Wound healing effects of dexpanthenol-loaded core/shell electrospun nanofibers: Implication of oxidative stress in wound healing.

Objectives: Knowing the detrimental role of oxidative stress in wound healing and the anti-oxidant properties of Dexpanthenol (Dex), we aimed to produce Dex-loaded electrospun core/shell nanofibers for wound healing study. The novelty was measuring oxidative stress in wounds to know how oxidative stress was affected by Dex-loaded fibers. Materials and Methods: TPVA solution containing Dex 6% (w/v) (core) and PVA/chitosan solution (shell) were coaxially electrospun with variable injection rates of the shell solution. Fibers were then tested for physicochemical properties, drug release profile, and effects on wound healing. Levels of tissue lipid peroxidation and superoxide dismutase activity were measured. Results: Fibers produced at shell injection rate of 0.3 ml/hr (F3 fibers) showed core/shell structure with an average diameter of 252 nm, high hydrophilicity (swelling: 157% at equilibrium), and low weight loss (13.6%). Dex release from F3 fibers seemed to be ruled by the Fickian mechanism based on the Korsmeyer-Peppas model (R2 = 0.94, n = 0.37). Dex-loaded F3 fibers promoted fibroblast viability (128.4%) significantly on day 5 and also accelerated wound healing compared to the neat F3 fibers at macroscopic and microscopic levels on day 14 post-wounding. The important finding was a significant decrease in malondialdehyde (0.39 nmol/ mg protein) level and an increase in superoxide dismutase (5.29 unit/mg protein) activity in Dex-loaded F3 fiber-treated wound tissues. Conclusion: Dex-loaded core/shell fibers provided nano-scale scaffolds with sustained release profile that significantly lowered tissue oxidative stress. This finding pointed to the importance of lowering oxidative stress to achieve proper wound healing.

Propranolol-loaded electrospun nanofibrous wound dressing: From fabrication and characterization to preliminary wound healing evaluation.

OBJECTIVES: The wound healing potential of beta-blocker drugs such as propranolol (PNL) has recently attracted attention. To date, incorporation of PNL into electrospun nanofibrous wound dressing mats has not been tested as a novel topical drug delivery system. Presently, electrospun nanofibrous mats loaded with PNL were fabricated, and their physicochemical properties and wound healing activities were evaluated. MATERIALS AND METHODS: Polyvinyl alcohol solutions containing 0, 2% or 4% (wt/vol) PNL were electrospun into mats, and the physicochemical properties and PNL release were evaluated. In vitro biocompatibility of selected PNL-loaded mats was tested in human foreskin fibroblasts and wound healing capability was evaluated in mouse skin wounds. RESULTS: The 4% PNL mat had thin fibers (160 nm), convincing porosity (79.5%), and good hydrophilicity (swelling: 89.1%, water contact angle: 42.1°) with little degradability (14.2%). The release of PNL was not in bursts and was best explained by the Korsmeyer-Peppas equation (R2 = 0.96, n = 0.40), suggesting Fickian release. The viability of fibroblasts was 173% on day 5 of incubation with 4% PNL mats, indicating good mat biocompatibility. In vivo treatment for 14 days with 4% PNL mats resulted in wounds with a surface area of only 9% of the original wound area. These wounds had better histopathologic characteristics and were associated with less oxidative stress. CONCLUSION: The wound dressing fabricated with 4% PNL showed good potential for wound healing because of a favorable drug release profile from the nanofiber scaffold, and can be considered eligible for further clinical research.

Diltiazem-loaded electrospun nanofibers as a new wound dressing: fabrication, characterization, and experimental wound healing.

Calcium channel blockers such as diltiazem have recently been investigated for their wound-healing potential. The aims of this study were to fabricate diltiazem-loaded nanofibers for a new wound dressing and investigate their beneficial properties for wound healing. Nanofibers were electrospun using polyvinyl alcohol solution containing 0, 2 or 4% diltiazem. Fibers were characterized in terms of physicochemical properties, drug release and fibroblast viability, and in animal wound healing assays. Compared to other formulations, nanofibers containing 4% diltiazem showed thin fiber size (152.7 nm), high porosity (88.4%), high swelling (110.4%), low water contact angle (29.1°) and little weight loss (17.3%). Drug release from 4%-diltiazem nanofibers showed good fit to a Korsmeyer-Peppas model, suggesting a non-Fickian release mechanism (R 2 = 96%, n = 0.52). In vitro, 4%-diltiazem mats were not cytotoxic and enhanced fibroblast proliferation by 263% after 5 days of treatment compared to control. In vivo, wounds treated with this mat for 14 days showed the smallest size (14.7%) and better histopathologic characteristics compared to other wounds. The 4%-diltiazem mat also demonstrated significant antioxidant activity by reducing tissue MDA and nitrite levels by 63 and 59% compared to normal saline. The findings support the eligibility of this novel wound dressing for additional clinical research.

N-acetylcysteine-loaded electrospun mats improve wound healing in mice and human fibroblast proliferation in vitro: a potential application of nanotechnology in wound care.

OBJECTIVES: N-acetylcysteine (NAC) has gained attention recently in dermatology as a unique anti-oxidant. In light of progress in nanotechnological methods, it was hypothesized that loading NAC onto nanofibers would positively affect skin wound healing. The objective of this study was to fabricate NAC-loaded electrospun mats and test their effect on wound healing in vivo and in vitro. MATERIALS AND METHODS: Polyvinyl alcohol (PVA)-based mats loaded with NAC at three concentrations were electrospun and characterized in terms of physicochemical properties and drug release profile. Human fibroblast cells (in vitro) and mouse full-thickness skin wounds (in vivo) were treated with mats for 5 and 14 days, respectively. Wound area, tissue histopathology, fibroblast proliferation and cellular oxidative state were evaluated. RESULTS: Mats containing 5% PVA/NAC showed thinner fibers with suitable physicochemical properties and a sustained drug release profile. PVA/NAC (5%) mats enhanced fibroblast proliferation and attachment in vitro. The mats resulted in significant wound closure with high levels of re-epithelialization and collagen fiber synthesis on day 14 post-surgery in vivo. The mats also reduced granulation tissue and edematous stroma to a higher extent. These findings were accompanied by a significant decrease in tissue lipid peroxidation and higher superoxide dismutase activity, which may explain how NAC improved wound healing. CONCLUSION: We propose an NAC-loaded nanofibrous mat that takes the advantage of a porous nanoscaffold structure to release NAC in a sustained manner. This mat may be a promising candidate for further clinical evaluation.

Air- and Dust-Borne Fungi in Indoor and Outdoor Home of Allergic Patients in a Dust-Storm-Affected Area.

Despite the recent increases in fungi-induced allergic diseases, there is no report yet in the region of the Persian Gulf on concentration levels of fungi in relationship with health state. Therefore, our aim was to measure fungi prevalence as well as to evaluate the relationships between air- and dust-borne fungal genera and allergic diseases. A matched case-control study was carried out including 45 allergic cases and 45 age- and gender-matched controls for each individual. Indoor and outdoor dust and indoor air samples were collected from participant homes during May to October 2015. A Quick Take 30 Pump and sterile wet swab were used to determine fungal types and their amounts in the air (CFU/m3) and dust (CFU/100 cm2) samples, respectively. A significant reverse association was found between indoor dust-borne Alternaria and asthma (Odds ratio (OR) = 0.14, 95% CI = 0.02-0.86). Contrarily, increased levels of indoor air-borne Aspegillus fumigatus (OR = 2.00, 95% CI = 0.37-10.55) and Alternaria (OR = 3.00, 95% CI = 0.34-25.83) were correlated with asthma development. Also, correlation analysis showed a significant relation between indoor air-borne Penicillium levels and reactivity to skin prick test in asthmatic patients (p = 0.04). Our findings support the notion that fungal exposures can either cause or prevent the development of allergic diseases. Accordingly, appropriate measures should be taken for a better management of fungi-induced allergic diseases.

Acute and Chronic Effects of N-acetylcysteine on Pentylenetetrazole-induced Seizure and Neuromuscular Coordination in Mice.

BACKGROUND: N-acetylcysteine (NAC) has been indicated against experimental seizures, but with relatively inconclusive results. This study was undertaken to evaluate whether NAC exerts a dose-dependent anticonvulsant effect and to determine NAC safe therapeutic dose range and its muscle-relaxant activity in both acute and chronic uses. METHODS: Following intraperitoneal (i.p.) administration of N-acetylcysteine acutely (50-300 mg/kg) or chronically for 8 days (25-300 mg/kg), mice were injected with PTZ (90 mg/kg, i.p.) and latency times to the onset of myoclonic and clonic seizures and protection against death were recorded. Changes in body weight and mortality rate were considered as parameters for drug safety. The muscle-relaxant activity of NAC was assessed by rotarod test. RESULTS: Acute and chronic treatment with NAC delayed latency times to myoclonic and clonic seizures in a dose-dependent manner, but with no significant prevention against PTZ-induced death. Chronic administration of 300 mg/kg NAC was fully lethal while lower doses (100 and 150 mg/kg) resulted in a significant weight loss and decreased stay time on rotarod. Acute treatment with NAC had no significant effect on stay time on rotarod at all studied doses. CONCLUSION: NAC exerts a dose-dependent anticonvulsant effect in acute and chronic uses, with no muscle relaxant activity. NAC has higher efficacy in preventing seizure in chronic than acute treatment, but its chronic use at higher doses of 75 mg/kg may be associated with side effects and/or toxicity. These findings suggest that low doses of NAC may have a potential use as a prophylactic treatment for absence seizure in human.

Decreased levels of canonical transient receptor potential channel 3 protein in the rat cerebral cortex after chronic treatment with lithium or valproate.

Lithium and valproate modulate disturbances in intracellular calcium homeostasis implicated in the pathophysiology of bipolar disorder, but the molecular mechanisms are not fully understood. Two subtypes of transient receptor potential (TRP) channel family, i.e. TRPC3 and TRPM2, are potential candidates involved in calcium signaling and implicated in the pathophysiology of bipolar disorder. This study was designed to investigate whether mood stabilizers such as lithium and valproate affect the expression of TRPC3 and TRPM2. Rats were treated with intraperitoneal injections of lithium (2 mEq/kg b.i.d.) or valproate (300 mg/kg b.i.d.) acutely (for 24 h) or chronically (for 4 weeks). The changes in mRNA and protein levels of TRPC3 and TRPM2 were measured with real-time polymerase chain reaction and western blotting. The chronic administration of lithium and valproate significantly reduced levels of TRPC3 by 19.7% and 19.3%, respectively. No change was detected in the mRNA level of this channel. Neither acute nor chronic treatment with lithium or valproate had any effect on TRPM2 levels. The results suggest that downregulation of the TRPC3 channel is an important shared mechanism by which lithium and valproate can modulate calcium disturbances, whereas the TRPM2 channel does not appear to be affected by mood stabilizers, at least under non stressed conditions.

Second-order calibration of excitation-emission matrix fluorescence spectra for determination of glutathione in human plasma.

A rapid non-separative spectroflourimetric method based on the second-order calibration of the excitation-emission data matrix was proposed for the determination of glutathione (GSH) in human plasma. In the phosphate buffer solution of pH 8.0 GSH reacts with ortho-phthaldehyde (OPA) to yield a fluorescent adduct with maximum fluorescence intensity at about 420 nm. To handle the interfering effects of the OPA adducts with aminothiols other than GSH in plasma as well as intrinsic fluorescence of human plasma, parallel factor (PARAFAC) analysis as an efficient three-way calibration method was employed. In addition, to model the indirect interfering effect of the plasma matrix, PARAFAC was coupled with standard addition method. The two-component PARAFAC modeling of the excitation-emission matrix fluorescence spectra accurately resolved the excitation and emission spectra of GSH, plasma (or plasma constituents). The concentration-related PARAFAC score of GSH represented a linear correlation with the concentration of added GSH, similar to that is obtained in simple standard addition method. Using this standard addition curve, the GSH level in plasma was found to be 6.10+/-1.37 micromol L(-1). The accuracy of the method was investigated by analysis of the plasma samples spiked with 1.0 micromol L(-1) of GSH and a recovery of 97.5% was obtained.