Pelargonium sidoides preparation EPs 7630 in COPD: health-related quality-of-life and other patient-reported outcomes in adults receiving add-on therapy

Objective: Patient-reported outcomes (PRO) such as health-related quality-of-life (HRQoL) belong to the most important criteria for the evaluation of medical therapies in clinical trials or practice-based benefit assessments. This study, therefore, revisited results of an earlier published clinical trial investigating the effects of the herbal drug preparation from the roots of Pelargonium sidoides EPs 7630, administered as add-on therapy in patients suffering from chronic obstructive pulmonary disease (COPD), with respect to HRQoL and other PRO.

Methods: A total of 199 adults diagnosed with COPD stages II/III and receiving standard treatment according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) were randomly assigned to add-on therapy with EPs 7630 or placebo for 24 weeks. HRQoL (disease-specific St. George’s Respiratory Questionnaire, SGRQ; current HRQoL state according to the EuroQuol visual analog scale, EQ VAS) and PRO (Integrative Medicine Outcomes Scale, IMOS; Integrative Medicine Patient Satisfaction Scale, IMPSS; symptom severity score of cough, sputum production and sternal pain while coughing; duration of inability to work) were assessed at each study visit or documented daily by the patient in a patient diary, respectively.

Results: At week 24, all HRQoL and PRO measures showed a more pronounced improvement under EPs 7630 than under placebo (EQ VAS, p?p?p?=?.021; duration of inability to work, p?=?.004; two-sided t-test each; IMOS, p?p?Conclusions: Add-on therapy with EPs 7630 led to an improvement in HRQoL and other PRO in adult patients with COPD compared to placebo while showing a good long-term tolerability.     

Platelet-derived growth factor triggers PKA-mediated signalling by a redox-dependent mechanism in rat renal mesangial cells

Inflammatory glomerular kidney diseases are often accompanied with a massive production of reactive oxygen species (ROS) that affect the function of the glomerular filtration barrier and contribute to mesangiolysis via the induction of cell death in mesangial cells. Intriguingly, ROS also trigger fine-tuned signalling processes that affect gene expression and cell proliferation or migration. To define such redox-driven signalling devices, a proteomics approach was performed to identify the formation of protein complexes induced by ROS. To this end, protein lysates of human podocytes were treated with or without hydrogen peroxide (250 μM). Thereafter cell lysates were subjected to diagonal 2D gel electrophoresis and putative redox-affected proteins were analysed by MS/MS analysis. Among others, the regulatory subunit of protein kinase A (PKA) could be identified that forms homodimers under oxidative conditions. To evaluate whether ROS dependent dimerization of PKA also occurs in a more physiological setting, rat mesangial cells were treated with platelet-derived growth factor-BB (PDGF-BB) to induce ROS formation. This regimen resulted in a redox dependent dimerization of the R-subunits of PKA. To demonstrate whether PDGF-BB induced ROS formation affects PKA dependent pathways, the effects of PDGF-BB on phosphorylation of serine 157 of vasodilator stimulated protein (VASP) a classical target of PKA were analysed. Interestingly PDGF-BB induced VASP phosphorylation in a ROS dependent manner but independent of changes in cAMP levels. Taken together, we demonstrate a redox-mediated activation of PKA by PDGF-BB thus highlighting a physiological role of ROS as regulator of PKA activity in rat mesangial cells.     

Renal dysfunction in methylmalonic acidurias: review for the pediatric nephrologist

Methylmalonic acidurias are a heterogeneous group of inborn errors of branched-chain amino acid metabolism. Depending on the underlying etiology, acute or chronic renal disease constitutes major (long-term) complications. In recent decades, overall survival has improved due to optimized treatment strategies based on the use of standardized emergency protocols and dialysis techniques. The majority of these patients, especially those having mut°, cblB, and cblA deficiency, are at increased risk of developing chronic kidney disease secondary to tubulointerstitial nephritis to require hemo- or peritoneal dialysis. Kidney and/or liver transplantation, as organ replacement, or even gene therapy on a limited scale, are controversially discussed treatment options in methylmalonic acidurias. The pathophysiological basis of renal disease has not been clarified in detail until now, but a severe mitochondrial dysfunction and an impairment of tubular dicarboxylic acid transport due to accumulated toxic metabolic compounds has been recently proposed. Another severe renal complication of methylmalonic acidurias is the occurrence of cblC-associated infantile atypical hemolytic syndrome, which can result in acute kidney injury. Close collaboration between (pediatric) nephrologists and metabolic specialists is required for the long-term management of these patients.     

Neurophysiology and the Problem of Human Free Will: A Case of “Nihil Sub Sole Novum”?

Over the last decade in Germany, a number of neuroscientists—and among them most prominently Wolf Singer—have claimed to be able to offer scientific evidence derived from neurophysiologic findings to conclusively negate the existence of human free will. In this paper, Singer’s position is examined according to its principal characteristics in order to answer the question whether it is a novel position as opposed to a position pertaining to one of the traditions of western philosophy and anthropology. Furthermore, we try to judge whether the neurobiological findings Singer and others use to justify their position are apt to satisfy the criteria for the presence of scientific evidence, i.e., if they are good reasons to believe that human will is unfree.     

The use of Ginkgo biloba in healthy elderly

To promote health-conscious behavior in the aging society and gain insight into the sources of knowledge on which preventive strategies are based, analyzing the behavior of elderly people who are recognized as highly health conscious may be useful. We focused on the use of Ginkgo biloba, which is commonly considered to be effective in preventing cognitive decline and dementia, among elderly adults. A total of 1,672 questionnaires were distributed among geriatric participants (60–94 years) who attended university lectures at 22 universities throughout Germany. Response rate was 36.1 %. We collected data on demographic characteristics, preventive strategies (use of Ginkgo and other supplements), health-conscious behavior, sources of knowledge concerning health behavior, and factors associated with the participants’ concept of aging. The prevalence of Ginkgo use was 15.3 %. Ginkgo was assumed to be effective for cognitive enhancement and the treatment of cognitive decline by two thirds of the surveyed participants and one third believed Ginkgo to be effective for preventing dementia. Ginkgo use was significantly higher among participants using natural remedies and herbal and food supplements. The use of Ginkgo was recommended by physicians (57.3 %), chemists (16 %), and healthcare magazines (10.7 %). Food supplements were taken by 65.8 % of the sample: this percentage was significantly higher among subjects who exhibited health-conscious behavior. “Knowledge” about strategies to enhance cognition or prevent cognitive decline among the elderly do not appear to be evidence based. Thus, there is a need to establish reliable and independent sources of scientific information for healthcare professionals and the general public.