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61.
《Expert review of anticancer therapy》2013,13(1):129-141
Introduction: we performed a systematic review and meta-analysis of mucocutaneous toxicities associatedwith sunitinib, an oral multi-tyrosine kinase inhibitor. Methods: eligible studies included randomized Phase II and III trials of patients with solid tumors on sunitinib daily, describing events of hand–foot syndrome, skin rash, stomatitis, and skin and hair discoloration. Results: the relative risk (RR) of all-grade hand–foot skin reaction, skin rash, stomatitis, skin and hair discoloration were 2.12 (95% CI: 1.28–3.51; p < 0.004), 1.33 (95% CI: 1.15–1.54; p < 0.0002), 1.88 (95% CI: 1.36–2.59; p = 0.0001), 16.6 (95% CI: 4.18–64.94 p < 0.003), 4.42 (95% CI: 0.8–24.5; p < 0.09); respectively. Conclusions: our meta-analysis has demonstrated that sunitinib is associated with a higher risk of developing all-grade hand–foot skin reaction, skin rash, stomatitis and skin discoloration compared with control. Clinicians should be aware of these risks and perform regular clinical monitoring. 相似文献
62.
Eight bibenzyl derivatives, namely dendrocandins J–Q (1–8), were isolated from the stems of Dendrobium candidum. Their structures were elucidated by 1D and 2D NMR experiments and mass spectrometry. Compounds 1–8 were examined for antioxidant activity by 1,1-diphenyl-2-picrylhydrazyl free radical scavenging assay, and the IC50 values were 36.8, 70.2, 45.0, 60.5, 87.6, 50.4, 22.3, and 30.3 μM, respectively. 相似文献
63.
《Current medical research and opinion》2013,29(9):2627-2637
ABSTRACTBackground: Aliskiren, an antihypertensive drug approved in the United States and Europe, is the first in a new class known as direct renin inhibitors. Aliskiren has been evaluated for safety and tolerability in more than 6400 patients. It has demonstrated a favorable safety and tolerability profile alone or in combination with other drugs.Objective: This article reviews the currently available safety and tolerability data for aliskiren.Methodology: Using the search term aliskiren, MEDLINE (no timeframe set) and major cardiovascular congresses (2005–2008) were searched. Articles and abstracts with safety and drug interaction data were included.Findings: Aliskiren may share common adverse effects observed with angiotensin-converting enzyme (ACE)-inhibitor and angiotensin receptor blocker (ARB) therapy. In placebo-controlled trials, those commonly reported for aliskiren at the approved dosage were headache, diarrhea, and fatigue, with incidences similar to those of placebo. Aliskiren has been well tolerated in black, geriatric, diabetic, or obese patients and patients with renal or hepatic impairment. Aliskiren neither inhibits nor induces the cytochrome P450 system; it does not inhibit P-glycoprotein, but is a substrate for this drug transporter. Adding a direct renin inhibitor to another renin–angiotensin–aldosterone system (RAAS) inhibitor may further improve cardiovascular outcomes, renal outcomes, or both, without increasing the incidence of adverse effects.Conclusions: Aliskiren is well tolerated, has an adverse effect profile comparable to that of placebo, and has a low potential for drug interactions. Data from ongoing trials evaluating the effects of aliskiren on surrogate markers, morbidity, and mortality will further define the role of direct renin inhibition in the antihypertensive armamentarium. 相似文献
64.
《Journal of microencapsulation》2013,30(7):701-708
AbstractNovel aptamer-functionalized polyethylene glycol–polylactic acid (PEG–PLA) (APP) micelles were developed with the objective to target the transferrin receptor on brain endothelial cells. Flurbiprofen, a potential drug for therapeutic management of Alzheimer’s disease (AD), was loaded into the APP micelles using the co-solvent evaporation method. Results indicated that 9.03% (w/w) of flurbiprofen was entrapped in APP with good retention capacity in vitro. Targeting potential of APPs was investigated using the transferring receptor-expressing murine brain endothelial bEND5 cell line. APPs significantly enhanced surface association of micelles to bEND5 cells as quantified by fluorescence spectroscopy. Most importantly, APPs significantly enhanced intracellular flurbiprofen delivery when compared to unmodified micelles. These results suggest that APP micelles may offer an effective strategy to deliver therapeutically effective flurbiprofen concentrations into the brain for AD patients. 相似文献
65.
《Renal failure》2013,35(7):1208-1218
AbstractThe furostanol glycoside isolated from the seed of fenugreek (SFSE-G) has an array of pharmacological activities. To date, no validated high-performance liquid chromatography (HPLC) method has been reported for quantification of SFSE-G in biological samples. Hence, the aim of the present study was to study the pharmacokinetics, tissue distribution and excretion profiles of SFSE-G after oral administration in rats. A rapid, sensitive, selective, robust and reproducible HPLC method has been developed for determination of SFSE-G in the rat biological samples. The chromatographic separation was accomplished on a reversed-phase C18 column using formic acid and acetonitrile (80:20) as mobile phase at a flow rate of 1.0?mL/min and 274?nm as a detection wavelength. The assay was linear for SFSE-G with the correlation coefficients (R2) >0.996. The analytes were stable during samples storage and handling, and no matrix effects were observed. After oral dosing of SFSE-G at a dose of 200?mg/kg, the elimination half-life was app. 40.10?h. It showed relatively slowly distribution and eliminated in urine and feces after 24?h, and could be detected until 108?h post-dosing. Following oral single dose (200?mg/kg), SFSE-G was detected in lung and brain which indicated that it could cross the blood–brain barrier. It is a major route of elimination is excretion through urine and feces. In conclusion, oral administration of SFSE-G showed slow distribution to tissues, such as lung and brain, but showed fast renal elimination. 相似文献
66.
There is a relationship between arterial blood pressure, cardiac output and vascular resistance which can be described mathematically, and helps us to understand the short-term control of blood pressure in the terms of a hydraulic system. The sensors in this system are the arterial baroreceptors which mediate changes in the hydraulic system though control of the autonomic nervous system, which in turn influences heart rate, inotropy and vascular tone. Altering the distribution of blood between the arterial and venous systems compensates for acute changes in total blood volume. The total blood volume is controlled predominantly by the kidney, with the renin–angiotensin–aldosterone system acting as both the ‘sensor’ of blood pressure/volume (via renin release in the juxtaglomerular apparatus) and the ‘effector’ of blood pressure/volume (via aldosterone secretion by the adrenal cortex). Overall control is shared; the baroreceptors being responsible for mediating short-term changes, and renal mechanisms determining the long-term control of blood pressure. These systems have to be adaptable in order to deal with physiological variation in the delivery of blood to tissues from rest to exercise, and with the large shifts in blood volume seen in acute haemorrhage. Pathophysiological changes in these systems lead to maladaptive responses, with systemic hypertension the most commonly seen. 相似文献
67.
Böhme J Wenz H Al-Zghloul M A Alonso Groden C Förster A 《Journal of neuroradiology. Journal de neuroradiologie》2019,46(1):3-8
Purpose
Aim of this study was to evaluate the collateral blood flow between more distal branches of the middle cerebral artery (MCA) in the case of peripheral MCA branch occlusion on dynamic 4D angiograms. We sought to individually predict the finally resulting infarction volume with regard to the extent of collateral blood flow.Methods
Overall, 35 acute ischemic stroke patients with peripheral MCA branch occlusion were included. Volumes of the ischemic infarctions and perfusion deficits were measured on diffusion-weighted images DWI and time-to-peak TTP (>?4?s). Collateral flow on 4D MR angiograms were classified as previously specified.Results
On DWI, the ischemic lesions had a mean volume of 3.4?±?15.1?mL while the mean volume on TTP (>?4?s) was significantly larger 22.0?±?18.1?mL (P?<?0.001). On dynamic 4D angiograms we observed grade 1 in 8 (22.9%), grade 2 in 4 (11.4%), grade 3 in 10 (28.6%), and grade 4 in 13 (37.1%) patients. In comparison to patients with better collateralization (grade 3–4) patients with less sufficient collateralization (grade 0–2) demonstrated larger infarction volumes on initial (11.1?mL (IQR 2.9–35.5) vs. 2.1?mL (IQR 0.5–4.5), P?=?0.03) and follow-up DWI (15.5?mL (IQR 12.6–23.3) vs. 1.9?mL (IQR 0.5–4.5), P?=?0.03) with prominent infarction growth (7.4?mL (IQR 2.6–10.1) vs. 0.9?mL (IQR 0.2–2.6), P?=?0.08).Conclusions
In the majority of cases with distal MCA branch occlusion a good collateral blood flow has been observed. Nevertheless, in approximately one quarter of patients an insufficient collateral blood flow has been detected that was associated with substantial infarction growth. 相似文献68.
《Expert review of clinical pharmacology》2013,6(2):105-109
Clinical pharmacologists have three distinct contributions to make in the economic evaluation of new and existing pharmaceutical products: they should play a significant role in promoting the principles of “opportunity costs” in healthcare; they need to have a broad understanding of the methodology of economic evaluation in healthcare; they have a critical role in bringing their specialist knowledge, skills and experience in decision-making. In fulfilling these essential roles clinical pharmacologists may find themselves outside their conventional “comfort zones”. Nevertheless, clinical pharmacologists need to rise to the occasion if they are to meet their obligations to patients and to society as a whole. 相似文献
69.
《Mayo Clinic proceedings. Mayo Clinic》2021,96(11):2856-2860
Although there have been several case reports and simulation models of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission associated with air travel, there are limited data to guide testing strategy to minimize the risk of SARS-CoV-2 exposure and transmission onboard commercial aircraft. Among 9853 passengers with a negative SARS-CoV-2 polymerase chain reaction test performed within 72 hours of departure from December 2020 through May 2021, five (0.05%) passengers with active SARS-CoV-2 infection were identified with rapid antigen tests and confirmed with rapid molecular test performed before and after an international flight from the United States to Italy. This translates to a case detection rate of 1 per 1970 travelers during a time of high prevalence of active infection in the United States. A negative molecular test for SARS-CoV-2 within 72 hours of international airline departure results in a low probability of active infection identified on antigen testing during commercial airline flight. 相似文献