Extraction and quantification of amino acids in human stratum corneum in vivo

Background Amino acid (AA) levels in stratum corneum (SC) are potential biomarkers of skin health while their systemic levels may be used to diagnose inherited metabolic diseases. Objectives To examine reverse iontophoresis, in human volunteers, as a minimally invasive tool to analyse AAs within the skin and subdermally. Methods In four volunteers, the amounts of iontophoretically extracted AAs were compared with those determined in the SC following repetitive tape stripping and with the plasma concentrations. Glucose levels, evaluated in the different compartments, were used as a control. Results SC concentrations of 13 essentially zwitterionic AAs were ∼100‐fold higher than the respective plasma levels. Passive and reverse iontophoretic extraction for 4 h did not deplete the SC depot of AAs, a fact reinforced by postextraction tape stripping, which revealed that AAs remained in the SC at this time. In contrast, glucose was much less abundant in the SC and was fully and relatively quickly extracted by reverse iontophoresis. Conclusions It follows that reverse iontophoresis is useful for quantifying AAs in the SC and these data are highly correlated with levels obtained by tape stripping. However, reverse iontophoresis is impractical for the routine monitoring of AA plasma concentrations (unlike the situation for glucose, the skin reservoir of which is much smaller).     

Pharmacokinetics of ivermectin applied topically by whole‐body bathing method in healthy volunteers

As a novel administration method of ivermectin (IVM) for scabies treatment, we proposed a “whole‐body bathing method (WBBM)”. In this method, the patients would bathe themselves in a bathing fluid containing IVM at an effective concentration. Previously, we demonstrated that WBBM could deliver IVM to the skin but not to the plasma in rats. In the present study, to assess the clinical validity of the method an arm bathing examination (first trial) and a whole‐body bathing examination (second trial) were conducted in healthy volunteers. In both the first and second trials, after bathing in fluid containing IVM, the exposure in the stratum corneum was higher compared with that after taking IVM p.o. as reported previously. IVM was not detected in plasma at any sampling point after the whole‐body bathing in the second trial. Furthermore no serious adverse events were found. These results in both trials suggest that WBBM can deliver IVM to the human stratum corneum without systemic exposure or serious adverse effects in healthy volunteers, and at concentrations that would be adequate for scabies treatment.     

Elucidated lipid structures of various human stratum corneum investigated by electron paramagnetic resonance spectroscopy

Background: Electron paramagnetic resonance (EPR) in conjunction with a slow‐tumbling simulation is useful for defining stratum corneum (SC) lipid structure. The objectives of this investigation were to evaluate and elucidate the lipid structure of various human SC as a function of the depth. Methods: The SC from mid‐volar forearms of human volunteers and a cadaver was stripped consecutively from one to three times using a glass plate coated with a cyanoacrylate resin. Spin probes were used to monitor SC ordering. EPR spectra were analyzed by an EPR slow‐tumbling simulation. Keratin solution from human epidermis was mixed with 5‐doxylstearic acid (5‐DSA) aqueous solution. Results: EPR analyses of 5‐DSA and CHL probes showed immobilized and mobile spectra, respectively. The simulation for 5‐DSA spectra showed differences in ordering values of the SC as a function of depth. EPR of keratin/5‐DSA showed mobile spectral pattern. In addition, EPR of CHL showed a weak and a broad signal. Conclusions: The keratin/5‐DSA results imply that the most likely location of 5‐DSA probe is in SC lipid. CHL probe may not easily permeate the SC. The EPR results along with the simulation analysis provide elucidated SC lipid structure.     

对贵刊《阿奇霉素和左氧氟沙星治疗女性……》一文的验证

<正>笔者读贵刊2004年第23卷第9期刊登的《阿奇霉素和左氧氟沙星治疗女性非淋菌性泌尿生殖道感染各45例比较》一文后,深受启发,并采用此法于2004年10月-2006年12月对我校医院门诊100例女性非淋菌性泌尿生殖道感染进行了临床验证,现报道如下。     

Laser assisted delivery of topical anesthesia for intramuscular needle insertion in adults

BACKGROUND AND OBJECTIVES: Currently there is no safe, effective, and rapid means to eliminate the pain associated with a needle insertion through the skin. It is hypothesized that ablation of the stratum corneum layer using a low energy Erbium(Er):YAG laser would allow rapid local anesthesia from a lidocaine product. STUDY DESIGN/MATERIALS AND METHODS: Eighty volunteers participated in a placebo-controlled, double blind, cross-over study employing the Norwood-Abbey (Chelsea Heights, Victoria, Australia) laser anesthesia device (LAD) and two lidocaine preparations. Upper-arm skin ablation was followed by a 5-minute application of study treatment. Pain scores were registered immediately following a needle insertion. RESULTS: Comparing the combined lidocaine preparations to placebo, there was a statistically significant reduction in pain when the LAD was employed (P < 0.001). The median pain reduction for lidocaine was 51.3% (95% CI = [40.9, 76.1]). CONCLUSIONS: Use of the low energy Er:YAG LAD device in combination with a 5-minute application of lidocaine significantly reduced the pain associated with a needle insertion.     

Photomechanical delivery of 100-nm microspheres through the stratum corneum: implications for transdermal drug delivery

BACKGROUND AND OBJECTIVES: Photomechanical waves (PWs) render the stratum corneum permeable and allow molecules to diffuse into the epidermis. The aim of this study was to investigate the probe size that could be delivered through the stratum corneum and into the epidermis. STUDY DESIGN/MATERIALS AND METHODS: A single PW was applied onto the rat skin in vivo. Aqueous suspensions of fluorescent microspheres, 100 nm in diameter, were used as probes for transdermal delivery. The presence of the microspheres in the epidermis was measured by a fiber-based spectrofluorimeter after the stratum corneum was removed by tape-stripping (TS). RESULTS: Exposure of the rat skin to a PW permeabilized the stratum corneum and allowed the fluorescent microspheres to diffuse into the epidermis. CONCLUSIONS: The experiments show that PWs can facilitate the delivery of very large molecules and probes into the epidermis.     

Evaluation of biophysical and clinical parameters of skin barrier function among hospital workers

The goal of this study was to evaluate biophysically and clinically the hand skin of nurses working in the operating room in comparison with the hand skin of a control group of female administrative employees. 19 nurses and 14 employees were included in this trial. Transepidermal water loss (TEWL) and stratum corneum (SC) hydration were evaluated on 4 different test sites - dominant and non-dominant pulse, and dominant and non-dominant hand dorsum. The clinical score Dermatology Life Quality Index (DLQI) and subjective evaluation of skin sensitivity were also recorded. In comparison with the control group, TEWL values among nurses were significantly higher on all test sites, while SC hydration was significantly lower on 3 of the 4 test sites. In addition, clinical score showed the presence of irritant contact dermatitis (ICD). DLQI reported a higher level of disability among the nurses group, while the subjective evaluation of skin sensitivity was identical in both groups. The results suggest the presence of skin barrier alterations and clinical signs of chronic ICD on the hands of nurses working in operating room units.     

肉豆蔻酸异丙酯对酮基布洛芬经皮渗透的影响

目的 评价皮肤角质层和真皮层对药物经皮渗透的影响。方法 选择酮基布洛芬为模型药物，采用Franz扩散池法，考察药物经完整皮肤和剥离角质层皮肤的体外表现透皮系数Kp，并比较吸收促进剂肉豆蔻酸异丙酯（IPM）共存进的促透差异。结果 酮基布洛芬经剥离角质层皮肤的Kp是完整皮肤的1.7倍，IPM能分布在真皮层并可明显增加药物在角质层的分布和经皮累积渗透量。结论 本实验为皮肤病态条件，如皮肤受伤或溃疡等时药物经皮吸收规律研究提供一种新的方法。     

Markers of collagen synthesis and degradation in urogenital tissue from women with and without stress urinary incontinence

AIMS: Multiparity and obesity are risk factors for stress urinary incontinence (SUI), but collagen synthesis and metabolism in the urogenital tissue itself may also affect its function and control of micturition. Whether changes in synthesis or degradation of collagen are part of the etiology of SUI is not known and published studies show diverging results. The aims of the present study was to investigate collagen turnover in urogenital tissue in women with SUI (n=71) and in urologically healthy women (n=31). METHODS: Markers of collagen synthesis and breakdown, the carboxy-terminal propeptide of type I procollagen (PICP), the carboxy-terminal telopeptide of type I collagen (ICTP), and the amino-terminal propeptide of procollagen III (PIIINP) were assayed in urogenital tissue homogenates and peripheral serum. RESULTS: In the total clinical material SUI patients were significantly older, had a significantly higher body mass index (BMI) and significantly lower serum PICP and tissue ICTP levels than the controls. When healthy controls were compared with SUI patients matched for age, BMI, parity, and hormonal/menopausal status (31 women in each group), the SUI patients had significantly lower serum concentrations of PICP and significantly lower tissue concentrations of PIIINP and ICTP than the controls. Within the total material of SUI patients, post-menopausal women with weak and strong HRT and pre-menopausal women had significantly lower S-ICTP concentrations than untreated post-menopausal patients. Significant negative correlations to parity were found for T-PIIINP and T-PICP and to BMI for T-ICTP. CONCLUSIONS: The low tissue collagen marker levels in women with SUI suggest a reduced collagen turnover, which may negatively affect tissue strength and elasticity.     

Mechanics of wound healing and importance of Vacuum Assisted Closure in urology

PURPOSE: We discuss the mechanisms of wound healing and our experience with the Vacuum Assisted Closure device (Kinetic Concepts, Inc., San Antonio, Texas) for complex urogenital wounds. MATERIALS AND METHODS: The literature obtained from a Medline search on wound healing, wound failure and vacuum assisted closure was reviewed. In addition, we reviewed our experience with negative pressure wound therapy. RESULTS: Wound healing is a complex interaction between the reticuloendothelial and immune systems, in addition to correctable internal and external factors. Understanding the healing process improves outcomes and decreases patient morbidity. Negative pressure wound therapy has hastened wound healing and it adds significant improvement in the arsenal of choices available. CONCLUSIONS: Vacuum Assisted Closure is a therapeutic alternative that complements surgical and medical intervention in patients with complex wounds.