A 15% Trichloroacetic Acid + 3% Glycolic Acid Chemical Peel Series Improves Appearance of Hand Lentigines: An Evaluator-Blinded, Split-Hand Prospective Trial.

BACKGROUND: Improving the appearance of lentigines on the hands is a key component to hand rejuvenation. Soft tissue fillers revolumize hands, but do not address pigmentary changes. OBJECTIVE: This study investigated the effiacy of a 15% trichloroacetic acid (TCA) + 3% glycolic acid (GA) combination peel in improvement of appearance of hand lentigines. METHODS: A prospective evaluator-blinded, split-hand study was performed using a 15% TCA + 3% GA peel to treat patients with hand lentigines. Subjects received a total of 3 treatments at 4-week intervals on 1 hand, with the other hand serving as an untreated control. Final photographs were taken 12 weeks after the last treatment. Two blinded board-certified dermatologists graded improvement in hand lentigines using a 5-point scale. RESULTS: Eighteen of 20 patients completed the study (90%). The mean age was 64.4 years (SE 1.6, range 51-71). The mean pain scores were 3.8 (SE 0.4) on a 10-point scale (1 = no pain, 10 = extremely painful). Blinded evaluators correctly identified the after-treatment photographs in 16 patients (88%). Physician and patient-graded mean improvement of lentigines was significant for treated versus control hands ( p < .01). No adverse events were noted. CONCLUSION: A series of three 15% TCA + 3% GA peels are effective and safe in the treatment of hand lentigines.

Comparison of efficacy and safety of tretinoin 0.05% and glycolic acid peeling 70% in axillary and neck lesions of acanthosis nigricans: A single-blinded, randomized trial.

BACKGROUND: Acanthosis nigricans is a non-inflammatory skin pigmentary disorder characterized by a dark, velvety appearance, primarily observed in the neck and axillary areas. It is commonly associated with obesity, diabetes, and insulin resistance. Although the primary treatment is correcting the underlying disorders, many aesthetic modalities have been established to improve appearance owing to cosmetic concerns. AIMS: We aimed to compare and investigate the effectiveness and side effects of tretinoin 0.05% and glycolic acid 70% in treating acanthosis nigricans lesions of the axillary and neck area. METHODS: This single-blinded, randomized trial recruited patients with neck or axillary involvement. Each patient was randomized to use cream tretinoin 0.05% every other night on one side, while the other side was treated with glycolic acid 70%, which was applied every 2 weeks at the clinic for four consecutive sessions. The study duration was 8 weeks, and patients were evaluated every 2 weeks based on their response to treatment, satisfaction, and side effects. RESULTS: Thirty patients, including 14 with neck lesions and 16 with axillary lesions, were included. Tretinoin was significantly more effective for axillary lesions in terms of treatment response and patient satisfaction (p = 0.02 and p = 0.008, respectively). It was also shown that as the severity of the lesions increased, the response to treatment and patient satisfaction decreased, specifically when treating axillary lesions with glycolic acid (p = 0.02 and p = 0.03, respectively). CONCLUSION: Neither method was significantly effective for neck lesions. However, tretinoin 0.05% was shown to be more efficacious in treating axillary lesions of acanthosis nigricans, despite causing minimal side effects.

Reproductive and developmental evaluations of triclopyr acid, triclopyr butoxyethyl ester and triclopyr triethylamine salt in the rat.

Reproductive and developmental toxicity studies have been conducted in rat and rabbit on triclopyr acid and its active-ingredient variants, triclopyr butoxyethyl ester (T-BEE) and triclopyr triethylamine salt (T-TEA). In this paper the results of a rat two-generation study on triclopyr acid are presented, together with a review of all the reproductive and developmental toxicity data available from the rat studies. In the rat two-generation study, triclopyr acid was administered in the diet, giving doses of 0, 5, 25 or 250 mg/kg bw per day. Parental toxicity, especially maternal toxicity, occurred at 250 mg/kg bw per day with reduced body weight and feed intake, organ weight changes, and kidney toxicity. Slight kidney toxicity was also evident at 25 mg/kg bw per day. Developmental toxicity, in the form of reduced postnatal survival in the F1 and F2 generations and reductions in pre-weaning offspring body weight in both generations, was seen only at a dose causing significant parental toxicity. There were no effects on any other reproductive or developmental parameters at any dose. It is concluded that the developmental toxicity, seen only at the highest dose, was most likely attributable to maternal toxicity. The no-observed-adverse-effect levels were 5 mg/kg bw per day for parental toxicity and 25 mg/kg bw per day for developmental toxicity. From the multigeneration and developmental toxicity studies on triclopyr and its variants, it can also be concluded that triclopyr is not specifically toxic to reproduction and is not selectively toxic to the embryo, fetus or neonate in the rat.

A Primeval Mechanism of Tolerance to Desiccation Based on Glycolic Acid Saves Neurons in Mammals from Ischemia by Reducing Intracellular Calcium-Mediated Excitotoxicity.

Stroke is the second leading cause of death and disability worldwide. Current treatments, such as pharmacological thrombolysis or mechanical thrombectomy, reopen occluded arteries but do not protect against ischemia-induced damage that occurs before reperfusion or neuronal damage induced by ischemia/reperfusion. It has been shown that disrupting the conversion of glyoxal to glycolic acid (GA) results in a decreased tolerance to anhydrobiosis in Caenorhabditis elegans dauer larva and that GA itself can rescue this phenotype. During the process of desiccation/rehydration, a metabolic stop/start similar to the one observed during ischemia/reperfusion occurs. In this study, the protective effect of GA is tested in different ischemia models, i.e., in commonly used stroke models in mice and swine. The results show that GA, given during reperfusion, strongly protects against ischemic damage and improves functional outcome. Evidence that GA exerts its effect by counteracting the glutamate-dependent increase in intracellular calcium during excitotoxicity is provided. These results suggest that GA treatment has the potential to reduce mortality and disability in stroke patients.

Phencynonate hydrochloride exerts antidepressant effects by regulating the dendritic spine density and altering glutamate receptor expression.

Phencynonate hydrochloride (PCH) is a drug that crosses the blood-brain barrier. Cellular experiments confirmed that PCH protects against glutamate toxicity and causes only weak central inhibition and limited side effects. As shown in our previous studies, PCH alleviates depression-like behaviours induced by chronic unpredictable mild stress (CUMS). Here we administered PCH at three different doses (4, 8 and 16 mg/kg) to male rats for two continuous days after CUMS and conducted behavioural tests to assess the dose-dependent antidepressant effects of PCH and its effects on the neuroplasticity in the hippocampus and medial prefrontal cortex (mPFC). Meanwhile, we measured the spine density and expression of related proteins to illustrate the mechanism of PCH. PCH treatment (8 mg/kg) significantly alleviated depression-like behaviours induced by CUMS. All doses of PCH treatment reversed the spine loss in prelimbic and CA3 regions induced by CUMS. Kalirin-7 expression was decreased in the hippocampus and mPFC of the CUMS group. The expression of the NR1 and NR2B subunits in the hippocampus, and NR2B in mPFC are increased by CUMS. PCH treatment (8 and 16 mg/kg) reversed all of these changes of Kalirin-7 in PFC and hippocampus, as well as NR1 and NR2B expression in the hippocampus. PCH is expected to be developed as a new type of rapid antidepressant. Its antidepressant effect may be closely related to the modulation of dendritic spine density in the prelimbic and CA3 regions and the regulation of Kalilin-7 and N-methyl-D-aspartic acid receptor levels in the hippocampus.

Effects of co-formulants on the absorption and secretion of active substances in plant protection products in vitro.

Currently, the authorisation process for plant protection products (PPPs) relies on the testing of acute and topological toxicity only. Contrastingly, the evaluation of active substances includes a more comprehensive set of toxicity studies. Nevertheless, mixture effects of active ingredients and co-formulants may result in increased toxicity. Therefore, we investigated effects of surface active co-formulants on the toxicity of two PPPs focussing on qualitative and quantitative toxicokinetic effects on absorption and secretion. The respective products are based on the active substances abamectin and fluroxypyr-meptyl and were tested for cytotoxicity in the presence or absence of the corresponding surfactants and co-formulants using Caco-2 cells. In addition, the effect of co-formulants on increased cellular permeation was quantified using LC-MS/MS, while potential kinetic mixture effects were addressed by fluorescence anisotropy measurements and ATPase assays. The results show that surface active co-formulants significantly increase the cytotoxicity of the investigated PPPs, leading to more than additive mixture effects. Moreover, analytical investigations show higher efflux ratios of both active substances and the metabolite fluroxypyr upon combination with certain concentrations of the surfactants. The results further point to a significant and concentration-dependent inhibition of Pgp transporters by most of the surfactants as well as to increased membrane fluidity. Altogether, these findings strongly support the hypothesis that surfactants contribute to increased cytotoxicity of PPPs and do so by increasing the bioavailability of the respective active substances.

Chitosan coated nanoparticles for efficient delivery of bevacizumab in the posterior ocular tissues via subconjunctival administration.

In several ocular diseases, vascular endothelial growth factor (VEGF) level has been found to be unregulated. Bevacizumab, an anti-VEGF drug, is the most commonly used off level drug for diabetic retinopathy (DR). The present study was to evaluate the chitosan-coated poly (lactide-co-glycolic acid) nanoparticles (CS-PLGA NPs) for sustained and effective delivery of bevacizumab to posterior ocular tissues. The penetration of NP through sclera was studied by confocal laser scanning microscopy (CLSM). For pharmacokinetic study, bevacizumab loaded NPs were administered into the rat eye through subconjunctival injection (SCJ) and pharmacokinetic parameters were compared to drug solution. CLSM and pharmacokinetic study showed better penetration of formulation and higher concentration of bevacizumab in posterior ocular tissues. In retinopathy model, CS-PLGA NPs by SCJ route showed more reduction of VEGF level in retina than the topical and intravitreal administration of formulation. Thus, CS-coated PLGA NPs can be potentially useful as carriers to target retina.

Formulation of topical acidic products and acidification of the skin - Contribution of glycolic acid.

OBJECTIVE: The acidic skin pH is one of the regulating factors of skin barrier homeostasis. Topical products as extrinsic factors which influence skin pH could be used for acidification of the skin and consequent beneficial effect. To formulate stabile and safe topical emulsion product with low pH is on-going challenge and areas interesting to explore are related to the effect of acidic products on the skin pH together with development of protocols for these studies. Aim of our work was to investigate formulations of acidic topical products with glycolic acid (GA) stabilized with long chain alkyl polyglucoside emulsifier, in regard to the specific colloidal structure of the vehicle, together with effect of products with different concentration of acidic active on skin pH. METHODS: Investigated formulations were basic vehicle and two creams with glycolic acid (concentration 2 and 10 wt%). Microstructure was investigated by polarization microscopy, Raman spectral imaging, thermal analysis and rheological measurements. Effects on the skin were assessed by measurement of biophysical skin parameters in vivo studies (5-hour, 24-hour and 7-days). In vitro screening of antimicrobial activity was performed against bacteria Staphylococcus epidermidis. RESULTS: Polarization micrographs and Raman images have shown that GA does not disturb the specific colloidal structure. Together with rheological and thermal analysis obtained results have shown that GA in higher concentrations contributes to vehicles' lamellar structure. In 5-hour study the mean values of skin pH ranged from 3.98-4.25 and 3.89-4.10 after application of products with smaller and higher GA concentration. GA samples lowered skin surface pH to 5 and less in 24-hour and 7-day study, with stronger effect of sample with more GA. Sample with 10% of GA had significant inhibitory effect on growth of S. epidermidis in 1:1 concentration. CONCLUSIONS: Investigated APG emulsifier could be used as a stabilizer for acidic topical products with GA which are characterized by satisfactory safety profile. Topical products induce acidification of the skin after short- and long-term application without barrier impairment or sign of irritation. Acidification of the skin depends on presence of ingredients which are proton donors and their concentrations.

OBJECTIF: Le pH acide de la peau est l'un des facteurs de régulation de l'homéostasie de la barrière cutanée. Les produits topiques pourraient être utilisés en tant que facteurs extrinsèques d'influence du pH cutané pour permettre l'acidification de la peau et obtenir l'effet bénéfique qui en résulte. Formuler des émulsions topiques stables et sûres à faible pH représente un défi constant et les domaines d'étude dignes d'intérêt portent sur l'effet des produits acides sur le pH cutané et sur l'élaboration de protocoles pour ces études. L'objectif de notre travail était d'étudier des formulations de produits topiques acides à base d'acide glycolique (AG) stabilisé à l'aide d'un émulsionnant à base d'alkylpolyglucoside (APG) à longue chaîne, par rapport à la structure colloïdale spécifique de l'excipient, ainsi que l'effet des produits à différentes concentrations d'acide actif sur le pH cutané. MÉTHODES: Les formulations étudiées étaient un excipient de base et deux crèmes à base d'acide glycolique (concentration égale à 2 % et 10 % de la fraction massique). La microstructure a été étudiée par microscopie à polarisation, par spectroscopie Raman, par analyse thermique et par mesures rhéologiques. Les effets cutanés ont été évalués par la mesure des paramètres cutanés biophysiques dans des études in vivo (5 heures, 24 heures et 7 jours). Un dépistage in vitro de l'activité antimicrobienne a été effectué sur la bactérie Staphylococcus epidermidis. RÉSULTATS: Les micrographies après polarisation et les images obtenues par spectroscopie Raman ont montré que l'AG ne perturbe pas la structure colloïdale spécifique. Avec les analyses rhéologique et thermique, les résultats obtenus ont montré que l'AG à des concentrations plus élevées joue un rôle dans la structure lamellaire des excipients. Dans l'étude de 5 heures, les valeurs moyennes du pH cutané allaient de 3,98 à 4,25 et de 3,89 à 4,10 après l'application des produits présentant une concentration d'AG plus faible et plus élevée. Grâce aux échantillons d'AG, le pH de la surface cutanée a diminué, passant ainsi à une valeur de 5 et à des valeurs inférieures dans les études de 24 heures et de 7 jours, et l'échantillon contenant davantage d'AG a eu un effet plus important. L'échantillon contenant 10 % d'AG a eu un effet inhibiteur significatif sur la croissance de la bactérie S. epidermidis à une concentration de 1:1. CONCLUSION: L'émulsionnant à base d'APG étudié pourrait être utilisé comme stabilisateur pour les produits topiques acides à base d'AG caractérisés par un profil d'innocuité satisfaisant. Les produits topiques induisent une acidification de la peau après une application à court et à long terme sans altération de la barrière cutanée ou signe d'irritation. L'acidification de la peau dépend de la présence de donneurs de proton parmi les composants et de leurs concentrations.

TAK-101 Nanoparticles Induce Gluten-Specific Tolerance in Celiac Disease: A Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND & AIMS: In celiac disease (CeD), gluten induces immune activation, leading to enteropathy. TAK-101, gluten protein (gliadin) encapsulated in negatively charged poly(dl-lactide-co-glycolic acid) nanoparticles, is designed to induce gluten-specific tolerance. METHODS: TAK-101 was evaluated in phase 1 dose escalation safety and phase 2a double-blind, randomized, placebo-controlled studies. Primary endpoints included pharmacokinetics, safety, and tolerability of TAK-101 (phase 1) and change from baseline in circulating gliadin-specific interferon-γ-producing cells at day 6 of gluten challenge, in patients with CeD (phase 2a). Secondary endpoints in the phase 2a study included changes from baseline in enteropathy (villus height to crypt depth ratio [Vh:Cd]), and frequency of intestinal intraepithelial lymphocytes and peripheral gut-homing T cells. RESULTS: In phase 2a, 33 randomized patients completed the 14-day gluten challenge. TAK-101 induced an 88% reduction in change from baseline in interferon-γ spot-forming units vs placebo (2.01 vs 17.58, P = .006). Vh:Cd deteriorated in the placebo group (-0.63, P = .002), but not in the TAK-101 group (-0.18, P = .110), although the intergroup change from baseline was not significant (P = .08). Intraepithelial lymphocyte numbers remained equal. TAK-101 reduced changes in circulating α4ß7+CD4+ (0.26 vs 1.05, P = .032), αEß7+CD8+ (0.69 vs 3.64, P = .003), and γδ (0.15 vs 1.59, P = .010) effector memory T cells. TAK-101 (up to 8 mg/kg) induced no clinically meaningful changes in vital signs or routine clinical laboratory evaluations. No serious adverse events occurred. CONCLUSIONS: TAK-101 was well tolerated and prevented gluten-induced immune activation in CeD. The findings from the present clinical trial suggest that antigen-specific tolerance was induced and represent a novel approach translatable to other immune-mediated diseases. ClinicalTrials.gov identifiers: NCT03486990 and NCT03738475.

Evidence-based topical treatments (azelaic acid, salicylic acid, nicotinamide, sulfur, zinc, and fruit acid) for acne: an abridged version of a Cochrane systematic review.

OBJECTIVE: The effects of topical azelaic acid, salicylic acid, nicotinamide, sulfur, zinc, and fruit acid (alpha-hydroxy acid) for acne are unclear. We aimed to assess the effects of these topical treatments by collecting randomized controlled trials. METHODS: We searched The Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS up to May 2019. We also searched five trials registers. Two review authors independently extracted data and assessed risk of bias. Meta analyses were performed by using Review Manager 5 software. RESULTS: We included a total of 49 trials involving 3880 participants. In terms of treatment response (measured using participants' global self-assessment of acne improvement, PGA), azelaic acid was probably less effective than benzoyl peroxide (RR = 0.82, 95% CI 0.72-0.95). However, there was probably little or no difference in PGA when comparing azelaic acid to tretinoin (RR = 0.94, 95% CI 0.78-1.14). There may be little or no difference when comparing salicylic acid to tretinoin (RR = 1.00, 95% CI 0.92-1.09). There were no studies measured PGA when evaluating nicotinamide. With respect to alpha-hydroxy acid, there may be no difference in PGA when comparing glycolic acid to salicylic-mandelic acid (RR = 1.06, 95% CI 0.88-1.26). We were uncertain about the effects of sulfur and zinc. Adverse events associated with these topical treatments were always mild and transient. CONCLUSIONS: Moderate-quality evidence was available for azelaic acid and low- to very-low-quality evidence for other topical treatments. Risk of bias and imprecision limit our confidence in the evidence.

Effectiveness of a combination of salicylic acid-based products for the treatment of mild comedonal-papular acne: a multicenter prospective observational study.

BACKGROUND: The most common therapeutic approach to acne is a combined treatment of retinoid and benzoyl peroxide, with oral antibiotics recommended for moderate-to-severe cases. These kinds of therapies often lead to adverse reactions, leading to the request for new therapeutic options. Recently, the combined use of three salicylic acid-based products for the topical treatment of acne has been related to a significant improvement in acne lesions. METHODS: A multicenter prospective observational study was carried out on patients with a diagnosis of mild comedonal-papular facial acne to provide new evidence on the clinical effectiveness, tolerability and acceptability of three salicylic acid-based products for the topical treatment of acne in the daily clinical practice. Clinical effectiveness on lesions improvement, the evaluation of personal discomfort related to acne and the assessment of overall clinical outcome were the primary endpoints. Treatment acceptability and tolerability were also evaluated. RESULTS: The treatment with the three salicylic acid-based products has been related to a significant improvement on acne lesions over 8 weeks of treatment, along with a reduction of personal discomfort related to acne and an improvement on lesions appearance. The products have also shown good acceptability and tolerability. CONCLUSIONS: The results of this observational study support the effective and well-tolerated use of a combined treatment with three salicylic acid-based products for the topical treatment of acne.

Efficacy and safety of a new topical gel formulation containing retinol encapsulated in glycospheres and hydroxypinacolone retinoate, an antimicrobial peptide, salicylic acid, glycolic acid and niacinamide for the treatment of mild acne: preliminary results of a 2-month prospective study.

BACKGROUND: Acne vulgaris is a common and chronic skin disease that impacts on physical and psychological perceptions. Combination therapy with topical retinoids and antimicrobial agent is considered the preferred approach for most of the subjects affected by mild-to-moderate acne. A correct therapeutic management should include a prolonged treatment to ensure therapeutic success and to prevent recurrences. The aim of this study was to evaluate the efficacy and tolerability of a new topical gel formulation that combines retinol encapsulated in glycospheres and hydroxypinacolone retinoate, associated with an anti-microbial peptide (BIOPEP-15) salicylic acid, glycolic acid, and niacinamide as monotherapy in mild acne vulgaris. METHODS: A 2-month prospective study was conducted at the Unit of Dermatology of the Federico II University. Twenty-five patients aged from 14 to 30 years with mild acne of the face (GAGS score ≤ 18) were consecutively enrolled. Each patient was asked to apply the gel formulation once daily in the evening for 8 weeks. The number of acne lesions with VISIA camera system, the global acne grading system (GAGS) score, trans epidermal water loss (TEWL), skin colorimetry (X-rite Spectrocolorimeter), reflectance confocal microscopy exam were evaluated at baseline, after 4 and 8 weeks of treatment for each patient. Tolerability and safety of the product were also evaluated. RESULTS: Twenty-five female patients with a median age of 23.4 were enrolled. Twenty-two (88%) completed the 2-month treatment period visits. At baseline the total acne lesion number, mean (SD), was 5.5 (4) and the GAG score 9 (4). A significant (P=0.001) reduction in number of total acne lesions was observed at week 4 (-57%) and at week 8 (-80%). All patients presented a significant reduction of the GAGS score values: -42% at week 4 and -78% at week 8, confirming the clinical efficacy of the product. At baseline TEWL was 10.2 g/m2/h (1.3) and 10.7 (1.4) at week 8, thus showing that the gel did not impair the skin barrier function. Skin colorimetry was significantly (P=0.0015) reduced by the treatment in comparison with baseline (62 vs. 58). Efficacy of the gel formulation was also confirmed with RCM exams, showing a reduction of dermal inflammation and exocytosis, and an improvement of infundibular hyperkeratinization. We observed that adherence to treatment correlated positively with the improvement of the single parameters. Moreover, side effects such as erythema, dryness, and excessive xerosis were not reported, resulting in a complete adherence to the treatment. CONCLUSIONS: Our findings provide favorable evidences of the efficacy and safety of this new product as a first line treatment in patients with mild acne, or, as a maintenance therapy for prolonged periods after the suspension of a systemic treatment. Furthermore, the tolerability of this topical product and the absence of any side effects increased the adherence to the therapy.

Sequential peeling as a monotherapy for treatment of milder forms of acne vulgaris.

BACKGROUND: Glycolic acid (GA) and salicylic acid (SA) peels have been used separately for acne treatment, not as a sequential peel. AIM: To evaluate the efficacy and safety of sequential peeling with 70% GA and 20% SA as a monotherapy and as an adjuvant to systemic doxycycline in treatment of mild to moderate acne and the effect on serum interleukin (IL) 17 and tissue IL-1α. PATIENTS/METHODS: Forty-five mild to moderate acne vulgaris patients were randomly assigned into three groups. Group [A] underwent sequential application of 70% GA followed by 20% SA biweekly for three months. Group [B] underwent sequential peeling and doxycycline PO100 mg BD for 1 month followed by 100 OD for 2 months. Group [C] received oral doxycycline. Acne grading, lesion counting, and patient satisfaction were assessed. Serum samples and perilesional skin biopsies were obtained at onset and 2 weeks after finishing the treatment for assessment of serum IL-17 and tissue IL-1α. RESULTS: All groups showed statistically significant decrease in acne grading and lesion count, increase in patient satisfaction, and decrease in serum IL-17 and tissue IL-1 α after treatment. There was no significant difference between the 3 groups before or after treatment, except regarding patient satisfaction after treatment, which was significantly higher in groups [A] and [B] than group [C] (P = .001). CONCLUSIONS: This study recommends using sequential GA 70% and SA 20% peels in the treatment of mild or moderate acne vulgaris as a new cost-effective mode, with low-down time and potential safety, in noncompliant patients on medical therapy.

Comparative study of 15% trichloroacetic acid peel combined with 70% glycolic acid and 35% trichloroacetic acid peel for the treatment of photodamaged facial skin in aging women.

BACKGROUND: Photoaging (extrinsic aging) is caused by environmental exposure to ultraviolet radiation. Superficial and medium-depth chemical peels with trichloroacetic acid (TCA) are performed to reduce wrinkles, hyperpigmentation, dryness, and erythema caused by photoaging process. AIM: The aim of this study was to compare the efficacy and tolerability of 15% TCA peel against the combined 70% glycolic acid and 35% TCA for the treatment of photodamaged facial skin. PATIENTS/METHODS: Forty female patients with types II and III of Glogau photoaging scale were divided into two groups of twenty subjects (GA/TCA and 35% TCA). The GA/TCA group was treated with combination peeling of 70% GA and 15% TCA, whereas the 35% TCA group was treated with monopeeling of 35% trichloroacetic acid. Each patient was submitted to five sessions of these peels, with an interval of 14 days between each session. The following skin aging parameters were examined before treatments, before each session, and 3 months after the last application: hydration, elasticity, melanin index, and erythema index (MPA-5; Courage-Khazaka, Germany); and depth and volume of wrinkles (PRIMOS; GFMesstechnik GmbH, Germany). RESULTS: Both peel methods achieved significant improvement in all skin parameters: elasticity, hydration, melanin index, and erythema index. Significant differences between the GA/TCA and 35% TCA groups were found only for hydration and melanin index. GA/TCA was characterized by significantly higher values of the hydration parameter and lower values of melanin index compared with 35% TCA. Combination peel GA/TCA did not cause dryness, edema, or intensive lysis of the epidermis, and the frequency of peel-induced erythema did not increase with the addition of glycolic acid, but with higher concentration of the TCA solution. However, subject-perceived improvements of the 35% TCA peel did not differ significantly from subject-perceived improvements of combination peel treatment. Adverse events requiring intervention or discontinuing treatment were not observed in either group. CONCLUSION: The addition of glycolic acid before 15% TCA chemical peel application significantly enhanced TCA-induced improvement in photoaging parameters (increase in skin elasticity and hydration; reduction in melanin index and erythema index), and subject-perceived improvements. However, 35% TCA peel is more effective in reducing wrinkles, despite a lower tolerability. Both medium-depth chemical peels including 15% TCA in combination with 70% GA and 35% TCA alone proved to be useful for the removal of epidermal or superficial lesions and to improve the texture of photodamaged facial skin (grade II-III Glogau photoaged skin).

Acute and 28-Day Repeated Inhalation Toxicity Study of Glycolic Acid in Male Sprague-Dawley Rats.

BACKGROUND/AIM: The use of glycolic acid is present in a variety of consumer products, including medicines, cleaners, cosmetics, and paint strippers. It has recently led to concerns about toxicity from inhalation exposure. Herein, the pulmonary toxicity of glycolic acid was investigated in rats. MATERIALS AND METHODS: We conducted acute (~458 mg/m3) and sub-acute (~49.5 mg/m3) inhalation tests to identify the potential toxicities of glycolic acid. RESULTS: Inhalation exposure to glycolic acid in the acute and subacute inhalation tests did not cause any specific changes in clinical examinations, including body weight, organ weight, hematology, serum biochemistry, and histopathology. The polymorphonuclear neutrophils (PMNs) and inflammatory cytokines in Bronchoalveolar lavage fluid (BALF) increased in rats exposed to single and repeated inhalations. In the sub-acute test, the changes induced by glycolic acid were minor or returned to normal during the recovery period. CONCLUSION: The No Observed Adverse Effect Concentration (NOAEC) for the nasal and pulmonary toxicity of glycolic acid was determined to be over 50 mg/m3 at the end of a 28-day inhalation test in male rats.

Comparative Efficacy of a 35% Glycolic Acid Peel Alone or in Combination With a 10% and 20% Trichloroacetic Acid Spot Peel for Melasma: A Randomized Control Trial.

BACKGROUND: To study and compare the therapeutic efficacy and side effects of a 35% glycolic acid (GA) full face peel alone or in combination with a 10% or 20% trichloroacetic acid (TCA) spot peel for facial melasma. METHODS: Thirty patients with facial melasma were randomly divided into 3 equal Groups A, B, and C. Group A was treated with a 35% GA full-face peel, Group B and C with 35% GA full-face peel followed by a 10% and 20% TCA spot peel respectively once every 15 days. Four peels were performed once every 15 days. The response to the treatment was evaluated by the percentage reduction in melasma area severity index (MASI) scoring. RESULTS: All 3 groups had significant reduction of MASI, but there was no significant difference between the groups. Group A had minimum side effects. CONCLUSION: Chemical peels with GA alone or in combination with TCA do result in a significant improvement in melasma, but the combination of the peels in the same sitting does not seem to have any additive or synergistic effect while they may increase the side effects.

UV fluorescence excitation spectroscopy as a noninvasive predictor of epidermal proliferation and clinical performance of cosmetic formulations.

BACKGROUND: The epidermis is the outermost layer of skin and is composed of cells primarily containing keratin. It consists of about ten layers of living cells (keratinocytes) and ten layers of dead cells (corneocytes). Thinning of the epidermis and decreased proliferation of its cells are associated with aging related changes in skin, including wrinkling and laxity. Fluorescence excitation spectroscopy is a noninvasive method of monitoring characteristic excitation-emission peaks in skin that have been related to the epidermal and dermal composition. The magnitude of the peak that occurs at 295nm excitation (F295) has been linked to changes in epidermal thickness, proliferation, and skin aging. AIM: The goal of this study is to correlate changes in the F295 signal with proliferation of cells and thickening of the epidermis induced by cosmetic formulations. We hypothesize that two commonly used cosmetic ingredients, retinol and glycolic acid, will increase these markers that have been implicated in skin anti-aging. METHODS: In a placebo-controlled study subjects' forearms were treated with formulations containing retinol or glycolic acid under occlusive patch for a period of 21 days. Skin fluorescence was measured at baseline and after treatment, and biopsies were taken following treatment for histological analysis of epidermal thickness and cell proliferation. RESULTS: After 21 days of treatment retinol and glycolic acid formulas significantly increased F295 (by 265.1±33.5% and 162.2±18.7% respectively), whereas the placebo control formula did not induce a change from baseline. Furthermore, retinol and glycolic acid treatments significantly increased epidermal thickness (by 63.1% and 7.8% respectively) and keratinocyte proliferation (by 236.9% and 62.8% respectively) versus placebo control. CONCLUSION: Increases in F295 were found to correlate with epidermal renewal, but more so with increased cell proliferation than epidermal thickness. We conclude that the F295 signal is a fast and reliable early indicator of epidermal remodeling in skin that can be used to distinguish between formulations with different cosmetic ingredients.

Evaluation of a biocide footbath solution in the occurrence and healing of digital dermatitis lesions in dairy cows: A clinical trial.

The objective of this study was to evaluate the effect of the implementation of different footbathing practices using a new biocide solution (Pink-Step™, Qalian, France) in the healing and the occurrence of bovine digital dermatitis (bDD) lesions. The investigation was conducted through a controlled within cow clinical trial in which the hind feet of cows from each farm were allocated either to the control group or to a moderate (MR) or (IR) intensive footbath-regimen groups. The trial involved 1036 cows (2072 feet) from 10 dairy farms located in western France where bDD was endemic. Split-footbaths were placed at the exit of the milking parlor of each farm, allowing the biocide to be administered to one side of the cows while using the other empty side as a negative control. The administration frequency for MR was of 2 days/week/1st-month, then 2 days/2 weeks/2nd-month, and then 2 days/month, and for IR was of 2 days/week/1st-2nd months, and then 2 days/2 weeks. Footbaths were administered during 140 days (approx.), and feet were evaluated for the at least once a month in the milking parlor. Nested survival models were used to estimate the relative impact of the footbath regimens and other concomitant risk factors on the time that bDD lesions occurred or healed. No effect of Pink-Step™ was evidenced on the bDD occurrence during the trial. The risk for bDD occurrence was increased by poor feet cleanliness at both the cow (HR 1.69, CI 1.21-2.39) and farm level (HR 2.06, CI 1.44-2.94). Otherwise, the use of Pink-Step™ in an IR was effective in improving the healing of bDD lesions (HR 1.79, CI 1.12-2.88). The time to healing was also improved in inactive lesions (HR 2.19, CI 1.42-3.37). Conversely, the time to healing was delayed in feet receiving hoof-trimming (HR 0.41, CI 0.26-0.62), in cows with a contralateral bDD lesion (HR 0.32, CI 0.22-0.46) or in late lactation (HR 0.61, CI 0.43-0.85), and finally in farms with more than 100 cows (HR 0.48, CI 0.34-0.67). These findings reinforce the crucial role of hygiene in bDD dynamics and highlight the importance of implementing multiple control measures simultaneously, such as hygiene improvements in the barn, early detection and treatment of bDD lesions and the correct usage of individual and collective treatments. The implementation of Pink-Step™ represents a promising strategy for reducing the persistence of bDD lesions in affected herds.

Comparative effects of scopolamine and phencynonate on organophosphorus nerve agent-induced seizure activity, neuropathology and lethality.

The efficacy of anticonvulsant therapies to stop seizure activities following organophosphorus nerve agents (NAs) has been documented as being time-dependent. We utilized the guinea pig NA-seizure model to compare the effectiveness of phencynonate (PCH) and scopolamine (SCP) when given at the early (at time of seizure onset) or late (40 min after seizure onset) phase of seizure progression. PCH possesses both anticholinergic and anti-NMDA activities, while SCP is a purely anti-muscarinic compound. Animals with cortical electrodes were pretreated with pyridostigmine bromide 30 min prior to exposure to a 2.0 x LD50 subcutaneous dose of a NA (GA, GB, GD, GF, VR, or VX), followed one min later with atropine sulfate and 2-PAM. At either early or late phase, animals were treated with either PCH or SCP and the 24-h anticonvulsant ED50 doses were determined. When administered at seizure onset, PCH, and SCP were both effective at terminating seizure activity against all NAs, with ED50 values for SCP generally being lower. At the 40 min time, ED50 values were obtained following GA, GD, GF, and VR challenges for SCP, but ED50 value was obtained only following GD for PCH, indicating a superior efficacy of SCP. When seizure activity was controlled, a significant improvement in weight loss, neuropathology, and survival was observed, regardless of treatment or NA. Overall, these results demonstrate the differing efficacies of these two similarly structured anticholinergic compounds with delayed administration and warrant further investigation into the timing and mechanisms of the seizure maintenance phase in different animal models.