Inactive lifestyle in adults with bilateral spastic cerebral palsy

Objective: To quantify the level of everyday physical activity in adults with bilateral spastic cerebral palsy, and to study associations with personal and cerebral palsy-related characteristics. Participants and methods: Fifty-six adults with bilateral spastic cerebral palsy (mean age 36.4 (standard deviation (SD) 5.8) years, 62% male) participated in the study. Approximately 75% had high gross motor functioning. Level of everyday physical activity was measured with an accelerometry-based Activity Monitor and was characterized by: (i) duration of dynamic activities (composite measure, percentage of 24 h); (ii) intensity of activity (motility, in gravitational acceleration (g)); and (iii) number of periods of continuous dynamic activity. Outcomes in adults with cerebral palsy were compared with those for able-bodied age-mates. Results: Duration of dynamic activities was 8.1 (SD 3.7) % (116 min per day), and intensity of activity was 0.020 (SD 0.007) g; both outcomes were significantly lower compared with able-bodied age-mates. Of adults with cerebral palsy, 39% had at least one period of continuous dynamic activities lasting longer than 10 min per day. Gross motor functioning was significantly associated with level of everyday physical activity (Rs -0.34 to -0.48; p≤0.01). Conclusion: Adults with bilateral spastic cerebral palsy, especially those with low-level gross motor functioning, are at risk for an inactive lifestyle

The presence of tissue renin-angiotensin system components in human burn wounds and scars

Objective: Healing of severe and large surface burn wounds is faced with hurdles such as aberrant wound healing and excessive scar formation. The tissue renin-angiotensin system (tRAS) is involved in dermal wound healing, and fibrosis of other organs. However, little is known about the presence of tRAS during burn wound healing in human skin. This study investigated the presence of tRAS components in human burn wounds and scars. Methods: Dermal tissue biopsies were collected from 39 patients and divided into six categories: burn wounds post burn day (PBD)0–9, PBD11–21 and PBD22–37; young scars (1.5–3.5 months), mature scars (>12 months) and control skin from 9 patients. The tRAS components angiotensin converting enzyme (ACE), chymase, angiotensin receptor 1 (AT1) and Mas receptor were detected via immunohistochemistry. Digital images were acquired and analyzed using image analysis software. Results: Burn wounds from PBD22–37 showed a decreased expression of ACE and chymase compared to earlier time points or control, respectively. In contrast, ACE expression was increased in young scars compared to control skin but was normalized in mature scars. In comparison to control, mature scars showed increased AT1 expression. Conclusions: These results show the presence of components of tRAS in human burn wounds and scars. In addition, they suggest that tRAS has a time-dependent response during burn wound healing. Reduced tRAS might play a role in delayed healing, while an increase during remodeling phase might contribute to scar formation. This research provides a basis for future studies exploring tRAS involvement in burn wounds and scars. Keywords: Tissue renin-angiotensin system, Burn wounds, Scars, Ski

Effects of oral paricalcitol and calcitriol treatment on peritoneal membrane characteristics of peritoneal dialysis patients — A pilot study

♦ Background: Long-term peritoneal dialysis (PD) is frequently complicated by technique failure preceded by peritoneal remodeling. Vitamin D has potent immunomodulatory characteristics: anti-inflammatory, anti-angiogenic, anti-fibrotic properties, and influences on the macrophage phenotype. Little is known about the relation between pleiotropic effects attributed to vitamin D3 and the peritoneal membrane and what is the most appropriate vitamin D sterol in prevention of peritoneal remodeling in PD patients. Animal studies have suggested that paricalcitol has advantageous effects: decrease in plasma markers of inflammation, less peritoneal fibrosis, less pronounced PD-induced omental angiogenesis, and prevention of loss of ultrafiltration. We investigated whether paricalcitol is advantageous over calcitriol in PD patients. ♦ Method: A multicenter open-label 1:1 randomized non-blinded clinical pilot study enrolled prevalent continous ambulatory PD (CAPD) patients for a period of 6 months comparing paricalcitol with calcitriol. All patients were treated with biocompatible PD fluids. The primary endpoint was peritoneal transport parameters, exploratory endpoints were biomarkers of peritoneal damage and cell analysis (including M1/M2 macrophages), and safety endpoints were metabolic parameters. ♦ Results: Twenty-seven patients were included. Fourteen were randomized to treatment with paricalcitol. There was no difference in peritoneal transport parameters between the groups. We found similar Kt/V, D/P creatinine, D/D0 glucose, ultrafiltration, residual renal function and 24-h urine volume during the study. There was no difference in biomarker concentrations in peritoneal effluents, and no difference in leucocyte differentiation or mesothelial cells between the groups at any time point. Parathyroid hormone (PTH) levels decreased after administration of calcitriol after 12 and 24 weeks compared with baseline (p = 0.001; p = 0.025). Parathyroid hormone levels in the paricalcitol group did not change significantly. ♦ Conclusion: In this pilot study we investigated the effect of active vitamin D in PD patients. We found no specific benefit of active vitamin D3 in vitamin D3-sufficient PD patients. Additional studies in preferably incident patients, with an adequate PTH suppression in the intervention groups and during a longer period, are required to test the beneficial effects of active vitamin D3 over no treatment and to investigate whether in 25(OH)D3-deficient PD patients the type of active vitamin D3 matters

Vitamin D attenuates endothelial dysfunction in uremic rats and maintains human endothelial stability

Background-—Dysfunctional endothelium may contribute to the development of cardiovascular complications in chronic kidney disease (CKD). Supplementation with active vitamin D has been proposed to have vasoprotective potential in CKD, not only by direct effects on the endothelium but also by an increment of a-Klotho. Here, we explored the capacity of the active vitamin D analogue paricalcitol to protect against uremia-induced endothelial damage and the extent to which this was dependent on increased a-Klotho concentrations. Methods and Results-—In a combined rat model of CKD with vitamin D deficiency, renal failure induced vascular permeability and endothelial-gap formation in thoracic aorta irrespective of baseline vitamin D, and this was attenuated by paricalcitol. Downregulation of renal and serum a-Klotho was found in the CKD model, which was not restored by paricalcitol. By measuring the real-time changes of the human endothelial barrier function, we found that paricalcitol effectively improved the recovery of endothelial integrity following the addition of the pro-permeability factor thrombin and the induction of a wound. Furthermore, immunofluorescence staining revealed that paricalcitol promoted vascular endothelial-cadherin-based cell-cell junctions and diminished F-actin stress fiber organization, preventing the formation of endothelial intracellular gaps. Conclusions-—Our results demonstrate that paricalcitol attenuates the CKD-induced endothelial damage in the thoracic aorta and directly mediates endothelial stability in vitro by enforcing cell-cell interactions