Impact of exercise training on oxidative stress in individuals with a spinal cord injury

Individuals with a spinal cord injury (SCI) have an increased cardiovascular risk. We hypothesize that (anti)oxidative imbalance is associated with the increased cardiovascular risk in SCI, while exercise can reverse this status. The aim of the study is to compare baseline levels of oxidative stress and antioxidative capacity between individuals with SCI and able-bodied (AB) subjects, and to assess acute and long-term effects of functional electrical stimulation (FES) exercise on oxidative stress and antioxidative capacity in SCI. Venous blood was taken from subjects with an SCI (n = 9) and age- and gender-matched AB subjects (n = 9) to examine oxidative stress through malondialdehyde (MDA) levels, while superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme levels represented anti-oxidative capacity. Subsequently, subjects with an SCI performed an 8-week FES exercise training period. Blood was taken before and after the first exercise bout and after the last FES session to examine the acute and chronic effect of FES exercise, respectively. Baseline levels of MDA, SOD and GPx were not different between individuals with SCI and AB subjects. SCI demonstrated a correlation between initial fitness level and MDA (R = −0.83, P = 0.05). MDA, SOD and GPx levels were neither altered by a single FES exercise bout nor by 8 weeks FES training. In conclusion, although individuals with an SCI demonstrate a preserved (anti)oxidative status, the correlation between fitness level and (anti)oxidative balance suggests that higher fitness levels are related to improved (anti)oxidative status in SCI. Nonetheless, the FES exercise stimulus was insufficient to acutely or chronically change (anti)oxidative status in individuals with an SCI.     

Clinical characteristics and outcome of intracerebral hemorrhage in young adults

Data on determinants of prognosis after intracerebral hemorrhage (ICH) in young adults are scarce. Our aim was to identify clinical determinants of prognosis after ICH in adults aged 18–50. We investigated 98 consecutive patients with an ICH, aged 18–50 years, admitted to our hospital between 1980 and 2010. Collected ICH characteristics included presenting symptoms, etiology, location, severity and Glasgow Coma Scale (GCS). Outcomes were case-fatality (death within 30 days), poor functional outcome (modified Rankin Scale >2), long-term mortality and recurrent ICH. We assessed discriminatory power of factors associated with case-fatality [area under receiver operating curve (AUC)]. Case-fatality was 20.4 % (n = 20) and well predicted by the GCS (AUC 0.83). Among 30-day survivors, a poor functional outcome at discharge was present in 51.3 %. During a mean follow-up of 11.3 years mortality was only increased in patients aged 40–50 years [standardized mortality ratio 4.8 (95 % CI 2.3–8.6)], but not in patients aged 18–40 years. Recurrent ICH occurred in 6 patients [10-year cumulative incidence 12.2 % (95 % CI 1.5–22.9 %)], all with the index ICH attributable to structural vascular malformations. Prognosis after ICH in young adults is poor, mainly due to high case-fatality, that is well predicted by the GCS. An exception is 30-day survivors <40 years, who have a similar risk of dying as the general population. Recurrence risk is especially present in patients with structural vascular malformations, whereas risk seems to be very low in other patients.     

Epicardium-derived cells enhance proliferation, cellular maturation and alignment of cardiomyocytes

During heart development, cells from the proepicardial organ spread over the naked heart tube to form the epicardium. From here, epicardium-derived cells (EPDCs) migrate into the myocardium. EPDCs proved to be indispensable for the formation of the ventricular compact zone and myocardial maturation, by largely unknown mechanisms. In this study we investigated in vitro how EPDCs affect cardiomyocyte proliferation, cellular alignment and contraction, as well as the expression and cellular distribution of proteins involved in myocardial maturation. Embryonic quail EPDCs induced proliferation of neonatal mouse cardiomyocytes. This required cell-cell interactions, as proliferation was not observed in transwell cocultures. Western blot analysis showed elevated levels of electrical and mechanical junctions (connexin43, N-cadherin), sarcomeric proteins (Troponin-I, α-actinin), extracellular matrix (collagen I and periostin) in cocultures of EPDCs and cardiomyocytes. Immunohistochemistry indicated more membrane-bound expression of Cx43, N-cadherin, the mechanotransduction molecule focal adhesion kinase, and higher expression of the sarcoplasmic reticulum Ca²⁺ ATPase (SERCA2a). Newly developed software for analysis of directionality in immunofluorescent stainings showed a quantitatively determined enhanced cellular alignment of cardiomyocytes. This was functionally related to increased contraction. The in vitro effects of EPDCs on cardiomyocytes were confirmed in three reciprocal in vivo models for EPDC-depletion (chicken and mice) in which downregulation of myocardial N-cadherin, Cx43, and FAK were observed. In conclusion, direct interaction of EPDCs with cardiomyocytes induced proliferation, correct mechanical and electrical coupling of cardiomyocytes, ECM-deposition and concurrent establishment of cellular array. These findings implicate that EPDCs are ideal candidates as adjuvant cells for cardiomyocyte integration during cardiac (stem) cell therapy.     

Lactoferrin Reduces Methotrexate-Induced Small Intestinal Damage, Possibly Through Inhibition of GLP-2-Mediated Epithelial Cell Proliferation

A strategy protecting the small intestine against deleterious side effects associated with anti-cancer therapy is arresting epithelial cell cycling temporally. Since endogenous glucagon-like peptide-2 (GLP-2) is a trophic factor specific for intestinal epithelia, the possibility of inhibiting GLP-2-mediated cell proliferation by lactoferrin, thereby protecting the small intestine against deleterious side effects of anticancer therapy, was investigated. In Caco-2 cells, GLP-2-mediated proliferation was reduced in a dose-dependent manner using lactoferrin. Furthermore, in a rat model for methotrexate-induced mucositis, lactoferrin reduced BrdU incorporation in small intestinal epithelial cells, indicating inhibition of epithelial cell proliferation in vivo. Subsequently, protection against methotrexate-induced intestinal damage was found in corresponding regions. These results show, for the first time, that lactoferrin interferes with GLP-2-induced intestinal epithelial proliferation. It may therefore be hypothesized that lactoferrin protects the intestine against anticancer therapy-induced intestinal damage, via inhibition of GLP-2-induced small intestinal epithelial cell proliferation.     

Rapid and sensitive routine detection of all members of the genus enterovirus in different clinical specimens by real-time PCR

We developed a rapid and sensitive method for the routine detection of all members of the enterovirus genus in different clinical specimens by using real-time TaqMan quantitative PCR. Multiple primer and probe sets were selected in the highly conserved 5'-untranslated region of the enterovirus genome. Our assay detected all 60 different enterovirus species tested, whereas no reactivity was observed with the viruses from the other genera of the picornaviridae family, e.g., hepatovirus and parechovirus. Weak cross-reactivity was observed with 7 of the 90 different high-titer rhinovirus stocks but not with rhinovirus-positive clinical isolates. Analysis of a well-characterized reference panel containing different enteroviruses at various concentrations demonstrated that the enterovirus real-time TaqMan PCR is as sensitive as most of the currently used molecular detection assays. Evaluation of clinical isolates demonstrated that the assay is more sensitive than the "gold standard" method, i.e., viral culture. Moreover, the PCR assay can be used on different clinical specimens, such as plasma, serum, nose and throat swabs, cerebrospinal fluid, and bronchoalveolar lavage, without apparent inhibition. Our data demonstrate that the real-time TaqMan PCR is a rapid and sensitive assay for the detection of enterovirus infection. The assay has a robust character and is easily standardized, which makes it an excellent alternative for the conventional time-consuming viral culture.     

Evaluation of the subjective effect of middle ear implantation in hearing-impaired patients with severe external otitis

The subjective benefit of middle ear implantation was studied in a group of 23 hearing-impaired patients who could not use conventional hearing aids owing to severe chronic external otitis. Changes in hearing disability (Abbreviated Profile of Hearing Aid Benefit [APHAB]) and changes in quality of life (Glasgow Benefit Inventory [GBI]) were determined. Mean benefit value on the APHAB for the subscale Ease of Communication was close to the mean reference value for conventional hearing aids. For the subscales Reverberation and Background Noise, a poorer result was found. Individual analysis of the APHAB scores showed significant benefit in 12 out of the 23 patients. According to the GBI, 16 out of 17 patients reported that middle ear implantation had made a positive impact on their quality of life. It is concluded that middle ear implantation has a positive effect on hearing difficulties and quality of life in hearing-impaired subjects who cannot use conventional devices. The APHAB outcomes were not better than those reported for conventional devices.