Enantiomeric Resolution of Drug Compounds by Liquid Chromatography

Novel techniques have recently emerged to separate chiral drug compounds into pure enantiomers. The mechanism, experimental difficulties, and applicability of these methods can vary greatly, and the choices involved are not straightforward. The most significant new advances in the field of chiral separations have come from work done with liquid chromatographic systems and chiral stationary-phase columns. This review describes several commonly used approaches to chiral separation, diastereomeric derivatization, chiral mobile-phase additives, and three major types of chiral stationary phases. Although no single method can be judged superior for every drug application, it appears that chiral stationary phases have received the most attention recently and they are emphasized here.     

Quantitative comparison of magnetic resonance imaging (MRI) and histologic analyses of focal ischemic damage in the rat

Hemispheric swelling and area of infarction, two parameters of cerebral focal ischemic damage, were identified and quantified from T2-weighted magnetic resonance imaging (MRI) two days after occlusion of the middle cerebral artery (MCAO) in spontaneously hypertensive rat (SHR) brains. Results were compared with these measures quantified from 2,3,5-triphenyltetrazolium hydrochloride (TTC)- and hematoxylin and eosin (H&E)-stained histologic sections in the same brains. The degree of hemispheric swelling and infarct size determined by MRI were highly correlated to the measurements as determined in the TTC- and H&E-stained tissues. These results demonstrate that the focal ischemic damaged area and associated tissue swelling identified by MRI is quantitatively similar to, and thus, is representative of actual tissue damage/changes that can be identified by gross or histologic examination.     

Mortality in neonatal septicemia with involvement of mother in management.

In most Special Care Neonatal Units (SCNUs) in India, mothers are excluded from the care of their sick babies for fear of over-crowding and dislocation. We have attempted to study the feasibility of involving mothers in the care of their babies admitted for neonatal septicemia and to analyse whether this changed the sepsis related case fatality rate. The study material consisted of 158 neonates with blood culture positive neonatal septicemia whose mothers were actively involved in their care during their stay in the SCNU of LNJPN Hospital throughout 1987-88. The mothers lived in with their sick neonates and were extremely useful in feeding, cleaning, and monitoring for some important signs and symptoms. There were no epidemics of infection in the nursery during this period. All the babies discharged were receiving breast feeds, and the mothers were confident in taking care of them before discharge. The mortality in this group was 43%. The onset of septicemia was most often in the first week (36%) being 25.9% in second week, 26.6% in the third, and 11.4% in the fourth. Mortality was maximum (64.5%) when the onset of illness was in the first 3 days. Klebsiella and S. aureus were commonly isolated organisms (38.6 and 21.5%, respectively). Gram negative organisms were isolated in 66.5% cases with higher mortality in this group. Nearly 46% of the babies weighed 2 kg or less, with a mortality of 60.2% compared to 28.2% in those more than 2 kg. Only 3 to 5% and 40 to 66.7% of Gram negative and 23 and 70% of Gram positive organisms were sensitive to ampicillin and gentamicin, respectively.     

Polyclonal and monoclonal antibodies monospecific to MMTV LTR orf protein produced in E. coli.

Monoclonal and polyclonal antibodies specific to an open reading frame of the mouse mammary tumor virus long terminal repeat were generated using an open reading frame-beta-galactosidase fusion protein produced in E. coli. Both antibodies reacted with the open reading frame-beta-galactosidase fusion protein but not with beta-galactosidase alone using an immunoblotting technique. It is concluded that these antibodies were specific for the protein encoded by the open reading frame of the mouse mammary tumor virus long terminal repeat.     

Deprivation of form vision suppresses diurnal cycling of retinal levels of leu-enkephalin

Deprivation of form vision by the fitting of translucent occluders suppressed the diurnal cycling of enkephalinergic amacrine cells (the ENSLI amacrine cells), in the chicken. Daily periods of normal vision or enforcing temporal contrast using strobe lighting appeared to restore normal functioning of the ENSLI cells. These results suggest that the ENSLI cells are involved in retinal circuits that assess the quality of the visual image and control eye growth.     

Ultrastructural study of micro-blood vessels in human brain tumors and peritumoral tissue

Summary Ultrastructural and tracer studies have demonstrated that vasogenic edema, a serious complication of brain tumor is the result of increased permeability of tumor vessels. However, not much information is available on the alterations in the vessels in the peritumoral areas. Therefore, we studied the ultrastructural changes in the tumor micro-blood vessels (MBVs) in 20 cases of glioma and compared these with the changes in the peritumoral MBVs in 10 of these cases.The tumor MBVs showed remarkable structural changes, viz, increase in pinocytotic vesicles, large vacuoles and microvilli in the endothelial cells, varying degrees of endothelial attenuation and fenestration, an occasional partially or completely opened-up junction and some pale and edematous endothelial cells, which can adequately explain their increased permeability.The peritumoral MBVs also showed evidence of increased permeability in the form of increased pinocytotic vesicles, large vacuoles and microvilli associated with pale and edematous cytoplasm of some endothelial cells. Thickened multilayered basement membrane, absence of ensheathment of capillary basement membrane by astrocytic cell processes and widened perivascular space were observed in both tumoral and peritumoral MBVs.An interesting observation was that in the peritumoral MBVs, the pinocytotic vesicles were most conspicuously seen on the abluminal side of the endothelial cells often fused with the abluminal plasma membrane. Although a static study like this cannot indicate any definite direction of movement of fluid, we feel that the occurrence of reverse pinocytosis is a distinct possibility in the peritumoral MBVs and that it may be an important means of resorption of edema fluid.     

Studies on 66,67Ga- and 199Tl-poly(N-vinylpyrrolidone) complexes.

Gallium and thallium radionuclides have both diagnostic and therapeutic applications in the field of nuclear medicine. Poly(N-vinylpyrrolidone) (PVP) is routinely used as a drug base because of its excellent biocompatibility. In this paper, complex formation abilities between no-carrier-added (66,)(67)Ga/(199)Tl radionuclides and PVP have been studied. It has been found that aqueous 5% PVP solution can almost quantitatively back extract (66,)(67)Ga/(199)Tl radionuclides from an organic phase, which proves the complexing ability of PVP with (66,)(67)Ga/(199)Tl. Tl(3+) is more efficient to form Tl-PVP complexes than Tl(+). However, Tl(3+)-PVP complexes are less stable than Ga(3+)-PVP complexes.