Comparative bacterial clearances of muscle and skin/subcutaneous tissues with and without dead bone: a laboratory study

Seventeen New Zealand White rabbits underwent implantation of three different concentrations of bacteria and a sterile saline control solution with and without dead autologous bone in eight separate muscular and eight separate subcutaneous sites. Following a period of 1 week, each site was surgically explored and samples of tissue were taken for histology and quantitative culture. Results reveal that final bacterial concentrations in the subcutaneous sites were significantly lower than in the muscle sites (p less than or equal to 0.0001) for each concentration of bacteria, with and without dead bone. Dead bone resulted in very significantly greater bacterial concentrations in both subcutaneous and muscle sites. Clinically, these results indicate that a thorough bony wound debridement is more important than the type of tissue used to close the wound. Flap tissue should be selected with regard to the perfusion, contour, and appearance of the recipient site.     

Control of mRNA translation in oocytes and developing embryos of giant moths. I. Function of the 5' terminal "Cap"in the tobacco hornworm, Manduca sexta

Injection of labeled leucine into oocytes and developing embryos of the tobacco hornworm, Manduca sexta, revealed that the rate of protein synthesis increases dramatically after fertilization and continues to rise until gastrulation. Cell-free preparations of oocytes and developing embryos show a similar pattern of in vitro incorporation. When messenger RNA extracted from unfertilized oocytes was examined by gradient density centrifugation under denaturing conditions, a broad peak was observed which centered around 15 S. In contrast to mRNA extracted from oocytes, that from embryos was found to be capped by 7-methylguanosine at the 5′ terminus. When translation of oocyte mRNA was compared with that of embryo mRNA in a cell-free translation system derived from wheat germ, oocyte RNA translated less efficiently. In the presence of an inhibitor of methylation, S-adenosylhomocysteine, the differences were further widened. In competition with a cap analog, 7-methylguanosine 5′-monophosphate, embryo mRNA translation was inhibited more than oocyte at low concentrations of analog. These results are taken to indicate that the lack of a cap at the 5′ terminus could be one mechanism to inhibit translation prior to fertilization.     

Correspondence between the development of hemopoietic tissue and the time of colony formation by colony-forming cells

The development of a haemopoietic tissue and the time when colony-forming cells in it formed detectable colonies were studied with in vivo spleen colony-forming units (CFUs) and in vitro high-proliferation-potential colony-forming cells (HPP CFC). Cells that form colonies first are developmentally more mature than those doing so later. Marrow containing mature spleen colony-forming cells formed fewer cells in the femora of recipients than that which contained early colony-forming cells. The growth curve of developmentally early high-proliferation potential-colony-forming cells was steeper than that of later cells. The time period before colony-formation occurs is a property of the colony-forming cell and is not due to regulatory mechanisms in the animal or to regulatory cells in the haemopoietic stroma.     

Electron-capture gas chromatographic assay for metoclopramide in plasma

An original electron-capture gas chromatographic assay has been developed for the quantitation of metoclopramide in human plasma. The method involves derivatization with heptafluorobutyryl imidazole after alkaline extraction, acid backwash, and a further alkaline extraction. Plasma levels of metoclopramide as low as 5 μg/l can be measured using 1 ml of plasma, and no interference from related substances or commonly prescribed drugs has been found.The percentage recovery of drug from plasma ranges from 88% to virtually 100%, and the between-run variation in the assay is 4.3%.The assay has been used for the study of metoclopramide pharmacokinetics in man following intravenous single-dose administration. The resultant plasma concentration vs. time curve was biexponential, with a terminal half-life of 5.0 h, and a distribution half-time of 0.3 h.     

Long-term anaesthesia with alfentanil and midazolam for lung transplantation in the dog

An anaesthetic regime was developed for lung transplantation in the dog using a continuous infusion of alfentanil and midazolam. This combination of agents provided excellent analgesia and also produced loss of consciousness. Cardiovascular stability was well maintained over a 24-h period of anaesthesia following lung transplantation. Although no animals were allowed to recover from anaesthesia in the present series, the regime described is likely to be suitable for recovery anaesthesia, particularly since both of the agents used can be reversed with specific antagonists.     

Prion Protein Is Decreased in Alzheimer's Brain and Inversely Correlates with BACE1 Activity,Amyloid-β Levels and Braak Stage

The cellular prion protein (PrP^C) has been implicated in the development of Alzheimer''s disease (AD). PrP^C decreases amyloid-β (Aβ) production, which is involved in AD pathogenesis, by inhibiting β-secretase (BACE1) activity. Contactin 5 (CNTN5) has also been implicated in the development of AD by a genome-wide association study. Here we measured PrP^C and CNTN5 in frontal cortex samples from 24 sporadic AD and 24 age-matched control brains and correlated the expression of these proteins with markers of AD. PrP^C was decreased in sporadic AD compared to controls (by 49%, p = 0.014) but there was no difference in CNTN5 between sporadic AD and controls (p = 0.217). PrP^C significantly inversely correlated with BACE1 activity (r_s = −0.358, p = 0.006), Aβ load (r_s = −0.456, p = 0.001), soluble Aβ (r_s = −0.283, p = 0.026) and insoluble Aβ (r_s = −0.353, p = 0.007) and PrP^C also significantly inversely correlated with the stage of disease, as indicated by Braak tangle stage (r_s = −0.377, p = 0.007). CNTN5 did not correlate with Aβ load (r_s = 0.040, p = 0.393), soluble Aβ (r_s = 0.113, p = 0.223) or insoluble Aβ (r_s = 0.169, p = 0.125). PrP^C was also measured in frontal cortex samples from 9 Down''s syndrome (DS) and 8 age-matched control brains. In contrast to sporadic AD, there was no difference in PrP^C in the DS brains compared to controls (p = 0.625). These data are consistent with a role for PrP^C in regulating Aβ production and indicate that brain PrP^C level may be important in influencing the onset and progression of sporadic AD.