Clinical and microstructural changes with different iontophoresis-assisted corneal cross-linking methods for keratoconus

AIM: To compare the clinical and microstructural changes induced by different transepithelial iontophoresis-assisted corneal cross-linking(I-CXL) methods for keratoconus. METHODS: A total of 42 eyes of 42 patients with progressive keratoconus were divided into two groups. Group A received I-CXL for 5 min, while group B received I-CXL for 10 min. Visual acuity, optical coherence tomography(OCT), specular microscopy and confocal microscopy were evaluated preoperatively and at 1, 3, 6, and 12 mo postoperatively. RESULTS: Twelve months after the operation, uncorrected visual acuity(UCVA) and corrected distance visual acuity(CDVA) were improved in both groups, with a better outcome in the I-CXL 10 min group(P=0.025, 0.021, respectively). Kmax values decreased by 0.94±3.00 D in the I-CXL 10 min group(P=0.033) but increased by 1.87±3.29 D in the I-CXL 5 min group(P=0.012). OCT scans showed that the demarcation line was most visible and substantially deeper in the I-CXL 10 min group. Confocal microscopy showed greater anterior stromal keratocyte decreases in the I-CXL 10 min group than in the I-CXL 5 min group at 3 and 6 mo postoperatively(P<0.001); however, anterior stromal keratocytes and subbasal nerve density were not significantly different between the two groups at 12 mo postoperatively. CONCLUSION: I-CXL for 10 min more effectively halts the progression of keratoconus than I-CXL for 5 min after 12 mo of follow-up. However, long-term studies are needed to evaluate the efficacy and safety of I-CXL.

Iontophoresis-assisted corneal crosslinking using 0.1% riboflavin for progressive keratoconus

AIM：To report the clinical results of iontophoresis-assisted epithelium-on corneal crosslinking（I-CXL） using 0.1% riboflavin in distilled water for progressive keratoconus. METHODS：In this prospective clinical study, we examined 94 eyes of 75 patients with progressive keratoconus who were treated with I-CXL using 0.1% riboflavin in distilled water. Best correct visual acuity（BCVA）, Scheimpflug tomography, corneal topography, anterior segment optical coherence tomography, intraocular pressure, and endothelial cell density were evaluated at baseline and 1, 3, 6, 12, and 24 mo after I-CXL.RESULTS：After 24 mo I-CXL, compared to the level at baseline, BCVA significantly improved 0.14±0.07（P=0.010）; mean keratometry signifi cantly decreased 0.72±1.97（P=0.021）; maximum keratometry significantly reduced 2.30±5.01（P=0.014）; central keratoconus index significantly reduced 0.04±0.08（P=0.007）. The demarcation line was visible in 83.1% of eyes at 1mo after treatment, with a depth of 298.95±51.97 μm, and gradually indistinguishable. One eye had repeat treatment. Intraocular pressure and endothelial cell density did not change significantly.CONCLUSION：I-CXL using 0.1% riboflavin halts keratoconus progression within 24 mo, resulting in a significant improvement in visual and topographic parameters. Moreover, the depth of the demarcation line is similar to that previously reported in standard epithelium-off CXL procedures.

Efficacy of iontophoresis-assisted epithelium-on corneal cross-linking for keratoconus

Corneal cross-linking（CXL） is a noninvasive therapeutic procedure for keratoconus that is aimed at improving corneal biomechanical properties by induction of covalent cross-links between stromal proteins. It is accomplished by ultraviolet A（UVA） radiation of the cornea, which is first saturated with photosensitizing riboflavin. It has been shown that standard epithelium-off CXL（S-CXL） is efficacious, and it has been recommended as the standard of care procedure for keratoconus. However, epithelial removal leads to pain, transient vision loss, and a higher risk of corneal infection. To avoid these disadvantages, transepithelial CXL was developed. Recently, iontophoresis has been adopted to increase riboflavin penetration through the epithelium. Several clinical observations have demonstrated the safety and efficacy of iontophoresisassisted epithelium-on CXL（I-CXL） for keratoconus. This review aimed to provide a comprehensive summary of the published studies regarding I-CXL and a comparison between I-CXL and S-CXL. All articles used in this review were mainly retrieved from the Pub Med database. Original articles and reviews were selected if they were related to the I-CXL technique or related to the comparison between I-CXL and S-CXL.

Pial iontophoresis of ferric chloride versus cortical ferric chloride injection in establishing iron-induced posttraumatic epilepsy animal models

BACKGROUND： In order to study the pathogenesis of iron-induced posttraumatic epilepsy （PTE）, foreign scholars have established several kinds of PTE animal models, among which, the iron- induced PTE animal models proposed by Willmore is the most famous. The iron-induced PTE animal models can be established by two methods： one is cortical ferric chloride injection （CFCI） and the other one is pial iontophoresis of ferric chloride （PIFC）. Because Willmore did not give out the elaboration of the behaviors and electroencephalograms （EEGs） of the iron induced PTE animal models established by these two methods, so we have known little about these animal models. OBJECTIVE： To observe the behaviors and EEGs of the iron-induced PTE animal models established by PIFC and CFCI, in order to compare the differences and the study value of these two methods. DESIGN： Qualitative controlled observation tria SETTING： Department of Neurosurgery, Urumqi General Hospital, Lanzhou Military Area Command of Chinese PLA. MATERIALS： Forty healthy adult male SD rats, weighing 200 to 250 g, were involved in this experiment. Reagents and instruments： Ferric chloride （FeCl3·6H2O, Sigma USA）, rat stereotaxic apparatus （ASI company, USA）, the wireless blue tooth electroencephlograms recording system （Nuocheng electric Co.Ltd, Shanghai）, a set of air turbine dental drill unit, dental base acrylic resin powder, microinjector （50 μL）, amperemeter （1 mA）, a pair of batteries, electric resistance （200 kΩ） , variable resistance （100 kΩ）, tubule with endo-meridians of 2 mm （used as import tube）, several silver wire segments and several acupuncture needles were employed in this study. METHODS： This study was carried out in the Experimental Animal Center of the Urumqi General Hospital, Lanzhou Military Area Command of Chinese PLA between November 2004 and April 2005. Establishing the PET animal models by CFCI method： Twenty SD rats were taken, intraperitoneally anesthetized with 50 mg/kg barbanylum and fixed on stereotaxic apparatus. A cranial burr hole with the diameter of 2 mm was drilled 3 mm behind the coronal suture and 2 mm lateral to the sagittal line on the left cranium. Another 5 cranial burr holes with diameter of 2 mm were drilled to place electrodes. The positions of holes were set that taking bregma as original point, sagittal line as Y-axis, the line through the original point and vertical to the Y-axis as X-axis. The unit of the coordinate axis was mm. The coordinate value of the electrodes were （4, 0）, （4, -6）, （-4, 0）, （-4, -6）, at last, a hole with the diameter of 2 mm was drilled on the center of the coronale. 5 μL ferric chloride solution （FeCl3, 100 mmol/L, pH 1.5） was injected into the sensorimotor cortex of rats using microinjector within 5 minutes. The needling depth was 3 mm. The needle was retained for 5 minutes so as to prevent the outflow of liquid. Establishing the PTE animal models by PIFC method： Twenty SD rats were chosen and weighed, and the procedures after weighing were as above.A cranial burr hole with the diameter of 4 mm was drilled in the position where needle inserted in animal models established by CFCI method. Cerebral dura mater was cut. Another 5 holes were drilled to place electrodes in the same position as above. The tip of tubule cotton stuffed inside （to prevent the rapid flow of FeCl3 solution, 100 mmol/L, pH 1.5） was gently connected to cerebral pia mater. The positive and negative electrodes of the amperemeter whose output current was 100 μA were connected to acupuncture needles. The acupuncture needle, which was connected to positive electrode, was inserted into ferric chloride solution, and that which was connected to negative electrode was inserted into the right forelimb of rats subcutaneously. The rats were galvanized for 10 minutes. Record of EEG： The silver wire with blunt anterior extremity was placed on the cerebral dura mater. Then, silver wire and cranial bones were firmly fixed with dental base acrylic resin power. The other side was connected to the wireless blue tooth electroencephlograms recording system to monitor EEG changes. Assessment criteria of seizure degree： Grade Ⅰ ： ＂wet dog-like＂ shudder, facial muscle convulsion and chewing;Grade Ⅱ： rhythmical nodding：Grade Ⅲ： forelimb clonus：Grade Ⅳ： forelimb clonus while standing： Grade Ⅴ： lost the balance, vert, limb＇s convulsion and the whole body＇s tic. MAIN OUTCOME MEASURES： Behaviors and EEGs changes of iron-induced PTE animal models established by PTFC and CFCI. RESULTS： All the 40 rats were involved in the result analysis. （1） The changes of the behaviors： The two animal models both had the epileptic seizures. The epileptic seizure of the animal model established by PIFC mainly presented automatic behavior of chewing, and facial muscle convulsion accompanied with chewing. Epileptic seizure reached the peak within 2.5 to 7 hours after model establishing.It was gradually decreased within 24 hours and hardly seen 1 day after model establishing. The epileptic seizure of the rat model established by CFCI mainly presented turnover upspring and limbs＇ convulsion and urinary incontinence accompanied. The epileptic seizure reached the peak within 3 to 8 hours.It was relatively frequent within 1 week and gradually decreased within 2 weeks after model establishing. The PTE animal models established by CFCI were more closed to clinical PTE process. （2） The form of seizures： The epileptic seizures of the rat model established by PIFC mainly presented grade Ⅰ , seldom presented grades Ⅲ, Ⅳ and Ⅴ; The epileptic seizures of rat model established by CFCI mainly presented the head turning to the right, body＇s rotation, then appeared as grades Ⅳ and Ⅴ, and the whole procedure lasted 1 minute. At the interval of big seizures, grade Ⅰ was observed. From the respect of seizure manifestation, the PTE models established by CFCI were more similar to human PTE. （3） EEGs changes： The sharp waves with average frequency of 9.66 Hz and average amplitude of 183.90 μV were observed on the EEGs of the model established by PIFC when the rats were suffering seizures. The spike waves with average frequency of 16.01 Hz and average amplitude of 143.60 μV were observed on the EEGs of the model established by CFCI when the rats were suffering seizures. CONCLUSTON： （1）Iron-induced PTE rat model is stable and credible. （2）Compared with PTE animal model established by PIFC, PTE animal model established by CFCI is a chronic animal model, and its seizure manifestation is more similar to human PTE. so it is worth further studies.

Effects of ginger moxibustion combined with Chinese medicine iontophoresis on patients with primary dysmenorrhea

Objective:To observe the effects of Ginger moxibustion combined with iontophoresis with traditional Chinese medicine on the improvement of symptoms, serum platelet activating factor (PAF) level and uterine artery pulsation index in patients with primary dysmenorrhea.Methods 114 patients with primary dysmenorrhea who were treated in our hospital from August 2017 to February 2019 were divided into two groups according to the different treatment schemes. 57 patients in the control group were treated with ibuprofen capsules, and 57 patients in the study group were treated with Ginger moxibustion combined with iontophoresis with traditional Chinese medicine. After three menstrual cycles of treatment, the curative effect was evaluated and the improvement of symptoms was counted. PAF, PAF-AH and platelet adhesion rate were compared, uterine artery hemodynamics was measured, and levels of serum hs-CRP and IL-6 were measured.Results The overall response rate of the study group was significantly higher than that of the control group (P < 0.05). After treatment, the scores of different symptoms in the two groups were significantly lower than those before treatment (P < 0.05), and the scores of different symptoms in the study group were significantly lower than those in the control group (P < 0.05). After treatment, PAF and platelet adhesion rate in the two groups were significantly lower than those before treatment (P < 0.05), PAF-AH was significantly higher than that before treatment (P < 0.05), and PAF and platelet adhesion rate in the study group were significantly lower than those in the control group (P < 0.05), PAF-AH was significantly higher than that in the control group (P < 0.05). After treatment, the pulsation index, resistance index and peak systolic-diastolic ratio in the study group were significantly lower than those before treatment (P < 0.05), and the pulsation index, resistance index and peak systolic-diastolic ratio in the study group were significantly lower than those in the control group (P < 0.05). After treatment, the levels of serum hs-CRP and IL-6 in the two groups were significantly lower than those before treatment (P < 0.05), and the levels of serum hs-CRP and IL-6 in the study group were significantly lower than those in the control group (P < 0.05).Conclusions Ginger moxibustion combined with iontophoresis with traditional Chinese medicine is helpful to improve the overall response rate of primary dysmenorrhea treatment, reduce the score levels of different symptoms, rationally improve PAF, PAF-AH, platelet adhesion rate, and the pulse index, resistance index, peak systolic-diastolic ratio are decreased significantly, and serum hs-CRP and IL-6 levels tend to be normal.

5% Ibuprofen Iontophoresis Compared with Transcutaneous Electrical Nerve Stimulation in the Management of Knee Osteoarthritis: A Feasibility Study

Objective: The study compared the inclusions of 5% ibuprofen iontophoresis and Transcutaneous Electrical Nerve stimulation (TENS) in the management of osteoarthritis (OA) of the knee joint. Subjects and Methods: Patients diagnosed with knee OA and referred for physiotherapy at a tertiary health facility in Accra, Ghana participated in the study. They were alternately assigned into either TENS or iontophoresis groups. Patients in TENS Group received conventional TENS mode while those in iontophoresis group were treated with 5% ibuprofen iontophoresis using galvanic electrical current. Both protocols were performed twice weekly for six weeks in addition to their prescribed therapeutic exercises. 15-minute walking time, Numerical Rating Scale and Goniometer were used as the main outcome measures to determine subjects’ walking speed, pain and active range of motion (AROM) respectively. Treatment evaluation was performed at baseline, week 3 and week 6 by an independent assessor. Comparisons of variables within and between groups were tested using Friedman’s mean rank and Mann-Whitney U tests respectively at p 0.05) for all the outcome measures. Conclusion: 5% ibuprofen iontophoresis and TENS add equal therapeutic value in the management of knee OA. Consideration of both modalities as adjuncts to therapeutic exercises is therefore worthwhile for managing the condition.

Iontophoresis-assisted versus standard corneal crosslinking for progressive keratoconus

Background:To compare the safety and efficacy of iontophoresis-assisted epithelial-on corneal crosslinking(I-CXL)using 0.1%riboflavin-distilled water solution with standard epithelium-off corneal crosslinking(S-CXL)for progressive keratoconus.Methods:In a retrospective analysis,progressive keratoconus patients treated with I-CXL(17 eyes of 17 patients)or S-CXL(13 eyes of 13 patients)were included.All patients were followed up at least 12 months.All patients underwent detailed ophthalmologic examinations involving pre-and postoperative visual acuity,topographic parameters and pachymetry.Intra-and postoperative complications were recorded.Results:No statistically significant differences were observed between the two groups at baseline with respect to visual acuity,age and thinnest corneal thickness(TCT).The postoperative decreases of K1 and Kmean in the S-CXL group represented statistically significantly better results than in the I-CXL group(t=2.093 and 2.123,P=0.046 and 0.043,respectively).Alterations of other parameters showed no significant differences between the two groups.There were no failure cases in the two groups.Conclusions:I-CXL using 0.1%riboflavin-distilled water solution provided effective treatment for progressive keratoconus at 12-month follow-up.However,the decreases of K1 and Kmean caused by I-CXL were less than those by S-CXL.Although treatment time,postoperative patient pain and risk of infection in I-CXL are all less than those in S-CXL,I-CXL is unable to completely replace S-CXL for progressive keratoconus temporarily.

Relationship between transdermal energy of electroporation and iontophoresis and permeably fluxes of tetracaini hydrochlordum and naproxenum

Transdermal drug delivery (TDD) using electroporation is an attractive novel method of facilitated transport of compounds across skin that a short electrical pulse is applied to the skin, forcing the creation of a reversible transient aqueous pore to enhance drugs transdermal permeability. Most of prior researches are difficult to put into the practical use, such as stimulation for user and designing electroporater apparatus for TDD, due to pulse with high intensive. In this paper, the effect of electroporative energy on the transdermal fluxes of Tetracaini Hydrochlordum (TH) and Naproxenum is studied to explore a way of electroporative technique with low voltage. We applied a 120 V and 4.2 J square pulse to SD male rats skin on abdomen, the transdermal flux of TH increased 5.1 times more than the passive transport. While a 400 V and 37.6 J exponential decaying pulse was employed to same skin, the transdermal flux of Naproxenum was 3.5 times than passive transport. The results show that: (1) drugs transdermal permeably flux will create a saturation as the electroporative energy raises to threshold; (2) the transdermal energy efficiency (F/E value) declines as time extends; and (3) the effect of electroporation is concerned with the transdermal energy and drugs characteristics, electroporation is more effective than iontophoresis for TH, but conversely for Naproxenum.

Therapeutic Efficacy Observation on Point-toward-point Acupuncture Combined with Herbs Iontophoresis for Knee Osteoarthritis

Objective： To observe the clinical efficacy of point-toward-point acupuncture combined with herbs iontophoresis in treating knee osteoarthritis. Methods： A total of 100 patients were randomly divided into a treatment group and a control group, 50 cases in each. Patients in the treatment group received point-toward-point acupuncture with long needle combined with herbs iontophoresis treatment; while those in the control group were only treated by point-toward-point acupuncture with long needle. Clinical efficacies of the two groups were compared after treatment. Results： The total effective rate was 92.0% in the treatment group, versus 82.0% in the control group, and the difference was statistically significant （P〈O.05）. Conclusion： The point-toward-point acupuncture with long needle combined with herbs iontophoresis treatment for knee osteoarthritis has a significant effect.

Electroacupuncture combined with iontophoresis of Chinese medicine for lumbar intervertebral disc herniation

Objective：To observe the clinical efficacy of electroacupuncture （EA） combined with iontophoresis of Chinese medicine for lumbar intervertebral disc herniation （LIDH）. Methods： A total of 80 LIDH cases were randomly allocated into a treatment group and a control group by the random number table, 40 in each group. Cases in the treatment group were treated with EA combined with iontophoresis of Chinese medicine, whereas cases in the control group were treated with EA alone. Cases in both groups were treated once a day, 10 times for one course and there was a 3-day interval between two courses. The therapeutic efficacies in two groups were assessed after two courses of treatment. The short-form McGill pain questionnaire （SF-MPQ） and Japanese Orthopedic Association （JOA） low back pain evaluation questionnaire were used for the scoring system before treatment, after the first treatment and 2 courses of treatment. Results： After two courses of treatment, the total effective rate was 95.0% in the treatment group, versus 87.5% in the control group, showing a statistical difference （P〈0.05）. The therapeutic efficacy in the treatment group was significantly better than that in the control group after the first treatment and 2 courses of treatment. The score of SF-MPQ in the treatment group was more significantly decreased and the JOA score in the treatment group was more significantly increased, showing statistical differences （P〈0.01）. Conclusion： EA at Jiaji （EX-B2） points combined with iontophoresis of Chinese medicine is better than EA alone in alleviating low back and leg pain and improving functions of the low back and leg as well as the quality of life of LIDH patients .

Warm Needling Combined with Iontophoresis of Chinese Medicine for Temporomandibular Joint Disorder

Objective: To observe the clinical efficacy of warm needling combined with iontophoresis of Chinese medicine for temporomandibular joint disorder(TMD). Methods: A total of 100 TMD cases were randomly allocated into a treatment group and a control group, 50 in each group. Cases in the treatment group were treated with warm needling combined with iontophoresis of Chinese medicine, whereas cases in the control group were treated with Western medication. The therapeutic efficacies in two groups were assessed after three courses of treatment. Results: The recovery rate and total effective rate were 54.0% and 98.0% respectively in the treatment group, versus 30.0% and 82.0% in the control group, showing significant differences(both P<0.05). The recovery rates in the treatment group were higher than those in the control group respectively after 1, 2 and 3 courses of treatment, indicating that warm needling combined iontophoresis of Chinese medicine could substantially shorten the course of treatment. Conclusion: Warm needling combined with iontophoresis of Chinese medicine is remarkably effective for TMD and deserves further clinical application.

The Effects of Some Penetration Enhancers on the Transdermal Iontophoretic Delivery of Insulin in Vitro *

The effects of some commonly used penetration enhancers such as laurocapram (AZ), oleic acid (OA), poloxamer (POL) and propylene glycol (PG) on the in vitro transdermal iontophoretic delivery of insulin through full-thickness mouse skin were investigated. The results showed that AZ had a synergistic effect on iontophoretic ability to enhance skin permeation of insulin, and PG could further increase this effect. 5% AZ / PG increased the iontophoretic steady state flux of insulin by a factor of 2.75 compared to that treated with iontophoresis alone. OA did not further enhance iontophoretic effect to increase skin permeation of insulin. The combination of iontophoresis and some enhancer provided a novel idea and possibility for transdermal delivery of insulin.

Passive Electrical Properties of Animal Skin and Human Epidermal Membranes In vitro

\ The suitability of three animal skin species as the model for iontophoresis study was discussed based on the current density measurement, compared with the electrical properties of the human epidermal membrane (HEM) in vitro. The hydration during 48 h period significantly and continuously decreased the animal skin resistance and had much smaller influence on the HEM. The relationship between the pulse voltage and the current across these skin models was similar to those of HEM in different hydration status, but there were some variations in the extent due to the various sensitivities. The profiles could be simulated by the equation of V=(4ART/F) sinh-1 (BI). The parameters A reflected the sensitivity of the skin species to the electrical field. The hairless mouse skin and hairless guinea pig skin were more sensitive than the HEM, the sensitivity of the hairless rat skin was the lowest among the skin species. The results were further proved by the tests of long period voltage regimens, but it was found that significant alteration of the skin resistance occurred in the very short time as the electrical field was set up or discontinued.

Physiological approaches to understanding molecular actions on dorsolateral prefrontal cortical neurons underlying higher cognitive processing

Revealing how molecular mechanisms influence higher brain circuits in primates will be essential for understanding how genetic insults lead to increased risk of cognitive disorders. Traditionally, modulatory influences on higher cortical circuits have been examined using lesion techniques, where a brain region is depleted of a particular transmitter to determine how its loss impacts cognitive function. For example, depletion of catecholamines or acetylcholine from the dorsolateral prefrontal cortex produces striking deficits in working memory abilities. More directed techniques have utilized direct infusions of drug into a specific cortical site to try to circumvent compensatory changes that are common following transmitter depletion. The effects of drug on neuronal firing patterns are often studied using iontophoresis, where a minute amount of drug is moved into the brain using a tiny electrical current, thus minimizing the fluid flow that generally disrupts neuronal recordings. All of these approaches can be compared to systemic drug administration, which remains a key arena for the development of effective therapeutics for human cognitive disorders. Most recently, viral techniques are being developed to be able to manipulate proteins for which there is no developed pharmacology, and to allow optogenetic manipulations in primate cortex. As the association cortices greatly expand in brain evolution, research in nonhuman primates is particularly important for understanding the modulatory regulation of our highest order cognitive operations.

Fifty-six Cases of Protrusion of Lumbar Intervertebral Disc Treated by Penetration and Oral Administration of Chinese Decoction Plus Traction

Fifty-six cases of the protrusion of the lumbar intervertebral disc in the treatment group were treated by drug-penetration and oral administration of traditional Chinese decoction plus traction, and the other 35 cases in the control group by oral administration of Chinese decoction and traction. The results showed that the cure rate in the treatment group was 83.9%, and that in the control group was 57.1%, with a statistically significant difference between the two groups (P<0.01), indicating that the former is a more effective therapy for protrusion of the lumbar intervertebral disc.

Surging footprints of mathematical modeling for prediction of transdermal permeability

In vivo skin permeation studies are considered gold standard but are difficult to perform and evaluate due to ethical issues and complexity of process involved. In recent past, a useful tool has been developed by combining the computational modeling and experimental data for expounding biological complexity. Modeling of percutaneous permeation studies provides an ethical and viable alternative to laboratory experimentation. Scientists are exploring complex models in magnificent details with advancement in computational power and technology. Mathematical models of skin permeability are highly relevant with respect to transdermal drug delivery, assessment of dermal exposure to industrial and environmental hazards as well as in developing fundamental understanding of biotransport processes.Present review focuses on various mathematical models developed till now for the transdermal drug delivery along with their applications.

Transdermal drug delivery models

In this paper, a preliminary study based on the different models of the skin impedance is carried out. The purpose is to examine the drug delivery method through iontophoresis, which relies on active trans- portation of the charged medication agent within an electric field. It is a kind of transdermal drug delivery method, and hence the method has to handle the variability in skin characteristics of a patient. This paper carries out a simulation study based on three different skin impedance models.

Evaluation of microvascular reactivity with laser Doppler flowmetry in chronic kidney disease

Cardiovascular diseases are the major causes of mortality in patients with chronic kidney disease(CKD).The complex process of accelerated athero- and arteriosclerosis in CKD is associated with this phenomenon,where endothelial dysfunction(ED) is one of the initial steps. Hence, the early diagnosis of ED can potentially lead to early interventions which could result in a better outcome for these patients. Several methodologies have been developed for the diagnosis of ED. Laser Doppler flowmetry(LDF) enables us to study the microcirculation continuously in a non-invasive manner. In our review we would like to focus on different tests developed for LDF, like postocclusive reactive hyperaemia,local heating, iontophoresis, microdialysis or analysis of flowmotion. We would also like to summarize the available data in CKD with these methodologies to enlighten their perspectives in the clinical use on this patient population.

Management of Spinal Osteochondrosis Rehabilitation Process

Background： Osteochondrosis of spine is the one of the most prevalent diseases among the all musculoskeletal conditions. Osteochondrosis is not a curable condition and its treatment/rehabilitation is a long-term process. The present work aims to assess clinical effectiveness and duration of outcomes of rehabilitation that includes complex and consequent methods （algorithm） of treatment. The pilot study has been continuing several years and now is going on. Methods： The subject were 220 patients, 122 females and 98 males, aged 50-65 （adherence to treatment 100%） with as reflex as well radicular syndromes in subacute phase. Informed consent was obtained from all patients. Rehabilitation process continued 2.5-3 months and its management included the following consequent methods： waist fixation, pain control with medication （NSAIDs and in some cases steroidal drugs）, iontophoresis with karipazim-20-25 sessions, after 8-10 sessions of the latter manual therapy was added-10-12 sessions, and kinesiotherapy （3 times per week） after 5 procedures. After pain management recommendation of daily life activity was given. Oral chondroprotectors after completion of a treatment were administered. Dynamic evaluation of subjective and objective symptoms, mobility and functional state of spine were done. Parameters were assessed before treatment, after 3 month and 1-3 years upon its completion. Results： Data were analyzed using SPSS program. Obtained results showed that after the first course of treatment （3 months） positive outcomes were observed in 198 patients （90%）, 22 （10%） of patients required the second course of rehabilitation. Stable outcome of treatment was maintained after 1 year in 204 patients （92.7%） and after 3 years in 196 patients （89%）. Conclusion： Approbated complex of treatment is established to be effective in rehabilitation of patients with lumbar osteochondrosis.

Enhanced Iontophoretic Delivery of Magnesium Ascorbyl 2-Phosphate and Sodium Fluorescein to Hairless and Hairy Mouse Skin

We recently reported that L-ascorbic acid 2-phosphate (AP) stimulates the growth of human dermal papilla (DP) cells, induces secretion of IGF-1 from the DP cells to promote hair shafts elongation in cultured human hair follicles, and triggers early progression from the telogen to anagen phase in mice. Since the magnesium salt of AP (APMg) is a highly hydrophilic ionic molecule, it is not easy to deliver this reagent to the skin or hair follicles by topical application alone. In order to enhance skin penetration of APMg without changing any molecular properties, a non-invasive iontophoretic delivery method was introduced. Iontophoresis of the negatively charged APMg under the electrode bearing same charge (cathode) significantly enhanced the in vitro penetration of APMg into a Franz cell equipped with mouse dorsal skin. In contrast, iontophoretic movement with the anode inhibited APMg penetration achieved with passive diffusion alone. The effect of iontophoresis on enhancing the penetration of APMg was also found to be much higher in the skin of hairy mice (3 - 8 times) compared to hairless mice (1.5 - 2.5 times). These findings indicated that iontophoretic movement induced the transfollicular pathway more strongly and effectively than the transdermal pathway. This phenomena was also demonstrated by the in vivo iontophoretic delivery of sodium fluorescein using hairy and hairless mice. The degree of iontophoretic enhancement during APMg penetration was also dependent on various conditions such as current density and application duration.