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PubMed1995

Percutaneous absorption of indomethacin from pluronic F127 gels in rats.

Thermally reversible gels of the poly(oxyethylene)-poly (oxypropylene)-(polyoxyethylene) triblock copolymer, Pluronic F127, were evaluated as vehicles for the percutaneous administration of drugs using indomethacin as a model drug. In-vivo percutaneous absorption studies using a rat model suggest that a 20% w/w aqueous gel of Pluronic F127 may be of practical use as a base for topical administration of the drug. The addition of isopropyl myristate or (+)-limonene to the gel formulation significantly improved percutaneous absorption, particularly when the gel was applied using an occlusive dressing technique.

Animals↗
PubMed1989

Efficacy of mupirocin in methicillin-resistant Staphylococcus aureus burn wound infection.

Methicillin-resistant Staphylococcus aureus strains (MRSA) have become increasingly prevalent as nosocomial pathogens, especially in burn wounds. MRSA constituted 38% of all S. aureus isolates in our 25-bed burns unit despite the utilization of a combination of 1% silver sulfadiazine and 0.2% chlorhexidine as topical therapy. Mupirocin, a new antibiotic, has proved in vitro and in vivo to be highly effective in the treatment of MRSA infections. A prospective clinical trial with mupirocin ointment in MRSA burn wound infection was untertaken. Forty-five children with 59 discrete burn wounds and from whom MRSA were isolated were treated with 2% mupirocin ointment under occlusive dressings, applied twice daily for 5 days. The average burned area treated was 8% (range, 2 to 20%) of the total body surface area. The burn wounds were assessed clinically and bacteriologically daily. Mupirocin eliminated MRSA in all 59 wounds treated, with the maximum therapeutic response seen within 4 days. In three wounds, gram-negative organisms persisted after 5 days of topical therapy. Treatment was well tolerated by all children. We recommend that mupirocin in its present polyethylene glycol base should be used only on a selective basis, when current prophylactic topical therapy has failed to control MRSA infection in burns of less than 20% of the total body surface area, and that it should be applied only for a limited period of 5 days. The safety and the efficacy of mupirocin in burns exceeding 20% of the total body surface area need to be established.

Anti-Bacterial Agents↗
PubMed1998

CD86 (B7-2), but not CD80 (B7-1), expression in the epidermis of transgenic mice enhances the immunogenicity of primary cutaneous Candida albicans infections.

Transgenic (Tg) mice whose epidermal keratinocytes constitutively overexpress either B7-1 (CD80) or B7-2 (CD86) exhibited exaggerated cutaneous delayed type hypersensitivity (DTH) to haptens compared to non-Tg mice. To determine whether enhanced DTH in these Tg mice is seen in response to cutaneous fungal infections, a primary infection with Candida albicans was established by inoculating this organism on the occluded skin of Tg and non-Tg mice. These infections resolved 7 days after removal of occlusive dressing in all three groups of mice, without evidence of exaggerated inflammation in either the Tg or non-Tg mice. Only B7-2 Tg mice developed enhanced Th1-lymphocyte-mediated immune responses to C. albicans antigens after resolving this infection: enhanced footpad swelling in response to intradermal C. albicans antigens, enhanced production of mRNA encoding Th1 lymphokines in draining lymph nodes, and increased gamma interferon secreted into culture supernatants by lymph node T lymphocytes stimulated with Candida antigens in vitro. Lastly, Western blotting of sera from mice that had resolved this fungal infection indicated that only B7-2 Tg mice recognized a wide range of Candida-associated antigens. These data suggest that these two costimulatory molecules, when expressed by keratinocytes, do not deliver identical signals to C. albicans antigen-reactive Th1 lymphocytes. The enhanced immune response in B7-2 Tg mice to a cutaneous C. albicans infection demonstrates the importance of antigen presentation and costimulation in immune reactivity to fungi. Furthermore, B7-2 Tg mice may be useful in identification of protective Candida antigens.

Animals↗
PubMed1988

Save the prepuce. Painless separation of preputial adhesions in the outpatient clinic.

In most boys referred for circumcision preputial adhesions are the only problem, but these can predispose to recurrent balanitis. A simple technique using Emla cream (eutectic mixture of lignocaine and prilocaine) has been devised which allows the adhesions to be separated painlessly in the outpatient clinic. The technique was used on 39 boys aged 2 to 12 years referred for circumcision, none of whom had a retractable foreskin. The cream was applied under an occlusive dressing and left for 60 minutes before the adhesions were separated with a probe and a gauze swab. The procedure was completely pain free in 32 boys. One boy had to undergo a repeated procedure because he failed to follow the advice regularly to retract his foreskin in the three weeks after the procedure. Only one boy had to undergo circumcision later because of fibrous phimosis. In many boys referred for circumcision separation of preputial adhesions is all that is needed, and the use of this local anaesthetic technique avoids the need for general anaesthesia.

Ambulatory Surgical Procedures↗
PubMed1995

Can topical lignocaine reduce behavioural response to heel prick?

In a randomised, double blind, controlled study the ability of 5% lignocaine ointment to reduce the behavioural response to heel lance in 30 healthy neonates was assessed. Five per cent lignocaine ointment applied to the heel under an occlusive dressing for one hour before heel prick did not reduce the infants' behavioural response to the heel prick procedure.

Administration, Topical↗
PubMed2004

Modulation of microvascular function following low-dose exposure to the organophosphorous compound malathion in human skin in vivo.

This study investigates whether malathion, a widely used organophosphate insecticide, has its effects on cutaneous vasculature in healthy human volunteers through its anticholinergic activity or through the modulation of other, noncholinergic pathways. Acute, low-dose exposure to malathion (10 mg/ml for 5 h under occlusive dressing) caused a significant increase in cutaneous blood flux, monitored by using laser-Doppler flowmetry and imaging. It had little effect on tissue levels of ACh, nitric oxide, and histamine assayed in dermal dialysate collected from malathion-exposed and control-treated skin. The duration of the cutaneous vascular response to exogenous ACh (2%) delivered by iontophoresis was significantly enhanced by preexposure to malathion, both <1 h after its removal and 24 h later (P < 0.001). At <1 h, the time to 50% decay of the response was 24 +/- 4 and 50 +/- 8 min in control and malathion-treated skin, respectively. Malathion also enhanced the size and duration of the axon reflex-mediated vasoresponse to ACh. The increase in blood flux to malathion and the endothelium-mediated response to exogenous ACh, both in the presence and absence of malathion, were attenuated by pretreatment of the skin with atropine and local anesthesia (P < 0.01). We conclude that short-term exposure to a single low dose of malathion causes prolonged modulation of the physiological function of the cutaneous vasculature and that this is, in part, through its action on acetylcholinesterase at both neuronal and nonneuronal sites.

Acetylcholine↗
PubMed1998

Photodynamic therapy of superficial basal cell carcinomas using topical 5-aminolevulinic acid in a nanocolloid lotion.

BACKGROUND: Photodynamic therapy (PDT) of superficial basal cell carcinomas using endogenous protoporphyrin IX generated by topically applied 5-aminolevulinic acid (5-ALA) is an innovative and clinically encouraging approach. OBJECTIVE: This paper reports on the first results of an ongoing clinical study on photodynamic therapy of 55 basal cell carcinomas in 19 patients. METHODS: Because of the chemical instability of 5-ALA, a novel nanocolloid lotion was developed. This formulation was applied to the lesions under occlusive dressing 6 h before irradiation with visible light from an unfiltered halogen lamp. Light-induced fluorescence was used to ascertain the superficial extension of the tumors. The response to the therapy was assessed by visual inspection and in 13 patients also by biopsies. RESULTS: After a single treatment, 47 (85%) basal cell carcinomas showed a complete response at a follow-up time of at least 6 months. For the remaining 8 (15%) lesions, a partial response was observed, indicated by a marked reduction of the tumor size. The treatment modality without local anesthetics was well tolerated by all patients, with only slight discomfort during light irradiation. CONCLUSION: Our results indicate that 5-ALA-PDT with our novel formulation, a nanocolloid lotion, is a highly effective and convenient therapy for the treatment of superficial basal cell carcinomas. Its use in the treatment of nodular tumors needs further investigations.

Administration, Topical↗
PubMed2006

The pH of the skin surface and its impact on the barrier function.

The 'acid mantle' of the stratum corneum seems to be important for both permeability barrier formation and cutaneous antimicrobial defense. However, the origin of the acidic pH, measurable on the skin surface, remains conjectural. Passive and active influencing factors have been proposed, e.g. eccrine and sebaceous secretions as well as proton pumps. In recent years, numerous investigations have been published focusing on the changes in the pH of the deeper layers of the stratum corneum, as well as on the influence of physiological and pathological factors. The pH of the skin follows a sharp gradient across the stratum corneum, which is suspected to be important in controlling enzymatic activities and skin renewal. The skin pH is affected by a great number of endogenous factors, e.g. skin moisture, sweat, sebum, anatomic site, genetic predisposition and age. In addition, exogenous factors like detergents, application of cosmetic products, occlusive dressings as well as topical antibiotics may influence the skin pH. Changes in the pH are reported to play a role in the pathogenesis of skin diseases like irritant contact dermatitis, atopic dermatitis, ichthyosis, acne vulgaris and Candida albicans infections. Therefore, the use of skin cleansing agents, especially synthetic detergents with a pH of about 5.5, may be of relevance in the prevention and treatment of those skin diseases.

Hand Disinfection↗
PubMed1983

Treatment of onychomycosis by ODT therapy with 20% urea ointment and 2% tolnaftate ointment.

20 patients with distal onychomycosis were given daily application of an ointment containing 2% tolnaftate and an ointment containing 20% urea under ODT. Following this, 17 of 20 patients developed onychomalacia and seven of these developed onycholysis 1 or 2 weeks later. The separated nails were cut as short as possible. Similarly to those patients with onychomalacia alone, occlusive dressing technique was continuously performed until the newly developed nails became macroscopically normal and no fungi were observed microscopically (responders). Following treatment, out of 20 patients, 14 responded. 5 patients who had a short course of treatment did not respond. Side-effects such as pain, hemorrhage and infection did not occur.

Administration, Oral↗
PubMed1979

Percutaneous absorption of chlorquinaldol (Sterosan).

The percutaneous absorption of chlorquinaldol from three different preparations for skin treatment (Sterosan-hydrocortison ointment and cream, Sterosan ointment) was evaluated by measuring the cumulative urinary excretion of chlorquinaldol and was compared to that found after an equivalent oral dose. In the blood the concentrations were below the detection limit of the analytical procedure, i.e., smaller than 0.02 microgram/ml. The study was carried out in 3 healthy volunteers using a four-period change-over design. The topical preparations were applied under occlusive dressings. Following epicutaneous application of the three topicals in quantities containing 30 mg chlorquinaldol each, the mean urinary excretion of the drug amounted to 11.1 +/- 6.6, 19.5 +/- 3.5 and 13.0 +/- 2.5% of the applied dose. When the same dose of chlorquinaldol was administered orally, 67.6 +/- 9.5% of the dose was excreted in the urine. Taking the urinary elimination as the minimal amount of drug absorbed, the extent of percutaneous absorption from the three dermatological preparations varied between 4.2 and 23.5% of the applied dose. There was no difference in the pattern of urinary excretion products among the three topicals and the oral formulation. The bulk of chlorquinaldol (mean 98.0 +/- 0.1%) was excreted as sulfate (mean 1.3 +/- 0.3%) or unchanged drug (mean 0.8 +/- 0.1%).

Administration, Oral↗
PubMed1979

Percutaneous absorption of clioquinol (Vioform).

The percutaneous absorption of clioquinol from three different preparations for skin treatment (Vioform cream, Locacorten-Vioform cream and Vioform-Hydrocortisone cream) was evaluated. After topical dosages corresponding to 30 mg clioquinol, concentrations in the blood were below the detection limit of the analytical procedure, i.e., smaller than 0.02 micrograms/ml; therefore the percutaneous absorption was evaluated by measuring cumulative urinary excretion of clioquinol and was compared to that found after an equivalent oral dose. The study was carried out in 4 healthy volunteers. The topical preparations were applied under occlusive dressings. Following epicutaneous application of the three topicals in quantities containing 30 mg clioquinol each, the urinary excretion of the drug was between 1.2 and 3.6% of the applied dose. When the same dose of clioquinol was administered orally to two volunteers, 52.4 and 92.9% of the dose was excreted in the urine. Taking the urinary elimination as the minimal amount of drug absorbed, the extent of percutaneous absorption from the three dermatological preparations amounted to 1.2-3.6% of the applied dose. There was no difference in the pattern of urinary excretion products among the three topicals and the oral formulation. The bulk of clioquinol was excreted as glucuronide (mean: 96 +/- 3%) and only a small fraction was excreted as sulfate (mean: 3.8 +/- 3%). A small amount of free clioquinol (1.1%) was measured in 1 subject only after the oral dose.

Administration, Oral↗
PubMed1976

Systemic effects and percutaneous absorption of topically applied 0.1% hydrocortisone 17-butyrate.

The systemic effects of topically applied 0.1% hydrocortisone 17-butyrate during treatment with and without occlusion were measured in terms of the functions of the pituitary-adrenal axis. Corticosteroid levels in the blood were determined by the modified method of MURPHY, a competitive protein-binding radioassay. Circulating eosinophils were counted and the urinary 17-OHCS and 17-KS excretion were also determined. Percutaneous absorption following the topical application of 14C hydrocortisone 17-butyrate 1 (HC 17-B, Locoid) was measured by means of autoradiography. The application of the corticosteroid to the normal skin without occlusion did not induce systemic effects, whilst the application of the drug under occlusive dressing showed that systemic effects may possibly be induced. The number of circulating eosinophils, corticosteroid levels in the blood and urinary 17-OHCS excretion all decreased. However, these values returned to normal about 2 days after the withdrawal of the application, so we consider the systemic effect induced by the topical corticosteroid to be of a temporary nature. The percutaneous absorption of the corticosteroid was proved by an autoradiographic technique using 14C-labelled HC 17-B. At various intervals after the application, radioactive substances were observed as silver grains in the horny layer of the epidermis and skin appendages, and the density of the silver grains gradually increased with the course of time. It may be surmised that locally applied HC 17-B will be retained in the horny layer of the epidermis at a very early stage after the application and then absorbed in the blood via the epidermis and skin appendages. The reservoir of the corticosteroid in the skin was demonstrated 24 h after the withdrawal of the application.

17-Hydroxycorticosteroids↗
PubMed1997

Hypoxia increases human keratinocyte motility on connective tissue.

Re-epithelialization of skin wounds depends upon the migration of keratinocytes from the cut margins of the wound and is enhanced when human keratinocytes are covered with occlusive dressings that induce hypoxia. In this study, two independent migration assays were used to compare cellular motility on connective tissue components under normoxic or hypoxic conditions. Human keratinocytes apposed to collagens or fibronectin exhibited increased motility when subjected to hypoxic (0.2 or 2% oxygen) conditions compared with normoxic (9 or 20% oxygen) conditions. When compared with normoxic cells, hypoxic keratinocytes exhibited increased expression and redistribution of the lamellipodia-associated proteins (ezrin, radixin, and moesin). Furthermore, hypoxic keratinocytes demonstrated decreased secretion of laminin-5, a laminin isoform known to inhibit keratinocyte motility. Hypoxia did not alter the number of integrin receptors on the cell surface, but did induce enhanced secretion of the 92-kD type IV collagenase. These data demonstrate that hypoxia promotes human keratinocyte motility on connective tissue. Hypoxia-driven motility is associated with increased expression of lamellipodia proteins, increased expression of collagenase and decreased expression of laminin-5, the locomotion brake for keratinocytes.

Adult↗
PubMedDate not supplied

Clinical experience with 0.05% halometasone/1% triclosan cream in the treatment of acute infected and infection-prone eczema in Egypt.

This is a report of a non-comparative trial to assess the usefulness of a 0.05% halometasone and 1% triclosan combination in a cream base in the treatment of acute infected and infection-prone eczematous skin disorders. The trial was carried out in three centres. Of the 126 patients admitted to the trial, 25 were lost to follow-up. The remaining 101 patients utilized the cream as the only treatment during the 3-week duration of therapy. Medication was applied to the lesions twice daily without occlusive dressing. The cream gave either excellent or good results in 89% of cases. Infection, which was initially present in 38 cases, disappeared within 5 days from 27 (71%) of them and within 6-10 days from a further six (16%) cases. The therapeutic effect was first noted (in 43 cases) within a mean of 2.7 days (+/- 1.01). The cream did not give rise to any serious local unwanted effects. Systemic unwanted effects were suspected in an 8-month old infant with extensive atopic dermatitis. The findings in this study substantiate those of other investigators that this halometasone/triclosan preparation combines potent and rapid therapeutic effect with excellent local and systemic tolerability.

Acute Disease↗
PubMedDate not supplied

Prevention of and therapies for nipple pain: a systematic review.

OBJECTIVE: To review the literature on nipple pain and to delineate effective strategies for the prevention and treatment of nipple pain in breastfeeding mothers. DATA SOURCES: Computerized searches on MEDLINE, Pre-MEDLINE, CINAHL, and the Cochrane Library. STUDY SELECTION: Articles from indexed journals relevant to the objective were reviewed from January 1983 to April 2004. Preference was given to research-based studies in English. DATA EXTRACTION: Data were extracted and organized under two headings: prevention of nipple pain or trauma and treatment of nipple pain or trauma. The Critical Appraisal Form by J. Briggs was used to extract the data from research-based articles. DATA SYNTHESIS: The health benefits of breastfeeding for mother and infant are well documented; however, nipple pain is a common reason reported by women for the early termination of breastfeeding. Several studies have compared various treatments for either the prevention of or treatment for nipple pain. These treatments include warm water compresses, tea bag compresses, heat, application of expressed mother's milk, lanolin, vitamin A, collagenase, dexpanthenol, hydrogel therapy, glycerin gel therapy, moist occlusive dressing, education regarding proper latch-on and positioning, and no treatment. CONCLUSIONS: No one topical agent showed superior results in the relief of nipple discomfort. The most important factor in decreasing the incidence of nipple pain is the provision of education in relation to proper breastfeeding technique and latch-on as well as anticipatory guidance regarding the high incidence of early postpartum nipple pain.

Administration, Cutaneous↗
PubMed2001

The prevention of central venous catheter-related sepsis.

Intravascular catheters continue to be a major source of sepsis which range from localised inflammation at the site of insertion to septicaemia. There are two main approaches which have been taken in an attempt to prevent these infections. These can be divided into the patient and the catheter. Approaches for prevention with patients include improved aseptic techniques, appropriate choice of antiseptic skin preparations, use of semi-occlusive dressings and cleaning schedules when using the devices. Catheters have also been developed to reduce the incidence of these infections. These include the production of polymers with smooth, anti-adhesive coatings, eg Hydromer, and more recently the introduction of devices which are either coated with antiseptics or antimicrobials. The antimicrobial coatings include antibiotics such as rifampicin and doxycycline or antiseptics, for example benzalkonium chloride or chlorhexidine. The efficacy of these approaches will be reviewed based on both laboratory and clinical studies. The treatment of intravascular catheter-related sepsis depends primarily on establishing the diagnosis. When the diagnosis has been made treatment ranges from the use of antimicrobials alone to removal of the device. More recent approaches have included the use of antibiotic locks within the catheters. Treatment schedules will also be reviewed.

Catheterization, Central Venous↗
PubMed2003

Cutaneous analgesia after transdermal application of amitriptyline versus lidocaine in rats.

UNLABELLED: Amitriptyline, a tricyclic antidepressant, has potent local anesthetic properties. However, there is no report of cutaneous analgesic effects after transdermal application. We report here that transdermally applied amitriptyline is more potent than lidocaine in providing cutaneous analgesia in rats. Solutions of amitriptyline base in 50, 100, and 500 mM concentrations were applied as a patch to rats, and their effects were compared with those of lidocaine base at the same concentrations and of the vehicle alone (45% water, 45% isopropyl alcohol, and 10% glycerin). Rats in each test group developed a concentration-dependent cutaneous analgesic block in the areas to which the drugs were applied; however, amitriptyline produced a longer block than lidocaine at the same concentration. The development of amitriptyline as a longer-lasting topical analgesic may improve our ability to treat chronic pain, such as neuropathic pain and neuralgia, and to prevent pain in procedures such as venipuncture. IMPLICATIONS: The tricyclic antidepressant amitriptyline, often used perorally for the management of chronic pain, is shown here to be more potent than lidocaine in providing cutaneous analgesia when applied transdermally with an occlusive dressing in rats.

Administration, Cutaneous↗
PubMedDate not supplied

Omeprazole absorption from a compounded transdermal formulation in healthy volunteers.

OBJECTIVE: To evaluate the plasma concentration versus time profile of omeprazole following the administration of a compounded transdermal gel formulation in healthy volunteers. DESIGN: Single-dose transdermal pharmacokinetic (PK) study including a comparison with historical data from an oral PK study. SETTING: Academic clinical research center. PARTICIPANTS: Eight healthy volunteers between 18 and 50 years of age. INTERVENTIONS: Omeprazole gel 40 mg (0.8 mL) was applied to the ventral surface of the forearm covering an area of 7 x 15 cm without an occlusive dressing. Blood samples were collected just before application and then at 1, 2, 3, 4, 6, and 8 hours. Plasma concentrations of omeprazole were determined using a validated liquid chromatography tandem mass spectrometry method. MAIN OUTCOME MEASURES: PK parameters (maximal plasma concentration [C(max)], the time of C(max), [T(max)], the area under the omeprazole concentration versus time curve from 0 to 8 hours, the elimination rate constant, and the half-life of the elimination phase) following transdermal administration, compared with historical controls who had received an oral omeprazole 40 mg dose during a previous study. RESULTS: Of the eight volunteers, five had undetectable plasma omeprazole concentrations throughout the 8-hour study, precluding a complete PK analysis. For the three volunteers with detectable plasma omeprazole concentrations, the values ranged from 0.204 to 0.552 ng/mL. Including values of 0 for the patients with undetectable levels, the mean (+/- SD) C(max) was 0.153 +/- 0.241 ng/mL, and the T(max) in patients with detectable levels occurred at approximately 6 hours. The plasma concentrations following transdermal administration were approximately 1,000-fold lower than those observed with oral dosing. CONCLUSION: Transdermal absorption from a single dose of the omeprazole gel formulation used in this study was poor. This transdermal gel formulation is clearly not bioequivalent to the oral capsule.

Administration, Cutaneous↗