In vivo characterization of the biodistribution profile of amphipol A8-35.

Amphipols (APols) are polymeric surfactants that keep membrane proteins (MPs) water-soluble in the absence of detergent, while stabilizing them. They can be used to deliver MPs and other hydrophobic molecules in vivo for therapeutic purposes, e.g., vaccination or targeted delivery of drugs. The biodistribution and elimination of the best characterized APol, a polyacrylate derivative called A8-35, have been examined in mice, using two fluorescent APols, grafted with either Alexa Fluor 647 or rhodamine. Three of the most common injection routes have been used, intravenous (IV), intraperitoneal (IP), and subcutaneous (SC). The biodistribution has been studied by in vivo fluorescence imaging and by determining the concentration of fluorophore in the main organs. Free rhodamine was used as a control. Upon IV injection, A8-35 distributes rapidly throughout the organism and is found in most organs but the brain and spleen, before being slowly eliminated (10-20 days). A similar pattern is observed after IP injection, following a brief latency period during which the polymer remains confined to the peritoneal cavity. Upon SC injection, A8-35 remains essentially confined to the point of injection, from which it is only slowly released. An interesting observation is that A8-35 tends to accumulate in fat pads, suggesting that it could be used to deliver anti-obesity drugs.

Amphipols from A to Z.

Amphipols (APols) are short amphipathic polymers that can substitute for detergents to keep integral membrane proteins (MPs) water soluble. In this review, we discuss their structure and solution behavior; the way they associate with MPs; and the structure, dynamics, and solution properties of the resulting complexes. All MPs tested to date form water-soluble complexes with APols, and their biochemical stability is in general greatly improved compared with MPs in detergent solutions. The functionality and ligand-binding properties of APol-trapped MPs are reviewed, and the mechanisms by which APols stabilize MPs are discussed. Applications of APols include MP folding and cell-free synthesis, structural studies by NMR, electron microscopy and X-ray diffraction, APol-mediated immobilization of MPs onto solid supports, proteomics, delivery of MPs to preexisting membranes, and vaccine formulation.

Semen analysis performed by different laboratory teams: an intervariation study.

Some recent studies have indicated that sperm concentration has decreased during the last 50 years. However, comparisons between laboratories have revealed that geographical differences seem to exist and that any decrease may not be global. One point of criticism concerning comparison of results from different laboratories has been that some of the discrepancies detected could reflect the lack of standardized methods used in the different laboratories. Four teams, each consisting of one physician and one technician from groups which have recently published data on semen quality, met in order to evaluate the variability between their laboratories on semen analysis. Twenty-six fresh semen samples from unselected men were analysed. The groups analysed the samples according to the normal practice in their laboratories, using their own equipment. The variation between laboratories was estimated through a random effects model. For sperm concentration and semen volume assessment a remarkable consistency between laboratories was detected, in contrast to the very considerable inter-individual variation. For sperm motility and morphology assessments interlaboratory consistency was much poorer. In conclusion, evaluation of sperm motility and morphology characteristics requires further standardization in order to achieve comparable data from different laboratories. However, semen volume and sperm concentration are characteristics which can be compared reliably between laboratories, when similar methodologies are used.

An ergonomic evaluation of a patient handling device: the elevate and transfer vehicle.

This study evaluated a Patient Handling Device (PHD) called the Elevate and Transfer Vehicle (ETV). The ETV works on the principle of leverage to transfer a patient from one seated position to another. Three types of product evaluation were used: expert appraisal; user trials; and performance tests. Expert appraisal was conducted by a panel of 11 people including an ergonomist, an industrial designer, two engineers, including one employed as an academic in a School of Mechanical, Manufacturing and Medical Engineering, and seven health professionals. The experts evaluated the ETV using a checklist and group discussions. They generally agreed that the advantages of the ETV tested were it's simplicity, the convenient position to adjust clothing for toileting and the need for only one carer. They noted comfort, security of straps, centre of gravity and manoeuvrability as the main areas for improvement. User trials consisted of nine male and nine female volunteer users assigned to carer/patient pairs. Following a training period, each user subjectively evaluated the ETV by structured interview. User trial results indicated ease of use, prevention of back injuries in carers and minimal body contact were advantages of the ETV. The main problems with using the ETV appeared to be the inadequate 'prop' and straps, the 'jolt' and lack of dignity for the patient. Several critical performance tests were conducted to determine compliance to Australian Standards for design. Areas of non-compliance included strength of frame and static stability. The findings suggest that most of the identified problems of the ETV could be overcome with minor design improvements. The general consensus of participants was to keep the design simple, maintain fast transfers and maintain the position of the patient to enable ease of clothing adjustment for toileting.