Laboratory Analytical Methods and Data Interpretation

Enantioselectivity in Drug Pharmacokinetics and Toxicity: Pharmacological Relevance and Analytical Methods

Molecules ◽

10.3390/molecules26113113 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3113

Author(s):

Maria Miguel Coelho ◽

Carla Fernandes ◽

Fernando Remião ◽

Maria Elizabeth Tiritan

Keyword(s):

Analytical Methods ◽

Dissociation Constants ◽

Data Interpretation ◽

Pharmacokinetic Studies ◽

Biological Processes ◽

Enantiomerically Pure ◽

Hepatic Diseases ◽

Different Types ◽

Drug Pharmacokinetics

Enzymes, receptors, and other binding molecules in biological processes can recognize enantiomers as different molecular entities, due to their different dissociation constants, leading to diverse responses in biological processes. Enantioselectivity can be observed in drugs pharmacodynamics and in pharmacokinetic (absorption, distribution, metabolism, and excretion), especially in metabolic profile and in toxicity mechanisms. The stereoisomers of a drug can undergo to different metabolic pathways due to different enzyme systems, resulting in different types and/or number of metabolites. The configuration of enantiomers can cause unexpected effects, related to changes as unidirectional or bidirectional inversion that can occur during pharmacokinetic processes. The choice of models for pharmacokinetic studies as well as the subsequent data interpretation must also be aware of genetic factors (such as polymorphic metabolic enzymes), sex, patient age, hepatic diseases, and drug interactions. Therefore, the pharmacokinetics and toxicity of a racemate or an enantiomerically pure drug are not equal and need to be studied. Enantioselective analytical methods are crucial to monitor pharmacokinetic events and for acquisition of accurate data to better understand the role of the stereochemistry in pharmacokinetics and toxicity. The complexity of merging the best enantioseparation conditions with the selected sample matrix and the intended goal of the analysis is a challenge task. The data gathered in this review intend to reinforce the importance of the enantioselectivity in pharmacokinetic processes and reunite innovative enantioselective analytical methods applied in pharmacokinetic studies. An assorted variety of methods are herein briefly discussed.

Download Full-text

High Resolution Microscopy of Multi-Layered Biological Crystals

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010005319x ◽

1982 ◽

Vol 40 ◽

pp. 80-83

Author(s):

H.A. Cohen ◽

T.W. Jeng ◽

W. Chiu

Keyword(s):

High Resolution ◽

Low Dose ◽

Three Dimensional ◽

Data Interpretation ◽

Two Dimensional ◽

Biological Objects ◽

Density Maps ◽

Density Map ◽

Complex Crystal ◽

High Resolution Microscopy

This tutorial will discuss the methodology of low dose electron diffraction and imaging of crystalline biological objects, the problems of data interpretation for two-dimensional projected density maps of glucose embedded protein crystals, the factors to be considered in combining tilt data from three-dimensional crystals, and finally, the prospects of achieving a high resolution three-dimensional density map of a biological crystal. This methodology will be illustrated using two proteins under investigation in our laboratory, the T4 DNA helix destabilizing protein gp32*I and the crotoxin complex crystal.

Download Full-text

Stereo modeling of HVEM specimens by serial tilting and computer graphics

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100141913 ◽

1986 ◽

Vol 44 ◽

pp. 34-35

Author(s):

J.R. McIntosh ◽

D.L. Stemple ◽

William Bishop ◽

G.W. Hannaway

Keyword(s):

Computer Graphics ◽

Analytical Methods ◽

Photographic Film ◽

Complex Structures ◽

Multiple Objects ◽

Multiple Images ◽

3 Dimensional

EM specimens often contain 3-dimensional information that is lost during micrography on a single photographic film. Two images of one specimen at appropriate orientations give a stereo view, but complex structures composed of multiple objects of graded density that superimpose in each projection are often difficult to decipher in stereo. Several analytical methods for 3-D reconstruction from multiple images of a serially tilted specimen are available, but they are all time-consuming and computationally intense.

Download Full-text