Design and validation of neuronal exocytosis blocking peptides as potential novel antiperspirants.

Thermoregulation and heat dissipation by sweat production and evaporation are vital for human survival. However, hyperhidrosis or excessive perspiration might affect people's quality of life by causing discomfort and stress. The prolonged use of classical antiperspirants, anticholinergic medications or botulinum toxin injections for persistent hyperhidrosis might produce diverse side effects that limit their clinical use. Inspired by botox molecular mode of action, we used an in silico molecular modelling approach to design novel peptides to target neuronal acetylcholine exocytosis by interfering with the Snapin-SNARE complex formation. Our exhaustive design rendered the selection of 11 peptides that decreased calcium-dependent vesicle exocytosis in rat DRG neurons, reducing αCGRP release and TRPV1 inflammatory sensitization. The most potent peptides were palmitoylated peptides SPSR38-4.1 and SPSR98-9.1 that significantly suppressed acetylcholine release in vitro in human LAN-2 neuroblastoma cells. Noteworthy, local acute and chronic administration of SPSR38-4.1 peptide significantly decreased, in a dose-dependent manner, pilocarpine-induced sweating in an in vivo mouse model. Taken together, our in silico approach lead to the identification of active peptides able to attenuate excessive sweating by modulating neuronal acetylcholine exocytosis, and identified peptide SPSR38-4.1 as a promising new antihyperhidrosis candidate for clinical development.

Deodorants and antiperspirants: New trends in their active agents and testing methods.

Sweating is the human body's thermoregulation system but also results in unpleasant body odour which can diminish the self-confidence of people. There has been continued research in finding solutions to reduce both sweating and body odour. Sweating is a result of increased sweat flow and malodour results from certain bacteria and ecological factors such as eating habits. Research on deodorant development focuses on inhibiting the growth of malodour-forming bacteria using antimicrobial agents, whereas research on antiperspirant synthesis focuses on technologies reducing the sweat flow, which not only reduces body odour but also improves people's appearance. Antiperspirant's technology is based on the use of aluminium salts which can form a gel plug at sweat pores, obstructing the sweat fluid from arising onto the skin surface. In this paper, we perform a systematic review on the recent progress in the development of novel antiperspirant and deodorant active ingredients that are alcohol-free, paraben-free, and naturally derived. Several studies have been reported on the alternative class of actives that can potentially be used for antiperspirant and body odour treatment including deodorizing fabric, bacterial, and plant extracts. However, a significant challenge is to understand how the gel-plugs of antiperspirant actives are formed in sweat pores and how to deliver long-lasting antiperspirant and deodorant benefits.

La transpiration est le système de thermorégulation de l'organisme, mais elle entraîne également une odeur corporelle désagréable qui peut diminuer la confiance en soi. Des nombreuses recherches ont été menées afin de trouver des solutions pour réduire à la fois la transpiration et l'odeur corporelle. La transpiration est le résultat de l'augmentation du flux de sueur, et les mauvaises odeurs sont dues à certaines bactéries et à certains facteurs écologiques tels que les habitudes alimentaires. Les recherches sur le développement des déodorants se concentrent sur l'inhibition de la croissance des bactéries responsables des mauvaises odeurs à l'aide d'agents antimicrobiens, tandis que les recherches sur la synthèse des anti-transpirants se concentrent sur les technologies diminuant le flux de sueur, ce qui réduire non seulement les odeurs corporelles, mais améliore également l'apparence des personnes. La technologie des anti-transpirants repose sur l'utilisation de sels d'aluminium qui peuvent former un bouchon de gel au niveau des pores sudoripares, empêchant le liquide sudoral d'apparaître à la surface de la peau. Dans cet article, nous effectuons une revue systématique des progrès récents réalisés dans le développement de nouveaux principes actifs anti-transpirants et déodorants qui sont sans alcool, sans parabène et d'origine naturelle. Plusieurs études ont été rapportées sur la classe alternative de principes actifs qui peuvent potentiellement être utilisés pour le traitement anti-transpirant et des odeurs corporelles, y compris les tissus désodorisants, les bactéries et les extraits végétaux. Cependant, un défi important consiste à comprendre comment les bouchons de gel des actifs anti-transpirants se forment au niveau des pores sudoripares, et comment offrir des effets anti-transpirants et déodorants durables.

Antiperspirant effects and mechanism investigation of Mulisan decoction in rats based on plasma metabolomics.

CONTEXT: Mulisan decoction (MLS) is a classic formula of traditional Chinese medicine for treating hyperhidrosis. The mechanism remains unclear. OBJECTIVE: To investigate the antiperspirant effect and underlying mechanisms of MLS. MATERIALS AND METHODS: Fifty rats were divided into control, model, and three doses of MLS intervention groups (n = 10). Rats except for control group were induced diseases features of the applicable scope of MLS via i.p. reserpine (0.5 mg/kg/d) for 10 days. From day 11, MLS groups were administrated orally MLS at 0.6, 3, and 15 g/kg once a day for 14 days, respectively. After the last administration, sweating was induced in all rats via s.c. pilocarpine (25 mg/kg), the right hind foot of rats was stained, and sweat point numbers were observed. Rat serum was collected to detect IL-2, IL-6, IFN-γ, and TNF-α. Rat plasma was collected for endogenous metabolite analysis via UPLC-QE-Focus-MS. RESULTS: Rats treated with MLS presented a significant decrease in sweat point numbers (13.5%), increase in body weight (13.2%), and promotion in the balance of Th1/Th2 cytokine ratio via increasing IL-2 (38.3%), IFN-γ (20.1%), and TNF-α (22.0%) and decreasing IL-6 (24.7%) compared with the model group (p < 0.05). Plasma metabolomics disclosed 15 potential biomarkers related to model rats, of which two could be significantly reversed by MLS (p < 0.05). The involved pathways were pantothenate and CoA biosynthesis, and porphyrin metabolism. CONCLUSIONS: MLS demonstrated a good antiperspirant effect and metabolism improvement. These findings inspire more clinical study validation on immune improvement and antiperspirant effect.

The potential prebiotic effect of 2-Butyloctanol on the human axillary microbiome.

OBJECTIVE: The human axilla is colonized by a wide array of microorganisms that contribute to the generation of body odour. Traditional antiperspirant/deodorant products are used to reduce perspiration in the axillary region and to treat or prevent the growth of bacteria in this region, thereby reducing or eliminating body odour. However, they may also compromise the axillary microbiome balance. The personal care industry has been seeking new ingredients, such as prebiotics or probiotics, to maintain a healthy balance of the skin microbiome by inhibiting odour-causing bacteria, whilst maintaining and promoting the growth of good bacteria. The aim of this study was to investigate the prebiotic effect of a skin-care ingredient, 2-butyloctanol, on the human axillary microbiome. METHODS: An in vitro growth inhibition/promotion assay was performed to test whether 2-butyloctanol inhibited or promoted skin bacterial growth. The impact of 2-butyloctanol on the axillary microbiome was also investigated in a human clinical study using 16S rRNA gene sequencing. RESULTS: In-vitro testing showed that 2-butyloctanol significantly inhibited the growth of corynebacteria at concentrations of 0.64%, 2.56% and 5.12%, whilst the growth of Staphylococcus epidermidis was maintained at the same concentrations. The impact of 2-butyloctanol on the axillary microbiome was also validated in a human clinical study. A deodorant roll-on product containing 3% of 2-butyloctanol significantly reduced the relative abundance of corynebacteria, whilst increasing the relative abundance of Staphylococcus and the ratio of Staphylococcus to corynebacteria after four weeks of application, whilst the placebo showed no significant change. CONCLUSION: For the first time, it was demonstrated that 2-butyloctanol had a potential prebiotic effect on the human underarm microbiome in inhibiting odour-causing Corynebacterium, whilst maintaining and promoting skin-friendly Staphylococcus in both in-vitro and in-vivo studies. Therefore, 2-butyloctanol could be used as a potential prebiotic ingredient in personal care products for underarm microbiome protection.

OBJECTIF: les aisselles humaines sont colonisées par un large éventail de micro-organismes qui contribuent à la génération de l'odeur corporelle. Les produits antitranspirants/déodorants traditionnels sont utilisés pour réduire la transpiration et traiter ou prévenir la croissance des bactéries dans la région axillaire, réduisant ou éliminant ainsi l'odeur corporelle. Cependant, ils peuvent également compromettre l'équilibre du microbiome axillaire. Le secteur des soins personnels recherche de nouveaux composants, tels que des prébiotiques ou des probiotiques, afin de maintenir un équilibre sain du microbiome cutané, en inhibant les bactéries responsables des odeurs tout en maintenant et en favorisant la croissance des bonnes bactéries. L'objectif de cette étude était d'étudier l'effet prébiotique sur le microbiome axillaire humain du 2-butyloctanol, un composant indiqué dans les soins cutanés. MÉTHODES: un test in vitro d'inhibition/de promotion de la croissance a été mené afin de déterminer si le 2-butyloctanol inhibait ou favorisait la croissance bactérienne cutanée. Les effets du 2-butyloctanol sur le microbiome axillaire a également fait l'objet d'une étude clinique chez l'homme qui reposait sur le séquençage du gène ARNr 16S. RÉSULTATS: les tests in vitro ont montré que le 2-butyloctanol inhibait significativement la croissance des corynébactéries à des concentrations de 0,64 %, de 2,56 % et de 5,12 %, tandis que la croissance de Staphylococcus epidermidis se maintenait aux mêmes concentrations. Une étude clinique chez l'homme a également permis de confirmer les effets du 2-butyloctanol sur le microbiome axillaire. Un produit déodorant à bille contenant 3 % de 2-butyloctanol a réduit significativement l'abondance relative des corynébactéries, tout en augmentant l'abondance relative de Staphylococcus et le rapport entre Staphylococcus et les corynébactéries après quatre semaines d'application, tandis que le placebo n'a montré aucun changement significatif. CONCLUSION: pour la première fois, des études in vitro et in vivo ont démontré que le 2-butyloctanol avait un possible effet prébiotique sur le microbiome axillaire humain, en inhibant Corynebacterium, la bactérie responsable des odeurs, tout en maintenant et en favorisant la croissance de Staphylococcus, une bactérie respectueuse de la peau. Par conséquent, le 2-butyloctanol pourrait servir de possible composant prébiotique dans les produits de soins personnels pour la protection du microbiome axillaire.

Quantitative ion determination in eccrine sweat gland cells correlates to sweat reduction of antiperspirant actives.

OBJECTIVE: Axillary wetness represents an unwanted effect of the physiologically vital sweating mechanism, especially when it becomes excessive. Cosmetic products reducing sweat secretion rely on aluminium salts as the active ingredient acting by physically blocking the sweat gland. Driven by the interest to better understand the sweat mechanism and to develop alternative technologies against excessive sweating a search for an effective testing approach started as up to now, cost- and time-consuming in vivo studies represent the standard procedure for testing and identifying these alternatives. MATERIAL AND METHODS: The herein described in vitro test system is based on the measurement of intracellular changes of the ion equilibrium in cultured eccrine sweat gland cells. Subsequently, in vivo studies on the back of volunteers were conducted to verify the sweat-reducing effect of in vitro newly discovered substance. RESULTS: In this study, we describe an effective cell-based in vitro method as a potent tool for a more targeted screening of alternatives to aluminium salts. Testing the commonly used aluminium chlorohydrate as one example of an aluminium-based active in this screening procedure, we discovered a distinct influence on the ion equilibrium: Intracellular levels of sodium ions were decreased while those of chloride increased. Screening of various substances revealed a polyethyleneimine, adjusted to pH 3.5 with hydrochloric acid, to evoke the same alterations in the ion equilibrium as aluminium chlorohydrate. Subsequent in vivo studies showed its substantial antiperspirant action and confirmed the high efficiency of the polyethyleneimine solution in vivo. Further, specific investigations connecting the chloride content of the tested substances with the resulting sweat reduction pointed towards a substantial impact of the chloride ions on sweating. CONCLUSION: The newly described in vitro cell-based screening method represents an effective means for identifying new antiperspirant actives and suggests an additional biological mechanism of action of sweat-reducing ingredients which is directed towards unbalancing of the ion equilibrium inside eccrine sweat gland cells.

OBJECTIF: l'humidité axillaire représente un effet indésirable du mécanisme physiologiquement vital de la sudation, en particulier lorsqu'elle devient excessive. Les produits cosmétiques réduisant la sécrétion de sueur reposent sur les sels d'aluminium comme principe actif agissant en bloquant physiquement la glande sudoripare. Motivée par l'intérêt de mieux comprendre le mécanisme de la sudation et de développer des technologies alternatives contre l'hypersudation, une recherche pour une approche de test efficace a commencé car, jusqu'à présent, les études in vivo coûteuses et chronophages représentent la procédure standard pour tester et identifier ces alternatives. MATÉRIELS ET MÉTHODES: le système de test in vitro décrit ici est basé sur la mesure des changements intracellulaires de l'équilibre ionique dans les cellules des glandes sudoripares exocrines cultivées. Par la suite, des études in vivo sur le dos de volontaires ont été menées pour vérifier l'effet réducteur de la sudation d'une substance nouvellement découverte in vitro. RÉSULTATS: dans cette étude, nous décrivons une méthode cellulaire efficace in vitro en tant qu'outil puissant pour un dépistage plus ciblé des alternatives aux sels d'aluminium. En testant le chlorohydrate d'aluminium couramment utilisé comme exemple d'un principe actif à base d'aluminium dans cette procédure de dépistage, nous avons découvert une influence distincte sur l'équilibre ionique : les taux intracellulaires d'ions sodium ont diminué tandis que ceux du chlorure ont augmenté. La recherche de diverses substances a révélé une polyéthylèneimine, ajustée au pH 3,5 avec de l'acide chlorhydrique, pour évoquer les mêmes altérations de l'équilibre ionique que le chlorohydrate d'aluminium. Des études in vivo ultérieures ont montré son action anti-transpirante substantielle et ont confirmé la haute efficacité de la solution de polyéthylèneimine in vivo. De plus, des études spécifiques établissant un lien entre la teneur en chlorure des substances testées et la réduction de la sudation qui en résulte ont indiqué que les ions chlorure ont un impact substantiel sur l'hypersudation. CONCLUSION: la nouvelle méthode de dépistage cellulaire in vitro décrite représente un moyen efficace d'identifier de nouveaux agents anti-transpirants actifs et suggère un mécanisme d'action biologique supplémentaire des ingrédients réducteurs de la sudation, dirigé vers le déséquilibre de l'équilibre ionique à l'intérieur des cellules des glandes sudoripares exocrines.

Evaporation-Induced Clogging of an Artificial Sweat Duct.

Metal-based antiperspirants have been in use for centuries; however, there is an increasing consumer demand for a metal-free alternative that works effectively. Here, we develop an artificial sweat duct rig and demonstrate an alternative, metal-free approach to antiperspiration. Instead of clogging sweat ducts with metal salts, we use a hygroscopic material to induce the evaporation of sweat as it approaches the outlet (i.e. pore) of the sweat duct. As a result, the sweat dehydrates almost completely while still being inside of the duct, forming a natural gel-like salt plug that halts the flow. We show that the critical pressure gradient within the duct (∼3 kPa), beneath which clogging occurs, can be rationalized by balancing the mass flow rates of the liquid (Poiseuille's law) and the evaporative vapor (Fick's law).

Aluminum Chloride-Induced Apoptosis Leads to Keratinization Arrest and Granular Parakeratosis.

Aluminum chloride (AlCl3) is the main active ingredient in commonly used antiperspirant. Antiperspirant use may cause a rare keratinization disease, granular parakeratosis (GP), then AlCl3 may be associated with the etiology of GP. The objective of this study is to elucidate the skin effect of topical aluminum application using a mouse model. We sprayed 20% aluminum chloride every day on the depilated mice skin and analyzed the skin clinically, histopathologically, and immunohistologically. We have succeeded in the histological replication of GP on mouse skin. The basophilic granules in the stratum corneum contained filaggrin, and processing of profilaggrin to filaggrin was disrupted in aluminum-treated mouse skin (Al-mouse). In Al-mouse, cytochrome c and cleaved-caspase 3 were upregulated mainly in the granular layer, and caspase 3 p20 subunit was upregulated. TUNEL-positive cells increased significantly in the Al-mouse from the granular to the horny layer. Caspase 3 inhibitor inhibited granular parakeratotic change of Al-mouse. Our results indicated that aluminum-induced apoptosis leads to keratinization arrest and acceleration of nuclear degradation before completion of profilaggrin processing. This could lead to retention of the basophilic granules composed of underprocessed profilaggrin in the horny layer of Al-mouse skin, the hallmark of GP.

Survival in patients with malignant pleural effusion undergoing talc pleurodesis.

OBJECTIVES: Recent observations indicate a potential survival benefit in patients with malignant pleural effusion (MPE) who achieve successful pleurodesis in comparison to patients who experience effusion recurrence post pleurodesis. This study aimed to explore this observation using two datasets of patients with MPE undergoing talc pleurodesis. MATERIALS AND METHODS: Dataset 1 comprised patients who underwent talc pleurodesis at Oxford Pleural Unit for MPE. Dataset 2 comprised patients enrolled in the TIME1 clinical trial. Pleurodesis success was defined as absence of need for further therapeutic procedures for MPE in the three months following pleurodesis. Data on various clinical, laboratory and radiological parameters were collected and survival was compared according to pleurodesis outcome (success vs. failure) after adjusting for the aforementioned parameters. RESULTS: Dataset 1 comprised 60 patients with mean age 74.1±10.3 years. The most common primary malignancies were mesothelioma, breast and lung cancer. 29 patients (48.3%) achieved pleurodesis. The adjusted odds ratio (aOR) for poor survival with pleurodesis failure was 2.85 (95% CI 1.08-7.50, =p 0.034). Dataset 2 comprised 259 patients from the TIME1 trial. The mean age was 70.8±10.3 and the most common primary malignancies were mesothelioma, lung and breast cancer. Pleurodesis was successful in 205 patients (79%). aOR for poor survival was 1.62 (95% CI 1.09-2.39, p = 0.015). CONCLUSION: Achieving pleurodesis seems to impart a survival benefit in patients with MPE. Further studies are required to explore factors that may contribute to this phenomenon and to address the difference in survival between pleurodesis and indwelling pleural catheter interventions.

Clinical evaluation of an antiperspirant for hyperhidrosis.

BACKGROUND: Hyperhidrosis is a fairly common condition characterized by excessive sweating, usually in axillary areas. Although not leading to major health problems, it causes significant psychological distress and bears a negative impact on sociality and quality of life in general. The first line of defense used to address this problem are antiperspirants, usually containing aluminum salts, capable of blocking the excessive sweating. METHODS: We made a clinical trial to test the deodorant effectiveness and anti-bacterial activity of an antiperspirant product, based on agaricine, aluminum hydrochloride, and silver citrate, in a cohort of 20 subjects following a single laboratory application under controlled conditions. Later, the same product has been tested for skin compatibility, effectiveness and cosmetic quality after repeated home applications under normal conditions of use for 14 consecutive days. RESULTS: After 6 and 24 hours from the application, the microbial load observed in treated axilla was inferior in a statistically significant way compared to the untreated axilla. Pathogenic bacteria have not been found on any of the two armpits. The tested product has shown an excellent anti-bacterial activity. CONCLUSIONS: Overall, the product has been highly appreciated by the volunteers for its effectiveness and its cosmetic qualities, particularly because it has a good deodorant activity, which persist throughout the day, it does not stain clothes, and it has a practical package.

Human axillary skin condition is improved following incorporation of glycerol into the stratum corneum from an antiperspirant formulation.

The study objectives were to demonstrate that glycerol, when topically applied from a roll-on antiperspirant formulation, can be delivered directly to human skin ex vivo and the axillary stratum corneum (SC) in vivo, and to assess whether it improves the quality of the axillary skin barrier. Ex vivo human skin absorption of glycerol was measured following application of a roll-on antiperspirant formulation containing 4% 13C3-glycerol. Skin distribution of 13C3-glycerol over 24 h was assessed using gas chromatography-mass spectrometry. In vivo axillary SC penetration was measured by confocal Raman spectroscopy and multivariate curve-resolution software 1 h after topical application of a roll-on antiperspirant formulation containing 8% deuterated glycerol (d5-glycerol). A clinical study was conducted to determine the efficacy of a roll-on antiperspirant formulation containing 4% glycerol in reducing shaving-induced visual irritation and in increasing axillary-skin hydration. Ex vivo skin absorption studies indicated that the formulation delivered 13C3-glycerol into the SC at all timepoints over the 24-h period. In vivo Raman measurements (1 h after application) demonstrated that d5-glycerol was detectable to a depth of at least 10 µm in the axillary SC. Application of 4% glycerol from a roll-on antiperspirant formulation to the axilla was associated with significantly less visible irritation and greater skin hydration than observed with the control (glycerol-free) product. These studies demonstrate that glycerol, incorporated in a roll-on antiperspirant formulation, is delivered directly and rapidly to all depths of the axillary SC, and results in improvements in visible irritation and hydration in the axilla.

Towards a bacterial treatment for armpit malodour.

Axillary malodour is a frustrating condition for many people. It can lead to significant discomforts and various psychological effects. The underarm microbiome plays a major role in axillary malodour formation. Not only the bacteria on the epidermis, but also and especially those living in the sweat glands, sweat pores and hair follicles play a pivotal role in malodour development. To treat underarm malodour, this viewpoint article envisions a bacterial treatment. Replacing the autochthonous malodour-causing microbiome with a non-odour-causing microbiome, through an armpit bacterial transplantation or direct application of probiotics/non-odour-causing bacteria, could resolve the condition. Selective steering of the microbiome with prebiotics, biochemicals or plant extracts can likewise greatly help in improving the underarm odour. Elimination/inhibition of the "bad bugs" and application/stimulation of the "good bugs" will be part of the future treatment for axillary body odour.

In vivo single human sweat gland activity monitoring using coherent anti-Stokes Raman scattering and two-photon excited autofluorescence microscopy.

BACKGROUND: Eccrine sweat secretion is of central importance for control of body temperature. Although the incidence of sweat gland dysfunction might appear of minor importance, it can be a real concern for people with either hypohidrosis or hyperhidrosis. However, sweat gland function remains relatively poorly explored. OBJECTIVES: To investigate the function of single human sweat glands. METHODS: We describe a new approach for noninvasive imaging of single sweat gland activity in human palms in vivo up to a depth of 100 µm, based on nonlinear two-photon excited autofluorescence (TPEF) and coherent anti-Stokes Raman scattering (CARS). RESULTS: These techniques appear to be useful compared with approaches already described for imaging single sweat gland activity, as they allow better three-dimensional spatial resolution of sweat pore inner morphology and real-time monitoring of individual sweat events. By filling the sweat pore with oil and tuning the CARS contrast at 2845 cm(-1) , we imaged the ejection of sweat droplets from a single sweat gland when oil is pushed out by sweat flow. On average, sweat events lasted for about 30 s every 3 min under the conditions studied. On the other hand, about 20% of sweat glands were found inactive. TPEF and CARS were also used to study, at the single pore level, the antiperspirant action of aluminium chlorohydrate (ACH) and to reveal, for the first time in vivo, the formation of a plug at the pore entrance, in agreement with reported ACH antiperspirant mechanisms. CONCLUSIONS: Although data were acquired on human palms, these techniques show great promise for a better understanding of sweat secretion physiology and should be helpful to improve the efficacy of antiperspirant formulations.

Prevention of palmar-plantar erythrodysesthesia with an antiperspirant in breast cancer patients treated with pegylated liposomal doxorubicin (SAKK 92/08).

BACKGROUND: Elevated concentrations of doxorubicin are found in eccrine sweat glands of the palms and soles. We therefore evaluated an antiperspirant as preventive treatment for palmar-plantar erythrodysesthesia (hand-foot syndrome) in patients with metastatic breast cancer treated with pegylated liposomal doxorubicin. PATIENTS AND METHODS: An antiperspirant containing aluminum chlorohydrate or placebo cream was applied to the left or right hand and foot in a double-blinded manner (intra-patient randomization). The primary endpoint was the rate of grade 2 or 3 palmar-plantar erythrodysesthesia. A secondary endpoint was the patient-reported symptom burden (tingling, numbness, pain, or skin problems). Using McNemar's matched pairs design, 53 patients were needed to detect a 20% difference between the treatment and placebo sides with a significance level of 5% and power of 90%. RESULTS: Grade 2 or 3 PPE occurred in 30 (58%) of 52 evaluable patients; in six patients adverse effects occurred on the placebo side but not on the treatment side, whereas one patient developed palmar-plantar erythrodysesthesia on the treatment side only (P = 0.07). Four patients developed grade 2 or 3 palmar-plantar erythrodysesthesia on their foot on the placebo side but not on the treatment side (P = 0.05). In the cohort with grade 2 or 3 palmar-plantar erythrodysesthesia there was a trend towards fewer dermatologic symptomatologies with the active treatment (P = 0.05), and no difference for other adverse events. CONCLUSION: Using topical aluminum chlorohydrate as an antiperspirant appears to reduce the incidence of grade 2 or 3 palmar-plantar erythrodysesthesia following pegylated liposomal doxorubicin chemotherapy for metastatic breast cancer.

Effects of antiperspirant aluminum percent composition and mode of application on mock microcalcifications in mammography.

OBJECTIVE: Active ingredients in antiperspirants - namely, aluminum-based complexes - can produce radiopaque particles on mammography, mimicking microcalcifications. The present study was designed to investigate whether the appearance of antiperspirant induced radiopaque particles observed on mammograms is dependent on the percentage of aluminum-based complexes in antiperspirants and/or on their mode of application. METHODS: A total of 43 antiperspirants with aluminum-based complex percentages ranging between 16% and 25% were tested. Each antiperspirant was applied to a single use plastic shield and then placed on an ultrasound gel pad, simulating breast tissue. Two experiments were performed, comparing antiperspirants based on (1) their percentage of aluminum-based complexes (20 antiperspirants) and (2) their mode of applications (solid, gel, and roll-on) (26 antiperspirants). Two experienced, blinded radiologists read images produced in consensus and assessed the appearance of radiopaque particles based on their density and shape. RESULTS: In experiment 1, there was no statistically significant association between the percent aluminum composition of invisible solid antiperspirants and the density or shape of the radiopaque particles (p-values>0.05). In experiment 2, there was a statistically significant association between the shape of the radiopaque particles and the mode of application of the antiperspirant (p-value=0.0015). CONCLUSIONS: Our study suggests that the mammographic appearance of the radiopaque antiperspirant particles is not related to their percent composition of aluminum complexes. However, their mode of application appears to influence the shape of radiopaque particles, solid antiperspirants mimicking microcalcifications the most and roll-on antiperspirants the least.

Thermoregulatory vs. event sweating--comparison of clinical methodologies, physiology and results.

OBJECTIVES: Although the mechanisms of sweating due to thermoregulation vs. stress are distinct, the antiperspirant industry focuses primarily on perspiration due to heat as their method of efficacy testing. To better understand the overall protection afforded by a 'Clinical Strength' over-the-counter antiperspirant product, we compare results from a standard hot-room study with results from two studies using the Trier Social Stress Test (TSST). METHODS: For each study, unscented antiperspirant was applied to one axilla, leaving the other untreated for internal control. The hot-room protocol involved a 40-min warm-up period with 2-20 min sweat collections at 100 ± 2 °F (35% RH). The TSST requires naïve subjects to give an impromptu speech and conduct mental arithmetic, with collections of sweat, heart rate and other biomarkers of stress before, during and after the event. RESULTS: During the TSST, heart rate and salivary cortisol data indicate significant emotional stress. Wetness results show that sweat was reduced by 69.4% in the hot-room study, compared with 83.7% and 89.3% reductions in the stress studies. CONCLUSION: We have found added value in investigating antiperspirancy from several causes of sweat production to give a more encompassing picture of the protection afforded by an antiperspirant product, specifically wetness protection from heat, activity and stress-induced sweat.

Efficient sweat reduction of three different antiperspirant application forms during stress-induced sweating.

OBJECTIVES: Stress sweating can occur in everyday situations independently of thermally-induced perspiration. It is triggered by emotionally challenging situations and leads to underarm wetness and a characteristic unpleasant malodor. In this study, we aimed to determine the long-term efficacy of three unperfumed antiperspirant (AP) formulas for different application forms (roll-on, stick, aerosol) against stress-induced sweating and malodor formation. METHODS: We utilized the widely accepted Trier Social Stress Test (TSST) to induce psychosocial stress in female and male volunteers (18 - 40 years) and determined physiological stress parameters. To additionally assess the efficacy of the test AP roll-on against thermally-induced sweating, a hot room study was performed. RESULTS: Increasing heart rates and an augmentation of saliva cortisol levels during the TSST indicated a substantial stress reaction which was paralleled by a pronounced sweat production in the untreated axillae of both males and females. Forty-eight hours after application, all three test APs significantly decreased the amount of sweat in the treated axillae independent of gender. With respect to AP effects on malodor production, trained sniffers assessed sweat samples collected during the TSST from the untreated axillae as significantly more malodorous than comparable samples from the AP-treated axillae. Also, independent of gender the test AP roll-on significantly decreased the thermally-induced sweat in the AP-treated axilla. CONCLUSION: We show for the first time a highly effective reduction of emotionally-induced axillary sweating and malodor production for three different application forms 48 h after the last product use. The specially developed roll-on, stick, and aerosol AP provide long-term protection against stress-induced sweat which is of high relevance in everyday life.

Influence of various environmental parameters on sweat gland activity.

The choice of environmental conditions when conducting antiperspirant studies greatly affects the quantity of sweat output. Our initial goal in this work was to develop an in-house procedure to test the efficacy of antiperspirant products using replica techniques in combination with image analysis. To ameliorate the skin replica method, we conducted rheological studies using dynamic mechanical analysis of the replica formulation. In terms of sweat output quantification, our preliminary results revealed a considerable amount of variation using the replica technique, leading us to conduct more fundamental studies of the factors that influence sweating behavior and how to best design the experimental strategy. In accordance with the FDA's protocol for antiperspirant testing, we carried out gravimetric analyses of axillae sweating under a variety of environmental conditions including temperature and humidity control. Subjects were first acclimatized in an environmentally controlled room for 30 min, and then placed in a sauna for an additional 30 or 45 min, depending on which test we administered. In Test 1 (30 min total in the sauna), the first 10 min in the sauna was another equilibration period, followed by a 20 min sweat production stage. We monitored axillae sweating during the last 20 min in the sauna by gravimetric analysis. At time (t) = 30 min in the sauna, skin replicas were taken and later analyzed using imaging and image analysis techniques. Test 1 was carried out on over 25 subjects, both male and female, from various racial backgrounds. In Test 2, subjects spent 45 min in the sauna after the initial 30-min period in the environmental room. During the 45 min, we obtained gravimetric readings of absorbent pads placed in the axillae. We conducted studies at various temperature and relative humidity settings. We also studied the influence of several external parameters on sudoriferous activity. Test 2 was a range-finding experiment on two subjects to determine the optimized environmental conditions for the hot room procedure. In addition to the replica and gravimetric techniques, we also measured flux density to determine the onset of firing of sweat glands to ensure that our environmental preconditioning step (30 min in the environmental room) brought subjects to the point that their sweat glands were activated. Although flux density measurements are usually carried out to determine transepidermal water loss (TEWL), we found that they can be equally useful for monitoring the onset of sweat production. Thermal infrared imaging experiments were also carried out allowing us to generate full-body images of subjects containing anatomical thermal distribution data with high accuracy. Overall, we conclude that our in-house hot room procedure offers much potential as an effective and cost-efficient screening tool for narrowing copious antiperspirant formulations to a select few for expensive clinical evaluation.

In vitro study of percutaneous absorption of aluminum from antiperspirants through human skin in the Franz™ diffusion cell.

Aluminum salts such as aluminum chlorohydrate (ACH) are known for use as an active antiperspirant agent that blocks the secretion of sweat. A local case report of hyperaluminemia in a woman using an aluminum-containing antiperspirant for 4 years raises the problem of transdermal absorption of aluminum (Al). Only a very limited number of studies have shown that the skin is an effective barrier to transdermal uptake of Al. In accordance with our analytical procedure, the aim of this study with an in vitro Franz™ diffusion cell was to measure aluminum uptake from three cosmetic formulations of antiperspirant: the base for an "aerosol" (38.5% of ACH), a "roll-on" emulsion (14.5% ACH), and a "stick" (21.2%), by samples of intact and stripped human skin (5 donors). The Al assays were performed by Zeeman Electrothermal Atomic Absorption Spectrophotometry (ZEAAS). Following contacts lasting 6, 12 and 24h, the Al assays showed only insignificant transdermal absorption of Al (≤0.07% of the quantity of Al deposited) and particularly low cutaneous quantities that varied according to the formulations (1.8 µg/cm² for "aerosol base" and "stick" - 0.5 µg/cm² for the "roll-on"). On stripped skin, for which only the "stick" formulation was tested, the measured uptake was significantly higher (11.50 µg/cm² versus 1.81 µg/cm² for normal skin). These results offer reassurance as regards to the use of antiperspirants for topical application of ACH-containing cosmetic formulations on healthy skin over a limited time span (24h). On the other hand, high transdermal Al uptake on stripped skin should compel antiperspirant manufacturers to proceed with the utmost caution.

Clinical studies of sweat rate reduction by an over-the-counter soft-solid antiperspirant and comparison with a prescription antiperspirant product in male panelists.

BACKGROUND: Individuals with axillary hyperhidrosis have much higher than average sweat rates and are often prescribed anhydrous aluminum chloride (AlCl(3)) solutions. Topical application of these solutions can be irritating to the skin, resulting in poor compliance and lower than desired efficacy. OBJECTIVE: Demonstrate the efficacy of an over the counter "clinical strength" soft-solid antiperspirant using a night time application regimen and compare to a prescription aluminum chloride (6.5%) antiperspirant using male panelists. METHODS: Gravimetric hot room efficacy testing (100 F and 35% Humidity) was performed comparing an over the counter soft-solid antiperspirant to placebo in a single test. Two separate gravimetric tests were placed comparing a prescription aluminum chloride (6.5%) antiperspirant to the same soft solid product using an intent to treat model. Skin irritation was assessed daily by a trained grader. RESULTS: Placebo testing resulted in 85% of panelists having a reduction in sweating rate greater than 50%. Comparison testing showed the over the counter soft solid reduced sweat rate by an average of 34% better than the prescription product while resulting significantly less skin irritation. CONCLUSIONS: Over the counter "clinical strength" soft-solid antiperspirants can be considered as an alternative treatment to aluminum chloride antiperspirants for the treatment of heavy sweating.

Changes in the pleural cavity by pleurodesis using talc or OK-432: an experimental study.

PURPOSE: To define the changes in the pleural cavity after pleurodesis induced by talc or OK-432. METHODS: A total of 30 rats were divided into three groups: a normal saline group (control group, n = 10), a group administered 400 mg/kg talc (talc group, n = 10), and a group administered 0.3 KE/kg OK-432 (OK-432 group, n = 10). Pleural cavities were examined and scored on the 30th day after the intrapleural administration of each agent. RESULTS: Both the talc group and OK-432 group showed significantly higher macroscopic or microscopic pleurodesis scores than the control group (P < 0.05). Upon microscopic evaluation, the pleurodesis scores in the talc group were significantly higher than those in the OK-432 group (P < 0.01).The majority of the pleural thickness was found on the visceral pleura, and the parietal pleura was very thin. The thickness of the visceral pleura in the talc group was significantly higher than that in the OK-432 group (P < 0.005). Pathologically, the pleural thickening in the talc group consisted of fibrous tissue with injury of the pleural mesothelium, and talc particles were seen in the submesothelial fibrotic tissue and inside the alveoli. CONCLUSIONS: Talc pleurodesis induces more marked changes in the pleural cavity than OK-432-induced pleurodesis.