Biomedical subjects

Jing Lin

Publications and source records attributed to Jing Lin.

61 records · Page 4Linked to original sources

PubMed2002

Developing strategies for isolation of minor impurities with mass spectrometry-directed fractionation.

Efficient and automated purification of new chemical entities/potential drug substances and isolation of minor impurities are important aspects of early drug discovery and development strategies, especially when combinatorial synthesis is applied. LC-MS controlled preparative LC and automated fraction collection have been developed for this purpose. The success of such an approach is greatly determined by the quality of the software controlling the application, the coordination between software and hardware, and the reliability of the hardware. The performance of a commercially-available LC-MS controlled autopurification system was evaluated by fractionating four impurities of buspirone as a model compound, eluting closely to the major component under both acidic and basic mobile-phase conditions. A purification strategy for these four components is proposed.

Buspirone↗

PubMed2002

Evidence for a strong hydrogen bond in the catalytic dyad of transition-state analogue inhibitor complexes of chymotrypsin from proton-triton NMR isotope shifts.

We present here the first accurate measurements of 1H (H) versus 3H (T) isotope shift (DeltadeltaT-H = deltaT - deltaH) in a protein. This approach was used to investigate the strength of the hydrogen bond between His57 and Asp102 in the catalytic dyad of chymotrypsin in three transition-state analogue inhibited complexes: N-acetyl-l-phenylalanyl trifluoromethyl ketone (N-AcF-CF3), N-acetyl-l-valyl-l-phenylalanyl trifluoromethyl ketone (N-AcVF-CF3), and N-acetyl-l-leucyl-l--phenylalanyl trifluoromethyl ketone (N-AcLF-CF3). The measured DeltadeltaT-H values for His57 Hdelta1 in these complexes were between -0.63 and -0.68 ppm. These values are consistent with a strong hydrogen bond in each of these complexes, but not with a very strong hydrogen bond, which would be expected to have a DeltadeltaT-H. value near or greater than zero.

Chymotrypsin↗

PubMed2002

A practical enantioselective fluorescent sensor for mandelic acid.

A novel optically active bisbinaphthyl fluorescent sensor, (S,S)- or (R,R)-1, is designed for the recognition of chiral alpha-hydroxycarboxylic acids. A convenient method has been developed to synthesize this compound. It is observed that (S)-mandelic acid enhances the fluorescence intensity of the (S,S)-sensor significantly more than (R)-mandelic acid does. The enantioselective fluorescent response is confirmed with the observation of a mirror image relationship for the interaction of (S,S)- and (R,R)-sensors with mandelic acid. The enantioselectivity in fluorescence response [(I(S) - I(0))/(I(R) - I(0)) = 2.49] is quite high, which makes the sensor useful for practical application. The fluorescence intensity change of the sensor is found to be linearly related to the enantiomeric composition of mandelic acid. This sensor is potentially useful for the combinatorial search of chiral catalysts for the asymmetric synthesis of alpha-hydroxycarboxylic acids.

Fluorescence↗

PubMed2002

Variable effects of short chain fatty acids and lactic acid in inducing intestinal mucosal injury in newborn rats.

BACKGROUND: Short chain fatty acids and lactic acid are colonic bacterial fermentation products. METHODS: To evaluate the effects of these organic acids on the intestinal mucosa, a total of 72 newborn Sprague-Dawley rats (10 days old) were studied. A 3.5F catheter was inserted per rectum 4.0 cm deep into the proximal colon for organic acid administration at a volume of 0.1 ml/10 g body weight. The pH of organic acid solutions and normal saline was adjusted to 4.0. Group 1 (n = 10) received normal saline as a control. Group 2 (n = 11) received 150 mM acetic acid. Group 3 (n = 11) received 300 mM acetic acid. Group 4 (n = 10) received 150 mM butyric acid. Group 5 (n = 11) received 300 mM butyric acid. Group 6 (n = 7) received 150 mM lactic acid, and group 7 (n = 12) received 300 mM lactic acid. Animals were killed 24 hours after colonic installation of test solutions. RESULTS: Both 300 mM acetic acid and 300 mM butyric acid were associated with impaired weight gain, increased colon wet weight, and increased histologic injury scores in the colon and distal ileum (P < 0.05, analysis of variance). Both 150 mM acetic acid and butyric acid at 150 mmol/L induced minimal injury in the colon and distal ileum. Neither 150 mM nor 300 mM lactic acid induced any identifiable gross or microscopic intestinal mucosal injury. CONCLUSION: Luminal short chain fatty acids can induce dose-dependent intestinal mucosal injury in newborn rats, resembling the pathology seen in neonatal necrotizing enterocolitis. Overproduction/accumulation of short chain fatty acids, but not lactic acid, in the proximal colon and/or distal ileum may play a role in the pathogenesis of necrotizing enterocolitis in premature infants.

Acetic Acid↗

PubMed2002

Blockade of human cardiac potassium channel human ether-a-go-go-related gene (HERG) by macrolide antibiotics.

Several macrolides have been reported to cause QT prolongation and ventricular arrhythmias such as torsades de pointes. To clarify the underlying ionic mechanisms, we examined the effects of six macrolides on the human ether-a-go-go-related gene (HERG)-encoded potassium current stably expressed in human embryonic kidney-293 cells. All six drugs showed a concentration-dependent inhibition of the current with the following IC(50) values: clarithromycin, 32.9 microM; roxithromycin, 36.5 microM; erythromycin, 72.2 microM; josamycin, 102.4 microM; erythromycylamine, 273.9 microM; and oleandomycin, 339.6 microM. A metabolite of erythromycin, des-methyl erythromycin, was also found to inhibit HERG current with an IC(50) of 147.1 microM. These findings imply that the blockade of HERG may be a common feature of macrolides and may contribute to the QT prolongation observed clinically with some of these compounds. Mechanistic studies showed that inhibition of HERG current by clarithromycin did not require activation of the channel and was both voltage- and time-dependent. The blocking time course could be described by a first-order reaction between the drug and the channel. Both binding and unbinding processes appeared to speed up as the membrane was more depolarized, indicating that the drug-channel interaction may be affected by electrostatic responses.

Anti-Bacterial Agents↗

PubMed2002

Vitamin A supplementation ameliorates butyric acid-induced intestinal mucosal injury in newborn rats.

Vitamin A (vit A) plays an important role in wound healing and therefore may help in repairing of intestinal mucosal injury. The purpose of this study was to determine if vit A supplementation could promote healing in intestinal mucosal injury as commonly seen in neonatal necrotizing enterocolitis (NEC). Mild intestinal mucosal injury was induced in 10-day-old Sprague-Dawley rats by luminal administration of 1.5% butyric acid (BA) at pH 4.0. Normal saline at the same pH was administered as control. Immediately after administrations of BA or normal saline, animals were randomly assigned to receive high dose vit A (20,000 IU/kg for one dose, i.p.), low dose vit A (5,000 IU/kg for two doses) or vehicle. Animals were followed for 48 hours and then sacrificed for histological examination. Rats with BA-induced intestinal mucosal injury had a reduction in daily weight gain (p < 0.05). Vit A supplementation significantly improved the daily weight gain in the rats with BA-induced intestinal mucosal injury and the effect is dose dependent. At sacrifice, the colon wet weight was significantly heavier and the histological injury scores from both ileum and proximal colon higher in the rats with BA-induced intestinal mucosal injury. All of those parameters were improved with vit A supplementation. We conclude that vit A supplementation ameliorates BA induced-intestinal mucosal injury in newborn rats.

Animals↗

PubMed2002

Changes in upper extremity position cause migration of peripherally inserted central catheters in neonates.

OBJECTIVE: The migration of peripherally inserted central catheters (PICCs) from the superior or inferior vena cava into the right atrium can pose a significant risk of lethal pericardial effusion and tamponade secondary to myocardial perforation. Arm movement has been reported to cause displacement of the catheter tip toward the heart and lead to ventricular tachycardia in adults. The objective of this study was to investigate whether adduction or abduction at the shoulder and flexion or extension at the elbow affect the position of PICCs placed via upper limb veins. We also hypothesized that arm movements can be used to reposition malpositioned catheters. METHODS: A total of 280 radiographs of 60 neonates with PICCs inserted via upper limb veins from July 2000 through June 2001 were reviewed. Differences in catheter tip position as a result of abduction versus adduction at the shoulder, flexion versus extension at the elbow, and combination changes in arm posture were determined by measurements in paired radiographs. Correction of malpositioned catheters was attempted in 10 patients by using arm movements without any alterations at the site of insertion. RESULTS: Arm movements were associated with significant displacement of catheters. Catheters that were placed via the basilic or axillary vein migrated toward the heart with adduction of the arm, whereas those that were placed via the cephalic vein moved away from the heart with adduction. Flexion of the elbow displaced catheters that were placed in the basilic or cephalic vein below the elbow toward the heart but did not have any effect on catheters that were placed via the axillary vein. For catheters that were placed in the basilic vein, simultaneous shoulder adduction and elbow flexion caused the greatest movement toward the heart (15.11 +/- 1.22 mm). We were able to reposition correctly inappropriately placed catheters in 9 of 10 patients by using arm movements. CONCLUSIONS: Arm movements significantly affect the position of the tip of the PICCs. Prevention of catheter migration into the right atrium requires radiographic determination of vein of insertion and monitoring of catheter tip position with upper extremity in position of maximum inward movement of catheter for that vein. Arm movements can be used to correct the malpositioned catheters.

Arm↗