Unique product quality considerations in vaccine development, registration and new program implementation in Malaysia.

This review aims to present the unique considerations for manufacturing and the regulation of new vaccines in Muslim-populated countries such as Malaysia. Our specific objectives are to highlight vaccine production and the ingredients of concern, summarize the current mechanism for ruling and recommendations on new vaccines, outline the different steps in decision-making on incorporating a new vaccine into the National Immunization Program, describe its issues and challenges, and explore the commercial viability and challenges of producing local permissible (halal) vaccines. Through this review, we hope readers understand that alternatives are present to replace ingredients of concern in vaccines. Halal certification and introduction of a new vaccine into a program are strictly conducted and health-care providers must be prepared to educate the public on this. At the same time, it is hoped that the production of halal vaccine in Malaysia will promote self-reliance in Muslim-populated countries.

Powering the ABC multidrug exporter LmrA: How nucleotides embrace the ion-motive force.

LmrA is a bacterial ATP-binding cassette (ABC) multidrug exporter that uses metabolic energy to transport ions, cytotoxic drugs, and lipids. Voltage clamping in a Port-a-Patch was used to monitor electrical currents associated with the transport of monovalent cationic HEPES+ by single-LmrA transporters and ensembles of transporters. In these experiments, one proton and one chloride ion are effluxed together with each HEPES+ ion out of the inner compartment, whereas two sodium ions are transported into this compartment. Consequently, the sodium-motive force (interior negative and low) can drive this electrogenic ion exchange mechanism in cells under physiological conditions. The same mechanism is also relevant for the efflux of monovalent cationic ethidium, a typical multidrug transporter substrate. Studies in the presence of Mg-ATP (adenosine 5'-triphosphate) show that ion-coupled HEPES+ transport is associated with ATP-bound LmrA, whereas ion-coupled ethidium transport requires ATP binding and hydrolysis. HEPES+ is highly soluble in a water-based environment, whereas ethidium has a strong preference for residence in the water-repelling plasma membrane. We conclude that the mechanism of the ABC transporter LmrA is fundamentally related to that of an ion antiporter that uses extra steps (ATP binding and hydrolysis) to retrieve and transport membrane-soluble substrates from the phospholipid bilayer.

The choreography of multidrug export.

Multidrug transporters have a crucial role in causing the drug resistance that can arise in infectious micro-organisms and tumours. These integral membrane proteins mediate the export of a broad range of unrelated compounds from cells, including antibiotics and anticancer agents, thus reducing the concentration of these compounds to subtoxic levels in target cells. In spite of intensive research, it is not clear exactly how multidrug transporters work. The present review focuses on recent advancements in the biochemistry and structural biology of bacterial and human multidrug ABC (ATP-binding cassette) transporters. These advancements point to a common mechanism in which polyspecific drug-binding surfaces in the membrane domains are alternately exposed to the inside and outside surface of the membrane in response to the ATP-driven dimerization of nucleotide-binding domains and their dissociation following ATP hydrolysis.