Dermatotoxicologic clinical solutions: hair dying in hair dye allergic patients?

This article describes how to identify allergic contact dermatitis resulting from hair dye, and outlines interventions and prevention principles for those who wish to continue dyeing their hair despite being allergic. Hair dye chemicals thought to be the most frequent sensitizers are discussed with instructions for health care providers on how to counsel patients about techniques to minimize exposure to allergenic substances. This framework should allow many patients to continue dyeing their hair without experiencing adverse side effects.     

Engineering the niche for hair regeneration — A critical review

Recent progress in hair follicle regeneration and alopecia treatment necessitates revisiting the concepts and approaches. In this sense, there is a need for shedding light on the clinical and surgical therapies benefitting from nanobiomedicine. From this perspective, this review attempts to recognize requirements upon which new hair therapies are grounded; to underline shortcomings and opportunities associated with recent advanced strategies for hair regeneration; and most critically to look over hair regeneration from nanomaterials and pluripotent stem cell standpoint. It is noteworthy that nanotechnology is able to illuminate a novel path for reprogramming cells and controlled differentiation to achieve the desired performance. Undoubtedly, this strategy needs further advancement and a lot of critical questions have yet to be answered. Herein, we introduce the salient features, the hurdles that must be overcome, the hopes, and practical constraints to engineer stem cell niches for hair follicle regeneration.     

Are cannabinoids detected in hair after washing with Cannabio shampoo?

Today, cannabis plants are used in shampoo preparations, in foodstuffs (e.g., oils, noodles, crackers, etc.), and in beverages (e.g., tea). These products often contain < 1% delta9-tetrahydrocannabinol (THC) in order to eliminate psychoactive effects, but some of them can include 1 to 3% of THC. Gas chromatography-mass spectrometry (GC-MS) analysis of Cannabio shampoo revealed the presence of THC (412 ng/mL) and two constituents of cannabis plants, cannabidiol (CBD, 4079 ng/mL) and cannabinol (CBN, 380 ng/mL). In order to verify if normal hygiene practices with Cannabio shampoo can result in positive tests for cannabinoids in hair, three subjects washed their hair with this shampoo once daily for two weeks. After this period, hair specimens were collected. In the three hair specimens, THC, CBD, and CBN were never detected within their limits of detection, 0.05, 0.02, and 0.01 ng/mg, respectively. We concluded that the use of Cannabio shampoo during normal hygiene practices cannot be considered as a source of potential contamination of hair. In a second experiment, drug-free hair specimens (200 mg) were incubated in 10 mL water/Cannabio shampoo (20:1, v/v) for 30 min, 2 h, and 5 h. After incubation, hair strands were washed with water and separated into two portions. One portion was extracted directly; the second was decontaminated with methylene chloride and then extracted. After an incubation period of 30 min, the analysis of hair by GC-MS did not reveal the presence of THC, CBD, and CBN in hair, regardless of whether the hair was decontaminated. After an incubation period of 2 h, specimens tested positive for CBD (0.11 ng/mg without decontamination and 0.10 ng/mg with decontamination) and CBN (0.02 ng/mg without decontamination and 0.02 ng/mg after decontamination). After an incubation period of 5 h, specimens tested positive for CBD (0.25 ng/mg without decontamination and 0.14 ng/mg after decontamination) and CBN (0.02 ng/mg without decontamination and 0.02 ng/mg after decontamination). In all cases, THC was never detected. Extensive but unrealistic use of Cannabio shampoo can cause drug-free hair to test positive for CBD and CBN but not for the primary psychoactive drug THC.     

How are the inner hair cells and auditory nerve fibers activated without the mediation of the outer hair cells and the cochlear amplifier?

The present study was designed to assess whether, in the presence of a depression of the cochlear amplifier i.e. a sensorineural hearing loss (SNHL), the inner hair cells (IHCs) require the presence of a normal endocochlear potential for transduction. An SNHL was induced by injecting salicylic acid (which binds to the motor protein prestin in the outer hair cells), and then furosemide (which depresses the endocochlear potential) was injected. Furosemide did not cause an additional elevation of the threshold of the auditory nerve brainstem evoked response (ABR) over that induced by the salicylic acid injection. Exposure to noise was also used to induce a SNHL in other mice, and then furosemide was injected. Here too furosemide did not cause an additional ABR threshold elevation over that induced by the noise. These results show that the IHCs (and the auditory nerve) can be excited in the presence of a SNHL (i.e. without the cochlear amplifier) and in the absence of an endocochlear potential. Possible mechanisms of excitation in such a state are discussed.     

Determination of endogenous levels of GHB in human hair. Are there possibilities for the identification of GHB administration through hair analysis in cases of drug-facilitated sexual assault?

We have developed a GC-MS-MS assay for GHB in human hair. Five milligrams of washed hair were hydrolyzed by 1M or 0.01M NaOH before a liquid-liquid extraction with ethyl acetate under acidic conditions. GHB-d(6) was used as the internal standard. TMS derivatives were formed before injection. TBDMS derivatives were used in cases of strong chromatographic interferences or in a confirmatory procedure. Analysis of basal levels of GHB in 61 drug-free donors gave the following results: the mean measured concentration for blond hair was 0.60 ng/mg (n = 12), SD = 0.19 ng/mg, and extreme figures were in the range 0.35-0.95 ng/mg. For brown hair, the mean measured concentration was 0.90 ng/mg (n = 30), SD = 0.42 ng/mg, and extreme figures 0.41-1.86 ng/mg. For black hair, the mean measured concentration was 0.90 ng/mg (n = 19), SD = 0.37 ng/mg, and extreme figures 0.32-1.54 ng/mg, showing no significant differences depending on hair color. Analysis of basal levels of GHB of 12 or more specimens in segmented hair showed a mean concentration of 1.22 ng/mg (0.31-8.4 ng/mg) and a relative standard deviation for each individual ranging from 6.75% to 37.98%. GHB was administered to a healthy 53-year-old white male (light brown hair) at oral dosages of 30, 45, and 60 mg/kg. Beard hair was collected just before administration and 24 h after (and each day for one week for the last dose), and a 7.5-cm scalp hair lock was collected 7 days after the last dose. A rise in GHB concentration was observed in beard hair for the 45 and 60 mg/kg dosages with a maximum at 24 h, whereas no change was observed for the 30 mg/kg dosage. Scalp hair was segmented into 3-mm long segments. The three proximal last segments showed significantly (0.0005 < p < 0.005) different concentrations of GHB (1.22, 1.27, and 1.66 ng/mg, respectively) when compared with the basal physiological level of GHB in this same person (mean = 0.62 ng/mg, SD = 0.15 ng/mg). A case of daily GHB abuse during bodybuilding allowed us to determine a concentration of GHB of 14 ng/mg, in a 2-cm long segment (black hair). A case of rape under the influence of GHB was documented through hair analysis (black hair) and positive analysis of the glass she used. Sampled 7 days after the sexual assault, the three last 3-mm long proximal segments tested for GHB exhibited concentrations of 3.1-5.3 and 4.3 ng/mg, respectively, whereas the mean physiological level determined in this woman was 0.71 ng/mg, SD = 0.17 ng/mg. The authors advise a two-step hair sampling as evidence of GHB consumption: the first sample at the time of exposure to show the contamination by sweat of the proximal segment in case of recent administration with a significant rise of hair level at the root, and the second after at least 3 or 4 weeks to avoid this contamination and determine the levels incorporated in the hair matrix before, during, and after the exposure.     

Accumulation of β-agonists clenbuterol and salbutamol in black and white mouse hair

Hair has been shown to be an excellent site for the accumulation of different drugs including β-agonists, and therefore, it would be an appropriate matrix for surveillance for the presence of drug residues. The aim of this study was to determine concentrations and to compare accumulation of two different β-agonists in black and white mice hair by use of ELISA as a screening quantitative method. The study included 200 8-week-old white and black mice. One group of black mice and one group of white mice were treated with clenbuterol in a dose of 2.5 mg/kg body mass per os for 28 days. Other animals were treated in the same way with salbutamol. The highest (±SD) clenbuterol concentration of 631.4 ± 23.5 ng/g in black hair and 228.5 ± 156.2 ng/g in white hair was determined on day 1 of treatment withdrawal. Study results revealed the black-to-white hair ratio of clenbuterol accumulation to be 1:2-1:4 and of salbutamol accumulation 1:1.4. The mean (±SD) salbutamol concentrations determined on day 1 of treatment withdrawal was 23.9 ± 0.9 ng/g and 16.4 ± 1.1 ng/g in black and white hair samples, respectively. The study demonstrated that residues could be determined in hair samples even after a 30-day withdrawal period.     

The nicotinic receptor of cochlear hair cells: A possible pharmacotherapeutic target?

Mechanosensory hair cells of the organ of Corti transmit information regarding sound to the central nervous system by way of peripheral afferent neurons. In return, the central nervous system provides feedback and modulates the afferent stream of information through efferent neurons. The medial olivocochlear efferent system makes direct synaptic contacts with outer hair cells and inhibits amplification brought about by the active mechanical process inherent to these cells. This feedback system offers the potential to improve the detection of signals in background noise, to selectively attend to particular signals, and to protect the periphery from damage caused by overly loud sounds. Acetylcholine released at the synapse between efferent terminals and outer hair cells activates a peculiar nicotinic cholinergic receptor subtype, the α9α10 receptor. At present no pharmacotherapeutic approaches have been designed that target this cholinergic receptor to treat pathologies of the auditory system. The potential use of α9α10 selective drugs in conditions such as noise-induced hearing loss, tinnitus and auditory processing disorders is discussed.     

Brinzolamide–loaded nanoemulsions: ex vivo transcorneal permeation,cell viability and ocular irritation tests

The aim of this study was to investigate the corneal penetration of brinzolamide (BZ) nanoemulsions (NEs) and evaluate their in vitro and ex vivo irritancy potential. Twelve BZ NEs were prepared by the spontaneous emulsification method and ex vivo permeability studies were conducted using excised bovine corneas fixed onto Franz diffusion cells. To confirm the safety of the formulations for ophthalmic use, preparations were examined for potential ocular irritancy using a cell viability assay on retinal cells, the Hen's Egg Test-Chorio-Allantoic Membrane (HET-CAM) and the bovine corneal opacity-permeability (BCOP) test. Seven BZ NEs exhibited superior penetration across isolated bovine cornea compared to the marketed BZ suspension. The half maximal inhibitory concentration (IC₅₀) values of various surfactants and oils determined using the sulforhodamine B cell viability assay on retinal cells showed that Transcutol P, Cremophor RH40 and Triacetin were the least toxic excipients and may be safely used in the eye at various concentrations. HET-CAM and BCOP tests revealed that NE6B and NE4C did not result in any irritation and were thus considered safe for ocular use. Our finding suggests that optimized NEs can be a safe and effective vehicle for ocular delivery of BZ.     

Human defensins: turning defense into offense?

Defensins are a family of antimicrobial cationic peptides that act as a rapid response force against microbial invasion in a wide range of organisms, including plants, insects, animals and humans. In humans, defensins are produced predominantly by leukocytes and epithelial cells and are an important factor of innate immunity. In addition to their major role as natural antibiotics, defensins are increasingly recognized as signaling molecules in adaptive immunity and aberrant defensin expression has been associated with infectious diseases. In this review, we discuss the role of human defensins in relation to infectious disease and the possibility of novel defensin-based therapeutic approaches.     

The safety,stability, and compatibility of fragrances in skin and hair products†

Abstract

The efforts of the formulating chemist, perfumer, and toxicologist represent the creative forces that ultimately merge to accomplish a finished formulation. Because the ingredients in a compounded fragrance are proprietary to the company that produces them, the formulating chemist must add a mixture of unknown substances to his basic formulation with the hope that they will be compatible in functionality, stability, and safety. A well-controlled stability and safety testing program is needed to assure complete compatibility between the base formulation and the fragrance.

Potential stability problems include changes in viscosity, color, odor, clarity of transparent systems, and emulsion stability. These changes may be caused by hydrolysis, oxidation, reaction to light, reaction to metals, insolubilities, reaction to processing conditions, and packaging materials. The interactions which occur during these changes can cause the formation of new materials that may have irritation or sensitization potential. We recommend that samples of product that have successfully passed shelf-life testing be furnished to the toxicologist for a complete battery of safety tests, including controlled use testing. This procedure should help to assure that untoward reactions do not occur during consumer use.     

Integration of PKPD relationships into benefit–risk analysis

Aim

Despite the continuous endeavour to achieve high standards in medical care through effectiveness measures, a quantitative framework for the assessment of the benefit–risk balance of new medicines is lacking prior to regulatory approval. The aim of this short review is to summarise the approaches currently available for benefit–risk assessment. In addition, we propose the use of pharmacokinetic–pharmacodynamic (PKPD) modelling as the pharmacological basis for evidence synthesis and evaluation of novel therapeutic agents.

Methods

A comprehensive literature search has been performed using MESH terms in PubMed, in which articles describing benefit–risk assessment and modelling and simulation were identified. In parallel, a critical review of multi-criteria decision analysis (MCDA) is presented as a tool for characterising a drug''s safety and efficacy profile.

Results

A definition of benefits and risks has been proposed by the European Medicines Agency (EMA), in which qualitative and quantitative elements are included. However, in spite of the value of MCDA as a quantitative method, decisions about benefit–risk balance continue to rely on subjective expert opinion. By contrast, a model-informed approach offers the opportunity for a more comprehensive evaluation of benefit–risk balance before extensive evidence is generated in clinical practice.

Conclusions

Benefit–risk balance should be an integral part of the risk management plan and as such considered before marketing authorisation. Modelling and simulation can be incorporated into MCDA to support the evidence synthesis as well evidence generation taking into account the underlying correlations between favourable and unfavourable effects. In addition, it represents a valuable tool for the optimization of protocol design in effectiveness trials.     

Biphasic flux profiles of melatonin: The Yin–Yang of transdermal permeation enhancement mediated by fatty alcohol enhancers

This study investigates physicochemical processes responsible for the biphasic transdermal flux profiles of melatonin in the presence of saturated fatty alcohols (SFAL) and unsaturated fatty alcohols (USFAL). The first phase melatonin flux (J_1st) in the presence of USFAL enhancers increased with increase in the number of double bonds and reached a limiting value with two double bonds in the molecule. In case of SFAL enhancers, J_1st increased with enhancer chain length and log formulation/skin partition coefficients (log Ps), which were calculated using the solubility parameters of various formulation components. But, melatonin flux in the second phase decreased with increase in the enhancer chain length and log P values. On the other hand, the transepidermal water loss (TEWL) from the SFAL treated skin increased drastically in the second phase and correlated with log P value of the enhancer. High TEWL value, indicative of a severely disrupted SC, may help the polar formulation components to accumulate in the SC. As a consequence, the SC polarity could change significantly and reduce the partitioning of lipophilic enhancer and/or melatonin in the second phase. This study demonstrated that an optimal level of barrier disruption enhances the transdermal permeation of drugs, whereas, a drastic barrier disruption impedes transdermal transport. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:209–218, 2010     

Inhibitory activities of Puerariae Flos against testosterone 5α-reductase and its hair growth promotion activities

Crude drugs expected to have an estrogenic effect were screened for their inhibitory activity on testosterone 5α-reductase. Testosterone 5α-reductase is an enzyme catalyzing the conversion of testosterone to dihydrotestosterone, which possesses high affinity for the androgen receptor. Among the crude drugs tested, we focused on Puerariae Flos (the flowers of Pueraria thomsonii) due to its potent inhibitory activity and suitability for commercial use. The 50% ethanolic extract of Puerariae Flos (PF-ext) showed inhibitory activity of 60.2% at 500 μg/ml against testosterone 5α-reductase. Interestingly, it was more potent than that of Puerariae Radix (roots of Pueraria lobata). PF-ext also showed in vivo anti-androgenic activity using a hair growth assay in testosterone-sensitive male C57Black/6NCrSlc strain mice. We demonstrated saponins, including soyasaponin I and kaikasaponin III, to be active components in PF-ext. In addition, hair growth promotion activity in C3H/He mice at 2 mg/mouse/day of the topical administration of PF-ext was demonstrated. Thus, Puerariae Flos is a promising crude drug for treating androgenic alopecia.