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Articles by M Lin
Total Records ( 4 ) for M Lin
  H Fu , M Lin , Y Katsumura , A Yokoya , K Hata , Y Muroya , K Fujii and N. Shikazono
 

Silybin (SLB) and similar analogues, namely, hesperetin (HESP), naringenin (NAN) and naringin (NAR), are believed to be active constituents of natural flavonoids that have been reported as chemopreventive agents for certain cancers. Moreover, SLB and analogues have been determined to fast repair DNA bases from oxidative damage by pulse radiolysis techniques. The present study was designed to evaluate the protective effects of SLB and analogues on soft X-ray-induced damage to plasmid DNA in vitro. The DNA damage was determined by agarose gel electrophoresis. SLB and analogues were found to protect DNA from radiation damage at micromolar concentrations. Among the compounds tested, HESP and SLB were the most effective in preventing X-ray-induced formation of DNA single-strand breaks (SSB). A comparison of these results with other experiments showed that the ability of SLB and analogues to inhibit DNA damage in vitro correlated with the ability of the compounds to scavenge free radicals. Our work revealed that natural flavonoids, SLB and analogues may be used as potent radioprotectors against radiation damage.

  M. Y Chan , J. L Sun , L. K Newby , L. K Shaw , M Lin , E. D Peterson , R. M Califf , D. F Kong and M. T. Roe
 

Background— There are limited contemporary data comparing long-term outcomes after cardiac catheterization for ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI).

Methods and Results— We studied patients undergoing cardiac catheterization for STEMI (n=2413) and NSTEMI (n=1974) between 1999 and 2005 with at least 1 significant coronary lesion ≥75%. We compared adjusted mortality rates over restricted time intervals and the differential impact of early revascularization on mortality stratified by ST-elevation status. Between 1999 and 2007, 1274 patients died, with a median follow-up of 4 years. A piece-wise analysis showed a higher adjusted mortality risk for STEMI during the first 2 months (adjusted hazard ratio, 1.85; 95% confidence interval, 1.45 to 2.38) and a lower adjusted mortality risk for STEMI after 2 months (adjusted hazard ratio, 0.68; 95% confidence interval, 0.59 to 0.83). Compared with late or no revascularization, early revascularization was associated with a lower adjusted risk of mortality for both STEMI (adjusted hazard ratio, 0.73; 95% confidence interval, 0.58 to 0.90) and NSTEMI (adjusted hazard ratio, 0.76; 95% confidence interval, 0.65 to 0.89) (P for interaction=0.22).

Conclusions— Among a contemporary cohort of acute MI patients with significant coronary disease during cardiac catheterization, STEMI was associated with a higher risk of short-term mortality, but NSTEMI was associated with a higher risk of long-term mortality. Early revascularization was associated with a similar improvement in long-term outcomes for both STEMI and NSTEMI. These data suggest that in clinical investigations of early revascularization among patients with NSTEMI, extended follow-up may be necessary to demonstrate treatment benefit.

  P Gershkovich , E. K Wasan , M Lin , O Sivak , C. G Leon , J. G Clement and K. M. Wasan
  Objectives

To assess the pharmacokinetics and biodistribution of amphotericin B (AmB) following oral administration in a novel mono/diglyceride–phospholipid formulation and to compare with intravenous (iv) administrations using commercial formulations.

Methods

Rats were allocated into the following treatment groups: oral gavage of AmB dispersed in mono/diglyceride–phospholipid formulation at doses of 4.5 and 10 mg/kg; iv bolus administration of 0.8 mg/kg Fungizone®; iv bolus of 5 mg/kg Abelcet® and iv bolus of 5 mg/kg AmBisome®. Blood was sampled from jugular vein cannula at certain time points. The animals were sacrificed 72 h following administration of AmB and multiple tissues were harvested. The concentration of AmB in plasma and tissues was determined by means of HPLC. The plasma creatinine concentrations were determined using an enzymatic kit.

Results

The pharmacokinetics and tissue distribution of AmB following iv administrations of the commercial formulations were found to be highly formulation dependent. The terminal half-life and biodistribution of orally administered AmB in a mono/diglyceride–phospholipid formulation resembled those of Fungizone®. The larger volume of the co-administered lipid-based formulation in the case of the higher dose of orally administered AmB resulted in flip-flop kinetics and in preferential distribution into the kidneys. No nephrotoxicity was detected for any formulation and route of administration.

Conclusions

Oral administration of AmB in a mono/diglyceride–phospholipid formulation to rats resulted in significant intestinal absorption into the systemic circulation with pharmacokinetic and biodistribution properties similar to a micellar iv preparation.

  M Lin , J. T Hatcher , Q. H Chen , R. D Wurster and Z. Cheng
 

Small conductance Ca2+-activated K+ channels (SK) regulate action potential (AP) firing properties and excitability in many central neurons. However, the functional roles of SK channels of parasympathetic cardiac motoneurons (PCMNs) in the nucleus ambiguus have not yet been well characterized. In this study, the tracer X-rhodamine-5 (and 6)-isothiocyanate (XRITC) was injected into the pericardial sac to retrogradely label PCMNs in FVB mice at postnatal days 7–9. Two days later, XRITC-labeled PCMNs in brain stem slices were identified. With the use of whole cell current clamp, single APs and spike trains of different frequencies were evoked by current injections. We found that 1) PCMNs have two different firing patterns: the majority of PCMNs (90%) exhibited spike frequency adaptation (SFA) and the rest (10%) showed less or no adaptation; 2) application of the specific SK channel blocker apamin significantly increased spike half-width in single APs and trains and reduced the spike frequency-dependent AP broadening in trains; 3) SK channel blockade suppressed afterhyperpolarization (AHP) amplitude following single APs and trains and abolished spike-frequency dependence of AHP in trains; and 4) SK channel blockade increased the spike frequency but did not alter the pattern of SFA. Using whole cell voltage clamp, we measured outward currents and afterhyperpolarization current (IAHP). SK channel blockade revealed that SK-mediated outward currents had both transient and persistent components. After bath application of apamin and Ca2+-free solution, we found that apamin-sensitive and Ca2+-sensitive IAHP were comparable, confirming that SK channels may contribute to a major portion of Ca2+-activated K+ channel-mediated IAHP. These results suggest that PCMNs have SK channels that significantly regulate AP repolarization, AHP, and spike frequency but do not affect SFA. We conclude that activation of SK channels underlies one of the mechanisms for negative control of PCMN excitability.

 
 
 
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