We have used the filamentous fungus, Neurospora crassa, as a model system to test the concept that antisense targeting of the cell-wall assembly enzyme, (1,3)beta-glucan synthase [E.C. 2.4.1.34; UDPglucose: 1,3-beta-D-glucan 3-beta-D-glucosyltransferase], leads to a corresponding decrease in growth of the organism. Previously, our laboratory isolated a gene (glucan synthase-1, gs-1) that is required for (1,3)beta-glucan synthase activity. Wild-type cells were transformed with DNA vectors encoding various RNAs complementary to the gs-1 messenger RNA (antisense RNA) cloned downstream from an inducible promoter (quinic acid-2[qa-2p]). Stable transformants, expressing a partially inverted antisense message of gs-1 (pMYX107), exhibited dramatic reduction ingrowth compared with empty vector controls. Hyphal measurements of these transformants grown on race tubes indicated that all of the transformants showed various degrees of inhibition. Microscopic observations of transformants revealed shorter hyphal lengths when grown under conditions expressing antisense. Further characterization revealed that the specific activities of (1,3)beta-glucan synthase were decreased by as much as 63% relative to empty vector controls. Together, these observations suggest that antisense against (1,3)beta-glucan synthase led to a reduction in enzyme levels that resulted in altered cell-wall morphology and inhibition of growth. It is possible that antisense oligonucleotides against gs-1 may be useful antifungal agents.
sodium salt, 5mM NaF, 250mM sucrose, and 10 mM NaH2PO4; and for A. fumigatus, 50mM HEPES, 10mM EDTA, 750mM sucrose, 10mM NaH2PO4, 100mM cellobiose and During the last three decades there has been a dramatic increase in the frequency of fungal infections, especially disseminated systemic mycoses in immunodeficient hosts1,2). Mycoses in compromised hosts are mainly the result of opportunistic infections by organisms that are normally harmless, asymptomatic commensals which can be, under certain conditions, pathogenic3,4). Species of Aspergillus, Candida, Coccidioides, Cryptococcus, Histo
expected to result in negligible alterations in the unbound drug as represented in our current patient profiles. On the basis of these data, we conclude that intravenous doripenem 500 mg once every 24 hours provides adequate concentrations throughout the dosing interval in patients with ESRD undergoing hemodialysis; however, controlled pharmacokinetic studies should be performed to confirm the best dosing strategy in this population and assess potential drug accumulation.
We study the relationship of West Texas Intermediate (WTI) crude oil returns and the stock market returns with the US airline stocks before, during and after the 2008 financial crisis. We confirm the positive relationship of the airline stock returns with the overall market and the negative relationship with WTI. However, we find that the crisis led to a structural change in this relationship. Our results differ for low-cost airlines which absorb the oil price shock better as compared to legacy airlines. We also find that there is a difference in the relationship between the airline stock returns and WTI returns when asymmetric WTI returns are considered. Investors punish airline stocks more when there are asymmetric negative WTI returns as compared to asymmetric positive returns. While our results are in line with the existing literature on the overall stock markets, this study is unique because it provides a context for the behavior of airline stocks.
The authors present a case of nightmares induced by the 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitors simvastatin and fluvastatin. A 79-year-old Caucasian male initially treated with simvastatin 10 mg every evening developed nightmares after the dose was increased to 40 mg. No relief was provided with a dose reduction to 20 mg, and simvastatin was held. Simvastatin was restarted 7 weeks later at 10 mg, with no complaints of nightmares until the dose was escalated to 20 mg. Simvastatin therapy was subsequently stopped. One month later, fluvastatin 80 mg was initiated and nightmares returned within 3 months, necessitating discontinuation of fluvastatin. The patient was rechallenged with fluvastatin 80 mg, and the nightmares returned 1 month later. Statin therapy was discontinued, and the patient was started on ezetimibe 10 mg. Lipophilic statins such as atorvastatin, lovastatin, and simvastatin have been associated with sleep disturbances. However, lipophilicity may not predict the likelihood of these adverse effects among the statins. Patients prescribed a statin should be counseled on sleep disturbances as potential adverse effects and should be encouraged to notify their providers if these disturbances develop.
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