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1.
Heat stress (HS) is a notable risk factor for female reproductive performance. In particular, impaired oocyte maturation was thought to contribute largely to the HS-induced reproductive dysfunctions. In this study, we confirmed that oocytes undergoing GVBD were much susceptible to HS, and thus compromising subsequent embryonic development. Using N-acetyl-l-cysteine (NAC), we found supplementation of a relatively high dose NAC during in vitro maturation, can protect oocytes from HS-induced complications, and thus rescuing impaired embryonic development. Further analysis indicated that mechanisms responsible for protecting GVBD oocytes from HS by NAC may include: (1) reversing disorganized spindle assembly and inhibited extracellular signal–regulated kinase (ERK) signaling; (2) correcting erroneous H3K27me3 modification and dysregulated expression of imprinted genes; (3) alleviating increased intraoocyte reactive oxygen species accumulation and apoptosis initiation. Our study, focusing on the oocyte meiotic maturation, may provide a safe and promising strategy for protecting reproductive sows under environmental hyperthermal conditions. 相似文献
2.
Jae Eun Choi Tyler Werbel Zhenping Wang Chia Chi Wu Tony L. Yaksh Anna Di Nardo 《Journal of dermatological science》2019,93(1):58-64
Background
Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.Objectives
To investigate the molecular mechanism by which botulinum toxin improves rosacea lesions.Methods
Primary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by β-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections.Results
Onabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers.Conclusions
These findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study. 相似文献3.
Hyperhidrosis can seriously impair patients’ quality of life. Medical history, including heredity and hyperhidrosis during youth, as well as current age and time elapsed since menopause, is important to consider when distinguishing between postmenopausal hyperhidrosis and vasomotor symptoms to enable adequate treatment. This report concerns a subgroup of eight postmenopausal patients participating in a randomized controlled trial regarding botulinum toxin (Btx) type B treatment in craniofacial hyperhidrosis. Even though the sample size is small and the enrolment is not yet completed, the promising data collected hitherto are interesting to present in advance because this subtype of craniofacial hyperhidrosis is often underrecognized and challenging to treat. Patients were randomized to receive Btx type B or placebo. Measurements were performed before treatment and 3 ± 1 weeks after. The Dermatology Life Quality Index (DLQI) score was improved for all patients after Btx type B treatment (n = 3) with a median decrease of 9 points (90% median improvement). The placebo group (n = 5) had a median increase of 2 points (–18% median decline). When the same group (n = 5) received Btx type B (open) the DLQI score decreased with a median of 7 points compared with baseline (91% median improvement). Treatment‐related adverse events were temporary and did not prevent improvement of life quality. Furthermore, background data evaluation uncovered interesting findings regarding vasomotor symptoms in relation to postmenopausal hyperhidrosis. In conclusion, the results indicated that Btx type B seems to be a safe and effective treatment in postmenopausal craniofacial hyperhidrosis. Further research is encouraged. 相似文献
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随着对肿瘤热疗和肿瘤免疫微环境(TIME)的深入研究,近年来热疗对TIME的作用越来越受到学者们的重视。本文就目前国内外研究进展,对热疗与TIME中几类主要免疫细胞和免疫相关细胞因子的影响及作用机制作一综述。全面而透彻的了解热疗对TIME的调控作用,有助于为肿瘤治疗提供新的思路和方法。 相似文献
6.
《Drug metabolism and pharmacokinetics》2019,34(1):87-94
The purpose of this study was to elucidate the involvement of Mate1 in the tubular secretion of trimethoprim and saturation of Mate1-mediated efflux to address the mechanisms underlying the pharmacokinetic drug interactions with trimethoprim. Trimethoprim is a more potent inhibitor of MATE2-K than MATE1 with Ki values (μM) of 0.030–0.28 and 2.4–5.9, respectively. Trimethoprim is a substrate of human MATE1 and MATE2-K with Km values of 2.3 ± 0.9 and 0.018 ± 0.004 μM, and mouse Mate1, but not human OCT2, mouse Oct1 and Oct2. Pyrimethamine significantly reduced the renal clearance (CLR) of trimethoprim (mL/min/kg) from 40.0 ± 5.1 to 20.1 ± 3.7 (p < 0.05). Trimethoprim was given to mice at three infusion rates (150, 500, and 1500 nmol/min/kg). Together with an increase in the plasma concentrations of trimethoprim, the CLR (mL/min/kg) of trimethoprim decreased to 25.9 ± 3.2, 13.5 ± 5.7, and 8.92 ± 1.50 at the respective rates. Trimethoprim decreased the CLR of rhodamine 123 in an infusion rate-dependent manner: 11.5 ± 1.3 (control), 5.17 ± 1.55, 1.31 ± 0.50, and 0.532 ± 0.180. These results suggest that Mate1 mediates the tubular secretion of trimethoprim, and at therapeutic doses, MATEs-mediated efflux can be saturated, and thereby, cause drug interactions with other MATE substrates. 相似文献
7.
目的探讨研究一次性湿热交换器在新生儿机械通气长途转运中应用的临床意义。方法 2017年1月-2017年12月,我院120转运中心长途转运接收786例机械通气新生儿,786例患儿随机分为常规气道护理(对照组)和转运途中应用一次性湿热交换器组(治疗组),对比转运过程中的吸痰次数、肉眼可见痰痂形成率、堵管发生率、脱管发生率、人机对抗发生率。结果研究数据显示治疗组吸痰次数、肉眼可见痰痂形成率、堵管发生率、脱管发生率、人机对抗发生率有显著性差异(P<0.05)明显低于对照组。结论在机械通气新生儿长途转运中,一次性湿热交换器的可减少转运患儿吸痰次数发生率、降低肉眼可见痰痂形成率、堵管发生率、脱管发生率、人机对抗发生率具有明显优越性,值得推广。 相似文献
8.
目的:观察糖尿病肾病不同分期内热证与肾功能及炎症指标的相关性。方法:收集202例糖尿病肾病患者的临床资料,采用酶联免疫吸附法检测微炎症指标,包括超敏C反应蛋白(high-sensitivity C-reactive protein,HS-CRP)、白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α),进行统计分析。结果:与非内热证组比较,中期、晚期内热证组24小时尿蛋白定量明显升高;晚期内热证组的血清肌酐明显升高,肾小球滤过率(glomerular filtration rate,GFR)明显降低;炎症因子CRP、IL-6、TNF-α随疾病进展均呈上升趋势;晚期内热证组与非内热证组比较,IL-6、TNF-α升高;中期HS-CRP与内热积分呈正相关,晚期TNF-α与内热积分呈正相关。结论:内热病机贯穿于糖尿病肾病的始终,与糖尿病肾病肾功能以及疾病进展密切相关;同时,内热积分与炎症因子HS-CRP、TNF-α的表达存在一定的相关性,这种相关性在疾病中期、晚期表现更加明显。 相似文献
9.
A. Esquenazi 《European journal of neurology》2006,13(S4):27-34
Spasticity is a widespread, disabling form of muscle overactivity affecting patients with central nervous system damage resulting in upper motor neurone syndrome. There is a range of effective therapies for the treatment of spasticity (e.g. physical, anaesthetic, chemodenervation and neurolytic injections, systemic medication and surgery), but all therapies must be based on an individualized, multidisciplinary programme targeted to achieve patient goals. Appropriate therapy should be based on the extent and severity of spasticity, but spasticity and its consequences, regardless of presentation or cause, are commonly treated with systemic agents. This may be ill-advised as systemic treatment is associated with many undesirable effects. In particular, elderly patients with post-stroke spasticity are at risk from the central adverse effects of systemic medication (e.g. sedation and gait disturbance), which make them more susceptible to falling, with an associated increased risk of fracture. The rising costs of fracture care and its sequelae are fast becoming an international problem contributing to high healthcare expenditure. Botulinum toxin type-A (BoNT-A) treatment is highly effective for some of the more common forms of spasticity and muscle overactivity, and has a favourable profile when compared with systemic agents and other focal treatments. Therefore, the clinical benefits of BoNT-A treatment outweigh the apparent high costs of this intervention, showing it to be a cost-effective treatment. 相似文献
10.
M. Naumann A. Albanese F. Heinen G. Molenaers M. Relja 《European journal of neurology》2006,13(S4):35-40
Botulinum toxin serotype A (BoNT-A) has long heritage of use leading to confidence in its safety and efficacy. The application of BoNT-A does not lead to persistent histological changes in the nerve terminal or the target muscle. Clinical trials defined the safety and tolerability profile of BoNT-A across common therapeutic indications and showed an incidence of adverse events of approximately 25% in the BoNT-A-treated group compared with 15% in the control group. Focal weakness was the only adverse event to occur more often following BoNT-A treatment. Long-term BoNT-A administration has been assessed in various treatment settings, with the level and duration of BoNT-A efficacy response being maintained over repeated rounds of injection with no major safety concerns. The treatment of children with cerebral palsy often require long-term, repeated, multimuscle BoNT-A injections that lead to the administration of comparably higher toxin doses. Despite the high total body doses used, their distribution over multiple muscles and injection sites means that systemic side effects are rare. Recent formulation changes have reduced the incidence of antibody development following treatment with BOTOX® . These findings show long-term BoNT-A treatment to be both safe and efficacious for a wide variety of indications. 相似文献