OBJECTIVE: To compare different non-invasive methods for determination of human endothelial function in peripheral circulation. DESIGN: Observational, cross-sectional study in 39 healthy subjects (21 females, age 17-56 years). SETTING: Vascular research laboratory at university hospital. METHODS: Laser Doppler (LD) flowmetry was used to compare skin microvascular perfusion changes during postocclusive reactive hyperaemia with those induced by iontophoretic administration of acetylcholine (ACh), an endothelial-dependent vasodilator. LD measurements were compared with ultrasonographic measurements of postocclusive flow-mediated dilatation (FMD) in the brachial artery (n = 21). RESULTS: Local ACh induced a larger and more sustained skin perfusion increase than reactive hyperaemia after 4 min of regional arterial occlusion (P<0.001). A significant correlation was found between the magnitude of ACh-induced vasodilatation and peak reactive hyperaemia, both in absolute (r = 0.62, P<0.001) and relative terms (r = 0.58, P<0.001). A correlation was also found between brachial artery FMD and the magnitude of ACh-induced skin perfusion increase (r = 0.43, P<0.05) but not between FMD and reactive hyperaemia. CONCLUSION: Endothelial function, an early marker of cardiovascular risk, can be non-invasively assessed and graded by LD and FMD-measurements and despite inherent differences, both methods do correlate. 相似文献
The objective of this study was to investigate the feasibility of rapid administration of iron via transdermal route as an alternative to parenteral route of administration. In vitro drug delivery studies were carried out using porcine epidermis mounted on Franz diffusion cells. The effect of chemical permeation enhancers and physical techniques (constant voltage iontophoresis, electroporation and combination of electroporation with iontophoresis) on the transport of ferric pyrophosphate (FPP) was studied. Transepidermal water loss (TEWL) and electrical resistance were measured in order to see the effect of these techniques on the skin barrier function. The amount of FPP permeated was not enhanced significantly with the use of any of the enhancers (P?>?0.05). It was found that constant voltage iontophoresis (0.5, 2 or 4?V) for about 30?min across electroporated epidermis (120?V, 100 pulses, 10?ms at 5 Hz) enhanced the delivery of FPP over control in the range of 2- to 42-fold. Hence, a therapeutically required dose of iron could be delivered by transdermal route using electrically-mediated techniques. 相似文献
Reverse electrodialysis (RED) technology generates energy from the salinity gradient by contacting waters with different salinity. Herein, we develop the disposable skin patch using this eco-friendly energy. The current density, which can be controlled easily without special circuit, is enough to iontophoretic drug delivery. In vitro study, this iontophoretic system enhanced the transdermal delivery of peptide, which is difficult to penetrate the skin barrier by simple diffusion. We design the disposable iontophoretic skin patch using RED system and suggest this patch can be apply on new cosmetic patch or disposable drug patch. 相似文献
The aim of this paper is to investigate the effects of hydrogel mesh size, a conductive polymer, and electric field strength on controlled drug delivery phenomena using drug-loaded polyacrylamide hydrogels prepared at various crosslinking ratios both with and without a conductive polymer system. Poly(p-phenylene vinylene), PPV, as the model conductive polymer, was used to study its ability to control aloin released from aloin-doped poly(p-phenylene vinylene)/polyacrylamide hydrogel (aloin-doped PPV/PAAM). In the passive release, the diffusion of aloin from five aloin-doped PPV/PAAM hydrogel systems each was delayed ranging from during the first three hours to during the first 14 h due to the ionic interaction between the anionic drug and PPV. After the delayed periods, aloin could diffuse continuously into the buffer solution through the PAAM matrix. The amount of aloin released from the aloin-doped PPV/PAAM rose with increasing electric field strength as a result of the three mechanisms: the expansion of PPV chains inside the hydrogel, iontophoresis, and the electroporation of the matrix pore size, combined. Furthermore, the conductive polymer and the electric field could be used in combination to regulate the amount of release drug to a desired level, to control the release rate, and to switch the drug delivery on/off. 相似文献
Peyronie’s disease is a connective tissue disorder involving the tunica albuginea of the penis. The fibrotic process may result in the formation of plaque, one of the classic findings on physical examination of the patient. Men afflicted with this disorder may present with pain, deformity, such as penile curvature, and/or erectile dysfunction. While surgical therapy has been the standard for definitive treatment for penile curvature associated with Peyronie’s disease, medical options are attractive due to their potential to avoid invasive procedures of the penis, affect all aspects of disease and intervene before the disease has stabilized and is perhaps still reversible. Oral therapy has been historically popular due to the ease of administration and low side-effect profile but clinical trials have failed to demonstrate clear benefit. Intraplaque injection with agents such as verapamil and interferon, has been demonstrated (in mostly uncontrolled studies) to offer mild-to-moderate benefit and stabilize disease. Studies focused on the topical administration of verapamil have been conflicting, while the use of iontophoresis has gained popularity as a means of improving drug delivery to the target tissues. Further controlled trials are needed to further elucidate effective therapies and their optimum dosing, while further research into the pathophysiology of the disorder will aid in the development of new treatments. 相似文献
Transdermal delivery has been at the forefront of research addressing the development of non-invasive methods for the systemic administration of peptide and protein therapeutics generated by the biotechnology revolution. Numerous approaches have been suggested for overcoming the skin’s formidable barrier function; whereas certain strategies simply act on the drug formulation or transiently increase the skin permeability, others are designed to bypass or even remove the outermost skin layer. This article reviews the technologies currently under investigation, ranging from those in their early-stage of development, such as laser-assisted delivery to others, where feasibility has already been demonstrated, such as microneedle systems, and finally more mature techniques that have already led to commercialisation (e.g., velocity-based technologies). The principles, mechanisms involved, potential applications, limitations and safety considerations are discussed for each approach, and the most advanced devices in each field are described. 相似文献
Although 70% of postmenopausal women suffer from hot flashes the pathophysiology is poorly understood. The serotonin and noradrenaline reuptake inhibitor (SNRI) venlafaxine provides relief of flushing although the mechanism is unknown and could involve a central effect and/or a peripheral effect. Using single photon emission computed tomography (SPECT) we studied the central serotonin transporter (SERT) in vivo using [123I]-beta-carbomethoxy-3-β-(4-iodophenyl)tropane (beta-CIT) and, as previous studies have shown that reactivity of the skin blood vessels is enhanced in those who flush, we examined cutaneous microvascular perfusion.
Methods
Cutaneous microvascular perfusion was assessed in 31 postmenopausal women, with flushing, using laser Doppler imaging with iontophoresis (LDI + ION), before and after 8 weeks of treatment with venlafaxine. A sub-group of 14 of these women also had SPECT imaging at both time points to evaluate the availability of SERT in the brain. Flush frequency and score was recorded, and Beck Depression Inventory (BDI) II scores were assessed before and after treatment.
Results
Following treatment with venlafaxine, there was a significant reduction in the [123I]-beta-CIT binding ratio, BDI scores, flushing and endothelial dependent perfusion response. [123I]-Beta-CIT reduction was associated with BDI reduction (r2 = 0.54; F = 8.8; p = 0.004), but not flushing reduction or perfusion reduction.
Conclusions
Venlafaxine resulted in a decrease in BDI II scores with an associated reduction in [123I]-beta-CIT binding in a group of non-depressed women. It also improved flush frequency and severity which may be as a result of decreases seen in enhanced cutaneous microvascular perfusion. 相似文献