Non-Metabolic Membrane Tubulation and Permeability Induced by Bioactive Peptides

BACKGROUND: Basic cell-penetrating peptides are potential vectors for therapeutic molecules and display antimicrobial activity. The peptide-membrane contact is the first step of the sequential processes leading to peptide internalization and cell activity. However, the molecular mechanisms involved in peptide-membrane interaction are not well understood and are frequently controversial. Herein, we compared the membrane activities of six basic peptides with different size, charge density and amphipaticity: Two cell-penetrating peptides (penetratin and R9), three amphipathic peptides and the neuromodulator substance P. METHODOLOGY/PRINCIPAL FINDINGS: Experiments of X ray diffraction, video-microscopy of giant vesicles, fluorescence spectroscopy, turbidimetry and calcein leakage from large vesicles are reported. Permeability and toxicity experiments were performed on cultured cells. The peptides showed differences in bilayer thickness perturbations, vesicles aggregation and local bending properties which form lipidic tubular structures. These structures invade the vesicle lumen in the absence of exogenous energy. CONCLUSIONS/SIGNIFICANCE: We showed that the degree of membrane permeabilization with amphipathic peptides is dependent on both peptide size and hydrophobic nature of the residues. We propose a model for peptide-induced membrane perturbations that explains the differences in peptide membrane activities and suggests the existence of a facilitated “physical endocytosis,” which represents a new pathway for peptide cellular internalization

Prevalence, diagnostics and management of musculoskeletal disorders in primary health care in Sweden : an investigation of 2000 randomly selected patient records

RATIONALE, AIMS AND OBJECTIVES: The aims of this study is to investigate the prevalence of patients seeking care due to different musculoskeletal disorders (MSDs) at primary health care centres (PHCs), to chart different factors such as symptoms, diagnosis and actions prescribed for patients that visited the PHCs due to MSD and to make comparisons regarding differences due to gender, age and rural or urban PHC. METHODS: Patient records (2000) for patients in working age were randomly selected equally distributed on one rural and one urban PHC. A 3-year period was reviewed retrospectively. For all patient records' background data, cause to the visit and diagnosis were registered. For visits due to MSD, type and location of symptoms and actions to resolve the patients problems were registered. Data was analysed using cross tabulation, multidimensional chi-squared. RESULTS: The prevalence of MSD was high; almost 60% of all patients were seeking care due to MSD. Upper and lower limb problems were most common. Symptoms were most prevalent in the young and middle age groups. The patients got a variety of different diagnoses, and between 13 and 35% of the patients did not receive a MSD diagnose despite having MSD symptoms. There was a great variation in how the cases were handled. CONCLUSIONS: The present study points out some weaknesses regarding diagnostics and management of MSD in primary care