Reduction of Inflammation and Enhancement of Motility after Pancreatic Islet Derived Stem Cell Transplantation Following Spinal Cord Injury

OBJECTIVE: Spinal cord injury (SCI) is a very serious health problem, usually caused by a trauma and accompanied by elevated levels of inflammation indicators. Stem cell-based therapy is promising some valuable strategies for its functional recovery. Nestin-positive progenitor and/or stem cells (SC) isolated from pancreatic islets (PI) show mesenchymal stem cell (MSC) characteristics. For this reason, we aimed to analyze the effects of rat pancreatic islet derived stem cell (rPI-SC) delivery on functional recovery, as well as the levels of inflammation factors following SCI.METHODS: rPI-SCs were isolated, cultured and their MSC characteristics were determined through flow cytometry and immunofluorescence analysis. The experimental rat population was divided into three groups : 1) laminectomy & trauma, 2) laminectomy & trauma & phosphate-buffered saline (PBS), and 3) laminectomy+trauma+SCs. Green fluorescent protein (GFP) labelled rPI-SCs were transplanted into the injured rat spinal cord. Their motilities were evaluated with Basso, Beattie and Bresnahan (BBB) Score. After 4-weeks, spinal cord sections were analyzed for GFP labeled SCs and stained for vimentin, S100β, brain derived neurotrophic factor (BDNF), 2’,3’-cyclic-nucleotide 3'-phosphodiesterase (CNPase), vascular endothelial growth factor (VEGF) and proinflammatory (interleukin [IL]-6, transforming growth factor [TGF]-β, macrophage inflammatory protein [MIP]-2, myeloperoxidase [MPO]) and anti-inflammatory (IL-1 receptor antagonis) factors.RESULTS: rPI-SCs were revealed to display MSC characteristics and express neural and glial cell markers including BDNF, glial fibrillary acidic protein (GFAP), fibronectin, microtubule associated protein-2a,b (MAP2a,b), β3-tubulin and nestin as well as antiinflammatory prostaglandin E2 receptor, EP3. The BBB scores showed significant motor recovery in group 3. GFP-labelled cells were localized on the injury site. In addition, decreased proinflammatory factor levels and increased intensity of anti-inflammatory factors were determined.CONCLUSION: Transplantation of PI-SCs might be an effective strategy to improve functional recovery following spinal cord trauma.

Reduction of Inflammation and Enhancement of Motility after Pancreatic Islet Derived Stem Cell Transplantation Following Spinal Cord Injury

OBJECTIVE: Spinal cord injury (SCI) is a very serious health problem, usually caused by a trauma and accompanied by elevated levels of inflammation indicators. Stem cell-based therapy is promising some valuable strategies for its functional recovery. Nestin-positive progenitor and/or stem cells (SC) isolated from pancreatic islets (PI) show mesenchymal stem cell (MSC) characteristics. For this reason, we aimed to analyze the effects of rat pancreatic islet derived stem cell (rPI-SC) delivery on functional recovery, as well as the levels of inflammation factors following SCI. METHODS: rPI-SCs were isolated, cultured and their MSC characteristics were determined through flow cytometry and immunofluorescence analysis. The experimental rat population was divided into three groups : 1) laminectomy & trauma, 2) laminectomy & trauma & phosphate-buffered saline (PBS), and 3) laminectomy+trauma+SCs. Green fluorescent protein (GFP) labelled rPI-SCs were transplanted into the injured rat spinal cord. Their motilities were evaluated with Basso, Beattie and Bresnahan (BBB) Score. After 4-weeks, spinal cord sections were analyzed for GFP labeled SCs and stained for vimentin, S100β, brain derived neurotrophic factor (BDNF), 2’,3’-cyclic-nucleotide 3'-phosphodiesterase (CNPase), vascular endothelial growth factor (VEGF) and proinflammatory (interleukin [IL]-6, transforming growth factor [TGF]-β, macrophage inflammatory protein [MIP]-2, myeloperoxidase [MPO]) and anti-inflammatory (IL-1 receptor antagonis) factors. RESULTS: rPI-SCs were revealed to display MSC characteristics and express neural and glial cell markers including BDNF, glial fibrillary acidic protein (GFAP), fibronectin, microtubule associated protein-2a,b (MAP2a,b), β3-tubulin and nestin as well as antiinflammatory prostaglandin E2 receptor, EP3. The BBB scores showed significant motor recovery in group 3. GFP-labelled cells were localized on the injury site. In addition, decreased proinflammatory factor levels and increased intensity of anti-inflammatory factors were determined. CONCLUSION: Transplantation of PI-SCs might be an effective strategy to improve functional recovery following spinal cord trauma.

Biventricular Noncompaction Cardiomyopathy Accompanied by Severe Pulmonary Valvular Stenosis and Patent Foramen Ovale.

Myocardial non-compaction (NC) is a rare genetic cardiomyopathy commonly believed to develop an intrauterine arrest of endomyocardial morphogenesis. NC is characterized by markedly hypertrabeculations in left ventricle or both ventricles with deep intertrabecular recesses. NC is usually seen isolated, but sometimes other congenital heart abnormalities may accompany to the myocardial NC. In this article we have presented an adult patient with biventricular myocardial NC cardiomyopathy accompanied by severe valvular pulmonary stenosis and patent foramen ovale.

Elevated levels of vitamin B12 in chronic stable heart failure: a marker for subclinical liver damage and impaired prognosis.

BACKGROUND: Elevated vitamin B12 is a sign for liver damage, but its significance in chronic stable heart failure (HF) is less known. The present study investigated the clinical correlates and prognostic significance of vitamin B12 levels in stable systolic HF. METHODS: A total of 129 consecutive patients with HF and 50 control subjects were enrolled. Data regarding demographics, clinical signs, therapeutic and conventional echocardiographic measurements were recorded for all patients. Right-sided HF was defined as the presence of at least one of the typical symptoms (ankle swelling) or specific signs (jugular venous distention or abdominojugular reflux) of right HF. Cox proportional hazards regression analyses were performed to determine the independent prognostic determinants of mortality. RESULTS: Baseline B12 levels in HF patients (n=129) with and without right sided HF were significantly higher compared to healthy controls (n=50): Median 311 pg/mL and 235 pg/mL vs 198 pg/mL, respectively (P=0.005). Folic acid levels were similar between the study groups. Age, ejection fraction, left atrial size, estimated glomerular filtration rate, and direct and indirect bilirubin levels were significantly correlated to serum B12 level in univariate analysis. In multivariate analysis, independent correlates of B12 were direct bilirubin (R=0.51, P<0.001) and age (R=0.19, P=0.028). Patients with HF were followed-up for a median period of 32 months. Median B12 levels were significantly higher in patients who subsequently died (n=35) compared to survivors, but folic acid was not different between the two groups. ROC analysis showed that B12 values ≥270 pg/mL had 80% sensitivity and 58% specificity for predicting all-cause mortality (area under the curve=0.672, 95% CI=0.562-0.781; P=0.003). However, in Cox regression analysis, only left atrial diameter, level of direct bilirubin, and the presence of abdominojugular reflux were independent predictors of death. CONCLUSION: Increased B12 in stable HF patients is associated with increased direct bilirubin due to right HF, indicating a cardiohepatic syndrome, but neither B12 nor folic acid are independently associated with mortality.

Effect of Oral Nitrates on All-Cause Mortality and Hospitalization in Heart Failure Patients with Reduced Ejection Fraction: A Propensity-Matched Analysis.

BACKGROUND: Hydralazine-nitrate combination is recommended for patients with heart failure with reduced ejection fraction (HFrEF)/systolic heart failure who are symptomatic despite guideline-directed medical therapy (GDMT). Use of nitrates alone for this indication is not well-established. This study aims to evaluate the effect of oral nitrates on all-cause mortality and hospitalization in HFrEF patients using GDMT. METHODS AND RESULTS: Nitrate prescription at discharge and its association with all-cause mortality and heart failure hospitalization were examined in a propensity-matched analysis of 648 HFrEF patients followed for a median of 56 months. A total of 269 (42%) patients died during that period. In Cox regression analysis, nitrate usage was associated with a slightly increased mortality risk compared with not using nitrates (hazard ratio 1.29; 95% confidence interval 1.01-1.65; P = .040), which continued modestly after the propensity-matched analysis (hazard ratio 1.26; 95% confidence interval 0.95-1.68; P = .102). In both prematch and propensity-matched analyses, nitrate use was not associated with risk of rehospitalization. No significant effect was detected on subgroups stratified by coronary artery disease, age, gender, and background medical therapy. CONCLUSIONS: In this study, oral nitrate use alone in addition to GDMT did not affect all-cause mortality and hospitalization risk in HFrEF patients during a long-term follow-up. There was even a modest tendency for increased risk of mortality.