Howard Maibach | UCSF - Academia.edu (original) (raw)
Papers by Howard Maibach
Journal of Dermatological Science, 1998
Biochemical Pharmacology, 1996
To diminish oxidative injury, topically applied antioxidants must reach susceptible cells. alpha-... more To diminish oxidative injury, topically applied antioxidants must reach susceptible cells. alpha-Lipoic acid is a potent thiol antioxidant that might be useful for skin protection; therefore, its skin penetration kinetics were assessed. The cutaneous and subcutaneous distributions of [7,8-14C]rac-alpha-lipoic acid were studied in anesthetized hairless mice after application of a 5% solution in propylene glycol for 0.5 to 4 hr. The mice were killed; then the skin was washed, and the stratum corneum was removed by 10 cellophane tape strippings. A punch biopsy of the frozen, stripped skin was sectioned, and amounts of [14C]-alpha-lipoic acid were determined in strippings and slices of epidermis (4 x 5 microns), dermis, and subcutaneous fat (10 x 10 microns, 20 x 20 microns). The rate of [14C]-alpha-lipoic acid absorption into skin was constant by 30 min (0.10 +/- 0.01 nmol/cm2/min); maximum skin concentrations were reached by 2 hr. The [14C]-alpha-lipoic acid penetration kinetics into the first layer of the stratum corneum predicted its penetration through the stratum corneum and subsequent percutaneous absorption (r2 = 0.96, P < 0.02). Cutaneous absorption of unlabeled alpha-lipoic acid and its reduction to the more potent antioxidant form, dihydrolipoic acid, were also demonstrated, using HPLC analysis with electrochemical detection. In conclusion, alpha-lipoic acid topically applied to skin penetrated readily, and was reduced to dihydrolipoic acid. Thus, alpha-lipoic acid could potentiate skin antioxidant protection.
Current problems in dermatology, Apr 20, 2015
The aim ofthe present study was to assess age-related regional variations in skin function, by me... more The aim ofthe present study was to assess age-related regional variations in skin function, by measuring the cutaneous microvascular response to histamine. Histamine was topically applied to the back and forearm of young and aged volunteers, and the response was quantified utilizing laser Doppler flowmetry. Each group comprised of 14 volunteers. The cutaneous vascular response to histamine was significantly greater on the back than on the forearm ofyoung healthy volunteers, whereas in aged ones the response over these two sites did not significantly differ. These observations indicate anatomical or functional differences between old and young skin as relates to regional variations. They may underlie some ofthe differences in the manifestations ofdisease processes in various age groups.
American Journal of Contact Dermatitis, 1995
Exogenous Dermatology, 2002
Background: Histamine, a major mediator in endogenous and exogenous skin disorders, has been exte... more Background: Histamine, a major mediator in endogenous and exogenous skin disorders, has been extensively investigated. Many experiments concern external provocation, yet the sequence of events as well as the influence of timing of the provocating factors require clarification. Objective: To document cutaneous reactivity to histamine rechallenge at different time points, as well as the response of irritated skin (irritant dermatitis) to histamine. Methods: Histamine was intradermally administered on the upper back of 20 volunteers at different time points to 3 sites and following SLS-induced irritant dermatitis to another site. The cutaneous vascular response was measured by laser Doppler flowmetry. Results: The response to a second prick when the first prick response had decayed to half its peak was significantly higher than all the other responses that resulted from a second prick (p < 0.01). The other responses did not significantly differ from each other or from the first pric...
International Journal of Dermatology, 2007
Within the last decade, there has been a considerable increase in the application of noninvasive ... more Within the last decade, there has been a considerable increase in the application of noninvasive optical techniques to study the cutaneous microcirculation of man. These investigations have not attempted to quantify skin blood flow in an absolute sense; instead, the focus of research has been to monitor perfusion levels' and to observe how basal flow values are perturbed by various types and degrees of stress. Thus, changes in skin blood flow have, for example, been used (1) to assess the percutaneous absorption of vasoactive molecules2-'"; (2) as a pharmacodynamic indication of systemically induced vasodilation"; and (3) to follow objectively the local physiologic consequences of several types of irritati~n.'~-'' Clinically, the methodology has been applied to the assessment of wound and burn healingt'8,'9 viability of skin flaps after plastic surgery,20.21 the severity of peripheral vascular disease (eg, Raynaud's p h e n o m e n ~ n ~ ~ ~ ~ ) and skin perfusion in pregnancy." The experimental work discussed in this article has been performed using two techniques: laser Doppler velocimetry (or flowmetry)28 and photoplethysmography.2' These procedures are noninvasive and collect information about skin blood flow via small probes attached to the skin surface with double-sided adhesive tape, Hence, the measurements themselves in no way perturb the microcirculation (as is often the case, for example, with the xenon washout technique that has frequently been used for character-
SPIE Proceedings, 1996
To study inherent differences in skin function related to regional variation, we tested the hypot... more To study inherent differences in skin function related to regional variation, we tested the hypothesis that different reactivities of small blood vessels via their direct and indirect activation by histamine play an important role in the observed regional variation of processes. Histamine was administered to three cutaneous regions in 20 volunteers, and the induced response was quantified utilizing spectrophotometry and
Skin Research and Technology, 2011
Journal of the American Academy of Dermatology, 1985
Preliminary experiments have been performed to determine whether there are age and racial differe... more Preliminary experiments have been performed to determine whether there are age and racial differences in the response of human skin to the topically applied vasodilator methyl nicotinate. With the use of a constant stimulus (a 15-second exposure to a 100 mM aqueous solution of drug), the subsequent time-course of the vasodilatation response was followed noninvasively and objectively with the optical technics of laser Doppler velocimetry (LDV) and photoplethysmography (PPG). Three groups of subjects were considered: young white subjects (20 to 30 years of age), elderly white subjects (63 to 80 years old), and young black subjects (20 to 30 years old). Analysis of the results shows that the time to peak response, the area under the response-time curve, and the time for the response to decay to 75% of its maximum value are statistically indistinguishable for all three groups at the p = 0.05 level of significance. Only the magnitude of the peak response revealed some significant differences between the cohorts (young greater than black, determined by PPG; young greater than old, determined by LDV). The data suggest, therefore, a remarkable similarity in response across a wide range of skin types. The origin of this consistency may, however, be complex and is not revealed by these experiments.
Journal of Pharmacokinetics and Pharmacodynamics, 2006
Laser Doppler flowmetry (LDF) may be used to quantify erythema response as a result of an increas... more Laser Doppler flowmetry (LDF) may be used to quantify erythema response as a result of an increased cutaneous microcirculation induced by methyl nicotinate (MN). Bioequivalence of a test and a standard preparation (vehicles: light mineral oil and medium chain triglycerides, respectively) was confirmed according to the pilot study of the FDA Guidance for Industry &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Topical dermatologic corticosteroids: In Vivo bioequivalence&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; applying the staggered application and synchronized removal method for one defined concentration. Furthermore, the influence of penetration enhancers (5% w/w Dimethylsulfoxide (DMSO) and 10% w/w diethylene glycol monoethyl ether) on MN penetration was investigated. It was shown that DMSO and diethylene glycol monoethyl ether altered cutaneous microcirculation and thus MN penetration in comparison to the standard formulation. However, true penetration enhancement could only be proved with diethylene glycol monoethyl ether resulting from an improved drug solubility in the skin which was confirmed by attenuated total reflectance fourier transform infrared spectroscopy (ATR-FTIR). Increased MN penetration by DMSO was only caused by thermodynamic effects, i.e. a decreased drug solubility in the vehicle.
Journal of Pharmaceutical Sciences, 1983
Journal of Investigative Dermatology, 1983
Journal of Investigative Dermatology, 1983
Dermatology, 1990
This report neologizes a new syndrome name, idiopathic recalcitrant facial flushing syndrome, to ... more This report neologizes a new syndrome name, idiopathic recalcitrant facial flushing syndrome, to describe all cases of persistent facial flushing with unknown etiology. Three cases of recalcitrant flushing are described. Therapy with a variety of modalities, monitored objectively with laser Doppler velocimetry, proved unsuccessful. Some investigational and management aspects of difficult cases of idiopathic flushing are reviewed.
Cutaneous and Ocular Toxicology, 2012
Nail Apparatus Melanoma (NAM) is rare, particularly in Caucasians. Understanding its pathogenesis... more Nail Apparatus Melanoma (NAM) is rare, particularly in Caucasians. Understanding its pathogenesis and collecting epidemiologic data may be difficult due to its location and the exiguity of the case series of this cancer. Cutaneous melanoma has been thought related to UV radiation, and NAM is considered an acral variant of melanoma, even if the nail presents a specific anatomy. Little is reported about pathogenesis, except reports suggesting traumatic injuries as a causal factor. UV exposure is debated in nail melanoma because of its structure. The nail is, in fact, a unique structure with sun-exposed and non exposed melanocytes. NAM arises from the nail melanocytes, located in the nail matrix, which is the germinative part of the nail and composed of a proximal and distal portion. The proximal nail matrix lays under the proximal nail fold that covers it and is non-sun exposed, while the distant nail matrix, clinically visible as the lunula, is sun-exposed, though lying underneath the nail plate. According to these anatomical data, NAM is a distinct melanoma type, and studies need to classify it as acral melanoma or as a particular type of melanoma with its own pathogenesis and prognostic criteria. This study investigates potential risk factors of NAM, emphasizing (i) trauma and (ii) UV exposure among our NAM patients.
Journal of Toxicology: Cutaneous and Ocular Toxicology, 2004
ABSTRACT One promising class of antioxidant compounds is polyphenols, contained abundantly in pin... more ABSTRACT One promising class of antioxidant compounds is polyphenols, contained abundantly in pine bark extract (Pycnogenol®—pine bark extract). This medicinal extract is utilized for its anti‐inflammatory properties. Its pharmacological action in skin depends on the kinetics of its absorption. In this study the dermal bioavailability of pine bark extract was investigated. Viable human skin, adapted on continuously perfused Franz cells, was applied with 5% (w/v) pine bark solution. Samples were taken at 0.5, 1, 2, 4, 6, 8, 10, and 12‐hour intervals and analyzed for detection of pine bark extract constituents by high performance liquid chromatography (HPLC) (reversed phase column, isocratic conditions) coupled with an electrochemical detector (EC). Several constituents of pine bark extract such as gallic acid, protocatechuic acid, catechin, p‐hydroxybenzoic acid, vanillin, and one unidentified constituent were detected. These findings indicate that pine bark extract is readily absorbed by human skin and can be used for topical application.
Contact Dermatitis, 1999
Other such reactions reported are Stevens-Johnson syndrome (4) and a fixed drug eruption (5). The... more Other such reactions reported are Stevens-Johnson syndrome (4) and a fixed drug eruption (5). The allergies to neomycin, nystatin and clioquinol were probably related to the use of these agents in topical treatments for intertrigo, though no records were available from the patient’s general practitioner to substantiate this. Our patient’s systemic reaction is difficult to characterize with certainty. The results of patch testing suggest a systemic Type IV reaction, but the flare within 24 h, with gastrointestinal upset and arthralgia, suggests an immune complex component (Type III hypersensitivity reaction).
Clinics in Dermatology, 2012
British Journal of Dermatology, 1987
Journal of Dermatological Science, 1998
Biochemical Pharmacology, 1996
To diminish oxidative injury, topically applied antioxidants must reach susceptible cells. alpha-... more To diminish oxidative injury, topically applied antioxidants must reach susceptible cells. alpha-Lipoic acid is a potent thiol antioxidant that might be useful for skin protection; therefore, its skin penetration kinetics were assessed. The cutaneous and subcutaneous distributions of [7,8-14C]rac-alpha-lipoic acid were studied in anesthetized hairless mice after application of a 5% solution in propylene glycol for 0.5 to 4 hr. The mice were killed; then the skin was washed, and the stratum corneum was removed by 10 cellophane tape strippings. A punch biopsy of the frozen, stripped skin was sectioned, and amounts of [14C]-alpha-lipoic acid were determined in strippings and slices of epidermis (4 x 5 microns), dermis, and subcutaneous fat (10 x 10 microns, 20 x 20 microns). The rate of [14C]-alpha-lipoic acid absorption into skin was constant by 30 min (0.10 +/- 0.01 nmol/cm2/min); maximum skin concentrations were reached by 2 hr. The [14C]-alpha-lipoic acid penetration kinetics into the first layer of the stratum corneum predicted its penetration through the stratum corneum and subsequent percutaneous absorption (r2 = 0.96, P &amp;lt; 0.02). Cutaneous absorption of unlabeled alpha-lipoic acid and its reduction to the more potent antioxidant form, dihydrolipoic acid, were also demonstrated, using HPLC analysis with electrochemical detection. In conclusion, alpha-lipoic acid topically applied to skin penetrated readily, and was reduced to dihydrolipoic acid. Thus, alpha-lipoic acid could potentiate skin antioxidant protection.
Current problems in dermatology, Apr 20, 2015
The aim ofthe present study was to assess age-related regional variations in skin function, by me... more The aim ofthe present study was to assess age-related regional variations in skin function, by measuring the cutaneous microvascular response to histamine. Histamine was topically applied to the back and forearm of young and aged volunteers, and the response was quantified utilizing laser Doppler flowmetry. Each group comprised of 14 volunteers. The cutaneous vascular response to histamine was significantly greater on the back than on the forearm ofyoung healthy volunteers, whereas in aged ones the response over these two sites did not significantly differ. These observations indicate anatomical or functional differences between old and young skin as relates to regional variations. They may underlie some ofthe differences in the manifestations ofdisease processes in various age groups.
American Journal of Contact Dermatitis, 1995
Exogenous Dermatology, 2002
Background: Histamine, a major mediator in endogenous and exogenous skin disorders, has been exte... more Background: Histamine, a major mediator in endogenous and exogenous skin disorders, has been extensively investigated. Many experiments concern external provocation, yet the sequence of events as well as the influence of timing of the provocating factors require clarification. Objective: To document cutaneous reactivity to histamine rechallenge at different time points, as well as the response of irritated skin (irritant dermatitis) to histamine. Methods: Histamine was intradermally administered on the upper back of 20 volunteers at different time points to 3 sites and following SLS-induced irritant dermatitis to another site. The cutaneous vascular response was measured by laser Doppler flowmetry. Results: The response to a second prick when the first prick response had decayed to half its peak was significantly higher than all the other responses that resulted from a second prick (p < 0.01). The other responses did not significantly differ from each other or from the first pric...
International Journal of Dermatology, 2007
Within the last decade, there has been a considerable increase in the application of noninvasive ... more Within the last decade, there has been a considerable increase in the application of noninvasive optical techniques to study the cutaneous microcirculation of man. These investigations have not attempted to quantify skin blood flow in an absolute sense; instead, the focus of research has been to monitor perfusion levels' and to observe how basal flow values are perturbed by various types and degrees of stress. Thus, changes in skin blood flow have, for example, been used (1) to assess the percutaneous absorption of vasoactive molecules2-'"; (2) as a pharmacodynamic indication of systemically induced vasodilation"; and (3) to follow objectively the local physiologic consequences of several types of irritati~n.'~-'' Clinically, the methodology has been applied to the assessment of wound and burn healingt'8,'9 viability of skin flaps after plastic surgery,20.21 the severity of peripheral vascular disease (eg, Raynaud's p h e n o m e n ~ n ~ ~ ~ ~ ) and skin perfusion in pregnancy." The experimental work discussed in this article has been performed using two techniques: laser Doppler velocimetry (or flowmetry)28 and photoplethysmography.2' These procedures are noninvasive and collect information about skin blood flow via small probes attached to the skin surface with double-sided adhesive tape, Hence, the measurements themselves in no way perturb the microcirculation (as is often the case, for example, with the xenon washout technique that has frequently been used for character-
SPIE Proceedings, 1996
To study inherent differences in skin function related to regional variation, we tested the hypot... more To study inherent differences in skin function related to regional variation, we tested the hypothesis that different reactivities of small blood vessels via their direct and indirect activation by histamine play an important role in the observed regional variation of processes. Histamine was administered to three cutaneous regions in 20 volunteers, and the induced response was quantified utilizing spectrophotometry and
Skin Research and Technology, 2011
Journal of the American Academy of Dermatology, 1985
Preliminary experiments have been performed to determine whether there are age and racial differe... more Preliminary experiments have been performed to determine whether there are age and racial differences in the response of human skin to the topically applied vasodilator methyl nicotinate. With the use of a constant stimulus (a 15-second exposure to a 100 mM aqueous solution of drug), the subsequent time-course of the vasodilatation response was followed noninvasively and objectively with the optical technics of laser Doppler velocimetry (LDV) and photoplethysmography (PPG). Three groups of subjects were considered: young white subjects (20 to 30 years of age), elderly white subjects (63 to 80 years old), and young black subjects (20 to 30 years old). Analysis of the results shows that the time to peak response, the area under the response-time curve, and the time for the response to decay to 75% of its maximum value are statistically indistinguishable for all three groups at the p = 0.05 level of significance. Only the magnitude of the peak response revealed some significant differences between the cohorts (young greater than black, determined by PPG; young greater than old, determined by LDV). The data suggest, therefore, a remarkable similarity in response across a wide range of skin types. The origin of this consistency may, however, be complex and is not revealed by these experiments.
Journal of Pharmacokinetics and Pharmacodynamics, 2006
Laser Doppler flowmetry (LDF) may be used to quantify erythema response as a result of an increas... more Laser Doppler flowmetry (LDF) may be used to quantify erythema response as a result of an increased cutaneous microcirculation induced by methyl nicotinate (MN). Bioequivalence of a test and a standard preparation (vehicles: light mineral oil and medium chain triglycerides, respectively) was confirmed according to the pilot study of the FDA Guidance for Industry &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Topical dermatologic corticosteroids: In Vivo bioequivalence&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; applying the staggered application and synchronized removal method for one defined concentration. Furthermore, the influence of penetration enhancers (5% w/w Dimethylsulfoxide (DMSO) and 10% w/w diethylene glycol monoethyl ether) on MN penetration was investigated. It was shown that DMSO and diethylene glycol monoethyl ether altered cutaneous microcirculation and thus MN penetration in comparison to the standard formulation. However, true penetration enhancement could only be proved with diethylene glycol monoethyl ether resulting from an improved drug solubility in the skin which was confirmed by attenuated total reflectance fourier transform infrared spectroscopy (ATR-FTIR). Increased MN penetration by DMSO was only caused by thermodynamic effects, i.e. a decreased drug solubility in the vehicle.
Journal of Pharmaceutical Sciences, 1983
Journal of Investigative Dermatology, 1983
Journal of Investigative Dermatology, 1983
Dermatology, 1990
This report neologizes a new syndrome name, idiopathic recalcitrant facial flushing syndrome, to ... more This report neologizes a new syndrome name, idiopathic recalcitrant facial flushing syndrome, to describe all cases of persistent facial flushing with unknown etiology. Three cases of recalcitrant flushing are described. Therapy with a variety of modalities, monitored objectively with laser Doppler velocimetry, proved unsuccessful. Some investigational and management aspects of difficult cases of idiopathic flushing are reviewed.
Cutaneous and Ocular Toxicology, 2012
Nail Apparatus Melanoma (NAM) is rare, particularly in Caucasians. Understanding its pathogenesis... more Nail Apparatus Melanoma (NAM) is rare, particularly in Caucasians. Understanding its pathogenesis and collecting epidemiologic data may be difficult due to its location and the exiguity of the case series of this cancer. Cutaneous melanoma has been thought related to UV radiation, and NAM is considered an acral variant of melanoma, even if the nail presents a specific anatomy. Little is reported about pathogenesis, except reports suggesting traumatic injuries as a causal factor. UV exposure is debated in nail melanoma because of its structure. The nail is, in fact, a unique structure with sun-exposed and non exposed melanocytes. NAM arises from the nail melanocytes, located in the nail matrix, which is the germinative part of the nail and composed of a proximal and distal portion. The proximal nail matrix lays under the proximal nail fold that covers it and is non-sun exposed, while the distant nail matrix, clinically visible as the lunula, is sun-exposed, though lying underneath the nail plate. According to these anatomical data, NAM is a distinct melanoma type, and studies need to classify it as acral melanoma or as a particular type of melanoma with its own pathogenesis and prognostic criteria. This study investigates potential risk factors of NAM, emphasizing (i) trauma and (ii) UV exposure among our NAM patients.
Journal of Toxicology: Cutaneous and Ocular Toxicology, 2004
ABSTRACT One promising class of antioxidant compounds is polyphenols, contained abundantly in pin... more ABSTRACT One promising class of antioxidant compounds is polyphenols, contained abundantly in pine bark extract (Pycnogenol®—pine bark extract). This medicinal extract is utilized for its anti‐inflammatory properties. Its pharmacological action in skin depends on the kinetics of its absorption. In this study the dermal bioavailability of pine bark extract was investigated. Viable human skin, adapted on continuously perfused Franz cells, was applied with 5% (w/v) pine bark solution. Samples were taken at 0.5, 1, 2, 4, 6, 8, 10, and 12‐hour intervals and analyzed for detection of pine bark extract constituents by high performance liquid chromatography (HPLC) (reversed phase column, isocratic conditions) coupled with an electrochemical detector (EC). Several constituents of pine bark extract such as gallic acid, protocatechuic acid, catechin, p‐hydroxybenzoic acid, vanillin, and one unidentified constituent were detected. These findings indicate that pine bark extract is readily absorbed by human skin and can be used for topical application.
Contact Dermatitis, 1999
Other such reactions reported are Stevens-Johnson syndrome (4) and a fixed drug eruption (5). The... more Other such reactions reported are Stevens-Johnson syndrome (4) and a fixed drug eruption (5). The allergies to neomycin, nystatin and clioquinol were probably related to the use of these agents in topical treatments for intertrigo, though no records were available from the patient’s general practitioner to substantiate this. Our patient’s systemic reaction is difficult to characterize with certainty. The results of patch testing suggest a systemic Type IV reaction, but the flare within 24 h, with gastrointestinal upset and arthralgia, suggests an immune complex component (Type III hypersensitivity reaction).
Clinics in Dermatology, 2012
British Journal of Dermatology, 1987