Objective:Amphotericin B (AMB),a potent antifungal agent,has been employed as topical and systemic therapy for sinonasal fungal infections.A novel formulation of nanodisc (ND) containing super aggregated AMB (ND-AMB) ...Objective:Amphotericin B (AMB),a potent antifungal agent,has been employed as topical and systemic therapy for sinonasal fungal infections.A novel formulation of nanodisc (ND) containing super aggregated AMB (ND-AMB) for the treatment of fungal infections has been recently developed to provide greater protection from AMB toxicity than current,clinically approved lipid-based formulations.The objective of the current study was to evaluate the safety and potency of ND-AMB for sinonasal delivery using an in vitro model.Methods:Human sinonasal tissue was harvested during endoscopic sinus surgery and grown at air-liquid interface until well-differentiated.Cultures were exposed to ND-AMB vs AMB and changes in K+ permeability and resistance were measured and recorded via Ussing chamber assay.Ciliary beat frequency (CBF) was analyzed in parallel as well as cytotoxic assay.Potency was assessed using real-time PCR measurement of the Aspergillus fumigatus 18S rRNA.Results:Ussing chamber studies revealed K+ currents that increased rapidly within 30 s of adding AMB (10 μg/mL) to the apical side,indicating apical membranes had become permeable to K+ ions.In contrast,negligible induction of K+ current was obtained following addition of NDAMB [AMB =(107.7 ± 15.9) μA/cm2 AMB vs ND-AMB =(2.3 ± 0.7) μA/cm2 ND-AMB;P =0.005].ND-AMB also protected nasal epithelial cells from cytotoxicity of AMB (P ＜ 0.05).There was no difference in ciliary beat frequency between the two groups (P =0.96).The expression of A.fumigatus 18S rRNA with exposure of lower dose of ND-AMB was significantly lower compared to that with AMB (P ＜ 0.05).Conclusions:Data from the present study suggests ND-AMB protects human nasal epithelia membranes from AMB toxicity by protecting against apical cell K+ permeability while maintaining uncompromised antifungal property compared to AMB.ND-AMB could provide a novel topical therapy for sinonasal fungal diseases.展开更多
This literature review examines the mechanisms of how exercise, specifically in the form of resistance training, may lead to pain relief in the cancer population. Primary data from three different cancer populations: ...This literature review examines the mechanisms of how exercise, specifically in the form of resistance training, may lead to pain relief in the cancer population. Primary data from three different cancer populations: breast, prostate, and lung, will be examined. A number of experimental studies have been conducted to confirm the effectiveness of resistance training on pain relief as well as the biochemical pathways that relate to this process. In this review, we will examine 5 randomized controlled trials. For the purposes of this review, pain is defined as physical suffering or discomfort associated with illness. Pain is the body’s natural signal, bringing attention to damage that has been sustained by tissues. However, chronic pain is common in the cancer population, and often serves no good purpose but instead will negatively impact both physical and mental health. The three types of pain: nociceptive, neuropathic, and inflammatory pathways have been investigated, and the knowledge of pain mechanisms allows for the understanding of how it is associated with pain. The purpose of this exploratory literature review is to give insight on how to maximize pain-relieving effects of resistance training. Research has indicated that resistance training modulates pain pathways by upregulating the release of pain-relieving substances including beta-endorphins, anti-inflammatory cytokines, and endocannabinoids. Understanding of the benefits of resistance training may be useful in relieving cancer pain, and reproducing effects of pain-relieving strategies while minimizing the symptoms related to cancer and its treatment.展开更多
Despite numerous published studies on the wear of dental composites,few have considered the influence of temperature on the two-body wear process.Additionally,no previous work has considered the influence of temperatu...Despite numerous published studies on the wear of dental composites,few have considered the influence of temperature on the two-body wear process.Additionally,no previous work has considered the influence of temperature on dominant wear mecha-nisms during the consumption of hot substances,hence the focus of this study.Recip-rocating wear tests were carried out at varying artificial saliva lubricant temperatures(37 and 57℃)and material loss was quantified using profilometry.The wear tracks were analysed using FIB/SEM/TEM.Results reveal that the wear rate of a dental composite can significantly increase with temperature,with fatigue/delamination and ploughing acting as dominant mechanisms.展开更多
文摘Objective:Amphotericin B (AMB),a potent antifungal agent,has been employed as topical and systemic therapy for sinonasal fungal infections.A novel formulation of nanodisc (ND) containing super aggregated AMB (ND-AMB) for the treatment of fungal infections has been recently developed to provide greater protection from AMB toxicity than current,clinically approved lipid-based formulations.The objective of the current study was to evaluate the safety and potency of ND-AMB for sinonasal delivery using an in vitro model.Methods:Human sinonasal tissue was harvested during endoscopic sinus surgery and grown at air-liquid interface until well-differentiated.Cultures were exposed to ND-AMB vs AMB and changes in K+ permeability and resistance were measured and recorded via Ussing chamber assay.Ciliary beat frequency (CBF) was analyzed in parallel as well as cytotoxic assay.Potency was assessed using real-time PCR measurement of the Aspergillus fumigatus 18S rRNA.Results:Ussing chamber studies revealed K+ currents that increased rapidly within 30 s of adding AMB (10 μg/mL) to the apical side,indicating apical membranes had become permeable to K+ ions.In contrast,negligible induction of K+ current was obtained following addition of NDAMB [AMB =(107.7 ± 15.9) μA/cm2 AMB vs ND-AMB =(2.3 ± 0.7) μA/cm2 ND-AMB;P =0.005].ND-AMB also protected nasal epithelial cells from cytotoxicity of AMB (P ＜ 0.05).There was no difference in ciliary beat frequency between the two groups (P =0.96).The expression of A.fumigatus 18S rRNA with exposure of lower dose of ND-AMB was significantly lower compared to that with AMB (P ＜ 0.05).Conclusions:Data from the present study suggests ND-AMB protects human nasal epithelia membranes from AMB toxicity by protecting against apical cell K+ permeability while maintaining uncompromised antifungal property compared to AMB.ND-AMB could provide a novel topical therapy for sinonasal fungal diseases.
文摘This literature review examines the mechanisms of how exercise, specifically in the form of resistance training, may lead to pain relief in the cancer population. Primary data from three different cancer populations: breast, prostate, and lung, will be examined. A number of experimental studies have been conducted to confirm the effectiveness of resistance training on pain relief as well as the biochemical pathways that relate to this process. In this review, we will examine 5 randomized controlled trials. For the purposes of this review, pain is defined as physical suffering or discomfort associated with illness. Pain is the body’s natural signal, bringing attention to damage that has been sustained by tissues. However, chronic pain is common in the cancer population, and often serves no good purpose but instead will negatively impact both physical and mental health. The three types of pain: nociceptive, neuropathic, and inflammatory pathways have been investigated, and the knowledge of pain mechanisms allows for the understanding of how it is associated with pain. The purpose of this exploratory literature review is to give insight on how to maximize pain-relieving effects of resistance training. Research has indicated that resistance training modulates pain pathways by upregulating the release of pain-relieving substances including beta-endorphins, anti-inflammatory cytokines, and endocannabinoids. Understanding of the benefits of resistance training may be useful in relieving cancer pain, and reproducing effects of pain-relieving strategies while minimizing the symptoms related to cancer and its treatment.
文摘Despite numerous published studies on the wear of dental composites,few have considered the influence of temperature on the two-body wear process.Additionally,no previous work has considered the influence of temperature on dominant wear mecha-nisms during the consumption of hot substances,hence the focus of this study.Recip-rocating wear tests were carried out at varying artificial saliva lubricant temperatures(37 and 57℃)and material loss was quantified using profilometry.The wear tracks were analysed using FIB/SEM/TEM.Results reveal that the wear rate of a dental composite can significantly increase with temperature,with fatigue/delamination and ploughing acting as dominant mechanisms.
