Administration methods and dosage of poly(lactic acid)-glycol intervention to myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalitis mice.

BACKGROUND: Myelin oligodendrocyte glycoprotein-associated disorders (MOGAD) is an autoimmune central nervous system disease. Antigen-specific immune tolerance using nanoparticles such as Polylactic-co-glycolic acid (PLGA) have recently been used as a new therapeutic tolerization approach for CNS autoimmune diseases. We examined whether MOG1-125 conjugated with PLGA could induce MOG-specific immune tolerance in an experimental autoimmune encephalitis (EAE) mouse model. EAE was induced in sixty C57BL/6 J wild-type mice using MOG1-125 peptide with complete Freund's Adjuvant. The mice were divided into 12 groups (n = 5 each) to test the ability of MOG1-125 conjugated PLGA intervention to mitigate the severity or improve the outcomes from EAE with and without rapamycin compared to antigen alone or PLGA alone. EAE score and serum MOG-IgG titers were compared among the interventions.Kindly check and confirm the processed Affiliation “4” is appropriate.I confirmed the Aff 4.Affiliation: Corresponding author information have been changed to present affiliation. Kindly check and confirm.I checked and confirmed the Corresponding author's information. RESULTS: Mice with EAE that were injected intraperitoneally with MOG1-125 conjugated PLGA + rapamycin complex showed dose-dependent mitigation of EAE score. Intraperitoneal and intravenous administration resulted in similar clinical outcomes, whereas 80% of mice treated with subcutaneous injection had a recurrence of clinical score worsening after approximately 1 week. Although there was no significant difference in EAE scores between unconjugated-PLGA and MOG-conjugated PLGA, serum MOG-IgG tended to decrease in the MOG-conjugated PLGA group compared to controls. CONCLUSION: Intraperitoneal administration of PLGA resulted in dose-dependent and longer-lasting immune tolerance than subcutaneous administration. The induction of immune tolerance using PLGA may represent a future therapeutic option for patients with MOGAD.

PLGA nanoparticles engineering extracellular vesicles from human umbilical cord mesenchymal stem cells ameliorates polyethylene particles induced periprosthetic osteolysis.

The wear particle-induced dissolution of bone around implants is a significant pathological factor in aseptic loosening, and controlling prosthetic aseptic loosening holds crucial social significance. While human umbilical cord mesenchymal stem cell-derived exosomes (HucMSCs-Exos, Exos) have been found to effectively promote osteogenesis and angiogenesis, their role in periprosthetic osteolysis remains unexplored. To enhance their in vivo application, we engineered HucMSCs-Exos-encapsulated poly lactic-co-glycolic acid (PLGA) nanoparticles (PLGA-Exos). In our study, we demonstrate that PLGA-Exos stimulate osteogenic differentiation while inhibiting the generation of reactive oxygen species (ROS) and subsequent osteoclast differentiation in vitro. In vivo imaging revealed that PLGA-Exos released exosomes slowly and maintained a therapeutic concentration. Our in vivo experiments demonstrated that PLGA-Exos effectively suppressed osteolysis induced by polyethylene particles. These findings suggest that PLGA-Exos hold potential as a therapeutic approach for the prevention and treatment of periprosthetic osteolysis. Furthermore, they provide novel insights for the clinical management of osteolysis.

Intra-amniotic Injection of Poly(lactic-co-glycolic Acid) Microparticles Loaded with Growth Factor: Effect on Tissue Coverage and Cellular Apoptosis in the Rat Model of Myelomeningocele.

BACKGROUND: Myelomeningocele (MMC) is a devastating congenital neurologic disorder that can lead to lifelong morbidity and has limited treatment options. This study investigates the use of poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) loaded with fibroblast growth factor (FGF) as a platform for in utero treatment of MMC. STUDY DESIGN: Intra-amniotic injections of PLGA MPs were performed on gestational day 17 (E17) in all-trans retinoic acid-induced MMC rat dams. MPs loaded with fluorescent dye (DiO) were evaluated 3 hours after injection to determine incidence of binding to the MMC defect. Fetuses were then treated with PBS or PLGA particles loaded with DiO, bovine serum albumin, or FGF and evaluated at term (E21). Fetuses with MMC defects were evaluated for gross and histologic evidence of soft tissue coverage. The effect of PLGA-FGF treatment on spinal cord cell death was evaluated using an in situ cell death kit. RESULTS: PLGA-DiO MPs had a binding incidence of 86% and 94% 3 hours after injection at E17 for doses of 0.1 mg and 1.2 mg, respectively. Incidence of soft tissue coverage at term was 19% (4 of 21), 22% (2 of 9), and 83% (5 of 6) for PLGA-DiO, PLGA-BSA, and PLGA-FGF, respectively. At E21, the percentage of spinal cord cells positive for in situ cell death was significantly higher in MMC controls compared with wild-type controls or MMC pups treated with PLGA-FGF. CONCLUSION: PLGA MPs are an innovative minimally invasive platform for induction of soft tissue coverage in the rat model of MMC and may reduce cellular apoptosis.

Prenatal exposure to glycol ethers and cryptorchidism and hypospadias: a nested case-control study.

OBJECTIVES: Glycol ethers (GE) are oxygenated solvents frequently found in occupational and consumer products. Some of them are well-known testicular and developmental animal toxicants. This study aims to evaluate the risk of male genital anomalies in association with prenatal exposure to GE using urinary biomarkers of exposure. METHODS: We conducted a case-control study nested in two joint mother-child cohorts (5303 pregnant women). Cases of cryptorchidism and hypospadias were identified at birth and confirmed during a 2-year follow-up period (n=14 cryptorchidism and n=15 hypospadias). Each case was matched to three randomly selected controls within the cohorts for region of inclusion and gestational age at urine sampling. Concentrations of five GE acidic metabolites were measured in spot maternal urine samples collected during pregnancy. ORs were estimated with multivariate conditional logistic regressions including a Firth's penalisation. RESULTS: Detection rates of urinary GE metabolites ranged from 8% to 93% and only two were sufficiently detected (>33%) in each cohort to be studied: methoxyacetic acid (MAA) and phenoxyacetic acid (PhAA). A significantly higher risk of hypospadias was associated with the highest tertile of exposure to MAA: OR (95% CI) 4.5(1.4 to 23.4). No association were observed with urinary concentration of PhAA, nor with the risk of cryptorchidism. CONCLUSIONS: In view of the toxicological plausibility of our results, this study, despite its small sample size, raises concern about the potential developmental toxicity of MAA on the male genital system and calls for thorough identification of current sources of exposure to MAA.

Hyperosmolar metabolic acidosis in burn patients exposed to glycol based topical antimicrobials-A systematic review.

BACKGROUND: The well documented susceptibility of burn patients to acquired infections via damaged skin mandates application of antimicrobial agents. These agents are dissolved in various vehicles that augment skin absorption thus allowing greater efficacy. Polyethylene glycol (PEG) and Propylene glycol (PropG) are among the most commonly used vehicles, and both have been used in numerous medications and cosmetic products over the past few decades. Rarely, burn patients treated with agents containing these glycols present with a life threatening systemic toxidrome of hyperosmolar metabolic acidosis. We present a systematic review of outcomes in burn patients treated with similar agents. METHODS: Relevant studies were identified through systematic searches conducted in MEDLINE (Ovid), Embase (Ovid), CENTRAL (Ovid), and Web of Science (Thomson Reuters), from database inception to August 4th, 2016. All publications of clinical burn patient studies included at least one arm receiving a glycol based topical therapy. RESULTS: A total of 61 studies involving 10,282 patients and 4 different antimicrobial medications fulfilled the inclusion criteria. Nine burn patients (0.09%) were documented to present with hyperosmolar metabolic acidosis during topical silver sulfadiazine treatment. Propylene glycol isolated from their blood accounted for the high osmole gap. CONCLUSION: This first systematic review found very few cases of documented hyperosmolar metabolic acidosis, all within one study that had set to specifically explore this toxidrome. High index of suspicion with frequent osmolar gap monitoring may help identify future toxicities in a timely manner.

Comparison of the effects of e-cigarette vapor and cigarette smoke on indoor air quality.

CONTEXT: Electronic cigarettes (e-cigarettes) have earned considerable attention recently as an alternative to smoking tobacco, but uncertainties about their impact on health and indoor air quality have resulted in proposals for bans on indoor e-cigarette use. OBJECTIVE: To assess potential health impacts relating to the use of e-cigarettes, a series of studies were conducted using e-cigarettes and standard tobacco cigarettes. METHODS AND MATERIALS: Four different high nicotine e-liquids were vaporized in two sets of experiments by generic 2-piece e-cigarettes to collect emissions and assess indoor air concentrations of common tobacco smoke by products. Tobacco cigarette smoke tests were conducted for comparison. RESULTS: Comparisons of pollutant concentrations were made between e-cigarette vapor and tobacco smoke samples. Pollutants included VOCs, carbonyls, PAHs, nicotine, TSNAs, and glycols. From these results, risk analyses were conducted based on dilution into a 40 m³ room and standard toxicological data. Non-cancer risk analysis revealed "No Significant Risk" of harm to human health for vapor samples from e-liquids (A-D). In contrast, for tobacco smoke most findings markedly exceeded risk limits indicating a condition of "Significant Risk" of harm to human health. With regard to cancer risk analysis, no vapor sample from e-liquids A-D exceeded the risk limit for either children or adults. The tobacco smoke sample approached the risk limits for adult exposure. CONCLUSIONS: For all byproducts measured, electronic cigarettes produce very small exposures relative to tobacco cigarettes. The study indicates no apparent risk to human health from e-cigarette emissions based on the compounds analyzed.

Volatile organic compounds enhance allergic airway inflammation in an experimental mouse model.

BACKGROUND: Epidemiological studies suggest an association between exposure to volatile organic compounds (VOCs) and adverse allergic and respiratory symptoms. However, whether VOCs exhibit a causal role as adjuvants in asthma development remains unclear. METHODS: To investigate the effect of VOC exposure on the development of allergic airway inflammation Balb/c mice were exposed to VOCs emitted by new polyvinylchloride (PVC) flooring, sensitized with ovalbumin (OVA) and characterized in acute and chronic murine asthma models. Furthermore, prevalent evaporated VOCs were analyzed and mice were exposed to selected single VOCs. RESULTS: Exposure of mice to PVC flooring increased eosinophilic lung inflammation and OVA-specific IgE serum levels compared to un-exposed control mice. The increased inflammation was associated with elevated levels of Th2-cytokines. Long-term exposure to PVC flooring exacerbated chronic airway inflammation. VOCs with the highest concentrations emitted by new PVC flooring were N-methyl-2-pyrrolidone (NMP) and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TXIB). Exposure to NMP or TXIB also increased the allergic immune response in OVA-sensitized mice. In vitro or in vivo exposure to NMP or TXIB reduced IL-12 production in maturing dendritic cells (DCs) and enhanced airway inflammation after adoptive DC transfer into Balb/c mice. At higher concentrations both VOCs induced oxidative stress demonstrated by increased isoprostane and glutathione-S-transferase-pi1 protein levels in the lung of non-sensitized mice. Treatment of PVC flooring-exposed mice with N-acetylcysteine prevented the VOC-induced increase of airway inflammation. CONCLUSIONS: Our results demonstrate that exposure to VOCs may increase the allergic immune response by interfering with DC function and by inducing oxidative stress and has therefore to be considerate as risk factor for the development of allergic diseases.

Allergic contact dermatitis to propyl gallate and pentylene glycol in an emollient cream.

A 62-year-old man, with a 20-year history of seborrhoeic dermatitis, presented with a worsening of his dermatitis. He had previously been demonstrated to be allergic to various topical corticosteroids, so he had been using an emollient cream (Sebclair), containing piroctone olamine and various anti-inflammatory substances, for 6 months, with good effect. Patch testing to the cream and its ingredients revealed positive reactions to both propyl gallate and pentylene glycol. A positive reaction to propylene glycol was also detected, whereas patch testing to butylene glycol was negative. Complete remission followed avoidance of the offending substances.

Emergent and unusual allergens in cosmetics.

Allergic contact dermatitis from cosmetics is a common problem that is occasionally caused by new or rare allergens. When a patient has a positive patch test to a cosmetic product but to none of the common or commercially available allergens, it is important to further patch-test this patient to the ingredients of the product. Thorough testing with the breakdown of ingredients, usually obtained through cooperation with the manufacturer, often allows identification of the culprit allergen in the cosmetic product. In this article, we discuss emerging or rare allergens discovered by this method, including nail lacquer and lipstick allergens, copolymers, shellac, alkyl glucosides, glycols, protein derivatives, idebenone, and octocrylene.

Contact urticaria with systemic symptoms due to hexylene glycol in a topical corticosteroid: case report and review of hypersensitivity to glycols.

We report a case of severe contact urticaria with systemic involvement resembling an anaphylactic reaction, following the application of a topical corticosteroid. This was caused by hexylene glycol, an excipient in the formulation. Glycols are widely used in cosmetics, foods and topical and systemic drugs. In particular, glycols are present in many topical drugs used by dermatologists. To our knowledge, this is the first case in the literature of a potentially life-threatening immediate-type reaction in the context of a contact urticaria syndrome due to hexylene glycol. The classification of contact urticaria syndrome and the allergenic potential of glycols are reviewed. Dermatologists should be aware of the contact urticaria syndrome and of the increasing use of glycols in topical drug formulation in order to identify possible adverse reactions.

Therapeutic effect of 1,5-pentanediol for herpes simplex labialis: a randomized, double-blind, placebo-controlled clinical trial.

INTRODUCTION: Most episodes of recurrent herpes labialis are self-limited and mild, but can be troublesome when they occur frequently with painful and unsightly lesions. Therefore, there has been much interest in developing agents that can suppress outbreaks in addition to being therapeutically effective. The objective of the present study was to examine the prophylactic and therapeutic efficacy of 1,5-pentanediol (PD) gel in patients with recurrent episodes of herpes labialis. METHODS: In this placebo-controlled, randomized, double-blind clinical trial, a total of 105 patients with frequent episodes of recurrent herpes were randomized to either PD or placebo. During the 26-week prophylactic phase of the study, the patients applied PD gel or placebo gel twice daily to both lips. Upon recurrence of an episode, a 5-day therapy phase started during which the gel was to be applied eight times daily. After the therapy phase, the patient resumed prophylactic treatment twice daily until the next herpes episode. The main outcome measures were number of herpes episodes during the prophylactic phase of 26 weeks, and successful therapy of occurring herpes episodes with a 5-day treatment. RESULTS: There was no significant difference in recurrence rate between the two groups (P>0.05). During recurrence there was a statistically significant improvement regarding the therapeutic effect of the symptoms "blistering," "swelling," and "pain" in the PD group. The global evaluation of efficacy by the investigators and patients showed a statistically significant superiority for PD as opposed to placebo (P<0.001). CONCLUSION: Under the conditions used in the present study, PD did not show any prophylactic effect against recurrence of herpes episodes. A significantly better therapeutic effect of PD over placebo could be demonstrated on the symptoms "blistering," "swelling," and "pain." PD was very safe as no side effects were observed during the course of the study.

A comparison of pentane-1,5-diol to other diols for use in dermatology.

BACKGROUND: The use of pentane-1,5-diol in topical pharmaceutical products is relatively new compared with, e.g., propane-1,2-diol (propylene glycol), also an aliphatic diol, which has been used for many years. Yet, what are the differences between diols in clinical efficacy, safety and other characteristics? OBJECTIVE: The objective of this overview was to compare the efficacy, safety, chemical and pharmaceutical characteristics of pentane-1,5-diol with other aliphatic diols used in pharmaceutical formulations in dermatology. METHODS: A survey of the literature was carried out based on searches limited to aliphatic diols. RESULTS/CONCLUSION: Pentane-1,5-diol was found to be safe and more effective than several other diols with respect to drug delivery-enhancing potency, pharmaceutical and cosmetic properties, antimicrobial spectrum and toxicity. Results from formal clinical trials with pentane-1,5-diol verify its efficacy and safety. These characteristics together with its low cost make pentane-1,5-diol an attractive substance for use in pharmaceutical formulations for topical administration.

[Contribution of statistical analytic tools to risk assessment]. / Intérêt des outils statistiques analytiques dans l'évaluation des risques.

Risk assessment is an important aspect of health safety. The main basis of information comes from the identification of adverse effects observed in animal studies, in vitro models, or in silico computer models. These data are used to construct a proof scaffold with an inherent double uncertainty about its clinical pertinence and the probability of occurrence in man. This uncertainty can be reduced with statistical analytical tools, particularly factorial analysis and principal component analysis. Factorial analysis describes a group of variables using a linear combination of underlying common factors associated with a single variable summarizing the specific contribution of each initial variable, thus providing evidence demonstrating the probability of the undesirable effect under consideration. Principal component analysis consists in expressing a group of variables (undesirable effects) by linear combinations of uncorrelated factors. These factors account for a more or less extensive proportion of the data variability thus limiting loss of data pertinence.