BACKGROUNDObservational studies suggest that orally administered guaifenesin (GGE) may thin lower respiratory tract secretions but none have examined its effects on mucociliary and cough clearance (MCC/CC) during a respiratory tract infection (RTI). The current study was a randomized, parallel-group, double-blind, placebo-controlled study in non-smoking adults who suffered from an acute upper RTI.METHODSWe assessed the effects of a single dose of Mucinex(®) 1200 mg (2 × 600 mg extended release tablets) (ER GGE) on 1) MCC/CC by assessing the rate of removal from the lung of inhaled radioactive tracer particles (Tc99m-sulfur colloid), 2) sputum dynamic rheology by stress/strain creep transformation over the linear part of the curve, 3) sessile drop interfacial tension by the deNouy ring technique, and 4) subjective symptom measures. MCC was measured during the morning (period 1) and compared to that in the afternoon 4 h later (period 2) immediately following either drug (n = 19) or placebo (n = 19). For both period 1 and 2 subjects performed 60 voluntary coughs from 60 to 90 min after inhalation of radio-labeled aerosol for a measure of CC. Sputum properties were measured from subjects who expectorated sputum during the cough period post treatment (n = 8-12 for each cohort).RESULTSWe found no effect of ER GGE on MCC or CC compared to placebo. MCC through 60 min for period 1 vs. 2 = 8.3 vs. 11.8% (placebo) and = 9.7 vs. 11.1% (drug) (NS) and CC for period 1 vs. 2 was 9.9 vs. 9.1% (placebo) and 10.8 vs. 5.6% (drug) (NS). There was no significant difference in sputum biophysical properties after administration of drug or placebo.CONCLUSIONSThere was no significant effect of a single dose of ER GGE on MCC/CC or on sputum biophysical properties compared to placebo in this population of adult patients with an acute RTI. ClinicalTrials.gov Identifier: NCT01114581.

2013-03-01·Current Topics in Medicinal Chemistry4区 · 医学

Endogenous Modulators of TRP Channels

4区 · 医学

Review

作者: Maione, Sabatino ; Palazzo, Enza ; Rossi, Francesco ; de Novellis, Vito

The transient receptor potential (TRP) superfamily consists of a large number of cation channels permeable to both monovalent and divalent cations. The 28 mammalian TRP channels can be divided into seven subfamilies: the TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (polycystin), TRPML (mucolipin), TRPN (no mechanopotential, NOMP) and the TRPA (ankyrin) groups. TRP channels are widely expressed in several cell types in every tissue and play a critical role in the regulation of various cell functions. Altogether these channels function as sensory transducers and detect chemical, thermal and mechanical stimuli. Endogenous substances acting on TRP channels can be released during the early stage of some pathological conditions. These substances can affect TRP channel functions and lead to the progression of diseases such as inflammation and chronic pain. For example, endogenous lipids, such as unsaturated fatty acids and their cyclooxygenase, lipoxygenase or epoxygenase related metabolites, were shown to modulate TRP channel activity by direct binding. Other lipidergic ligands include isoprene derivatives (e.g. diacylglycerol, lysophospholipids and resolvine) which play diverse activity on different TRP channels. This review focuses on lipidergic mediators which affect TRP channel activity. Opportunities to exploit TRP channels for novel therapeutic strategies will be discussed.

2011-09-01·British Journal of Pharmacology2区 · 医学

Resolvins and arthritic pain

2区 · 医学

Article

作者: Ru-Rong Ji ; Zhen-Zhong Xu

Arthritis-associated inflammatory pain represents a serious medical problem worldwide. Current treatments for arthritic pain are not very effective and cause unwanted side effects. Resolvins, including the resolvin D and resolvin E series, are a family of novel endogenous lipid mediators derived from ω-3 polyunsaturated fatty acids and display potent anti-inflammatory and pro-resolution actions in animal models of inflammation. Emerging evidence also points to a potent anti-hyperalgesic role of resolvins in animal models of inflammatory pain. The study by Lima-Garcia et al. in this issue of the BJP demonstrated that systemic treatment with 17(R)-hydroxy-docosahexaenoic acid (17(R)HDoHE), the precursor of resolvin D series and its product, aspirin-triggered resolvin D1 (AT-RvD1), at very low doses (1 µg·kg(-1)), reduced inflammatory pain in an adjuvant-induced arthritis model. Particularly 17(R)HDoHE reduced joint stiffness but not paw and joint oedema. Given their potency and safety profile, resolvins may represent a new class of analgesics well suited to treating inflammatory pain associated with arthritis. LINKED ARTICLE This article is a commentary on Lima-Garcia et al., pp. 278-293 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2011.01345.x.

项与 Resolvine 相关的新闻（医药）

2022-02-17

·美通社

Kato视网膜疾病药物人体研究获FDA批准

2022年2月17日-- 私营临床阶段生物制药公司Kato Pharmaceuticals今日宣布，美国食品药品监督管理局（FDA）已批准该公司就运用Resolv ER™治疗玻璃体黄斑粘连（VMA）而实施人体研究所提出的试验性新药（IND）申请。这款同类领先的专利配方治疗药物旨在将玻璃体与视网膜分离，以阻断许多视网膜病变发展的风险。获得这项批准后，Kato可以着手研究Resolv ER™在治疗玻璃体黄斑粘连方面的疗效。玻璃体黄斑粘连可能导致视网膜裂孔、视网膜脱离和黄斑裂孔。 Kato将实施一项多中心、随机、双盲、假对照单次和重复玻璃体内治疗的安全性及疗效研究，这项研究共招募100名患者入组。该研究旨在评估Resolv ER™玻璃体内给药在治疗玻璃体黄斑粘连并使视网膜恢复正常状态方面的安全性。该疗法的目标是维持、改善或恢复视力。Resolv ER™以在玻璃体内注射载有脂质体脲类化合物的方式给药。作为视网膜研究领域的专家，医学学士、文学硕士暨这项研究的主要研究者 Arshad M.Khanani博士表示：“我们正在继续寻找治疗玻璃体黄斑粘连的安全有效非手术选项。Resolv ER™的设计是通过在内部注射药物诱导黄斑与玻璃体脱离，具有帮助治疗玻璃体-黄斑粘连患者的潜力。我期待着参与这一重要的临床试验。” Kato Pharmaceuticals首席执行官Terrance McGovern表示：“我们坚信，根据相关适应症随访，Resolv ER™有可能最终帮助到美国500万至600万成年人。许多视网膜疾病尚无治愈方法，现有疗法通常只能暂时缓解此类病症，而病程将随着患者年龄增加和病理学进展逐渐恶化。有关Resolv ER™的初步研究结果令我们倍感振奋，同时我们也希望新试验会验证我们早期的研究结果。” 患者招募工作将很快展开，预计此项研究将于2022年第三季度陆续开展。临床研究即将在美国全境的15处核心研究中心和10处后备研究中心开展。预计招募期将为三至六个月，治疗期为三个月，随访期则为六个月。该研究将量化通过宽视野光学相干断层扫描确定的单次或重复治疗后获得玻璃体黄斑粘连分辨率的受试者百分比，同时还将量化通过眼科检查、眼内压和最佳矫正视力确定的不良事件发生率及严重程度。内容来源于网络，如有侵权，请联系删除，谢谢。

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适应症	最高研发状态	国家/地区	公司	日期
玻璃体黄斑粘连	临床1期	美国	Kato Pharmaceuticals, Inc.	2013-10-01
玻璃体黄斑牵拉综合征	临床1期	美国	Kato Pharmaceuticals, Inc.	2013-10-01