril + indapamide on microalbuminuria, which becomes an early indicator of hypertensive benign nephropathy, and serum and urinary TGF-β2 levels in patients with mild to moderate essential hypertension. In addition, we examined the possible relationship between TGF-β2 gene polymorphism and essential hypertension.Methods:This study was conducted at the Department of Nephrology, Medical Faculty, Gazi University, Ankara, Turkey. Patients aged ≥18 years with newly diagnosed mild to moderate essential hypertension (systolic/diastolic blood pressure [SBP/DBP] >120/>80 mm Hg) who had not previously received antihypertensive treatment were included in the study. Patients with stage I hypertension received perindopril 2 mg + indapamide 0.625 mg (tablet), and patients with stage lI hypertension received perindopril 4 mg + indapamide 1.125 mg (tablet). All study drugs were given OD (morning) PO with food for 6 months. Serum and urinary TGF-β2 and creatinine levels and serum and urinary albumin levels were measured before and after perindopril + indapamide administration. Amplified DNA fragments of the TGF-β2 primer region were screened using amplification refractory mutation system polymerase chain reaction analysis, and the number of ACA repeats was confirmed by DNA sequencing. Genetic studies were performed using a commercial TGF-β2 kit.Results:Forty patients were enrolled in the study, and 38 patients (27 women, 11 men; mean [SD] age, 46.3 [6.5] years) completed it. SBP and DBP were significantly decreased from baseline with perindopril/indapamide (both, P < 0.001). Microalbuminuria and urinary TGF-β2 levels also decreased significantly from baseline (P = 0.04 and P < 0.001, respectively), whereas the serum TGF-β2 level did not change significantly. Three patients, all of whom were found to have TGF-β2 gene mutations, had increased urinary TGF-β2 levels despite good blood pressure control.Conclusions:The results of this study in patients with mild to moderate hypertension suggest that, despite good clinical control of blood pressure, the persistence of microalbuminuria and high urinary TGF-β2 levels might predict renal impairment. When treating these patients, genetic tendencies and possible polymorphisms on the TGF-β2 locus should be kept in mind

HLA Genotypes in Turkish Hematopoietic Cell Recipients and Likelihood of Finding a Matched Donor Through Family Searches.

Allogeneic hematopoietic stem cell transplant is a life-saving treatment, but donor numbers in Turkey do not meet the increasing demand for this procedure. Here, our objectives were (1) to assess the frequency of HLA-matched related donors in the Turkish population and (2) to identify the HLA antigens and haplotypes that are most frequent in Turkey

Role of transforming growth factor-beta(2) in, and a possible Transforming Growth Factor-beta(2) gene polymorphism as a marker of, renal dysfunction in essential hypertension: A study in Turkish patients

WOS: 000231920000002PubMed: 24672129Background: Many studies have shown that transforming growth factor (TGF)-beta has a major role in renal scarring in many renal diseases and hypertension. Objectives: The primary aim of this study was to investigate both the relationship between hypertension and serum and urinary levels of TGF-beta(2) (a more sensitive isoform for glomeruli than TGF-beta(1))), and the effects of combination therapy with perindopril + indapamide on microalbuminuria, which becomes an early indicator of hypertensive benign nephropathy, and serum and urinary TGF-beta(2) levels in patients with mild to moderate essential hypertension. In addition, we examined the possible relationship between TGF-beta(2) gene polymorphism and essential hypertension. Methods: This study was conducted at the Department of Nephrology, Medical Faculty, Gazi University, Ankara, Turkey. Patients aged >= 18 years with newly diagnosed mild to moderate essential hypertension (systolic/diastolic blood pressure [SBP/DBP] > 120/> 80 mm Hg) who had not previously received antihypertensive treatment were included in the study. Patients with stage I hypertension received perindopril 2 mg + indapamide 0.625 mg (tablet), and patients with stage 11 hypertension received perindopril 4 mg + indapamide 1.125 mg (tablet). All study drugs were given OD (morning) PO with food for 6 months. Serum and urinary TGF-beta(2) and creatinine levels and serum and urinary albumin levels were measured before and after perindopril + indapamide administration. Amplified DNA fragments of the TGF-beta(2) primer region were screened using amplification refractory mutation system polymerase chain reaction analysis, and the number of ACA repeats was confirmed by DNA sequencing. Genetic studies were performed using a commercial TGF-beta(2) kit. Results: Forty patients were enrolled in the study, and 38 patients (27 women, 11 men; mean [SD] age, 46.3 [6.5] years) completed it. SBP and DBP were significantly decreased from baseline with perindopril/indapamide (both, P < 0.001). Microalbuminuria and urinary TGF-beta(2) levels also decreased significantly from baseline (P = 0.04 and P < 0.001, respectively), whereas the serum TGF-beta(2) level did not change significantly. Three patients, all of whom were found to have TGF-beta(2) gene mutations, had increased urinary TGF-beta(2) levels despite good blood pressure control. Conclusions: The results of this study in patients with mild to moderate hypertension suggest that, despite good clinical control of blood pressure, the persistence of microalbuminuria and high urinary TGF-beta(2) levels might predict renal impairment. When treating these patients, genetic tendencies and possible polymorphisms on the TGF-beta(2) locus should be kept in mind

Factors Affecting Bone Health in Kidney Transplant Recipients: Klotho Gene Single-Nucleotide Polymorphisms and Other Clinical Features

Objectives: Posttransplant bone diseases are a major cause of morbidity in kidney transplant recipients. We investigated the relationship between klotho gene single-nucleotide polymorphisms and bone diseases after kidney transplant. We also aimed to identify possible risk factors for development of bone disease. Materials and Methods: The study consisted of 251 kidney transplant recipients (164 men and 87 women) with minimum follow-up of 3 years after kidney transplant. Patients with prolonged immobilization, malignancy, parathyroidectomy, glomerular filtration rates less than 30 mL/min/1.73 m2, hypo-or hyperthyroidism, and treatment with drugs that affect bone metabolism were excluded. We investigated the relationship between 6 single-nucleotide polymor-phisms of the klotho gene (rs480780, rs211234, rs576404, rs211235, rs9536314, and rs1207568) and development of osteoporosis, avascular bone necrosis, and persistent hyperparathyroidism. Results: Longer dialysis treatment (odds ratio, 1.13; P = .002) and rs211235 single-nucleotide polymor-phism in the klotho gene (odds ratio, 9.87; P = .001 for GG genotype) were significantly associated with persistent hyperparathyroidism. A higher magnesium level was detected as a protective factor from development of persistent hyperparathyroidism (odds ratio, 0.19; P = .009). Persistent hyperparathyroidism was defined as a risk factor for development of osteopenia/osteoporosis (odds ratio, 2.76; P = .003) and avascular bone necrosis (odds ratio, 2.52; P = .03). Although the rs480780 (odds ratio, 8.73; P = .04) single-nucleotide polymorphism in the klotho gene was defined as a risk factor for development of osteopenia/osteoporosis, none of the klotho single-nucleotide polymorphisms was found to be associated with development of avascular bone necrosis. Conclusions: Persistent hyperparathyroidism could be an important indicator for development of bone disease in kidney transplant recipients. Also, some of the klotho gene single-nucleotide polymorphisms are associated with higher risk for bone disease after kidney transplant

Impact of medium cut-off membranes on S100A12 and soluble receptor for advanced glycation end products

Introduction: Of the most remarkable molecules associated with atherosclerosis and the cardiovascular outcome are S100A12 (10,379.5 Da) and soluble receptor for advanced glycation end products (sRAGE-42,803 Da) in the hemodialysis (HD) population. We designed a study investigating the effects of the medium cut-off (MCO) dialyzers focusing on S100A12 and sRAGE in HD patients compared with low-flux and high-flux dialyzers. Methods: This single-site, prospective, observational study comprises age and sex-matched HD groups (low-flux, high-flux, and MCO). Blood samples were drawn at baseline (predialysis and postdialysis) and the sixth month (predialysis). Results: Groups had similar demographic features and laboratory parameters. Baseline S100A12 levels of the groups were similar [34.3 (±66.5), 30.9 (±42.7), and 40.6 (±29.6); p = 0.13]. Compared to their baseline, the sixth-month S100A12 levels were constant in low-flux and high-flux group and significantly lower in MCO group (p = 0.16, p = 0.33, and p = 0.004). Baseline sRAGE levels of the groups were similar at baseline [2.8 (±0.8), 2.7 (±0.6), and 2.6 (±0.7); p = 0.65], and the sixth-month [2.9 (±0.5), 2.4 (±0.7), and 2.4 (±0.8); p = 0.24]. sRAGE levels remained constant in all groups [p = 0.84, p = 0.13, and p = 0.39]. S100A12/sRAGE ratio at baseline and sixth month was constant in low-flux [22.3 (±63.7) and 18.1 (±24.8); p = 0.17] and high-flux groups [11.9 (±15.3) and 13.1 (±5.8); p = 0.26], the ratio decreased significantly in MCO group [16.5 (±11.6) to 7.8 (±5.5); p = 0.03]. Conclusion: Our study suggests that prolonged use of MCO dialyzers is associated with better S100A12 and sRAGE levels. Long-term studies with larger samples are needed to understand the effects of a better S100A12-sRAGE profile provided by MCO dialyzers on HD patients' cardiovascular outcomes