H I Maibach

Publications (376)1047.34 Total impact

• Article: Modest but increased penetration through damaged skin: an overview of the in vivo human model.

  S Gattu, H I Maibach
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  ABSTRACT: Quantifying percutaneous penetration of topical drugs as well as those compounds relevant to occupational exposure is important for assessing their delivery, efficacy and toxicology. Methods for assessing penetration are established for intact skin; however, what may be equally relevant is how much penetration occurs through damaged skin. The Embase database was accessed online in March 2009 in search of human in vivo studies measuring penetration through damaged or diseased skin. Few studies have measured penetration through damaged human skin in vivo. A majority demonstrate a modest enhancement in penetration, with the exception of microdialysis studies that show a significant enhancement. The enhancement generally favored hydrophilic molecules over lipophilic molecules. Damaged or diseased skin may display a modest increase in penetration compared to intact skin, which is dependent on the method of measurement; however, additional studies with consistent methods are needed to fully elucidate how much penetration occurs through the many types and degrees of damaged skin.
  Skin pharmacology and physiology 01/2011; 24(1):2-9. · 2.92 Impact Factor
• Article: Contact urticaria to cosmetic and industrial dyes.

  P Davari, H I Maibach
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  ABSTRACT: Contact urticaria (CU) defines the weal-and-flare reaction that occurs after external cutaneous contact with a causative agent. These reactions often cause discomfort for patients, affect their quality of life, and in severe cases may be life-threatening. Some dyes are known to be urticariogens. Many people have daily exposure to these urticariogens, because of the widespread use of dyes, for example in textiles, cosmetics and foods. We reviewed industrial and cosmetic dyes such as hair dyes, basic blue 99 dye, patent blue dyes, henna, red dyes, curcumin and reactive dyes, which can potentially cause CU. Overall, the reported cases of CU lacked appropriate controls. Hair-dye constituents such as preservatives and intensifiers may play an important role as causative agents of CU. We recommend appropriate protection guidelines to reduce the incidence of CU in high-risk groups such as hairdressers, dye-factory workers or workers in dye-related industries.
  Clinical and Experimental Dermatology 04/2010; 36(1):1-5. · 1.20 Impact Factor
• Article: Enhanced absorption through damaged skin: an overview of the in vitro human model.

  S Gattu, H I Maibach
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  ABSTRACT: Quantifying percutaneous absorption of topical drugs as well as those compounds relevant to occupational exposure is important for assessing delivery, efficacy and toxicology. Methods for assessing absorption are established for intact skin; however, what may be equally relevant is how much absorption occurs through damaged skin. The Embase database was accessed online in March 2009 in search of human in vitro studies measuring absorption through damaged or diseased skin. Few studies have measured absorption through damaged human skin in vitro but those that have demonstrate a modest but clear enhancement in absorption with enhancement favoring hydrophilic molecules. Damaged or diseased skin may display a modest increase in absorption compared to intact skin; however, more studies with consistent methods and correlations to in vivo data are needed to fully elucidate how much absorption occurs through damaged skin.
  Skin pharmacology and physiology 02/2010; 23(4):171-6. · 2.92 Impact Factor
• Article: Chondrodermatitis nodularis chronica helicis in monozygotic twins.

  H P Chan, I M Neuhaus, H I Maibach
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  ABSTRACT: Chondrodermatitis nodularis chronica helicis (CNCH) is a benign inflammatory nodule of the helix. Patients report severe tenderness upon pressure. Commonly seen in middle-aged men, there are no reports of this disease in twins. We report middle-aged male monozygotic twins who simultaneously developed CNCH. This suggests, but does not prove, the possibility of a hereditary factor in the pathogenesis of CNCH.
  Clinical and Experimental Dermatology 11/2008; 34(3):358-9. · 1.20 Impact Factor
• Article: Tape stripping on a human nail: quantification of removal.

  E Tudela, A Lamberbourg, M Cordoba Diaz, H Zhai, H I Maibach
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  ABSTRACT: Tape stripping is commonly used to investigate the stratum corneum (SC). This study assesses if protein quantitative tape stripping method was suitable for human nails. We used a colorimetric method to quantify proteins removed by the tape. Water barrier functions as a result of tape stripping were also observed by changes in transonychial water loss (TOWL) from the baseline. Using tape stripping, we observed no difference between nails in the protein quantity removed by tape stripping (P=0.39). The mean TOWL before and after tape stripping were 6.9 and 9.3 g/m2/h, respectively; this was significantly increased in tape stripped nails (P<0.0001). Tape stripping seems to be an effective method to extract proteins from human nail plate and may aid the study of nail structure and function. Further studies are needed to extend our results in terms of age, gender, ethnicity and disease.
  Skin Research and Technology 11/2008; 14(4):472-7. · 1.71 Impact Factor
• Article: Role of physical chemical properties in drug relay into skin compartments.

  C R Fortenbach, B S Modjtahedi, H I Maibach
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  ABSTRACT: The ability of a drug to reach the interstitial fluid is an important aspect of drug efficacy - as a possible indicator of skin and cell compartment concentration. This overview addresses the relationship of the physical properties of several antibiotics to their ability to enter the interstitial fluid utilizing a cantharidin blister model. By collecting pharmacokinetic data for 12 antibiotics administered orally and 11 intravenously, we compared the fraction of drug that reaches the interstitial fluid (AUC(blister)/AUC(serum)) to partition coefficients. Following data analysis, we found no correlation (p = 0.98 and 0.09, respectively) between hydrophobicity and the ability to reach the interstitium. Both orally and intravenously administered antibiotics display a strong linear correlation (p < 0.001 and p = 0.006, respectively) in the total concentration found in the serum and interstitial fluid indicating that serum concentration may be an important factor in dictating interstitial fluid concentration. This correlation may prove useful in clinical application as a means of determining interstitial fluid concentration by measuring only serum levels.
  Skin pharmacology and physiology 08/2008; 21(6):294-9. · 2.92 Impact Factor
• Article: Skin decontamination of glyphosate from human skin in vitro.

  H Zhai, H P Chan, X Hui, H I Maibach
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  ABSTRACT: This study compared three model decontaminant solutions (tap water, isotonic saline, and hypertonic saline) for their ability to remove a model herbicide (glyphosate) from an in vitro human skin model. Human cadaver skin was dosed (approximately 375microg) of [14C]-glyphosate on 3cm2 per skin. After each exposure time (1, 3, and 30min post-dosing, respectively), the surface skin was washed three times (4ml per time) with each solution. After washing, the skin was stripped twice with tape discs. Lastly, the wash solutions, strippings, receptor fluid, and remainder of skin were liquid scintillation analyzer counted to determine the amount of glyphosate. There were no statistical differences among these groups at any time points. The total mass balance recovery at three time exposure points was between 94.8% and 102.4%. The wash off rates (glyphosate in wash solutions) at three different exposure times is 79-101.2%. Thus the three tested decontaminants possess similar effectiveness in removing glyphosate from skin. This in vitro model is not only economic and rapid, but also provides quantitative data that may aid screening for optimal decontaminants.
  Food and Chemical Toxicology 07/2008; 46(6):2258-60. · 3.00 Impact Factor
• Article: In vitro model for decontamination of human skin: formaldehyde.

  H Zhai, S Barbadillo, X Hui, H I Maibach
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  ABSTRACT: Decontamination of a chemical from skin is often an emergency measure. This study utilized an in vitro model to compare the decontamination capacity of three model decontaminant solutions (tap water, isotonic saline, and hypertonic saline). Human cadaver skin was dosed (approximately 0.25 microg on 3 cm(2) per skin) with radio-labeled [(14)C]-formaldehyde. After a defined exposure time (1, 3, and 30 min post-dosing, respectively), the surface skin was washed three times (4ml per time) with each solution. After washing, the skin was stripped with tape discs twice. Lastly, the wash solutions, strippings, receptor fluid, and remainder of skin were liquid scintillation analyzer counted to determine the amounts of formaldehyde. Additionally, an evaporation test at different exposure times (1min, 3min, 15min, 30min, and 60min, respectively) was conducted to monitor formaldehyde % evaporation. There were no statistical differences among these groups except isotonic saline, at 3min post-exposure (in wash solutions), showed a significantly difference (p<0.05) when compared to tap water. Formaldehyde % evaporation increased linearly with extending application times, and were 7.7%, 13.6%, 19.7%, 24.4%, and 35.9% (1min, 3min, 15min, 30min, and 60min, respectively). This data suggests that isotonic saline may be effective in removing formaldehyde from skin. However, results from this model need validation in vivo. The model may provide a facile and robust method of accelerating knowledge of decontamination mechanism and lead to enhanced efficacy.
  Food and Chemical Toxicology 05/2007; 45(4):618-21. · 3.00 Impact Factor
• Article: Percutaneous penetration enhancers: an overview.

  H-Y Thong, H Zhai, H I Maibach
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  ABSTRACT: Transdermal drug delivery is the controlled release of drugs through the skin to obtain therapeutic levels systematically. Several technological advances have been made in the recent decades to enhance percutaneous drug penetration. This overview focuses on the physical, biochemical, and chemical means of penetration enhancement, as well as the classification and mechanisms of chemical penetration enhancers, their application in transdermal drug delivery, and trends and development in penetration enhancement.
  Skin pharmacology and physiology 02/2007; 20(6):272-82. · 2.92 Impact Factor
• Article: Gender differences of enzymatic activity and distribution of 17beta-hydroxysteroid dehydrogenase in human skin in vitro.

  T Hikima, H I Maibach
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  ABSTRACT: The interconversion of estrone (E1) and 17beta-estradiol (E2) is catalyzed by 17beta-hydroxysteroid dehydrogenase (17beta-HSD) in peripheral steroidogenic organs such as the skin. To investigate gender differences of activity and skin distribution of 17beta-HSD in human skin, enzymatic activity was measured in skin homogenates and skin horizontally sliced by 10 microm thickness in vitro. Reductive 17beta-HSD (E2 formation from E1) in female skin has a lower substrate affinity than in male skin; Km (Michaelis-Menten constant) of female and male skin is 11.8 +/- 6.5 and 2.0 +/- 2.0 microM, respectively. Female skin had a tendency to activate estrogen; Vmax (maximum rate) for E2 formation, 5.8 +/- 4.0 pmol/min/mg protein, is 1.7 times larger than E1 formation, 3.5 +/- 1.5 pmol/min/mg protein, and, on the other hand, male skin tends to deactivate estrogen; Vmax for E1 and E2 is 10.5 +/- 6.1 and 4.2 +/- 3.7 pmol/min/mg protein, respectively. The concentration of metabolite had a peak value at 80-120 microm from the skin surface. Therefore, these in vitro results suggest that the enzymatic activities of 17beta-HSDs have a gender difference in estrogen formation/metabolism and are distributed around the basement layer of the epidermis irrespective of sex. 17Beta-HSDs distributed around the basement epidermis may be effectively supplied with circulating estrogen from the papillary plexus to maintain the estrogen level in skin. This distribution pattern having a peak surrounding 100 microm from the skin surface indicates the importance for defense from noxae (e.g. detoxication) and maintenance of the internal environment (e.g. biosynthesis of hormones). Future studies should increase sample size and confirm these results by stricter statistical analysis.
  Skin pharmacology and physiology 01/2007; 20(4):168-74. · 2.92 Impact Factor
• Article: Corticosteroid skin atrophogenicity: assessment methods

  J. Y. Lee, H. I. Maibach
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  ABSTRACT: Background/aims: Skin atrophy manifests itself as fragile and easily bruised skin, telangiectasia and striae distensae.Methods: Various methods have been used to predict the atrophogenicity potential of topical corticosteroids in man. Assay standardization, including reference corticosteroid, anatomic site, method of administration, and quantification, has not been accomplished.Results/Conclusion: This report reviews the literature and proposes a standard assay method.
  Skin Research and Technology 10/2006; 4(4):161 - 166. · 1.71 Impact Factor
• Article: Blood flow in psoriatic skin lesions: the effect of treatment

  AMY KHAN, L. M. SCHALL, ETHEL TUR, H. I. MAIBACH, R. H. GUY
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  ABSTRACT: Laser Doppler velocimetry (LDV) was used to assess the effect of treatment upon cutaneous blood flow in psoriatic skin lesions. The resolution of two separate plaques in each of seven subjects was followed. Six of the subjects received the Goeckerman regimen, the seventh was reated with psoralen-ultraviolet A (PUVA) therapy. Control LDV readings were taken from uninvolved skin sites during the treatment period. Cutaneous blood flow in the psoriatic lesions of the Goeckerman-treated patients decreased to levels comparable to those in uninvolved skin early in the course of treatment and significantly preceeded the observed clinical resolution from 4 to 8 days after initiation of therapy (P < 0.05). Visible flare-ups sometimes appeared when patients were untreated (over a weekend, for example) and these eruptions were accompanied by a transient elevation of LDV readings. Perfusion of the lesions of the PUVA-treated patient remained consistently higher than perfusion of uninvolved skin despite clinical healing. In a separate series of experiments, blood flow at the extensor surface of the forearm was measured in the skin of normal subjects, the uninvolved skin of psoriatic patients and the untreated lesional skin of psoriatic patients. While the lesional skin had significantly higher perfusion levels than uninvolved psoriatic or normal control skin (P < 0.01), there was no significant difference between blood flow to the uninvolved psoriatic skin of psoriatics and that to the skin of healthy controls.
  British Journal of Dermatology 07/2006; 117(2):193 - 201. · 3.67 Impact Factor
• Article: Pharmacodynamic measurements of methyl nicotinate percutaneous absorption: the effect of aging on microcirculation

  K.V. ROSKOS, A.J. BIRCHER, H.I. MAIBACH, R.H. GUY
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  ABSTRACT: The penetration of drugs through aged skin is important both in terms of transdermal delivery to elicit systemic pharmacological effects, and for topical treatment. Cutaneous microcirculation efficiency, an integral parameter in the overall process of percutaneous absorption, was studied in young (20–34 years) and old (64–86 years) individuals. Cutaneous erythema as induced by topical administration of methyl nicotinate to the ventral forearm, was monitored non-invasively using laser-Doppler flowmetry. Dose-response behaviour was characterized by five parameters: (i) the time of onset of action; (ii) the time to reach maximum response; (iii) the magnitude of the maximum response; (iv) the area under the response-time curve; and (v) the time to decay to 75% of the maximum response. Additionally, the sensitivity and efficiency of the cutaneous microcirculation in both age groups was evaluated using a pharmacokinetic-pharmacodynamic model. Statistical analysis of all data showed no significant differences between the age groups for the same concentrations. The results indicate that microvessel reactivity to the applied stimulus is comparable in the ventral forearm of both young and old populations.
  British Journal of Dermatology 07/2006; 122(2):165 - 171. · 3.67 Impact Factor
• Article: Chemical and pharmacologic skin irritation in man

  P. H. Andersen, A. Nangia, P. Bjerring, H. I. Maibach
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  ABSTRACT: Attention is increasingly being focused on the relationship of dissocial Ion constant (pKa) of chemicals and skin irritation presumably caused by pH effects at epidermal levels. Human skin Studies of irritation have utilized both subjective visual-palpation scores and reflectance spectroscopy (RS) or laser Doppler velocimetry (LDV) respectively. Several studies document that erythema determined subjectively and objectively correlates with the degree of skin irritancy, but others report lack of correlation between LDV and irritancy scored subjectively. In this study, pharmacologicol and chemical in vivo, skin irritation was evaluated utilizing an improved reflectance spectrophotometer equipped with computerized data analysis. In 16 white females, a model for skin irritation was induced by a 24-h patch application of 4 basic chemicals, imipramine, norephedrine, nicotine and 8-aminoquinoline, with pKa's ranging from 3.8 to 9.5. Skin pigmentation (melanin) and the relative amounts of oxygenized (arterial) and deoxygenized (venous) hemoglobin present in the erythematous skin were calculated. A clear increase in the hemoglobin content was observed in chemical and vehicle exposed sites. Although skin irritation is a complex phenomenon involving chemical and solution properties, percutaneous absorption and the biological drug response, high pKa (p > 0.01) was predictive of acute skin irritation in man using computerized analysis of reflectance spectroscopy, A high correlation between visual score and RS was found (r= 0.91).
  Contact Dermatitis 04/2006; 25(5):283 - 289. · 3.51 Impact Factor
• Article: Sodium lauryl sulfate-induced irritation in the human face: regional and age-related differences.

  S Marrakchi, H I Maibach
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  ABSTRACT: The particular sensitivity of the human face to care products prompted us to study irritation induced by sodium lauryl sulfate (SLS) in its various regions. We examined regional and age-related differences, correlating basal transepidermal water loss (TEWL) and capacitance to SLS irritation. SLS (2% aq.) was applied under occlusion for 1 h to the forehead, cheek, nose, nasolabial and perioral areas, chin, neck and forearm to two groups of subjects--one with 10 subjects with an average age of 25.2 +/- 4.7 years and another with 10 subjects with an average age of 73.7 +/- 3.9 years. TEWL was measured before and 1 h and 23 h after patch removal. Baseline stratum corneum hydration was also measured. Irritation was assessed by the changes in TEWL (deltaTEWL = TEWL after patch removal - basal TEWL) after corrections to the control. In the younger group, all areas of the face and the neck reacted to SLS, whereas the forearm did not. In the older group, the nose, perioral area and forearm did not react. In both age groups, some significant differences between the regions of the face were detected. The younger group showed higher changes in TEWL than the older group in all the areas studied, but only in the chin and nasolabial area were the differences statistically significant. Significant correlations were found between basal TEWL and deltaTEWL in 5 of the 7 areas which reacted to SLS. Baseline TEWL is one parameter that correlates with the susceptibility of the face to this irritant.
  Skin pharmacology and physiology 02/2006; 19(3):177-80. · 2.92 Impact Factor
• Article: 'Keratolytic' properties of benzoyl peroxide and retinoic acid resemble salicylic acid in man.

  J M Waller, F Dreher, S Behnam, C Ford, C Lee, T Tiet, G D Weinstein, H I Maibach
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  ABSTRACT: Retinoic acid (RA) and benzoyl peroxide (BP) were studied, comparing their keratolytic efficacy and water barrier disruption to that of salicylic acid (SA), a well-established keratolytic, under similar conditions. Six volunteers were included in this blinded study. Eleven randomized test sites were marked on the volar forearms, containing sites for untreated skin at time zero, unoccluded, occlusion, and vehicle controls for 3 and 6 h, and each of BP, RA, and SA solutions for 3 and 6 h. At each time point, occlusion at 5 of the test sites was removed, and chromameter measurements were performed over 30 min. Each site then underwent 25 stratum corneum (SC) tape strippings. At 1, 5, and 30 min after the last stripping at each site, TEWL measurements were performed. Quantitative protein analysis of the SC from the tapes was then performed. after 3 h, bp was significantly more effective in disrupting sc cohesion than sa and ra, indicating bp is a moderate keratolytic agent in addition to its antimicrobial properties. After 6 h, all three agents were similarly effective in keratolysis. Barrier disruption, as measured by TEWL, paralleled depth of SC removal. SA tended to exhibit the greatest keratolytic efficacy superficially, hence its clinical effectiveness in superficial conditions such as comedonal acne, whereas BP was more effective at deeper levels, complimenting its antimicrobial effects and enabling it to treat deeper, more inflammatory lesions. None of the agents significantly affected skin erythema. These techniques provide a robust and rapid assay for in vivo keratolytic demonstration.
  Skin pharmacology and physiology 02/2006; 19(5):283-9. · 2.92 Impact Factor
• Article: Elastic vesicles as topical/transdermal drug delivery systems.

  M J Choi, H I Maibach
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  ABSTRACT: Skin acts a major target as well as a principle barrier for topical/transdermal drug delivery. Despite the many advantages of this system, the major obstacle is the low diffusion rate of drugs across the stratum corneum. Several methods have been assessed to increase the permeation rate of drugs temporarily. One simple and convenient approach is application of drugs in formulation with elastic vesicles or skin enhancers. Elastic vesicles are classified with phospholipid (Transfersomes((R)) and ethosomes) and detergent-based types. Elastic vesicles were more efficient at delivering a low and high molecular weight drug to the skin in terms of quantity and depth. Their effectiveness strongly depends on their physicochemical properties: composition, duration and application volume, and entrapment efficiency and application methods. This review focuses on the effect of elastic liposomes for enhancing the drug penetration and defines the action mechanism of penetration into deeper skin.
  International journal of cosmetic science 09/2005; 27(4):211-21.
• Source

  Available from: iopeskincare.com

  Article: Glutathione as a depigmenting agent: an overview.

  C D Villarama, H I Maibach
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  ABSTRACT: Glutathione is an ubiquitous compound found in our bodies. Aside from its many ascribed biologic functions, it has also been implicated in skin lightening. We review in vitro and in vivo studies that show evidence of its involvement in the melanogenic pathway and shed light on the its anti-melanogenic effect. Proposed mechanisms of action include: (a) direct inactivation of the enzyme tyrosinase by binding with the copper-containing active site of the enzyme; (b) mediating the switch mechanism from eumelanin to phaeomelanin production; (c) quenching of free radicals and peroxides that contribute to tyrosinase activation and melanin formation; and d) modulation of depigmenting abilities of melanocytotoxic agents. These concepts supported by the various experimental evidence presented form basis for future research in the use of glutathione in the treatment of pigmentary disorders.
  International journal of cosmetic science 07/2005; 27(3):147-53.
• Article: Quantification of stratum corneum removal by adhesive tape stripping by total protein assay in 96-well microplates.

  F Dreher, B S Modjtahedi, S P Modjtahedi, H I Maibach
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  ABSTRACT: Examination of stratum corneum (SC) content with tape stripping and a colorimetric method is increasingly used. We examined the possible use of microplates in tandem with a colorimetric method to examine SC removed with tape stripping. As a corollary to this examination, the homogeneity of tape strips was examined. The commonly used Lowry assay was adapted for 96-well plates. Tapes were divided into four regions and sample disks of 5 mm diameter were taken from each and analyzed for SC mass using the adapted Lowry assay. Homogeneity of SC removal over different areas across a tape strip is limited. Quantification of SC by means of a 96-well microplate-based colorimetric method is feasible and shortens the time of analysis. However, when using D-Squame tape disks, SC removal on a limited area of the tape is not predictive for SC removal on the entire tape as removal is inhomogenous. Therefore, SC protein extraction should be performed on a large enough area, eventually on the entire tape when quantifying SC mass removed by tape stripping.
  Skin Research and Technology 06/2005; 11(2):97-101. · 1.71 Impact Factor
• Article: Cutaneous bioassay of salicylic acid as a keratolytic.

  S J Bashir, F Dreher, A L Chew, H Zhai, C Levin, R Stern, H I Maibach
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  ABSTRACT: Keratolytic efficacy of topical preparations containing salicylic acid was studied in humans utilizing adhesive tape stripping and quantifying SC removal by protein analysis. In combination with tape stripping, squamometry was used to evaluate the influence of salicylic acid on skin surface scaliness and desquamation. Furthermore, skin barrier perturbation and skin irritancy was recorded and related to the dermatopharmacological effect of the preparations. In contrast to squamometry, tape stripping combined with protein analysis was sensitive in detecting keratolytic effect of salicylic acid within hours of application. Importantly, whereas the pH of the preparations only minimally influenced efficacy, local dermatotoxicity was significantly increased at acidic pH. This indicates that the quest to increase the amount of free, non-dissociated SA is, in fact, counterproductive as the more acidic preparations resulted in skin irritation and barrier disruption.
  International Journal of Pharmaceutics 04/2005; 292(1-2):187-94. · 3.35 Impact Factor