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241.
Niccolo Marchionni Mauro De Bari Luigi Ferrucci Guya Moschi Adam Schneeweiss 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》1988,2(4):529-532
Summary We compared the time-course of the hemodynamic effect of isosorbide dinitrate (ISDN), 5 mg, in the form of sublingual tablet and oral spray, in 15 patients with isolated chronic pulmonary congestion (pulmonary arterial end-diastolic pressure of 15 mmHg or more in the presence of normal or only slightly reduced cardiac index). Both formulations produced significant reductions in the pulmonary arterial end-diastolic pressure. The effect of ISDN tablet (sublingually) became evident at 10 minutes after administration and was maximal at 30 minutes. The effect of ISDN oral spray became evident at 3 minutes and reached a peak at 10 minutes. The magnitude of hemodynamic response was similar. These findings indicate that ISDN oral spray is superior to ISDN sublingual tablets for rapid relief of pulmonary congestion 相似文献
242.
Zhang W Dichtel WR Stieg AZ Benítez D Gimzewski JK Heath JR Stoddart JF 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(18):6514-6519
Mechanically interlocked compounds, such as bistable catenanes and bistable rotaxanes, have been used to bring about actuation in nanoelectromechanical systems (NEMS) and molecular electronic devices (MEDs). The elaboration of the structural features of such rotaxanes into macromolecular materials might allow the utilization of molecular motion to impact their bulk properties. We report here the synthesis and characterization of polymers that contain pi electron-donating 1,5-dioxynaphthalene (DNP) units encircled by cyclobis(paraquat-p-phenylene) (CBPQT(4+)), a pi electron-accepting tetracationic cyclophane, synthesized by using the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The polyrotaxanes adopt a well defined "folded" secondary structure by virtue of the judicious design of two DNP-containing monomers with different binding affinities for CBPQT(4+). This efficient approach to the preparation of polyrotaxanes, taken alongside the initial investigations of their chemical properties, sets the stage for the preparation of a previously undescribed class of macromolecular architectures. 相似文献
243.
In the literature various regimes are described for successful collection of haematopoietic stem cells in patients with multiple myeloma. Most frequently cyclophosphamide is used, 5 g/m2 combined with different doses of haematopoietic growth factors. In our group the yields and tolerance of three stimulating regimes are compared: 1. cyclophosphamide 5 g/m2 and filgrastim (G-CSF) 5 micrograms/kg 2. cyclophosphamide 5 mg/m2 and filgrastim 10 micrograms/kg 3. cyclophosphamide 5 g/m2 and figrastim 5 micrograms/kg along with erythropoitin 50 IU/kg. Cyclophsphamide is administered always on the first day and the haematopoietic growth factors then from the third day till the end of collection of haematopoitic cells. In patients with multiple myeloma where only four cycles of VAD chemotherapy preceded and where radiotherapy of the axial skeleton was not used, optimal collection of haematopoietic stem cells was achieved after administration of cyclohosphamide 5 g/m2 with subsequent administration of 5 micrograms/kg G-CSF. By increasing the dose of G-CSF to 10 micrograms/kg or adding 50 IU/kg erthropoietin did not lead to a significant improvement of the tolerance and yield of this procedure. 相似文献
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Christopher C. Waller Sumudu A. Weththasinghe Lauren McClure Adam T. Cawley Craig Suann Emily Suann Emma Sutherland Elliot Cooper Alison Heather Malcolm D. McLeod 《Drug testing and analysis》2020,12(6):752-762
Hemapolin (2α,3α‐epithio‐17α‐methyl‐5α‐androstan‐17β‐ol) is a designer steroid that is an ingredient in several “dietary” and “nutritional” supplements available online. As an unusual chemical modification to the steroid A‐ring could allow this compound to pass through antidoping screens undetected, the metabolism of hemapolin was investigated by an in vivo equine drug administration study coupled with GC‐MS analysis. Following administration of synthetically prepared hemapolin to a thoroughbred horse, madol (17α‐methyl‐5α‐androst‐2‐en‐17β‐ol), reduced and dihydroxylated madol (17α‐methyl‐5α‐androstane‐2β,3α,17β‐triol), and the isomeric enone metabolites 17β‐hydroxy‐17α‐methyl‐5α‐androst‐3‐en‐2‐one and 17β‐hydroxy‐17α‐methyl‐5α‐androst‐2‐en‐4‐one, were detected and confirmed in equine urine extracts by comparison with a library of synthetically derived reference materials. A number of additional madol derivatives derived from hydroxylation, dihydroxylation, and trihydroxylation were also detected but not fully identified by this approach. A yeast cell‐based androgen receptor bioassay of available reference materials showed that hemapolin and many of the metabolites identified by this study were potent activators of the equine androgen receptor. This study reveals the metabolites resulting from the equine administration of the androgen hemapolin that can be incorporated into routine GC‐MS antidoping screening and confirmation protocols to detect the illicit use of this agent in equine sports. 相似文献
247.
Simon D. Brandt Pierce V. Kavanagh Folker Westphal Alexander Stratford Anna U. Odland Adam K. Klein Geraldine Dowling Nicola M. Dempster Jason Wallach Torsten Passie Adam L. Halberstadt 《Drug testing and analysis》2020,12(6):812-826
Lysergic acid diethylamide (LSD) is a prototypical serotonergic psychedelic drug and the subject of many clinical investigations. In recent years, a range of lysergamides has emerged with the production of some being inspired by the existing scientific literature. Others, for example various 1‐acyl substituted lysergamides, did not exist before their appearance as research chemicals. 1‐Cylopropanoyl‐LSD (1CP‐LSD) has recently emerged as a new addition to the group of lysergamide‐based designer drugs and is believed to be psychoactive in humans. In this investigation, 1CP‐LSD was subjected to detailed analytical characterizations including various mass spectrometry (MS) platforms, gas and liquid chromatography, nuclear magnetic resonance spectroscopy, solid phase and GC condensed phase infrared spectroscopy. Analysis by GC–MS also revealed the detection of artificially induced degradation products. Incubation of 1CP‐LSD with human serum led to the formation of LSD, indicating that it may act as a prodrug for LSD in vivo, similar to other 1‐acyl substituted lysergamides. The analysis of blotters and pellets is also included. 1CP‐LSD also induces the head‐twitch response (HTR) in C57BL/6 J mice, indicating that it produces an LSD‐like behavioural profile. 1CP‐LSD induced the HTR with an ED50 = 430.0 nmol/kg which was comparable to 1P‐LSD (ED50 = 349.6 nmol/kg) investigated previously. Clinical studies are required to determine the potency and profile of the effects produced by 1CP‐LSD in humans. 相似文献
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Richard W Tothill Jason Li Linda Mileshkin Ken Doig Terence Siganakis Prue Cowin Andrew Fellowes Timothy Semple Stephen Fox Keith Byron Adam Kowalczyk David Thomas Penelope Schofield David D Bowtell 《The Journal of pathology》2013,231(4):413-423
The clinical management of patients with cancer of unknown primary (CUP) is hampered by the absence of a definitive site of origin. We explored the utility of massively‐parallel (next‐generation) sequencing for the diagnosis of a primary site of origin and for the identification of novel treatment options. DNA enrichment by hybridization capture of 701 genes of clinical and/or biological importance, followed by massively‐parallel sequencing, was performed on 16 CUP patients who had defied attempts to identify a likely site of origin. We obtained high quality data from both fresh‐frozen and formalin‐fixed, paraffin‐embedded samples, demonstrating accessibility to routine diagnostic material. DNA copy‐number obtained by massively‐parallel sequencing was comparable to that obtained using oligonucleotide microarrays or quantitatively hybridized fluorescently tagged oligonucleotides. Sequencing to an average depth of 458‐fold enabled detection of somatically acquired single nucleotide mutations, insertions, deletions and copy‐number changes, and measurement of allelic frequency. Common cancer‐causing mutations were found in all cancers. Mutation profiling revealed therapeutic gene targets and pathways in 12/16 cases, providing novel treatment options. The presence of driver mutations that are enriched in certain known tumour types, together with mutational signatures indicative of exposure to sunlight or smoking, added to clinical, pathological, and molecular indicators of likely tissue of origin. Massively‐parallel DNA sequencing can therefore provide comprehensive mutation, DNA copy‐number, and mutational signature data that are of significant clinical value for a majority of CUP patients, providing both cumulative evidence for the diagnosis of primary site and options for future treatment. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献