Effect of liposome surface charge on the stability of technetium (99mTc) radiolabelled liposomes

Using liposomes radiolabelled by the 99mTechnetium-stannous chloride technique we have investigated the effect of surface charge on the stability of the isotope in vitro and in vivo. Dialysis of 99mTc-labelled positive, negative and neutral liposomes, which had been incubated in either saline or normal rat serum showed no significant loss of the isotope from the liposome surface with only 2 per cent of the isotope dialysed. A comparison of gel chromatography with dialysis confirmed that most of the isotope remained attached to the liposome surface, but it did reveal greater loss of the isotope, between 15 and 23 per cent. The liposome clearance rates obtained from 125I-egg phosphatidylcholine (EPC) and 99mTc dual-labelled positive or neutral liposomes were significantly different. The 99mTc marker was cleared five times faster from the positive liposomes and twice as fast from the neutral liposomes as the 125I-EPC integral membrane marker. The 99mTc attached to liposomes with a negative surface charge was stable in vivo and had the same clearance rate from the circulation as the 125I-EPC marker. These results indicate that the commonly used in vitro techniques for assessing liposome radiolabel stability are unsuitable for predicting the stability of the 99mTc in vivo.     

Interactions of small polypeptides with dimyristoylphosphatidylcholine monolayers: effect of size and hydrophobicity

The effects of size and hydrophobicity of small (molecular weights below 2,000) polypeptides on their predominantly hydrophobic interactions with a neutral phospholipid monolayer were studied. The changes in surface pressure were determined when various concentrations of Gly, Gly-Gly-Gly, -Ala, -Ala- -Ala- -Ala, -Ala-Gly-Gly-Gly-Gly, -Phe- -Leu- -Glu- -Glu- -Leu, adrenocorticotropic hormone fragments 1–10 (ACTH-(1–10)), porcine β-lipotropin, -endorphin and human fibrinopeptide A were injected under dimyristoylphosphatidylcholine (DMPC) monolayers at an initial surface pressure of 10 dyne/cm. In all cases, when peptides with the same number of residues are compared, the concentration needed to increase the surface pressure of the film by 1 dyne/cm was inversely related to its hydrophobicity. A reasonably good correlation was found to exist between the calculated free energy of transfer of a polypeptide from ethanol to water (a measure of its hydrophobicity) and its ability to increase the surface pressure of the DMPC film (a measure of the extent of its interaction with the neutral lipid monolayer).     

Similar dose responsiveness of hepatic glycogenolysis and gluconeogenesis to glucagon in vivo

This study was undertaken to determine whether the dose-dependent effect of glucagon on gluconeogenesis parallels its effect on hepatic glycogenolysis in conscious overnight-fasted dogs. Endogenous insulin and glucagon secretion were inhibited by somatostatin (0.8 micrograms X kg-1 X min-1), and intraportal replacement infusions of insulin (213 +/- 28 microU X kg-1 X min-1) and glucagon (0.65 ng X kg-1 X min-1) were given to maintain basal hormone concentrations for 2 h (12 +/- 2 microU/ml and 108 +/- 23 pg/ml, respectively). The glucagon infusion was then increased 2-, 4-, 8-, or 12-fold for 3 h, whereas the rate of insulin infusion was left unchanged. Glucose production (GP) was determined with 3-[3H]glucose, and gluconeogenesis (GNG) was assessed with tracer (U-[14C]alanine conversion to [14C]glucose) and arteriovenous difference (hepatic fractional extraction of alanine, FEA) techniques. Increases in plasma glucagon of 53 +/- 8, 199 +/- 48, 402 +/- 28, and 697 +/- 149 pg/ml resulted in initial (15-30 min) increases in GP of 1.1 +/- 0.4 (N = 4), 4.9 +/- 0.5 (N = 4), 6.5 +/- 0.6 (N = 6), and 7.7 +/- 1.4 (N = 4) mg X kg-1 X min-1, respectively; increases in GNG (approximately 3 h) of 48 +/- 19, 151 +/- 50, 161 +/- 25, and 157 +/- 7%, respectively; and increases in FEA (3 h) of 0.14 +/- 0.07, 0.37 +/- 0.05, 0.42 +/- 0.04, and 0.40 +/- 0.17, respectively. In conclusion, GNG and glycogenolysis were similarly sensitive to stimulation by glucagon in vivo, and the dose-response curves were markedly parallel.     

Use of a violence risk assessment tool in an acute care hospital: effectiveness in identifying violent patients.

This study examined the use and effectiveness of the Alert assessment form. The form is part of the Alert system, used by one large acute care hospital to identify patients with a propensity for violence. All reported incidents of patient violence from August 1, 2003, through December 31, 2004, were included in patient charts. One hundred seventeen violent patient charts were reviewed and compared with 161 non-violent patient charts, randomly chosen from the same time period. Overall use of the Alert assessment form for violent and non-violent patients was 75.7% and 35.4%, respectively. The assessment form was found to have moderate sensitivity (71%) and high specificity (94%). It is reasonably effective in identifying potentially violent or aggressive patients when it is used according to protocol. Efforts to improve the tool are warranted, as is evaluation of its benefit in settings with low prevalence of violence. Also, greater effort must be taken to prevent violence once an aggressive patient has been identified.     

Urinary cyclic AMP response to bovine parathyroid hormone during treatment with neuroleptics

The urinary cyclic AMP response to bovine parathyroid hormone and urinary concentrating ability (max Uosm) after des-amino-D -arginine vasopressin were studies in nine volunteers and seven patients receiving long-term neuroleptic treatment. Max Uosm was lower in the patient group (770 ± 70 mosmol/kg) compared with the controls (948 ± 152 mosmol/kg) but the trend to a lower cAMP response to bovine PTH was not statistically significant. These results suggest that, although adenylate cyclase inhibition may contribute, other mechanisms are also important in the genesis of reduced uring concentrating ability in patients treated with psychotropic drugs.     

The quantity of rhodopsin in human eyes

The content of rhodopsin in the eyes of 15 donors (30 eyes) was determined. Both retinal and pigment epithelial fractions were collected from each globe, extracted using 1% CTAB, and the rhodopsin difference spectrum of each fraction was obtained separately. The total amount of rhodopsin, obtained by summing the amounts recovered from the retinal and PE fractions, ranged from 2.00 to 11.94 (median: 6.40) nmoles/eye. Previously reported mean values of about 3.5 to 4.0 nmoles per retina have been obtained using a variety of methods. The present higher values, perhaps largely dependent on procedural details described herein, appear plausible given the known concentrations of rhodopsin in rod outer segments, rod outer segment volumes, and number of rods in the human retina.     

Variation in venom composition and reactivity in two specimens of yellow-faced whip snake (Demansia psammophis) from the same geographical area

Gel filtration chromatography and SDS-PAGE of venom from two specimens of Demansia psammophis showed little similarity. Amidolytic activity of the venoms, however, was in the same order of reactivity against various chromogenic substrates. The venom from both snakes produced precipitin lines with brown snake antivenom but the venom detection kit (Commonwealth Serum Laboratories) identified one venom as brown snake (Pseudonaja sp.) and the other as tiger snake (Notechis sp.). These results raise questions about the phylogeny of this species.