THE METABOLISM OF TESTOSTERONE BY HUMAN SKIN IN DISORDERS OF HAIR GROWTH

1973 ◽  
Vol 59 (2) ◽  
pp. 345-351 ◽  
Author(s):  
J. S. JENKINS ◽  
S. ASH
Keyword(s):  
Human Skin ◽  
Metabolic Activity ◽  
Hair Growth ◽  
Normal Skin ◽  
Rare Condition ◽  
Testicular Feminization ◽  
Body Hair ◽  
Testosterone Levels ◽  
Localized Failure

SUMMARY The metabolism of testosterone by skin from patients with disorders of hair growth in the presence of normal testosterone levels has been studied in vitro and compared with the metabolic activity of normal skin. The main metabolites formed were dihydrotestosterone, androstenedione, androsterone and androstanedione. In four out of six females with hirsutism, the skin produced increased amounts of dihydrotestosterone and also androstenedione. A patient with the rare condition of unilateral hirsutism showed no difference in metabolic activity between the hirsute and non-hirsute sides. In localized failure of androgenically determined hair growth, seen in three beardless males, the metabolism of the hairless area was greater than that of the normally hairy abdomen. Four patients with testicular feminization and complete absence of body hair were studied and the formation of dihydrotestosterone ranged from low to high normal levels.

scholarly journals Immunohistochemical and mutation analyses demonstrate that procollagen VII is processed to collagen VII through removal of the NC-2 domain.

1995 ◽  
Vol 131 (2) ◽  
pp. 551-559 ◽  
Author(s):  
L Bruckner-Tuderman ◽  
O Nilssen ◽  
D R Zimmermann ◽  
M T Dours-Zimmermann ◽  
D U Kalinke ◽  
...  
Keyword(s):  
Human Skin ◽  
Polyclonal Antibodies ◽  
Normal Skin ◽  
Positive Staining ◽  
Strong Reaction ◽  
Normal Human Skin ◽  
Cultured Keratinocytes ◽  
Exon Junctions ◽  
Collagen Vii

Collagen VII is the major structural constituent of anchoring fibrils in the skin. It is synthesized as a procollagen that is larger than the collagen deposited in the tissue. In this study, we investigated the conversion of procollagen VII to collagen VII in human skin and in cutaneous cells in vitro and identified the propeptide using domain-specific antibodies. For this purpose, two bacterial fusion proteins containing unique sequences of the carboxy-terminal globular NC-2 domain of procollagen VII were prepared, and polyclonal antibodies raised against them. Immunoblotting showed that the anti-NC2 antibodies reacted with procollagen VII isolated from cultured keratinocytes, but not with collagen VII extracted from the skin. Immunohistochemical experiments with the NC-2 antibodies revealed a strong reaction in cultured keratinocytes, but the basement membrane zone of normal skin remained negative. The staining could not be rendered positive by chemical or enzymatic unmasking of potential hidden epitopes in the skin, indicating that most of the NC-2 domain is absent from normal skin. In contrast, a positive staining with NC-2 antibodies was observed in the skin of a patient with NC-2 antibodies was observed in the skin of a patient with dystrophic epidermolysis bullosa, who carried a 14-bp deletion at one of the intro-exon junctions of the collagen VII gene. This aberration led to an in-frame skipping of exon 115 from the mRNA and eliminated 29 amino acids from the NC-2 domain which include the putative cleavage site for the physiological processing enzyme, procollagen C-proteinase. The results indicate that in normal human skin, the removal of the NC-2 domain from procollagen VII precedes its deposition at the dermal-epidermal junction. Furthermore, they suggest that an aberration in the procollagen VII cleavage interferes with the normal fibrillogenesis of the anchoring fibrils.

Mechanism of action of ingenol mebutate gel in reconstructed human skin assessed by transcriptomics.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19056-e19056
Author(s):  
John Robert Zibert ◽  
Maria Helena Hoeyer-Hansen ◽  
Andre Huss Eriksson ◽  
Marianne Begtson Loevendorf ◽  
Josselyn Matthews ◽  
...  
Keyword(s):  
Cell Death ◽  
Human Skin ◽  
Mechanism Of Action ◽  
Normal Skin ◽  
Gene Set Enrichment Analysis ◽  
Transcriptional Level ◽  
Ingenol Mebutate ◽  
Reconstructed Human Skin

e19056 Background: Ingenol mebutate (IM) gel topical applied once daily for 2-3 consecutive days, has recently been approved by FDA in treating actinic keratoses (AK), as a safe, tolerable and effective treatment. IM, a highly active biological diterpene ester, has shown in vitro and in vivo to induce a dual mechanism of action characterized by, first, cell death induced at high micromolar concentrations and, second, a protein kinase C dependent immune activation in the nanomolar range. The aim of this study was to investigate the mechanism of action of IM in reconstructed human skin (RHS). Methods: IM 0.05% gel or vehicle was applied topically to RHS (EpiDermFT) and normal pigskin and IM concentrations were measured after 2 and 24 hrs. In RHS, biopsies were obtained 1, 6 and 24 hrs after treatment and global transcriptomic profiling (Affymetrix HG 1.0 ST) was assessed. The analysis included transcription factor binding site (TFBS) and gene set enrichment analysis (GSEA). Results: We compared IM’s penetration through normal skin to RHS and found a 10-fold higher permeability in RHS, which likely models the increased permeability of AK lesions. Consequently we further investigated IM’s effects on RHS. Based on GSEA, we identified the major effects of IM to comprise: cell death, inflammation and wound healing responses, indicated by differential expression of e.g. caspases, DAPK1, chemokine ligands, HAS2, MMPs, SERPINs, ILs (and their receptors). A TFBS analysis identified E2F regulated genes as overrepresented, albeit in opposite directions in dermis (up-regulated) compared to epidermis (down-regulated). IM transiently activates PKC, and via this activation causes transcriptional silencing of E2F-responsive genes. The differential effect on dermis and epidermis could be due to different levels of PKC isoforms in the different skin layers. Indeed, a specific, inflammatory response was observed and several genes, including MMP10 and IL1R2, displayed a time-dependent increase in expression, reaching a maximum at 24h. Conclusions: In conclusion, IM displays pleiotropic effects, of which many are identified on a transcriptional level. Our data suggest involvement of in particular PKC, ERK2, and E2F regulated genes.

THE METABOLISM OF TESTOSTERONE BY SKIN IN NORMAL SUBJECTS AND IN TESTICULAR FEMINIZATION

1971 ◽  
Vol 49 (3) ◽  
pp. 515-520 ◽  
Author(s):  
J. S. JENKINS ◽  
S. ASH
Keyword(s):  
Human Skin ◽  
Normal Subjects ◽  
Testicular Feminization ◽  
Normal Human Skin ◽  
Normal Manner ◽  
Normal Human

SUMMARY The metabolism in vitro of testosterone by normal human skin has been studied and the results have been compared with those obtained in two cases of testicular feminization. The predominant metabolite was 5α-dihydrotestosterone followed by androstenedione, androsterone, and 5α-androstanedione. Suprapubic skin from patients with testicular feminization metabolized testosterone in a completely normal manner. There was no evidence to support the view that a failure to produce an essential metabolite of testosterone is responsible for the condition of testicular feminization.

Fibroblasts During Hypertrophic Scar Formation and Resolution

1973 ◽  
Vol 31 ◽  
pp. 428-429
Author(s):  
C. W. Kischer
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Cell Proliferation ◽  
Fine Structure ◽  
Metabolic Activity ◽  
Hypertrophic Scar ◽  
Normal Skin ◽  
Ground Substance ◽  
Hypertrophic Scars ◽  
Scanning Electron

The morphology of the fibroblasts changes markedly as the healing period from burn wounds progresses, through development of the hypertrophic scar, to resolution of the scar by a self-limiting process of maturation or therapeutic resolution. In addition, hypertrophic scars contain an increased cell proliferation largely made up of fibroblasts. This tremendous population of fibroblasts seems congruous with the abundance of collagen and ground substance. The fine structure of these cells should reflect some aspects of the metabolic activity necessary for production of the scar, and might presage the stage of maturation.A comparison of the fine structure of the fibroblasts from normal skin, different scar types, and granulation tissue has been made by transmission (TEM) and scanning electron microscopy (SEM).

Desmosomal distribution in the epidermis of a non-contracting human skin equivalent

1992 ◽  
Vol 50 (1) ◽  
pp. 896-897
Author(s):  
L.X. Oakford ◽  
S.D. Dimitrijevich ◽  
R. Gracy
Keyword(s):  
Human Skin ◽  
Basal Layer ◽  
Skin Equivalent ◽  
Tissue Component ◽  
Intact Skin ◽  
Similar Sequence ◽  
Sequence Of Events ◽  
Suprabasal Keratinocytes ◽  
Human Skin Equivalent

In intact skin the epidermal layer is a dynamic tissue component which is maintained by a basal layer of mitotically active cells. The protective upper epidermis, the stratum corneum, is generated by differentiation of the suprabasal keratinocytes which eventually desquamate as anuclear comeocytes. A similar sequence of events is observed in vitro in the non-contracting human skin equivalent (HSE) which was developed in this lab (1). As a part of the definition process for this model of living skin we are examining its ultrastructural features. Since desmosomes are important in maintaining cell-cell interactions in stratified epithelia their distribution in HSE was examined.

Mechanisms involved in effects of antimicrobial peptides, bactenectins ChBac3.4, ChBac5, and mini-ChBac7.5Nb, on bacterial cells

2017 ◽  
pp. 43-50
Author(s):  
О.В. Шамова ◽  
М.С. Жаркова ◽  
П.М. Копейкин ◽  
Д.С. Орлов ◽  
Е.А. Корнева
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Innate Immunity ◽  
Infectious Diseases ◽  
Metabolic Activity ◽  
Capra Hircus ◽  
Bacterial Cells ◽  
Antibiotic Resistant ◽  
Resistant Strains

Антимикробные пептиды (АМП) системы врожденного иммунитета - соединения, играющие важную роль в патогенезе инфекционных заболеваний, так как обладают свойством инактивировать широкий спектр патогенных бактерий, обеспечивая противомикробную защиту живых организмов. В настоящее время АМП рассматриваются как потенциальные соединения-корректоры инфекционной патологии, вызываемой антибиотикорезистентными бактериями (АБР). Цель данной работы состояла в изученим механизмов антибактериального действия трех пептидов, принадлежащих к семейству бактенецинов - ChBac3.4, ChBac5 и mini-ChBac7.5Nb. Эти химически синтезированные пептиды являются аналогами природных пролин-богатых АМП, обнаруженных в лейкоцитах домашней козы Capra hircus и проявляющих высокую антимикробную активность, в том числе и в отношении грамотрицательных АБР. Методы. Минимальные ингибирующие и минимальные бактерицидные концентрации пептидов (МИК и МБК) определяли методом серийных разведений в жидкой питательной среде с последующим высевом на плотную питательную среду. Эффекты пептидов на проницаемость цитоплазматической мембраны бактерий для хромогенного маркера исследовали с использованием генетически модифицированного штамма Escherichia coli ML35p. Действие бактенецинов на метаболическую активность бактерий изучали с применением маркера резазурина. Результаты. Показано, что все исследованные пептиды проявляют высокую антимикробную активность в отношении Escherichia coli ML35p и антибиотикоустойчивых штаммов Escherichia coli ESBL и Acinetobacter baumannii in vitro, но их действие на бактериальные клетки разное. Использован комплекс методик, позволяющих наблюдать в режиме реального времени динамику действия бактенецинов в различных концентрациях (включая их МИК и МБК) на барьерную функцию цитоплазматической мембраны и на интенсивность метаболизма бактериальных клеток, что дало возможность выявить различия в характере воздействия бактенецинов, отличающихся по структуре молекулы, на исследуемые микроорганизмы. Установлено, что действие каждого из трех исследованных бактенецинов в бактерицидных концентрациях отличается по эффективности нарушения целостности бактериальных мембран и в скорости подавления метаболизма клеток. Заключение. Полученная информация дополнит существующие фундаментальные представления о механизмах действия пролин-богатых пептидов врожденного иммунитета, а также послужит основой для биотехнологических исследований, направленных на разработку на базе этих соединений новых антибиотических препаратов для коррекции инфекционных заболеваний, вызываемых АБР и являющимися причинами тяжелых внутрибольничных инфекций. Antimicrobial peptides (AMPs) of the innate immunity are compounds that play an important role in pathogenesis of infectious diseases due to their ability to inactivate a broad array of pathogenic bacteria, thereby providing anti-microbial host defense. AMPs are currently considered promising compounds for treatment of infectious diseases caused by antibiotic-resistant bacteria. The aim of this study was to investigate molecular mechanisms of the antibacterial action of three peptides from the bactenecin family, ChBac3.4, ChBac5, and mini-ChBac7.5Nb. These chemically synthesized peptides are analogues of natural proline-rich AMPs previously discovered by the authors of the present study in leukocytes of the domestic goat, Capra hircus. These peptides exhibit a high antimicrobial activity, in particular, against antibiotic-resistant gram-negative bacteria. Methods. Minimum inhibitory and minimum bactericidal concentrations of the peptides (MIC and MBC) were determined using the broth microdilution assay followed by subculturing on agar plates. Effects of the AMPs on bacterial cytoplasmic membrane permeability for a chromogenic marker were explored using a genetically modified strain, Escherichia coli ML35p. The effect of bactenecins on bacterial metabolic activity was studied using a resazurin marker. Results. All the studied peptides showed a high in vitro antimicrobial activity against Escherichia coli ML35p and antibiotic-resistant strains, Escherichia coli ESBL and Acinetobacter baumannii, but differed in features of their action on bacterial cells. The used combination of techniques allowed the real-time monitoring of effects of bactenecin at different concentrations (including their MIC and MBC) on the cell membrane barrier function and metabolic activity of bacteria. The differences in effects of these three structurally different bactenecins on the studied microorganisms implied that these peptides at bactericidal concentrations differed in their capability for disintegrating bacterial cell membranes and rate of inhibiting bacterial metabolism. Conclusion. The obtained information will supplement the existing basic concepts on mechanisms involved in effects of proline-rich peptides of the innate immunity. This information will also stimulate biotechnological research aimed at development of new antibiotics for treatment of infectious diseases, such as severe in-hospital infections, caused by antibiotic-resistant strains.

Human Skin-Derived Fibroblasts Acquire In Vitro Anti-Tumor Potential after Priming with Paclitaxel

2013 ◽  
Vol 13 (3) ◽  
pp. 523-530 ◽  
Author(s):  
Augusto Pessina ◽  
Valentina Cocce ◽  
Arianna Bonomi ◽  
Loredana Cavicchini ◽  
Francesca Sisto ◽  
...  
Keyword(s):  
Human Skin

scholarly journals In VitroAnalyses of the Effects of Heparin and Parabens on Candida albicans Biofilms and Planktonic Cells

2011 ◽  
Vol 56 (1) ◽  
pp. 148-153 ◽  
Author(s):  
Marisa H. Miceli ◽  
Stella M. Bernardo ◽  
T. S. Neil Ku ◽  
Carla Walraven ◽  
Samuel A. Lee
Keyword(s):  
Candida Albicans ◽  
Metabolic Activity ◽  
Biofilm Formation ◽  
High Dose ◽  
Dependent Manner ◽  
Planktonic Cells ◽  
Content Type ◽  
Heparin Sodium ◽  
The Individual

ABSTRACTInfections and thromboses are the most common complications associated with central venous catheters. Suggested strategies for prevention and management of these complications include the use of heparin-coated catheters, heparin locks, and antimicrobial lock therapy. However, the effects of heparin onCandida albicansbiofilms and planktonic cells have not been previously studied. Therefore, we sought to determine thein vitroeffect of a heparin sodium preparation (HP) on biofilms and planktonic cells ofC. albicans. Because HP contains two preservatives, methyl paraben (MP) and propyl paraben (PP), these compounds and heparin sodium without preservatives (Pure-H) were also tested individually. The metabolic activity of the mature biofilm after treatment was assessed using XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction and microscopy. Pure-H, MP, and PP caused up to 75, 85, and 60% reductions of metabolic activity of the mature preformedC. albicansbiofilms, respectively. Maximal efficacy against the mature biofilm was observed with HP (up to 90%) compared to the individual compounds (P< 0.0001). Pure-H, MP, and PP each inhibitedC. albicansbiofilm formation up to 90%. A complete inhibition of biofilm formation was observed with HP at 5,000 U/ml and higher. When tested against planktonic cells, each compound inhibited growth in a dose-dependent manner. These data indicated that HP, MP, PP, and Pure-H havein vitroantifungal activity againstC. albicansmature biofilms, formation of biofilms, and planktonic cells. Investigation of high-dose heparin-based strategies (e.g., heparin locks) in combination with traditional antifungal agents for the treatment and/or prevention ofC. albicansbiofilms is warranted.

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