Effective interaction between helical bio-molecules

The effective interaction between two parallel strands of helical bio-molecules, such as deoxyribose nucleic acids (DNA), is calculated using computer simulations of the "primitive" model of electrolytes. In particular we study a simple model for B-DNA incorporating explicitly its charge pattern as a double-helix structure. The effective force and the effective torque exerted onto the molecules depend on the central distance and on the relative orientation. The contributions of nonlinear screening by monovalent counterions to these forces and torques are analyzed and calculated for different salt concentrations. As a result, we find that the sign of the force depends sensitively on the relative orientation. For intermolecular distances smaller than $6\AA$ it can be both attractive and repulsive. Furthermore we report a nonmonotonic behaviour of the effective force for increasing salt concentration. Both features cannot be described within linear screening theories. For large distances, on the other hand, the results agree with linear screening theories provided the charge of the bio-molecules is suitably renormalized.Comment: 18 pages, 18 figures included in text, 100 bibliog

Plasma levels of imipramine in depression: Environmental and genetic factors

On the basis of tentative evidence obtained with 26 patients with unipolar affective illness, the variability in the response to imipramine is mostly due to interindividual differences in hydroxylating microsomal enzymes which are genetically controlled but whose activities are subject to modification by environmental factors such as overall pharmacological exposure and tobacco smoking. Additional significant pharmacodynamic variability (twofold) was found in the range of the volumes of distribution of imipramine in the patients. Clinical outcome was unequivocally related to plasma level. Unipolar nondelu- sional patients with levels less than 180 ng/ml had a low probability of recovery, while levels above 180 ng/ml were associated with a high probability of recovery. Unlike the findings of investigators working with nortriptyline, our data do not suggest an upper limit on plasma levels beyond which clinical response deteriorates. It appears that, on the basis of family studies, similar genetic properties lead to imipramine response among unipolar depressives. Whether the genetic characteristics are related to the ones controlling the pharmacodynamics will be the subject of further examination in our continuing studies. © 1976 S. Karger AG, Basel.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Coagulation, oncotic and haemodilutional effects of a third‐generation hydroxyethyl starch (130/0.4) solution in horses

REASONS FOR PERFORMING STUDY : Clinical indications for hydroxyethyl starches (HES) in horses include rapid plasma volume expansion and oncotic support during periods of hypoproteinaemia. Side effects such as coagulopathies associated with HES administration pose limitations to their use in veterinary medicine. In humans, tetrastarch [hydroxyethyl starch (130/0.4)] has demonstrated less profound effects on coagulation compared to 1st and 2nd generation HES. OBJECTIVES : To evaluate the haemostatic and oncotic effects of tetrastarch (130/0.4) administered at 10, 20 and 40 ml/kg bwt in healthy horses. Study design: Randomised crossover study design. METHODS : Tetrastarch (130/0.4) was administered to 6 healthy pony mares at 10, 20 and 40 ml/kg bwt with a 2-week washout period. Packed cell volume (PCV), total solids (TS), plasma colloid oncotic pressure (pCOP), platelet count and thromboelastography (TEG) was measured at baseline, immediately after infusion (0 h), 1, 6, 12, 24, 48, and 96 h after tetrastarch infusion. RESULTS : All TEG variables remained within normal reference ranges in all 3 treatment groups. Administration of tetrastarch at 40 ml/kg bwt resulted in a prolonged K-time (P=0.049) at 6 h post-infusion, and decreased maximum amplitude at 0 (P<0.001), 1 (P=0.022), 6 (P=0.006), 24 (P<0.001) and 48 h (P=0.013) postinfusion compared to baseline. Administration of tetrastarch increased mean pCOP values above baseline in all 3 treatment groups, persisting to 24, 6 and 48 h for the 10, 20 and 40 ml/kg bwt dose respectively. CONCLUSION : Although still within established reference ranges, compared to lower dosages, the administration of 40 ml/kg bwt tetrastarch (130/0.4) is more likely to induce changes in coagu lation as measured by TEG. Tetrastarch increased pCOP at all dosages evaluated in healthy horses.Faculty of Veterinary Science Research Fund ; Department of Companion Animal Clinical Studies, University of Pretoria ; and the Abe Bailey Trust.http://onlinelibrary.wiley.com/journal/10.1001/(ISSN)2042-33062015-11-30hb201

Perspectives on acceptance and use of a mobile health intervention for the prevention of atherosclerotic cardiovascular disease in singapore: mixed-methods study

10.2196/11108JMIR mHealth and uHealth73e1110