Pig Ear Skin ex Vivo as a Model for in Vivo Dermatopharmacokinetic Studies in Man

Objective The objective was to investigate pig ear skin as a surrogate for human skin in the assessment of topical drug bioavailability by sequential tape-stripping of the stratum corneum (SC). The potential benefits of ex vivo investigations are manifold: ethical approval is not required, multiple replicate experiments are more easily performed, and toxic compounds can be evaluated.Materials and Methods Ex vivo experiments on isolated pig ears were compared with in vivo studies in human volunteers. Four formulations, comprising the model drug, ibuprofen, in different propylene glycol (PG)-water mixtures (25:75, 50:50, 75:25 and 100:0), were compared.Results Derived dermatopharmacokinetic parameters characterizing the diffusion and partitioning of the drug in the SC ex vivo were consistent with those in vivo following a 30-minute application period. Further, the non-steady-state ex vivo results could be used to predict the in vivo concentration profile of the drug across the SC when a formulation was administered for 3 h (i.e., close to steady-state).Conclusions Taken together, the results obtained suggest that pig ear skin ex vivo has promise as a tool for topical formulation evaluation and optimization.     

A Novel in Vitro Percutaneous Penetration Model: Evaluation of Barrier Properties with P-Aminobenzoic Acid and Two of Its Derivatives

Purpose The objective of this study was to evaluate the utility of a stratum corneum substitute (SCS) as a novel in vitro percutaneous penetration model. The SCS consists of synthetic stratum corneum (SC) lipids (cholesterol, free fatty acids, and specific ceramides) applied onto a porous substrate. The composition, organization, and orientation of lipids in the SCS bear high resemblance to that of the intercellular barrier lipids in SC. Methods The barrier integrity of the SCS was evaluated by means of passive diffusion studies, using three model compounds with different lipophilicities. The effects of lipid layer thickness, permeant lipophilicity, and altered lipid composition on the barrier properties were investigated, using isolated human SC as a control sample. Results For all three model compounds, the permeability characteristics of the SCS with a 12-μm-thick lipid layer closely resemble those of human SC. Modification of the lipid composition, generating an SCS that lacks the characteristic long periodicity phase as present in SC, was accompanied by a 2-fold increased permeability. Conclusions The SCS offers an attractive tool to predict solute permeation through human skin. Moreover, as its lipid composition can be modified, they may also serve as a suitable screening model for diseased skin.     

Haematoxylin stainable epidermal protein of the newborn rat. II. Further characterization by different purification steps

A haematoxylin stainable protein (HSP) extracted from the EDTA-separated epidermis of 3-day-old rats was purified through preparative isoelectric focusing followed by fast protein liquid chromatography (FPLC) using a Superose 12 column and a Mono-Q anion exchange column. The purified protein was a single protein in SDS-PAGE; it had a molecular weight of 14,500 daltons and an isoelectric point of pH 4.7. The amino acid composition included 14% glutamic acid, 13.7% lysine, 12% aspartic acid, 10% glycine, 8% valine and 0.3% ornithine, but only 1.2% histidine. An antibody elicited by the purified antigen also localized in the cell membrane region of the stratum corneum cells of the flank skin, but not in the keratohyalin granules, in indirect immunofluorescent studies.     

多聚酶链反应检测尿中结核杆菌的临床意义

应用多聚酶链反应（ＰＣＲ）对８６例患者（１０例经病理诊断为肾结核，６９例可疑肾结核，７例单纯附睾结核）和３０例健康对照者进行连续２日晨尿结核菌检测。１０例肾结核患者检出均阳性；可疑肾结核者第一次检出９例，第二次为６例；７例附睾结核者两次无一阳性；对照组有１例二次检查均为阳性。认为ＰＣＲ对尿中结核杆菌检出率高、准确、快速，值得在临床上推广应用。     

Sensitive skin and stratunm corneum reactivity to household cleaning products

Products intended for individuals with sensitive skin are being increasingly developed by formulators of household cleaning products. However, there is currently no consensus about the definition and recognition of the biological basis of sensitive skin. We sought to determine the relation between the nature of environmental threat perceived as aggressive by panelists, and the stratum corneum reactivity lo household cleaning products as measured by the corneosurfametry lest. Results indicate substantial differences in irritancy potential between proprietary products. Corneosurfametry data show significant differences in stratum corneum reactivity between, on file one hand, individuals with cither non-sensitive skin or skin sensitize to climate-fabrics, and, on the other hand, individuals with detergent-sensitive skin. It is concluded that sensitive skin is not one single condition. Sound information in rating detergent sensitive skin may be gained by corneosurfametry.     

Influence of staphylococcal lipoteichoic acid on the frustrated phagocytosis of neutrophils against opsonized corneocytes

Abstract Stratum corneum (SC) exerts a proinflammatory effect in the presence of complement. When Staphylococcus aureus (S. aureus) invades the skin through damaged SC. neutrophils accumulate at the sub-corneal portion of epidermis to phagocytize the S. aureus as noted in impetigo. Besides the phagocytosis of bacteria. neutrophils interact with opsonized SC in a form of frustrated phagocytosis, increasing a damage of the surrounding tissues. Based on our previous finding that staphylococcal protein A promotes the interaction between SC and neutrophils. we investigated whether lipoteichoic acid (LTA), another cell wall component of S. aureus, also shows similar properties. We found that LTA significantly promoted the binding of neutrophils to opsonized SC, resulting in an increase in SC-induced respiratory burst of neutrophils assessed by chemiluminescence (CL). The binding of neutrophils to the SC was almost completely inhibited by the blocking of CR3 with anti-CD11b antibody, suggesting that the binding between SC and neutrophils is mediated by interaction between C3bi and CR3 (Mac-1). Such enhanced interaction seems to function in the primary host defence mechanism against the invading S. aureus through the skin such as in impetigo.     

Genital tuberculosis in a HIV infected woman: a case report

The incidence of HIV-associated tuberculosis is increasing worldwide, especially in developing countries. HIV infected patients rapidly develop clinically significant disease, respond poorly to complete treatment and present with extrapulmonary tuberculosis. Although a relative increase of genital tuberculosis would be expected, this has not been reported. Probably, tuberculous systemic disease is diagnosed earlier, before genital tuberculosis occur. The present study is a report of case of a young African female patient, who was admitted with symptoms of acute pelvic inflammatory disease due to genital tuberculosis and proved to be HIV infected. The patient was managed by intravenous antibiotic administration, but since no clinical or laboratory improvement was achieved, a laparotomy and salpingooophorectomy was performed. Histopathology revealed tuberculosis and after that the patient proved to be HIV infected. Further investigation did not reveal pulmonary or other extragenital manifestation of tuberculosis. The only manifestation of HIV infection and genital tuberculosis was the symptoms of an acute pelvic inflammatory disease, which is extremely rare.     

Stratum Corneum Lipids of Human Epidermal Keratinocyte Air-Liquid Cultures: Implications for Barrier Function

Purpose. The purpose of this study is to investigate the permeability barrier, i.e., the stratum corneum (SC) lipids, of human epidermal keratinocyte air-liquid cultures and compare them with those of human SC. Methods. The SC lipids composition was analyzed by TLC technique, the organization by electron microscopic procedure, and the phase transition temperature by Infrared spectroscopic method. Results. Electron microscopy demonstrated that The SC lipids of cultures were largely retained inside the corneocytes, and that the intercellular lipids lack both the basic unit repetition (i.e., broad : narrow : broad : broad : narrow : broad of electron lucent bands) and the covalently-bound lipid envelope normally found in human SC. These characteristics are similar to those found in SC from patients with atopic dermatitis or psoriasis, or from animals with essential fatty acid deficiency, suggesting that the cultures may be hyperproliferative. In addition, the high free sterol content and the altered fatty acid/ceramide composition of these cultures argue that the compromised barrier function is linked to hyperproliferation and lipid synthesis, or vice versa. Infrared spectroscopic analyses confirm that there are major conformational differences between the lipids of human and cultured SC. Conclusions. The profound differences in SC lipid composition, organization and conformational properties attest that permeability alone is not a sufficiently sensitive marker to define barrier equivalence between cultures and human skin.     

Structural determinants of the response of the skin to chemical irritants

A study was made of the relationships between structural parameters of the epidermis and stratum corneum and the skin's sensitivities to chemical irritation by dithranol or ammonium hydroxide. Statistically significant positive correlations were found between the minimal blistering time to ammonium hydroxide and the area bounded by the skin surface contour line as determined by a skin surface replica technique. A significant positive correlation was also found between the minimal irritancy dose of dithranol and (a) the mean corneocyte area, and (b) the mean epidermal thickness in cell numbers. Mean corneocyte area was also found to increase with age and to be significantly less in UV-sensitive Types I and II subjects than in the relatively UV-insensitive Types III and IV subjects. These correlations are further evidence that there are inherent structural differences in the skin which influence the way the skin reacts to chemical trauma.