Differential dynamics of membrane proteins in yeast

Lateral diffusion of lipids and proteins in yeast plasma membranes has been reported to be anomalously slow, and implicated as a possible reason for polarization in yeast. In order to gain insight into the observed slow diffusion in yeast membranes, we explored lateral diffusion of two proteins of different origin. We compared lateral dynamics of the Candida drug resistance protein-1 (Cdr1p), and the human serotonin1A receptor (5-HT1AR) by fluorescence recovery after photobleaching (FRAP). Our results show that while Cdr1p-GFP displays slow diffusion, the diffusion of 5-HT1AR-EYFP is significantly faster. Interestingly, upon ergosterol depletion, the mobility of Cdr1p-GFP did not exhibit appreciable change, while 5-HT1AR-EYFP mobility showed an increase. On the other hand, upon actin cytoskeleton destabilization, the mobile fraction of 5-HT1AR-EYFP showed considerable increase, while the mobility of Cdr1p-GFP was not altered. Our results represent the first report on the dynamics of the important drug resistance protein Cdr1p and provide novel insight on diffusion of membrane proteins in yeast membranes

A randomized trial of intravenous labetalol & oral nifedipine in severe pregnancy induced hypertension

Background: Hypertension is the most frequently encountered medical disorder in obstetrics practice & remain a major cause of maternal, fetal & neonatal morbidity & mortality. The present study was undertaken to compare the time taken to reach the therapeutic goal blood pressure after using intravenous labetalol & oral nifedipine in severe pregnancy induced hypertension.Methods: Randomly allocated patients received labetalol 20 mg initially, followed by escalating doses of 40, 80, 80 & 80 mg & a placebo tablet every 20 minutes or initially nifedipine tablet 10 mg orally with repeated doses of 20 mg every 20 minutes up to 5 doses & intravenous placebo 0.9% isotonic saline until the therapeutic goal blood pressure, Systolic ≤ 150 mmHg & diastolic ≤ 100 mmHg was achieved. Primary and secondary outcomes like the time interval required to achieve a blood pressure of ≤150/100 mmHg and urinary output, agent failure & adverse effects respectively were reported.Results: Patients received oral nifedipine achieved the goal therapeutic blood pressure more rapidly in 28.2±11.7 minutes (mean±SD) as compared with 48.4±23.5 minutes in those received intravenous labetalol (p=0.001). The nifedipine group also required significantly fewer doses (3.5±0.5 vs 4.5±1.5; p=0.001) to reach the goal blood pressure. Urine output was significantly increased (p<0.001) at one hour after nifedipine therapy (95.6±1.2) compared with labetalol (41.9±1.6 ml) & remained significantly increased at 4,8,16&24 hours after initial therapy. Few adverse effects were reported but not significant. No patients required cross over therapy.Conclusions: Oral nifedipine & intravenous labetalol regimens are effective in the management of severe hypertension in pregnancy; however nifedipine controls hypertension more rapidly & is associated with a significant increase in urinary output