Iontophoresis to Overcome the Challenge of Nail Permeation: Considerations and Optimizations for Successful Ungual Drug Delivery.

Iontophoresis is a widely used drug delivery technique that has been used clinically to improve permeation through the skin for drugs and other actives in topical formulations. It is however not commonly used for the treatment of nail diseases despite its potential to improve transungual nail delivery. Instead, treatments for nail diseases are limited to relatively ineffective topical passive permeation techniques, which often result in relapses of nail diseases due to the thickness and hardness of the nail barrier resulting in lower permeation of the actives. Oral systemic antifungal agents that are also used are often associated with various undesirable side effects resulting in low patient compliance. This review article discusses what is currently known about the field of transungual iontophoresis, providing evidence of its efficacy and practicality in delivering drug to the entire surface of the nail for extended treatment periods. It also includes relevant details about the nail structure, the mechanisms of iontophoresis, and the associated in vitro and in vivo studies which have been used to investigate the optimal characteristics for a transungual iontophoretic drug delivery system. Iontophoresis is undoubtedly a promising option to treat nail diseases, and the use of this technique for clinical use will likely improve patient outcomes.Graphical abstract.

Allium sativum Extract Chemical Composition, Antioxidant Activity and Antifungal Effect against Meyerozyma guilliermondii and Rhodotorula mucilaginosa Causing Onychomycosis.

Onychomycosis is a major health problem due to its chronicity and resistance to therapy. Because some cases associate paronychia, any therapy must target the fungus and the inflammation. Medicinal plants represent an alternative for onychomycosis control. In the present work the antifungal and antioxidant activities of Alium sativum extract against Meyerozyma guilliermondii (Wick.) Kurtzman & M. Suzuki and Rhodotorula mucilaginosa (A. Jörg.) F.C. Harrison, isolated for the first time from a toenail onychomycosis case, were investigated. The fungal species were confirmed by DNA molecular analysis. A. sativum minimum inhibitory concentration (MIC) and ultrastructural effects were examined. At the MIC concentration (120 mg/mL) the micrographs indicated severe structural alterations with cell death. The antioxidant properties of the A. sativum extract were evaluated is a rat turpentine oil induced inflammation, and compared to an anti-inflammatory drug, diclofenac, and the main compound from the extract, allicin. A. sativum reduced serum total oxidative status, malondialdehyde and nitric oxide production, and increased total thiols. The effects were comparable to those of allicin and diclofenac. In conclusion, the garlic extract had antifungal effects against M. guilliermondii and R. mucilaginosa, and antioxidant effect in turpentine-induced inflammation. Together, the antifungal and antioxidant activities support that A. sativum is a potential alternative treatment in onychomycosis.

Onychomycosis in diabetic patients in Fako Division of Cameroon: prevalence, causative agents, associated factors and antifungal sensitivity patterns.

BACKGROUND: Onychomycosis is an infection of the nail unit by a fungus. This is a very common infection amongst diabetics. Its occurrence among diabetics in Fako division is unknown. In this study we provide information on the characteristics of onychomycosis in diabetics in Fako division, Cameroon. METHODS: A cross-sectional descriptive and analytical hospital-based study was conducted in two diabetic clinics in the Buea and Limbe regional hospitals. We recruited 152 consenting diabetics into the study. Demographic, behavioural, and clinical data of patients were obtained through the use of structured questionnaires. Toenail, finger nail, skin scrapings and nail clippings were collected from participants, KOH mounts were prepared and observed under the microscope and cultured on Sabouraud Dextrose Agar supplemented with chloramphenicol to isolate causative fungi. Identification of isolates was done to species level using the cello tape flag method and slide culture. The presence of a dermatophyte by either microscopy or culture or both methods was considered positive for onychomycosis. Antifungal susceptibility testing was carried out using selected antifungals by the Kirby-Bauer disk diffusion method on Sabouraud Dextrose Agar. RESULTS: Clinical onychomycosis was found in 77 of the 152 diabetics tested giving a prevalence of 50.7% (95% CI 42.4-58.9) in diabetics in Fako. No socio-demographic or clinical factor studied was significantly associated with onychomycosis. Trichophyton rubrum was the most common isolate (62%). Other isolates included Trichophyton metagraphyte (22%) and Trichophyton tonsurans (16%). Dermatophytes were sensitive to miconazole (66%), amphotericin B (19%) and ketoconazole (14%). CONCLUSION: Onychomycosis is common in diabetics in Fako signifying the need for regular screening by either microscopy or culture. Infected nails could be treated with miconazole.

[Skin sampling for the general practitioner]. / Prélèvements cutanés en médecine générale.

Skin samplings are easily performed in general practice. They include skin biopsies, nail clippings, skin scrappings, hair pluckings as well as trichograms. The different types of skin biopsies are curetage, shaving, punch and elliptic biopsies. They are most commonly used for the diagnosis of inflammatory skin conditions and cutaneous tumors. The biopsies are performed under local anesthesia and each has specific indications. Their complications are minimal. In order to obtain as much information as possible the lesion to be biopsied should be judiciously selected, harvested without being harmed and sent to a skin-oriented pathologist. Nail clippings, skin scrapings and hair plucking allow diagnosis of superficial skin mycosis (tinea, pityriasis versicolor) and are mandatory before prescribing systemic treatment. Scrapping of an itch mite burrow may sometimes reveal the sarcopte. Trichogram may be useful in the work up of a hair loss.

Nail surgery: best way to obtain effective anesthesia.

Nail procedures require an effective and reliable approach to anesthesia of the distal digit. Several techniques have been described in the literature. Herein, the relevant anatomy of the nail unit, pain pathways, anesthetic options, and several injection approaches to achieve complete anesthesia are reviewed. Also considered are the potential pitfalls and complications and their management. Ultimately, the physician's approach must be individualized to the patient, procedure, and setting.

Best way to perform a punch biopsy.

Nail punch biopsy is used to obtain a tissue sample for the diagnosis and treatment of nail diseases. The best results will be possible if the surgeon is familiar with the anatomy and physiology of the nail apparatus. A punch biopsy can be used in all regions of the nail apparatus in the presence or absence of nail plate. When the procedure is performed with a careful handling of the anatomic site and specimen, in most cases a successful diagnosis can be achieved.

A clinical trial to investigate the effect of Cynatine HNS on hair and nail parameters.

OBJECTIVE: A new, novel product, Cynatine HNS, was evaluated for its effects as a supplement for improving various aspects of hair and nails in a randomized, double-blind, placebo-controlled clinical trial. METHODS: A total of 50 females were included and randomized into two groups. The active group (n = 25) received 2 capsules containing Cynatine HNS, comprised of Cynatine brand keratin (500 mg) plus vitamins and minerals, per day, and the placebo group (n = 25) received 2 identical capsules of maltodextrin per day for 90 days. End points for hair loss, hair growth, hair strength, amino acid composition, and hair luster were measured. End points were also measured for nail strength and the appearance of nails. RESULTS: The results show that subjects taking Cynatine HNS showed statistically significant improvements in their hair and nails when compared to placebo. CONCLUSION: Cynatine HNS is an effective supplement for improving hair and nails in 90 days or less. EudraCT number is 2014-002645-22.

Efficacy and safety of Indigo naturalis extract in oil (Lindioil) in treating nail psoriasis: a randomized, observer-blind, vehicle-controlled trial.

Treating nail psoriasis is notoriously difficult and lacks standardized therapeutic regimens. Indigo naturalis has been demonstrated to be safe and effective in treating skin psoriasis. This trial was conducted to evaluate the efficacy and safety of refined indigo naturalis extract in oil (Lindioil) in treating nail psoriasis. Thirty-one outpatients with symmetrically comparable psoriatic nails were enrolled. Lindioil (experimental group) or olive oil (control group) was applied topically to the same subjects' two bilaterally symmetrical psoriatic nails twice daily for the first 12 weeks and then subjects applied Lindioil to both hands for 12 additional weeks. Outcomes were measured using Nail Psoriasis Severity Index (NAPSI) for five nails on one hand and for the single most severely affected nail from either hand. The results show a reduction of NAPSI scores for the 12-week treatment for the Lindioil group (49.8% for one hand and 59.3% for single nail) was superior to the reduction in the scores for the control group (22.9%, 16.3%, respectively). There were no adverse events during the 24 weeks of treatment. This trial demonstrates that Lindioil is a novel, safe and effective therapy for treating nail psoriasis.

Nail surgery.

Nail surgery is a special branch of hand and dermatologic surgery. It is not widely performed, and many physicians do not feel at ease to perform it. The objective of this contribution is to give a short overview of the most important surgical procedures in clinical practice. References from the literature and the author's own experiences are condensed to describe what a dermatologic practitioner with knowledge of the nail and some surgical skills can perform. Nail surgery is a precise technique that requires careful administration and attention to details. Proper patient preparation starts with a patient history to identify potential contraindications and to prevent unnecessary complications. The author recommends isopropyl alcohol scrub and chlorhexidine for disinfection and ropivacaine 1% for anesthesia. The technique used for anesthesia depends on the type of surgery. Surgical procedures are described for diagnostic biopsies, nail avulsion in general, onychogryposis, paronychia treatment, hematomas and bone fracture due to trauma, removal of subungual foreign bodies, ingrowing nails, pincer nails, warts, ungual fibrokeratomas, digital myxoid pseudocyst, subungual exostoses, and various tumors. If performed correctly with adequate skills, nail surgery will lead to functionally and aesthetically satisfying results in the majority of instances.

Effectiveness of systemic treatment agents on psoriatic nails: a comparative study.

BACKGROUND: Nails, one of the most visible sites of body, are frequently involved in psoriasis and accepted as the most difficult site for topical treatment because of their anatomical structure. Healing of the psoriatic nails usually occurs when systemic therapy is initiated to treat severe skin psoriasis or joint involvement, but sometimes systemic therapy is essential for severe nail psoriasis, although Psoriasis Area and Severity Index (PASI) score is low or none of the joints are affected. In this case, knowing which systemic agent is most potent on nail findings is important. AIM: We aimed to evaluate the effect of systemic antipsoriatic agents on nail findings. METHODS: Eighty-seven psoriatis patients with fingernail involvement who required systemic treatment but had not used any systemic treatment in the previous 12 weeks were included in this study. Different systemic treatment agents were given to patients, considering factors such as age, sex, and joint involvement, but not nail involvement. The control group was recruited from psoriatis patients with nail involvement who were not receiving any systemic treatment. Baseline and week 16 Nail Psoriasis Severity Index (NAPSI) and PASI were detected in all groups. At the end of the study, effects of the agents on both PASI and NAPSI were compared statistically. RESULTS: Patients were divided into 5 groups to receive either: 1) methotrexate, 2) narrow-band ultraviolet B phototherapy, 3) biological agents, 4) acitretin, or 5) no treatment (control group). None of the conventional treatment agents caused any significant difference on NAPSI at the end of week 16 compared with control group, although PASI decreased significantly. Rate of NAPSI changes were more prominent in the biological treatment group, and a statistically significant difference was detected when compared with the control group.

Onychomycosis in patients of nail psoriasis on biologic therapy: a randomized, prospective open label study comparing Etanercept, Infliximab and Adalimumab.

INTRODUCTION AND OBJECTIVE: The association between patients of psoriasis on anti TNF therapy and onychomycosis has not been explored. The aim of this study was to determine the rate of onychomycosis in patients of psoriasis with nail involvement on anti TNF therapy. MATERIALS AND METHODS: All patients of psoriasis with nail involvement seen between February 2007 - July 2012 were examined. All the patients with negative nail scrapings for fungus were enrolled. Patients found fit for biologics after investigations were randomly divided into 3 groups (Group A: Infliximab, Group B: Etanercept and Group C: Adalimumab). The patients were followed up every 4 weeks for 24 weeks. Repeat nail scrapings were done at week 24. The results were compared with controls. RESULT: In total, 315 (178 males and 137 females) patients were enrolled. The mean age was 37.5 ± 11.4 years. The results for scraping for fungus at the end of 24 weeks were as follows: 33% (33/100) in patients on Infliximab followed by 15.45% (17/110), 13.33% (14/105) in patients on treatment with Etanercept and Adalimumab respectively as compared to 13.89% (25/180) among controls. Onychomycosis in association with nail psoriasis was more common in males. CONCLUSION: This study revealed statistically significant association between fungal infections of the nail in patients of psoriasis on treatment with Infliximab.

Hazardous concentrations of selenium in soil and groundwater in North-West India.

Soil and groundwater samples were collected for bulk elemental analyses in particular for selenium (Se) concentrations from six agricultural sites located in states of Punjab and Haryana in North-West India. Toxic concentrations of Se (45-341 µg L(-1)) were present in groundwater (76 m deep) of Jainpur and Barwa villages in Punjab. Selenium enrichments were also found in top soil layers (0-15 cm) of Jainpur (2.3-11.6 mg kg(-1)) and Barwa (3.1 mg kg(-1)). Mineralogical analyses confirmed silicates and phyllosilicates as main components of these soils, also reflected by the high content of SiO(2) (40-62 wt.%), Al(2)O(3) (9-21 wt.%) and K(2)O (2.2-3.2 wt.%). Prevailing intensive irrigation practices in Punjab with Se enriched groundwater may be the cause of Se accumulation in soils. Sequential extraction revealed >50% Se bioavailability in Jainpur soils. Appearance of selenite was observed in some of the batch assays with soil slurries under reducing conditions. Although safe Se concentrations were found in Hisar, Haryana, yet high levels of As, Mo and U present in groundwater indicated its unsuitability for drinking purposes. Detailed biogeochemical studies of Se in sediments or groundwater of Punjab are not available so far; intensive investigations should be started for better understanding of the problem of Se toxicity.

Juvenile psoriasis: rewarding endeavours in contemporary dermatology and pediatrics.

Childhood psoriasis is a well-known entity, which is different from adult onset psoriasis in many ways. Recent data from Germany, where a total of 33981 patients with psoriasis were identified from a database of about 1.3 million non-selected persons of a German statutory health insurance, revealed a total rate of 0.71% in children younger than 18 years. The prevalence rates increased in a linear way from 0.2% at the age of one year to 1.2% at the age of 18 years. Although the different types of psoriasis are present in both children and adults, the individual course of the disease and its distribution shows differences. The overall rate of comorbidity in psoriatic persons younger than 20 years seems to be twice as high as in persons without psoriasis. Treating children with psoriasis still remains challenging and represents one of the most rewarding endeavours in contemporary dermatology, since psoriasis can present with both joint and skin symptoms. An interdisciplinary approach with pediatricians, dermatologist and rheumatologists might be crucial. The multifactorial etiology of the disease has led to the development of a wide variety of different treatments, providing physicians with a multitude of options that must be tailored to the age of the patient and the severity of their symptoms. The provision of adequate care for juvenile psoriasis patients depends to a large extent on a precise knowledge of the range of severity and burden imposed by the disease.

Therapeutic efficacy of topical OLEOZON® in patients suffering from onychomycosis.

The results of the use of ozonised sunflower oil (OLEOZON(®)) in the treatment of onychomycosis, based on its known antimycotic action and good skin tolerance, by means of a controlled randomised phase III assay are presented. A total of 400 outpatients were randomly divided into two groups: experimental, treated with topical OLEOZON(®), two times per day and control, treated also two times per day, with ketoconazole cream 2%, for 3 months. A patient was considered cured when the sick nails regained the normal colour, growth and thickness, with a negative mycological study. In the experimental group, a regression of signs was achieved from the first month of treatment, while in the control group, it was obtained after the third month of treatment. All patients treated with OLEOZON(®) had improvement in their condition (9.5%) or were cured (90.5%). However, in the control group, only 13.5% of patients were cured, 27.5% improved and 59% remained the same, with significant differences between both the groups. After 1 year of follow-up, experimental and control groups presented 2.8% and 44.4% of relapses, respectively. Topical OLEOZON(®) demonstrated effectiveness in the treatment of onychomycosis, superior to that of ketoconazole. No side effects were observed.

Longitudinal association between toenail selenium levels and measures of subclinical atherosclerosis: the CARDIA trace element study.

OBJECTIVES: To examine the longitudinal association between toenail selenium levels and subclinical atherosclerosis over an 18-year period. METHODS: Toenail selenium concentrations were examined among 3112 Americans age 20-32 years in 1987 and measured by instrumental neutron-activation analysis. Subclinical atherosclerosis, including common, bulb and internal carotid intima-media thickness (CIMT), was measured in 2005 and coronary artery calcium (CAC) score in 2000 and 2005. General linear regression was developed examining the relation between toenail selenium levels and CIMTs, and logistic regression for repeated outcomes was employed estimating the risk of having CAC>0. RESULTS: After adjustment for potential confounders, no associations were observed between toenail selenium levels and CIMTs as well as CAC score. Comparing participants in the highest with the lowest quintile of selenium, the CIMT was 0.005 mm (SE=0.008 mm, Ptrend=0.39), 0.018 mm (SE=0.019 mm, Ptrend=0.49), and 0.017 mm (SE=0.014 mm, Ptrend=0.21) thicker measured in common, bulb and internal carotid, respectively. The adjusted odds ratio of having CAC>0 was 0.95 (95% CI: 0.67-1.35; Ptrend=0.999). CONCLUSIONS: No associations were observed between toenail selenium and measures of subclinical atherosclerosis among American young adults. This study does not support an atherosclerotic mechanism of selenium for risk reduction of cardiovascular disease.

Acute selenium poisoning by paradise nuts (Lecythis ollaria).

Two previously healthy women developed nausea, vomiting, headache and dizziness for several days, a massive hair loss about 2 weeks later and a discoloration of the fingernails. Detailed diagnostic procedures did not reveal any pathological results. Therapeutic measures did not show any effect. Thallium and arsenic were within normal range in plasma. Delayed quantitative determination of selenium in blood, however revealed toxic values (in case I: 479 microg/L of serum, 8 weeks after ingestion, and in case II 300 microg/L of serum, 9 weeks after ingestion). In retrospect, a relation to the ingestion of paradise nuts could be established.