A case of in vivo iontophoresis-assisted corneal collagen cross-linking for keratoconus: An immunohistochemical study.

The standard corneal collagen cross-linking (CXL), that includes the removal of corneal epithelium to permit adequate penetration of riboflavin in the stroma, is an established procedure to halting keratoconus progression. However, as epithelial removal may cause postoperative pain and an increased risk of corneal infection, new therapeutic approaches have been proposed. Iontophoresis is a recently developed non-invasive technique which provides the use of electrical current during CXL to enhance transepithelial penetration of riboflavin into the corneal stroma. Here, we describe for the first time the morphological changes of the corneal stromal compartment in a patient with keratoconus who underwent in vivo iontophoresis-assisted CXL (ionto-CXL) before full-thickness corneal transplantation. Immunohistochemistry for type I collagen and CD34 was performed to investigate the stromal distribution of collagen fibers and keratocytes, respectively. The histology of ionto-CXL-treated keratoconic cornea, collected 6 months after the intervention, was compared with that of healthy corneas and either untreated or standard CXL-treated keratoconic corneas. An attempt to restore a normal stromal architecture was observed in the ionto-CXL-treated cornea compared with untreated keratoconic corneas. In particular, the ionto-CXL-treated cornea showed a parallel distribution of type I collagen fibers, although fiber interweaving appeared less organized than in healthy corneas and standard CXL-treated keratoconic corneas. Moreover, the distribution of CD34-positive keratocytes was improved in keratoconic corneas following ionto-CXL treatment, though a scattered CD34 immunoreactivity was still noticeable in the subepithelial stroma. This study provides histological evidence that ionto-CXL may represent a non-invasive alternative in the management of progressive keratoconus in adults.

Characterization of solute distribution following iontophoresis from a micropipet.

Iontophoresis uses a current to eject solution from the tip of a barrel formed from a pulled glass capillary and has been employed as a method of drug delivery for neurochemical investigations. Much attention has been devoted to resolving perhaps the greatest limitation of iontophoresis, the inability to determine the concentration of substances delivered by ejections. To further address this issue, we evaluate the properties of typical ejections such as barrel solution velocity and its relation to the ejection current using an amperometric and liquid chromatographic approach. These properties were used to predict the concentration distribution of ejected solute that was then confirmed by fluorescence microscopy. Additionally, incorporation of oppositely charged fluorophores into the barrel investigated the role of migration on the mass transport of an ejected species. Results indicate that location relative to the barrel tip is the primary influence on the distribution of ejected species. At short distances (<100 µm), advection from electroosmotic transport of the barrel solution may significantly contribute to the distribution, but this effect can be minimized through the use of low to moderate ejection currents. However, as the distance from the source increases (>100 µm), even solute ejected using high currents exhibits diffusion-limited behavior. Lastly a time-dependent theoretical model was constructed and is used with experimental fluorescent profiles to demonstrate how iontophoresis can generate near-uniform concentration distributions near the ejection source.

Reducing the risk of burns and shocks during lontophoresis.

Although uncommon, burns and shocks can occur during iontophoresis treatments. A thorough understanding of the proper operation of iontophoresis equipment, along with proper preparation of the treatment site, can significantly reduce the likelihood of injuries.

Current concepts in assessment of microvascular endothelial function using laser Doppler imaging and iontophoresis.

Effective evaluation of endothelial function is a powerful tool for determining patients at risk of development and progression of cardiovascular disease. As an alternative to invasive tests of endothelial function, several noninvasive methods have been developed, including the use of laser Doppler flowmetry/imaging to measure cutaneous perfusion accompanied by iontophoresis of acetylcholine and sodium nitroprusside. It is clear from previous studies that this technique provides an easy, validated, and reproducible method for investigators to assess and monitor endothelial function in patients with a variety of pathologic conditions, but it may also be used to examine disease progression over time and responsiveness to treatment, thereby facilitating clinical trials. However, a standardization of protocols would help reduce the apparent controversy seen in the literature. With its increasing use by other groups, it is anticipated that further published studies will help to provide a better understanding of the development and progression of cardiovascular disease.

Reverse iontophoresis of L-lactate: in vitro and in vivo studies.

This work investigates the reverse iontophoretic extraction of lactate, a widely used marker of tissue distress in critically ill patients and of sports performance. In vitro experiments were performed to establish the relationship between subdermal lactate levels and lactate iontophoretic extraction fluxes. Subsequently, the iontophoretic extraction of lactate was performed in vivo in healthy volunteers. Lactate was quickly and easily extracted by iontophoresis both in vitro and in vivo. During a short initial phase, iontophoresis extracts the lactate present in the skin reservoir, providing information of relevance, perhaps, for dermatological and cosmetic applications. In a second step, lactate is extracted from the interstitial subdermal fluid allowing local lactate kinetics to be followed in a completely non-invasive way. The simultaneous in vivo extraction of chloride, and its possible role as an internal standard to calibrate lactate reverse iontophoretic fluxes, was also demonstrated. Despite these positive findings, however, considerably more research is necessary to eliminate potential artefacts and to facilitate interpretation of the data.

Sweat testing infants detected by cystic fibrosis newborn screening.

OBJECTIVE: Describe and define limitations of early pilocarpine iontophoresis (sweat testing) for cystic fibrosis (CF) newborn screening (NBS). STUDY DESIGN: Population-based results from follow-up of CF NBS-positive newborns. RESULTS: Insufficient quantity of sweat is more likely if the sweat test is done too early, but testing is generally successful after 2 weeks of age. Sweat chloride levels drop over the first weeks of life. CF carriers have higher sweat chloride concentrations than non-carriers. CONCLUSIONS: Sweat testing can be performed effectively after 2 weeks of age for CF NBS-positive newborns. Earlier testing has a higher risk of insufficient sweat for completing testing.

Electroosmosis in transdermal iontophoresis: implications for noninvasive and calibration-free glucose monitoring.

Reverse iontophoresis uses a small low electric current to noninvasively extract blood analytes, e.g., glucose, across the skin. The simultaneous quantification of the analyte extracted and of an additional endogenous substance of fixed and known concentration in the body permits the blood level of interest to be found without the need for an invasive calibration procedure. The transport phenomena underlying this approach, applied to glucose monitoring, has been investigated in vitro, using Na+ and neutral model solutes as endogenous "internal standards" (specifically, urea, glycerol, mannitol, and sucrose). The cathodal extracted fluxes of glucose under conditions of modified skin permselectivity were related to those of the different, potential internal standards. Flux ratios depended upon the iontophoretic conditions and the size of the neutral internal standards, whereas high variability was observed with Na+. Constant flux ratios were obtained with mannitol, glycerol, urea, and sucrose for which the mechanism of electrotransport was identical to that of glucose. The advantage of using a neutral internal standard, however, must be weighed against the need to identify and validate the marker under physiological conditions and the additional analytical chemistry necessary for the practical quantification of this substance.

Ion-exchange fibers and drugs: a novel device for the screening of iontophoretic systems.

The objective of this study was to theoretically model and experimentally measure the extent of drug release from ion-exchange fibers. The release was measured as a function of current density and NaCl concentration using a novel iontophoretic cell. The fibers tested contained weak carboxylate (-COOH) ion-exchange groups. The cationic model drugs tacrine and metoprolol were chosen on the basis of previous research, where tacrine had the lowest release rate and metoprolol the highest release rate. An in-house designed three compartment test cell was developed to test the suitability of drugs for iontophoretic drug delivery. In this cell, the anode and the drug containing ion-exchange fiber compartments were separated with a Nafion ion-selective membrane, while the fiber and the return electrode compartments were separated with a porous membrane. Tacrine proved to be a good drug candidate for this system as the release of the tacrine from the device was controllable with salt concentration and current density. Metoprolol release from the device was, however, not controllable.

Noninvasive glucose monitoring by reverse iontophoresis in vivo: application of the internal standard concept.

BACKGROUND: The GlucoWatch Biographer uses reverse iontophoresis to extract glucose across the skin to monitor glycemia in diabetes. The invasive daily calibration with a conventional "fingerstick" has been perceived as a disadvantage. We used an "internal standard" to render the approach completely noninvasive. METHODS: The simultaneous extraction of glucose and sodium by reverse iontophoresis was performed on human volunteers over 5 h, and blood glucose was measured in the conventional manner at each collection interval. These data were used for each volunteer to calculate an extraction constant (K), which equals the ratio of the extracted fluxes (JGlucose/JNa+) normalized by the corresponding ratio of the concentrations in the blood ([Glucose]/[Na+]). The values of K were compared between and within volunteers. RESULTS: The iontophoretically extracted glucose flux reflected the glucose concentration profiles in the blood, and sodium extraction remained essentially constant, consistent with the fact that its systemic concentration does not vary significantly. A constant value of K was established for two thirds of the study population. However, the efficiency of glucose extraction varied seasonally, whereas the reverse iontophoresis of Na+ did not; i.e., variation in K became apparent. CONCLUSIONS: Use of the sodium ion as an internal standard could refine the determination of glycemia by reverse iontophoresis without requiring calibration with a blood sample.

Iontoforesis en el diagnóstico de fibrosis quística

La fibrosis quística es un desorden autosómico recesivo en el cual se compromete el transporte del cloro a través de las células epiteliales de diferentes órganos. Las manifestaciones son diversas, ya que se pueden afectar diferentes órganos. La prueba del sudor o iontoforesis continúa siendo uno de los exámenes más específicos e importantes para el diagnóstico de fibrosis quística. Esta prueba debe ser realizada en todo niño que presente un enfermedad pulmonar recurrente, infecciones a repetición, manifestaciones obstructivas bronquiales, enfermedad hepática, pólipos nasales, pancreatitis o malabsorción. Es importante tener en cuenta las implicaciones que tiene un diagnóstico oportuno en el niño; mientras más temprano se sospeche y se compruebe el diagnóstico, mejor calidad de vida se le podrá brindar al paciente.

Iontophoresis in drug delivery: basic principles and applications.

Passive delivery of most compounds across different epithelia is limited due to the barrier properties afforded by these epithelia. Iontophoresis is a novel drug delivery system designed to improve the delivery rate of compounds. The technique generates an electrical potential gradient that facilitates the movement of solute ions across the membrane. Iontophoresis has been used has been used greatest success in therapy of hyperhidrosis. The potential of iontophoresis for systemic delivery is being rediscovered, and the technique has been observed to be particularly effective for ionic drugs. It also enhances transdermal permeation of neutral compounds by the process of electroosmosis. The recent enthusiasm for iontophoresis may also be attributed to successful production of therapeutically active protein and peptide drugs by employing recombinant DNA technology. Because of their charged nature and relatively large molecular size, iontophoresis may provide means for their effective delivery. This review discusses the basic principles and applications of iontophoresis in dermatology, ophthalmology, otolaryngology, and dentistry. In addition, the systemic applications of iontophoresis with emphasis on protein and peptide delivery are reviewed.

Iontophoretic delivery of morphine for postoperative analgesia.

Iontophoresis is a method of transdermal administration of ionized drugs in which electrically charged molecules are propelled through the skin by an external electrical field. This was a prospective, randomized, single-blind study to determine the effectiveness of iontophoretically delivered morphine HCl for the control of postoperative pain. Thirty-eight patients who underwent total knee or hip replacement completed this clinical trial. Informed consent was obtained before surgery and patients were instructed on the use of a patient-controlled analgesia (PCA) device. Postoperatively, pain in the recovery room was initially controlled with IV meperidine, and thereafter with PCA therapy using meperidine, 2 mg/cc, with a dose of 10 mg IV and a lock-out period of 15 min. The dose was adjusted as necessary and the lock-out period remained the same. The number of patient requests and the dose (mg) administered was recorded hourly. On the morning following surgery, iontophoresis devices were attached for 6 hr to patients who received either morphine HCl or lactated ringers solution. During this period and for 12 hr following completion of iontophoresis, PCA analgesia remained available to patients. Venous blood samples for determination of morphine levels were obtained every 30 min during iontophoresis, then every 60 min for 2 hr following iontophoresis. Of the 38 patients, 17 received iontophoresed morphine, and 21 received iontophoresed lactated ringers. The morphine group utilized the PCA device more than the control group during the baseline period. However, following the institution of iontophoresis and continuing up to 12 hr following completion of iontophoresis, the morphine group used significantly less PCA meperidine to maintain analgesia than the control group (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

[Simulation studies on depot iontophoresis]. / Simulationsversuche zur Depot-Ionophorese.

The rapidity with which OH-ions as well as long-acting Cu-compounds are transported from a depot of copper calcium hydroxide through all canals of the apical delta to all openings of the delta even when mechanically inaccessible is demonstrated by means of model experiments in extracted teeth.

Emprêgo da iontoforese no tratamento do pé caído leprótico

The use of iontophoresis in the treatment of the fallen leprotic foot. By Walter Belda and Luiz Eugˆnio Reginato. Out of 16 cases of leprosy feet-drops the authors present 8 cases of total revertion by iontophoresis with galvanic current, In their experience the treatment of the late foot-drop is a problem of orthopaedics, with tendon transplant or arthrodesis. In the early foot-drop, in the absent of total degeneration revealed by electrical examens, good results can be obtained by iontophoresis.