So far, various approaches have been proposed to improve dermal drug delivery. The use of chemical penetration enhancers has a long history of application, while methods based on the electrical current (such as iontophoresis) stand out as promising \"active\" techniques. Aiming to evaluate the contribution of different approaches to dermal delivery, in this work curcumin-loaded nanoemulsions with and without monoterpenes (eucalyptol or pinene) as chemical penetration enhancers, and a custom-made adhesive dermal delivery system based on iontophoresis were designed and assessed. In an in vivo study applying skin bioengineering techniques, their safety profile was proven. Three examined iontophoresis protocols, with total skin exposure time of 15 min (continuous flow for 15 min (15-0); 3 min of continuous flow and 2 min pause (3-2; 5 cycles) and 5 min of continuous flow and 1 min pause (5-1; 3 cycles) were equally efficient in terms of the total amount of curcumin that penetrated through the superficial skin layers (in vivo tape stripping) (Q3-2 = 7.04 ± 3.21 μg/cm2; Q5-1 = 6.66 ± 2.11 μg/cm2; Q15-0 = 6.96 ± 3.21 μg/cm2), significantly more efficient compared to the referent nanoemulsion and monoterpene-containing nanoemulsions. Further improvement of an efficient mobile adhesive system for iontophoresis would be a practical contribution in the field of dermal drug application.

The medial collateral ligament (MCL) of the knee is a commonly injured ligament structure. Calcification of the MCL is very infrequent, benign, related to metabolic disorders and is a consequence of the deposition of calcium hydroxyapatite in the periarticular region. The clinical, histological and radiological picture of calcific tendonitis is defined and the etiology is multifactorial. Treatment is initially conservative and if it fails, interventionist; surgery being the last therapeutic step. There are very few reports in the literature, with only 10 cases/case series published. It is important to differentiate it from the Pellegrini-Stieda sign and/or syndrome, where the traumatic history is essential to diagnose it. The clinical case is that of a 64-year-old woman in whom we present the treatment of calcification of the MCL using radial electro shock wave therapy plus iontophoresis, we report the effectiveness of the treatment in the management of pain and calcification, and we carry out a brief review on the subject.

Insulin-like growth factor 1 (IGF-1) is indicated for growth failure in pediatric patients with primary IGF-1 deficiency and for patients with neutralizing antibodies to growth hormone. IGF-1 was cloned, expressed and purified in-house. Preliminary stability studies prior to the transdermal delivery experiments showed that although stable in contact with stratum corneum, the solution concentration of IGF-1 decreased to 23.63 ± 2.48 and 21.58 ± 2.62% of the initial value upon exposure for 8 h to porcine dermis of 250 and 750 µm thickness. This led to an investigation into how it might be possible to improve the stability of IGF-1 in the presence of porcine/human skin. The stability of IGF-1 in the presence of dermis improved upon heating the skin samples at 60 °C for 2 min suggesting that IGF-1 was subject to enzymatic degradation. Although addition of the protease inhibitor, phenylmethanesulfonyl fluoride (PMSF) alone, did not improve stability, the use of a protease inhibitor cocktail completely blocked proteolytic degradation of IGF-1; the solution concentration after an 8 h exposure to porcine skin was equivalent to the initial level (103.87 ± 9.15%). The results obtained with porcine skin were confirmed with human skin (IGF-1 recovery was 99.31 ± 9.98%). These findings suggest that the inclusion of protease inhibitor cocktails may be useful in limiting the degradation of therapeutic proteins during iontophoresis and transdermal delivery in general - this could be of particular interest for local delivery of peptide/protein therapeutics for dermatological applications.

Hematidrosis is a rare disorder involving spontaneous excretion of sweat contaminated by blood cells. We report the case of a 6-year-old girl with hematidrosis from her palms with no underlying disease or psychotic disorder. Before the onset of this symptom, the patient was given an indoor horizontal exercise bar with which she had been frequently playing. This symptom appeared without apparent triggers and was not associated with subjective symptoms. To examine her hematidrosis, metabolites in the red bodily fluid were analyzed using nuclear magnetic resonance analysis. We found the fluid had a metabolome profile similar to that of eccrine sweat. Pathological analysis revealed no abnormal findings, including expression of the tight junction protein claudin 3. Her symptom decreased after treatment with tap-water iontophoresis. Here, we describe our case and discuss its etiology by reviewing previous reports.

We report results from an acute, single case study in the pig liver on the effects of a tissue ablation protocol (we named cryoelectrolysis) in which 10 min of cryosurgery, with a commercial cryosurgical probe, are delivered after 10 min of electrolysis generated by a current of about 60 mA. The histological appearance of tissue treated with cryoelectrolysis is compared with the appearance of tissue treated with 10 min of cryosurgery alone and with 10 min of electrolysis alone. Histology done after 3 h survival shows that the mixed rim of live and dead cells found around the ablated lesion in both cryosurgery and electrolytic ablation is replaced by a sharp margin between life and dead cells in cryoelectrolysis. The appearance of the dead cells in each, cryoelectrolysis, cryosurgery and electrolytic ablation is different. Obviously, this is an acute study and the results are only relevant to the conditions of this study. There is no doubt that additional acute and chronic studies are needed to strengthen and expand the findings of this 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.

Fentanyl iontophoretic transdermal system (ITS) [IONSYS®, The Medicines Company, Parsippany, NJ, USA] is a needle-free, patient-controlled, postoperative opioid pain management treatment. It is indicated for the short-term management of acute postoperative pain in adults requiring opioid analgesia in the hospital. The safety and effectiveness of fentanyl ITS for acute postoperative pain management has been demonstrated in a range of surgery and patient types studied in seven phase 3 trials (three placebo-controlled trials and four active-comparator trials). The majority of the patients in the phase 3 trials had undergone either abdominal/pelvic, orthopedic, or thoracic surgery. Consistent with the prescribing information, physicians in clinical practice may treat patients with this system following any type of surgery including those that may not have been included in the phase 3 trials. The purpose of this case series is to illustrate how fentanyl ITS is being utilized for postoperative pain management in real-world clinical practice following a variety of surgeries and in current pain management protocols that may have evolved since the completion of the phase 3 program. There are seven cases from three clinical centers described within this case series, each using fentanyl ITS according to the prescribing information. The surgery types included are bariatric (N = 3), prostate (N = 2), colorectal (N = 1), and perirectal abscess drainage (N = 1). A systematic review of each patient chart was conducted via a standardized retrospective assessment by the clinicians who managed each patient. Additionally, each healthcare professional was interviewed regarding their overall experience and key learnings using fentanyl ITS. Overall, fentanyl ITS was effective and well tolerated in these case reports in current-day clinical practice settings. These case studies are informative about fentanyl ITS use shortly after product approval and set the stage for additional clinical research.

Buccal administration of sumatriptan succinate might be an interesting alternative to the present administration routes, due to its non-invasiveness and rapid onset of action, but because of its low permeability, a permeation enhancement strategy is required. The aim of this work was then to study, in-vitro, buccal iontophoresis of sumatriptan succinate. Permeation experiments were performed in-vitro across pig esophageal epithelium, a recently proposed model of human buccal mucosa, using vertical diffusion cells. The iontophoretic behavior of the tissue was characterized by measuring its isoelectric point (Na(+) transport number and the electroosmotic flow of acetaminophen determination) and by evaluating tissue integrity after current application. The results obtained confirm the usefulness of pig esophageal epithelium as an in-vitro model membrane for buccal drug delivery. The application of iontophoresis increased sumatriptan transport, proportionally to the current density applied, without tissue damage: electrotransport was the predominant mechanism. Integrating the results of the present work with literature data on the transport of other molecules across the buccal mucosa and across the skin, we can draw a general conclusion: the difference in passive transport across buccal mucosa and across the skin is influenced by permeant lipophilicity and by the penetration pathway. Finally, buccal iontophoretic administration of sumatriptan allows to administer 6mg of the drug in 1h, representing a promising alternative to the current administration routes.

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OBJECTIVE: To create awareness of myositis ossificans (MO) as a potential complication of muscle contusion by presenting its clinical presentation and diagnostic features. An effective method of treatment is offered for those patients who develop traumatic MO.
RESULTS: Patients in this case series developed traumatic MO, confirmed on diagnostic ultrasound. Patients participated in a treatment regimen consisting of phonophoresis of acetic acid with ultrasound.
RESULTS: In all cases, a trial of phonophoresis therapy significantly decreased patient signs, symptoms and the size of the calcification on diagnostic ultrasound in most at a 4-week post diagnosis mark.
CONCLUSIONS: Due to the potential damage to the muscle and its function, that surgical excision carries; safe effective methods of conservative treatment for MO are crucial. MO deserves more attention in the literature due to its common presentation in athletes.
Sensibilisation à la myosite ossifiante (MO) comme complication possible de contusions musculaires grâce à la présentation de son tableau clinique et de ses symptômes. Une méthode efficace de traitement est offerte pour les patients qui sont atteints de myosite ossifiante traumatique.
Les patients de cette série de cas souffrent de myosite ossifiante traumatique, confirmée par échographie. Les patients ont participé à un régime de traitement consistant en une irrigation d’acide acétique par phonophorèse.
Dans tous les cas, un essai de traitement par phonophorèse a diminué considérablement les signes et les symptômes des patients ainsi que la taille de la calcification détectée par échographie dans la plupart des cas 4 semaines après le diagnostic.
En raison de la lésion possible au muscle et des dommages potentiels à sa fonction posés par l’excision chirurgicale, il est essentiel d’adopter une approche sécuritaire et efficace de traitement conservateur de la myosite ossifiante. La myosite ossifiante mérite plus d’attention dans les revues scientifiques en raison de sa fréquence chez les athlètes.