Duration of spinal anaesthesia is determined by the partition coefficient of local anaesthetic

We have compared the duration of motor block produced by four local anaesthetics administered into a chronically implanted subarachnoid catheter in rabbits. Each group (n = 6) received four different doses of amethocaine, bupivacaine, lignocaine or procaine, and the duration of the resulting motor block was assessed. Dose-response curves were plotted for each drug. As a measure of activity of the anaesthetics, we used the dose of each drug required to produce block of 60-min duration (D60 min) and the correlation between D60 min and different drug properties was examined. An inverse linear correlation (r = 0.995; P < 0.01) was observed between log D60 min and the log of the partition coefficient of the local anaesthetics. No correlation was found between the effect and degree of protein binding, pKa or molecular weight. These results suggest that, in spinal anaesthesia, the partition coefficient could be used as a predictor of the duration of anaesthetic action.     

Inefficiency of lactation in primiparous rats: the costs of first reproduction

To investigate the energetic costs of lactation in a female mammal in relation to previous reproductive history, we compared the performance of adult female Long-Evans rats that had previously bred (multiparous) with young females that had not previously given birth (primiparous). All litters were standardized to 10 +/- 1 young. We compared maternal production (growth of pups), body mass, and energy intake (food consumption) of mothers, as well as their energy expenditure (resting oxygen consumption). The mass of litters at birth and the growth of pups during lactation did not differ according to reproductive history of the mothers. The body mass of primiparous mothers was less than that of multiparous mothers, and primiparous mothers showed an increase in mass during early lactation. To accomplish the essentially identical production of offspring under these circumstances, the primiparous mothers consumed and expended more energy than the multiparous mothers. This remarkable performance of first-time mothers results in an overall efficiency of energy allocation to reproduction amounting to only 25%, compared with 38% in multiparous mothers. The energetic inefficiency of primiparous female lactation results largely from the excessive expenditures associated with physiological and behavioral performances of first-time reproduction, together with a small component of additional expenditure due to further growth by the primiparous mothers. We suggest that this inefficiency probably contributes to the observed low reproductive success of novice breeders; furthermore, active restraint of fecundity may be an evolutionary response to the constraints of the energetic inefficiency of primiparous breeding by female mammals.     

Mechanisms of virus assembly probed by Raman spectroscopy: the icosahedral bacteriophage P22

A microdialysis flow cell has been developed for time-resolved Raman spectroscopy of biological macromolecules and their assemblies. The flow cell permits collection of Raman spectra concurrent with the efflux of small solute molecules into a solution of macromolecules and facilitates real-time spectroscopic detection of structural transitions induced by the effluent. Additionally, the flow cell is well suited to the investigation of hydrogen-isotope exchange phenomena that can be exploited as dynamic probes of viral protein folding and solvent accessibility along the assembly pathway. Here, we describe the application of the Raman dynamic probe to the maturation of the icosahedral capsid of bacteriophage P22, a double-stranded DNA virus. The P22 virion is constructed from a capsid precursor (procapsid) consisting of 420 coat subunits (gp5) in an outer shell and a few hundred scaffolding subunits (gp8) within. Capsid maturation involves expulsion of scaffolding subunits coupled with shell expansion at the time of DNA packaging. Raman static and dynamic probes reveal that the scaffolding subunit is highly alpha-helical and highly thermolabile, and lacks a typical hydrophobic core. When bound within the procapsid, the alpha-helical fold of gp8 is thermostabilized; however, this stabilization confers no apparent protection against peptide NH-->ND exchange. A molten globule model is proposed for the native scaffolding subunit that functions in procapsid assembly. Accompanying capsid expansion, a small conformational change (alpha-helix-->beta-strand) is also observed in the coat subunit. Domain movement mediated by hinge bending is proposed as the mechanism of capsid expansion. On the basis of these results, a molecular model is proposed for assembly of the P22 procapsid.     

Refinements in validity generalization methods: Implications for the situational specificity hypothesis.

Using a large database, this study examined 3 refinements of validity generalization procedures: (1) a more accurate procedure for correcting the residual standard deviation (SD) for range restriction to estimate SDp, (2) use of r? instead of study-observed rs in the formula for sampling error variance, and (3) removal of non-Pearson rs. The 1st procedure does not affect the amount of variance accounted for by artifacts. The addition of the 2nd and 3rd procedures increased the mean percentage of validity variance accounted for by artifacts from 70 to 82%, a 17% increase. The cumulative addition of all 3 procedures decreased the mean SDp estimate from .150 to .106, a 29% decrease. Six additional variance-producing artifacts were identified that could not be corrected for. In light of these it was concluded that the obtained estimates of mean SDp and mean validity variance accounted for were consistent with the hypothesis that the true mean SDp value is close to zero. These findings provide further evidence against the situational specificity hypothesis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Bone SPECT of the jaws after fracture, onlay osteoplasty of insertion of implants

AIM: The aim of this study was early differentiation between uncomplicated and complicated processes of healing in the jaw using bone SPECT. METHODS: Investigations were performed in 40 mandibular fractures and 26 jaws after onlay osteoplasty as well as secondary insertion of implants. Bone SPECT was carried out within 1-2 months and after approximately 4-5 months. The uptake in the jaw was assessed semi-quantitatively using ROI analysis. RESULTS: Fractures with uncomplicated healing showed a decrease of uptake in follow-up, whereas fractures with an infection in the later course showed an increase, resulting in a significantly higher uptake at the follow-up investigation for the latter group. 1-2 months after onlay osteoplasty significantly lower uptake was found in regions with later occurrence of sequestration. In regions with implants in which osseointegration failed, there was significant reduction of uptake initially and significant elevation at the follow-up investigation. CONCLUSION: These results indicate a prognostic relevance of bone SPECT in the evaluation of processes of healing in the jaw.     

Pharmacology of ATP-sensitive potassium channel (KATP) openers in models of myocardial ischemia and reperfusion

Cancer cells release various antigens, some of which appear in the urine. Oral autourotherapy is suggested as a new treatment modality for cancer patients. It will provide the intestinal lymphatic system with the many tumor antigens against which antibodies may be produced. These antibodies may be pierced through the blood stream and attack the tumor and its cells.     

Disappearing subdural hematomas in children

Serum glucose and plasma C-peptide response to i.v. glucagon administration was evaluated in 24 healthy dogs, 12 dogs with untreated diabetes mellitus, 30 dogs with insulin-treated diabetes mellitus, and 8 dogs with naturally acquired hyperadrenocorticism. Serum insulin response also was evaluated in all dogs, except 20 insulin-treated diabetic dogs. Blood samples for serum glucose, serum insulin, and plasma C-peptide determinations were collected immediately before and 5, 10, 20, 30, and (for healthy dogs) 60 minutes after i.v. administration of 1 mg glucagon per dog. In healthy dogs, the patterns of glucagon-stimulated changes in plasma C-peptide and serum insulin concentrations were identical, with single peaks in plasma C-peptide and serum insulin concentrations observed approximately 15 minutes after i.v. glucagon administration. Mean plasma C-peptide and serum insulin concentrations in untreated diabetic dogs, and mean plasma C-peptide concentration in insulin-treated diabetic dogs did not increase significantly after i.v. glucagon administration. The validity of serum insulin concentration results was questionable in 10 insulin-treated diabetic dogs, possibly because of anti-insulin antibody interference with the insulin radioimmunoassay. Plasma C-peptide and serum insulin concentrations were significantly increased (P < .001) at all blood sampling times after glucagon administration in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Five-minute C-peptide increment, C-peptide peak response, total C-peptide secretion, and, for untreated diabetic dogs, insulin peak response and total insulin secretion were significantly lower (P < .00l) in diabetic dogs, compared with healthy dogs, whereas these same parameters were significantly increased (P < .01) in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Although not statistically significant, there was a trend for higher plasma C-peptide concentrations in untreated diabetic dogs compared with insulin-treated diabetic dogs during the glucagon stimulation test. Baseline C-peptide concentrations also were significantly higher (P < .05) in diabetic dogs treated with insulin for less than 6 months, compared with diabetic dogs treated for longer than 1 year. Finally, 7 of 42 diabetic dogs had baseline plasma C-peptide concentrations greater than 2 SD (ie, > 0.29 pmol/mL) above the normal mean plasma C-peptide concentration; values that were significantly higher, compared with the results in healthy dogs (P < .001) and with the other 35 diabetic dogs (P < .001). In summary, measurement of plasma C-peptide concentration during glucagon stimulation testing allowed differentiation among healthy dogs, dogs with impaired beta-cell function (ie, diabetes mellitus), and dogs with increased beta-cell responsiveness to glucagon (ie, insulin resistance). Plasma C-peptide concentrations during glucagon stimulation testing were variable in diabetic dogs and may represent dogs with type-1 and type-2 diabetes or, more likely, differences in severity of beta-cell loss in dogs with type-1 diabetes.