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Biomedical subjects

E Berardesca

Publications and source records attributed to E Berardesca.

At least 19 recordsLinked to original sources

Effect of occlusive dressings on the stratum corneum water holding capacity.

Occlusion of the skin is used in clinical dermatology to promote wound healing and to increase the transcutaneous penetration of topically applied drugs. These effects are related to the degree of occlusion exerted and depend on the physicochemical nature of the dressing. We have evaluated the effects of four different materials on the skin barrier and the stratum corneum water holding capacity (WHC) using the Plastic Occlusion Stress Test (POST). The following materials were compared: hydrocolloid dressing, polyurethane film, polyethylene film, and a plastic chamber. These devices were applied on the volar forearm for 24 hours in 10 healthy volunteers (mean age 32 +/- 4 years). Upon their removal, the stratum corneum WHC, measured as skin surface water loss (SSWL), was recorded continuously for 25 minutes using an Evaporimeter. SSWL decay curves showed significant differences between the occlusive materials (analysis of variance, p less than 0.01). Higher SSWL values were recorded in sites occluded with the plastic chamber, whereas the polyurethane film resulted in poor occlusive capacity. Hydrocolloid dressing and polyethylene gave similar responses with higher WHC values compared to polyurethane (p less than 0.05). The relevance of these findings to clinical dermatology in terms of wound healing and drug absorption is discussed.

Adult

Blood transfusions in the therapy of a case of prolidase deficiency.

A case is reported of a 15-year-old boy with prolidase deficiency and marked urinary excretion of the iminodipeptide gly-pro. Prolidase activity of erythrocytes against substrate glycyl-proline was deficient, but after blood transfusions this was increased to 15.7% of donor activity and declined to 12% and 3.4% of normal activity after 8 and 45 days, respectively. Urinary iminodipeptide levels following transfusion remained unaltered.

Adolescent

Immune defects in families and patients with xeroderma pigmentosum and trichothiodystrophy.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disease characterized by photosensitivity, a high incidence of cancer in sun-exposed portions of the skin and a reduced capacity to repair the u.v.-induced DNA damage. One of the XP mutations (XP-D) has also been identified in patients affected by trichothiodystrophy (TTD), a rare autosomal recessive disease characterized by brittle hair, mental and physical retardation, peculiar face and ichthyosis. However, in these patients there is no evidence of increased skin tumour incidence. Since an impairment of cell-mediated immunity has been proposed as a co-factor in the cancer proneness of XP patients, we investigated the involvement of immune defect(s) in five XP patients, five TTD patients, their parents, and 24 TTD relatives. We evaluated the phenotype of circulating lymphocytes, natural killer (NK) cell lytic activity, target cell binding of NK cells at single cell level and the effect of interferons (IFN) alpha and beta on NK cell activity. The relative proportion of CD3+ and CD4+ circulating lymphocytes was reduced in XP but not in TTD patients. NK cell lytic activity was decreased in XP patients and their mothers, but their fathers showed normal lytic activity. NK activity varied among TTD families: four out of five patients and their relatives presented low NK cell activity, and one family was normal. In TTD family members, NK activity increased after incubation with IFN-alpha or IFN-beta, but never reached normal values. In contrast, in XP patients and their mothers, the defect was almost completely corrected after in vitro incubation with IFN-alpha or IFN-beta. Our study indicates impaired NK lytic activity in the majority of TTD and XP patients and that this defect is present also in members of their families. In addition, XP patients present a low number of circulating T cells. These multiple abnormalities, together with DNA repair defects, could be related to the increased cancer risk in XP patients.

Abnormalities, Multiple

Erythema induced by organic solvents: in vivo evaluation of oxygenized and deoxygenized haemoglobin by reflectance spectroscopy.

OBJECTIVE: (i) using a new non-invasive technique capable of evaluating quantitatively and qualitatively the haemoglobin content of the skin (ii) to evaluate delipidization induced by organic solvents. PATIENTS: 11 Caucasians treated for 1 min in a randomized manner on the volar forearm with a mixture of chloroform/methanol (2:1) (CM) and ether/acetone (1:1) (EA) to delipidize the skin. METHOD: erythema was evaluated by computerized remittance spectroscopy immediately after delipidization and hourly for 2 h. RESULTS: only CM application induced subjectively observed and objectively quantified erythema. Erythema was related to a significant increase in oxygenized haemoglobin content due to dilatation of arterioles in the subpapillary plexus (P less than 0.01). The increased blood flow induced a significant (P less than 0.01) reduction in de-oxygenized haemoglobin in venous vessels immediately after CM application. CONCLUSION: short contact with certain potent solvent mixtures causes erythema, possibly due to massive lipid extraction and damage of the skin barrier. Using computerized remittance spectroscopy the visible erythema was composed of an increase in oxygenized haemoglobin and a relative decrease in deoxygenized haemoglobin.

Dermatitis, Irritant

Objective prick test evaluation: non-invasive techniques.

Prick test reactions are evaluated and quantified, comparing visual assessment with two non-invasive techniques: remittance spectroscopy and pulsed ultrasound for erythema and skin thickness measurements. Different information is provided by the two methods. Remittance spectroscopy discriminates well between negative and positive reactions (+ or ++), while failing to differentiate stronger reactions, where edema is a prominent feature. The latter reactions are better evaluated by skin thickness measurements, which, on the contrary, are less sensitive in revealing small skin thickness increases in weak reactions.

Adult

In vivo transcutaneous penetration of nicotinates and sensitive skin.

Proclivity to develop irritant reactions and transcutaneous penetration of nicotinates has been investigated in 20 subjects of both sexes, divided into reactors and nonreactors on the basis of the responses to irritant stimuli. 1% sodium lauryl sulphate (patch application for 24 h) and 5% lactic acid in aqueous solutions were used to detect chemical and sensory (subjective) irritation. The vasodilatation induced was measured using a chromameter for 1 h after topical application of the chemical. The area-under-the-curve response and the peak response was used to assess the in vivo penetration of methyl nicotinate (10 mM in aqueous solution). Significant differences were found between reactors and non-reactors. Non-reactors showed a significantly decreased area-under-the-curve response and peak response to methyl nicotinate compared to reactors. Nicotinate-induced vasodilatation has been used as a model to study transcutaneous penetration of chemicals; the correlation between increased penetration of nicotinates and skin hyperreactivity to irritant substances may suggest an increased transcutaneous penetration of water-soluble chemicals in individuals with sensitive skin.

Administration, Cutaneous

Skin bioengineering in the noninvasive assessment of cutaneous aging.

Cutaneous changes induced by aging can be quantified and monitored noninvasively by means of bioengineering tools. Skin elasticity, hydration, skin blood flow and skin surface pattern show age-related changes reflecting the damage of cutaneous structures involved. Impairment and degeneration of elastic and collagen networks are responsible for the progressive decrease in skin elasticity recorded during aging. Reduction in blood flow and water supply with probably defective stratum corneum binding result in reduced stratum corneum water content and transepidermal water loss. Morphological changes such as increased skin roughness, pigmentation and alteration of skin surface pattern appearing from the age of 30 years onwards may be investigated at a subclinical level allowing the detection of early signs of aging.

Biomechanical Phenomena

In vivo biophysical characterization of skin physiological differences in races.

The role of race in modulating skin responses has been investigated. Several parameters (skin thickness, transepidermal water loss, water content of the stratum corneum and skin biomechanics) have been measured using noninvasive tools in whites, Hispanics and blacks to assess whether the melanin content could induce changes in skin biophysical properties. Marked differences between races appear in stratum corneum water content and in skin extensibility, recovery and elastic modulus. Measurements done in different sun-exposed sites highlight the effects of solar irradiation on the skin and the role of melanin in preventing skin damage. The study shows that racial differences in skin physiology exist and are mainly related to the protective role of melanin present in races with darker skin. Moreover, differences in skin hydration are not fully explained according to the site and presence of hair.

Black People

Sensitive and ethnic skin. A need for special skin-care agents?

Sensitive skin is a complex problem with genetic, individual, environmental, occupational, and ethnic implications. Further work is needed to rank irritants and irritant reactions to classify sensitive skin on the basis of standard models. The development of topical products designed for sensitive and ethnic skin may be advisable to optimize drug activity with minimal side effects. The availability of transdermal systems for drug delivery highlights the problem. Occlusive transdermal patch systems for delivery of clonidine show sensitization rates of 34% in white women, 18% in white men, 14% in black women, and 8% in black men. Besides ethnic differences in transcutaneous penetration, individual and ethnic skin sensitivity may play an important role in determining both patient compliance and therapeutic efficacy of drugs and cosmetics; furthermore, a drug formulation considering skin physiology may prevent unwanted local and general adverse effects.

Dermatitis, Contact

In vivo tretinoin-induced changes in skin mechanical properties.

Topical tretinoin has been reported as having anti-aging effects on photodamaged skin. The purpose of this study was to evaluate tretinoin-induced changes in the mechanical properties of the skin of 18 patients (aged 39 +/- 8 years) after 4 months of treatment with topical 0.05% tretinoin on one forearm and a placebo base cream on the other. The biomechanical skin parameters investigated were elasticity, extensibility and hysteresis and data were normalized for skin thickness. A slight but non-significant increase of skin elasticity was detected in the tretinoin-treated sites using low-stressing forces (1.2 X 10(4) Nm-2) and at higher loads (3.8 X 10(4) Nm-2), the increase in skin elasticity was significant (P less than 0.01). This improved skin elasticity was dependent on the increased collagen resulting from topical tretinoin and the replacement of elastotic material. However, topical tretinoin treatment did not improve the responses mediated by elastic fibres.

Adult

Monitoring the water-holding capacity in visually non-irritated skin by plastic occlusion stress test (POST).

Skin-surface water loss (SSWL) and transepidermal water loss (TEWL) were studied after a plastic occlusion stress test (POST) in visually non-damaged skin treated with 7% sodium lauryl sulphate for 3 days (open application). After removal of the 24-h plastic occlusion, SSWL and TEWL were recorded continuously for 25 min. SSWL decay curves show significant differences between control and treated areas. The total amount of water trapped within the stratum corneum and released after 1 min is significantly reduced (P less than 0.01) in the treated site. Higher TEWL (P less than 0.02) in visually non-irritated skin is noticeable in the terminal part of the curve reflecting the damage of the water barrier in irritated skin. The data suggest that clinically normal skin exposed to subliminal irritant stimuli is less capable of storing water within the stratum corneum resulting in decreased hydration. The POST appears to be a simple and reliable tool to investigate non-visible but biologically relevant changes in stratum corneum function.

Adult

Ranking of surfactant skin irritancy in vivo in man using the plastic occlusion stress test (POST).

Irritant effects and disturbance of water-holding capacity induced by surfactants were investigated using the plastic occlusion stress test (POST) technique. 4 surfactants (sodium lauryl sulphate (SLS), sorbitan monolaurate, cocoamidopropyl betaine and benzalkonium chloride) and an amphoteric/nonionic (A/N) mix were investigated. 1 x daily for 3 days, test surfactants were applied to marked sites (open) on the volar forearm. After 24 h occlusion with a plastic chamber on the 4th day, skin surface water loss (SSWL) (g/m2h) was recorded continuously for 25 min with an evaporimeter. The differences between the surfactants were statistically significant (Friedman's test p less than 0.01). SLS and the A/N mix revealed significant differences compared to the other compounds (p less than 0.05), both in decay constants and in values recorded at the beginning and at the end of the decay curve. The study suggests a mechanism for the high irritant potential of sodium lauryl sulphate compared to other surfactants: sorbitan monolaurate and benzalkonium chloride seem to influence (at the concentrations tested) to a lesser extent the water-holding capacity of the stratum corneum. The clinical and biological relevance of these observations requires long-term clinical correlations with final product use tests.

Adult

Racial differences in pharmacodynamic response to nicotinates in vivo in human skin: black and white.

This study evaluated the vasodilation induced in young whites and blacks by topical application of two nicotinates, methylnicotinate (MN) and hexylnicotinate (HN) at the same concentration and in the same vehicle. To assess the influence of skin surface lipids and water content of the stratum corneum on the penetration of the substances, the drugs were applied on the back, on untreated skin and pre-occluded and pre-delipidized sites. Skin blood flow was monitored with laser Doppler velocimetry. The initial response recorded at 15 min (IR), the peak response (PR) and the area under the curve (AUC) were used to characterize the pharmacodynamic response. Statistically significant racial differences in the penetration of nicotinates were detected for the area under the response curve in the untreated and occluded sites, for the initial response and peak response in the pre-occluded site. Occlusion increased (even though not significantly) penetration, except for blacks in the methylnicotinate experiment. Delipidization elicited significantly lower responses for the IR and PR in the MN study, rendering the penetration similar in the two groups. No major differences were recorded between the two nicotinates. The effect of delipidization was most noticeable in blacks in the MN study. We suggest that there are racial (blacks vs. whites) differences in percutaneous penetration of nicotinates, with decreased levels in black skin recorded in all sites investigated.

Administration, Topical

In vivo hydration and water-retention capacity of stratum corneum in clinically uninvolved skin in atopic and psoriatic patients.

Hydration and the water-retention capacity of stratum corneum have been investigated in uninvolved psoriatic and atopic skin and compared with that of healthy controls. Thirty-three subjects of either sex and matched for age entered the study. The subjects were free from all signs of skin disease and skin dryness. Hydration was evaluated by means of transepidermal water loss and skin capacitance measurements. Water-retention capacity was investigated using the plastic occlusion stress test. Atopic skin differed significantly from uninvolved psoriatic and control skin which had a reduced water content and an increased transepidermal water loss. Furthermore, the skin surface water loss profile representing the stratum corneum water-retention capacity was significantly lower in normal atopic skin. The data suggest that clinically normal skin may be functionally abnormal, resulting in a defective barrier that could lead to higher risk of irritant or contact dermatitis.

Adult

Clonal chromosome rearrangements in a fibroblast strain from a patient affected by xeroderma pigmentosum (complementation group C).

We report the results of DNA repair studies and cytogenetic investigations in a patient presenting acute phothosensitivity and cancerous skin lesions. In lymphocytes and fibroblasts a reduced level of unscheduled DNA synthesis after UV irradiation was found and the presence of xeroderma pigmentosum, complementation group C, mutation was demonstrated by complementation analysis. In lymphocyte and fibroblast cultures the frequency of spontaneous chromosome gaps and breaks was normal, whereas the frequency of chromosome rearrangements was higher than expected. In fibroblasts from the 4th to the 18th passage of the culture, 4 reciprocal translocations with a clonal distribution were identified. The rearranged chromosomes were Nos. 2, 13, 14 and 15, Nos. 2 and 13 being both involved in 3 different translocations with breakpoints at 2q21, 2q31, 2p23 and 13q31, 13q12 or 3. The biological significance of this finding is discussed in view of a possible correlation with the DNA repair defect and a possible relevance in tumor development of specific chromosome rearrangements.

Adult

Chromosome instability in lymphocytes from a patient with Werner's syndrome is not associated with DNA repair defects.

Different cellular parameters used to detect genetic instability were analyzed in lymphocytes from a patient affected by Werner's syndrome (WS). Cytogenetic studies indicated the presence of structural and numerical chromosomal abnormalities and the occurrence of variegated translocation mosaicism. The baseline mutation frequency was similar to that observed in normal donor samples. DNA repair investigations showing a normal capability to perform UV-induced DNA repair synthesis and a normal sensitivity to various mutagens (UVC light, mono- and bi-functional alkylating agents) indicate that different DNA repair mechanisms act normally in WS. In this feature, WS appears to differ from the other genetically determined syndromes in which chromosomal instability is associated with a marked hypersensitivity to specific DNA-damaging agents.

Cells, Cultured

Tendency to irritation: sensitive skin.

The plausibility of the concept of "sensitive skin" evokes discussion and often amusement, because of the variance of the number of opinions compared with the amount of data, at least until recently. This report presents recent biologically oriented data that suggest that sensitive skin is a reality and is assessable with the use of contemporary methods.

Body Water

Cutaneous reactive hyperaemia: racial differences induced by corticoid application.

The postocclusive hyperaemic reaction before and after a single 1 h application of a potent corticoid (clobetasol 0.05% in ointment) was recorded by means of laser Doppler velocimetry in order to elucidate different racial responses in skin vasoconstriction. Fourteen young male subjects entered the study (eight Caucasians, six Blacks). Reactive hyperaemia was recorded after 4 min of occlusion of the forearm blood flow. The following parameters of the hyperaemic reaction were investigated: area under the curve response, peak response, rise of blood flow slope to peak and decay of blood flow slope after peak. Different responses were recorded in the Black subjects after the vasoconstrictive stimulus compared to the Caucasians, namely: decreased area under the curve response (P less than 0.04); decreased peak response (P less than 0.01); decreased decay slope after peak blood flow (P less than 0.04). These data are consistent with a different reactivity of blood vessels in black skin and possibly not related to the transcutaneous penetration of the chemical compound.

Adult