Recombinant scrapie-like prion protein of 106 amino acids is soluble

The N terminus of the scrapie isoform of prion protein (PrPSc) can be truncated without loss of scrapie infectivity and, correspondingly, the truncation of the N terminus of the cellular isoform, PrPC, still permits conversion into PrPSc. To assess whether additional segments of the PrP molecule can be deleted, we previously removed regions of putative secondary structure in PrPC; in the present study we found that deletion of each of the four predicted helices prevented PrPSc formation, as did deletion of the stop transfer effector region and the C178A mutation. Removal of a 36-residue loop between helices 2 and 3 did not prevent formation of protease-resistant PrP; the resulting scrapie-like protein, designated PrPSc106, contained 106 residues after cleavage of an N-terminal signal peptide and a C-terminal sequence for glycolipid anchor addition. Addition of the detergent Sarkosyl to cell lysates solubilized PrPSc106, which retained resistance to digestion by proteinase K. These results suggest that all the regions of proposed secondary structure in PrP are required for PrPSc formation, as is the disulfide bond stabilizing helices 3 and 4. The discovery of PrPSc106 should facilitate structural studies of PrPSc, investigations of the mechanism of PrPSc formation, and the production of PrPSc-specific antibodies.     

Managing side effects of interferon-beta in patients with relapsing-remitting multiple sclerosis

In separate clinical trials, two preparations of recombinant interferon (IFN)-beta, IFN beta-1a and IFN beta-1b, reduced exacerbation rates in relapsing-remitting multiple sclerosis (RR-MS). Further, IFN beta-1a slows the progression of disability in patients with RR-MS. Although they are effective in the treatment of MS, use of these drugs is associated with both class-specific and agent-specific side effects. Class-specific side effects include fever, chills, myalgias, arthralgias, and other flulike symptoms beginning 2 to 6 hours after injection and resolving within 24 hours of injection. Transient worsening of preexisting MS symptoms also occurs infrequently. Agent-specific side effects include injection-site reactions with IFN beta-1b. Simple management strategies can be used to minimize these reactions, including patient education; tailoring the dose and time of administration of IFN-beta; and prescribing appropriate combinations of acetaminophen, non-steroidal anti-inflammatory drugs, and steroids. Although side effects tend to diminish with treatment, successful management allows long-term administration of these drugs to achieve a reduction in disease activity and commensurate improvement in outcomes.     

Absorption and distribution of arachidonate in rats receiving lysophospholipids by oral route

Absorption and distribution of polyunsaturated fatty acids was investigated in rats receiving lysophospholipids per os (30 mg kg-1). Lysophosphatidylcholine (lysoPC) increased [3H]arachidonate absorption and its incorporation into mucosal phosphatidylcholine. Transport of [3H]arachidonate by the phospholipid fraction of lymph lipoproteins and the level of [3H]arachidonate in plasma and liver lipids was also increased by lyso PC. Lysophosphatidylserine also increased [3H]arachidonate absorption but channeled the fatty acids into the aminophospholipid fraction of mucosal phospholipids, thus decreasing its efflux in lymph lipoproteins. As a consequence, lysophosphatidylserine caused [3H]arachidonate accumulation in mucosa. As similar results were obtained with [14C]linoleate, the data suggest that the addition of an appropriate lysophospholipid to the diet may direct absorption and distribution of polyunsaturated fatty acids.     

Using drug chronotherapy to wean patients from mechanical ventilation

Discontinuation of positive pressure mechanical ventilation results in decreased intrathoracic pressure. Although there has been extensive research into factors associated with weaning adults from mechanical ventilatory support, little attention has been paid to the role of left ventricular performance. Research also has not focused on interventions that might optimize ventricular performance. The purpose of this article is to explore the potential effect of cardiac dysfunction in weaning and the role of drug chronotherapy as a strategy to modify patients' responses to weaning from mechanical ventilatory support. Biophysical principles involved are reviewed, and the development of a chronotherapeutic intervention is described. Two case examples illustrate the use of drug chronotherapy during the weaning process.     

Screening for carcinoma of the prostate

In India, cholera is endemic and affects usually the 3 to 5-year-old age group. There have been occasional reports in the neonatal period with Vibrio cholerae O139 Bengal. We report here a case of Vibrio cholerae O1 diarrhea in a 2-day-old, breastfed male, who had been delivered in the hospital and developed severe dehydration.