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Excessive radiofrequency application: effects on capsular tissue in an animal model.

Capsular attenuation has been seen after thermal capsulorrhaphy surgery. The purpose of this study was to evaluate the mechanical, histologic, and morphologic effects on capsular tissue after cumulative applications of radiofrequency energy. Ovine patellofemoral capsular tissue was treated with 1, 2, 4, or 8 applications of bipolar radiofrequency energy and then analyzed. No acute capsular ablation or destruction was seen grossly, even in the 8-application group. No definitive visual clues that excessive radiofrequency energy had been applied were seen. There was significant shrinkage and loss of tensile stiffness for all thermal application groups. Given the small sample sizes, post-application failure load, percent relaxation, and stiffness were not observed to be significantly different among the groups. Cumulative applications produced minimal further tissue shrinkage but were accompanied by larger, though not statistically significant, mechanical property losses and increased depth of tissue penetration. These findings suggest that there is no benefit to repeated applications of radiofrequency energy to capsular tissue.

Animals↗

Dynamics of changes in methanogenesis and associated microflora in a flooded alluvial soil following repeated application of dicyandiamide, a nitrification inhibitor.

Influence of repeated application of the nitrification inhibitor dicyandiamide (DCD), on CH(4) production and associated microflora in a flooded alluvial soil, was investigated in a laboratory incubation study. Application of DCD at the time of soil incubation resulted in a substantial reduction in CH(4) production (31% over that of untreated control). Second repeat application of DCD, on the contrary, annulled the inhibitory effect on CH(4) production, restoring it to the level of unamended soil. Application of the third dose of DCD maintained CH(4) production almost to the same extent as that of second application. The alleviation of the initial inhibitory effect of DCD on CH(4) production was linked to the enhanced degradation of DCD following its repeated application to the flooded soil. Admittedly, abatement of the initial inhibitory effect of DCD on CH(4) production in soil repeatedly amended with DCD was also related to the inhibition of CH(4)-oxidizing bacterial population and noticeable stimulation of heterotrophic bacterial population. Results suggest that repeat application of DCD with fertilizer-N to flooded rice soils might not be effective in controlling CH(4) production under field condition.

Anaerobiosis↗

Reduced heat sensitivity and epidermal nerve fiber immunostaining following single applications of a high-concentration capsaicin patch.

Capsaicin-containing plant extracts have been used as topical treatments for a variety of pain syndromes for many centuries. Current products containing capsaicin in low concentrations (usually 0.025-0.075% w/w) have shown efficacy against a variety of pain conditions in clinical studies. However, in order to produce significant analgesic effects, these formulations require frequent re-dosing, often as much as three to five times daily for several weeks. Previous functional and immunohistochemical studies following prolonged exposures to low-concentration capsaicin cream suggested that the duration and onset of analgesic efficacy correlate with a reduction of cutaneous nociceptive sensory nerve fiber responsiveness and immunostaining. The purpose of the present study was to determine whether a single topical application of a high-concentration capsaicin-containing (8%w/w) patch for 120 min or less would induce similar effects on cutaneous nociceptive nerve fibers. Seven days following patch application, changes in heat and cold perception thresholds were determined by quantitative sensory testing and punch biopsies were collected to assess epidermal nerve fiber (ENF) immunostaining density at the application site using PGP 9.5 as a marker. The results show a significant reduction of heat, but not cold, sensitivity and reduction of ENF immunostaining with high-capsaicin concentration patch applications for 60 or 120 min, compared to placebo patch applications. Application sites exposed to low-capsaicin concentration (0.04%w/w) patches for 120 min or high-concentration patches for 30 min were not significantly different from placebo with respect to either thermal threshold detection or ENF immunostaining. The ability of a single 60 min high-concentration patch application to mimic effects produced by prolonged exposure to low-concentration capsaicin creams suggests a new approach to the management of chronic pain syndromes.

Adolescent↗

Effect of season of application on the adhesion, retention and recontamination of herbage by potentially toxic metals and sewage sludge.

Grassland in the United Kingdom can accept sewage sludge when, as a result of cropping restrictions, arable land cannot. However, one of the uncertainties associated with the application of sewage sludge to grassland is the potential exposure of the grazing ruminant to sewage sludge particulates adhered to the grass or deposited on the soil surface. The implications of elevated levels of sludge particulates and associated potentially toxic metals (PTMs) are the potential accumulation of PTMs into edible tissues of the grazing animal. Two experiments were performed to investigate the effect of season of application on the adhesion, retention and recontamination of herbage by sewage sludge and PTMs. In each experiment, three treatments were installed, an untreated control, application of sludge in the autumn and application of sludge in the spring. Sewage sludge particulates and PTMs were eluted sequentially 21 days after the application of sludge using water and detergent and the residual (tissue) concentrations were monitored. Total concentrations in each fraction and adhesion indices were calculated. Soil samples taken from the sward treatments after each application showed no elevated concentrations of PTMs or concentrations that approached the maximum concentrations allowed for soils amended with sewage sludge. The amounts of sludge adhered to herbage ranged from 114 to 360 g sludge DM/kg herbage DM. There was evidence of preferential retention of PTMs to herbage. However, during the 21-day no grazing period there was a general decline in concentration of all PTMs. Copper was retained on the herbage for greater periods of time compared to Zn, CD, Pb and Fe (P < 0.01). The proportion of Pb recovered from the water phase increased during the 21-day no grazing period in comparison to Cu, Zn and Fe (P < 0.001). It is concluded that the concentrations of PTMs adhered and integral to herbage as a result of surface application of sewage sludge are likely to fall to acceptable levels in well-managed permanent grassland.

Adsorption↗

Safe and effective topical application dose of lidocaine for surgery with laryngomicroscopy.

A clinical case of a patient in whom seizure developed after topical application of lidocaine to the oropharyngeal region was described. The exploratory studies on the optimal dosage of lidocaine in the surgery under laryngomicroscope was performed in 22 patients. During the application of 2% lidocaine viscous and 4% lidocaine solution to the oropharyngeal region, the patient was instructed to expectorate the excess intermittently to avoid absorption. In addition, the oropharyngeal region was swabbed with gauze. The serum lidocaine concentrations after application were less than 1.8 micrograms/ml. The total application dose of the drug was within the range of 324 to 640 mg, and the total recovery rate from the saliva and gauze was 52% to 81%. We found a good correlation between net application dose (total application dose minus excessive lidocaine dose) and serum lidocaine concentration. In this study, it was shown that the safe and effective net application dose of lidocaine for the surgery may be within the range of 127 to 260 mg.

Administration, Topical↗

Neuropsychological performance among agricultural pesticide applicators.

To assess the potential effects on neuropsychiatric performance of chronic occupational exposure to organophosphate insecticides, we performed a prospective longitudinal study of a cohort of apple orchard pesticide applicators and a comparison cohort of beef slaughter-house workers. The study group consisted of 49 applicators and 40 comparison subjects who completed both an initial evaluation (preseason) prior to the onset of the approximately 6-month pesticide spraying season and a follow-up evaluation (postseason) about 1 month following the end of spraying season. The applicator cohort had a greater number (n = 22, 45%) of individuals who identified primary preference for Spanish-language testing than did the comparison cohort (n = 5, 13%). Stratification by language preference revealed no significant differences in background characteristics between the two cohorts, except for fewer years of education in the Spanish-language preference applicators versus control subgroups (5.0 +/- 3.1 vs 7.8 +/- 3.7 years, respectively). After controlling for language preference, there were no statistically significant differences between the applicators and control cohorts on neuropsychological subtests of the computerized test battery. Preseason baseline performance on individual tests was a significant predictor of postseason test performance. After controlling for baseline performance, the only statistically significant exposure related across-season changes in neuropsychological performance was for one subtest (Symbol Digit Substitution) and was confined to the Spanish language preference subgroups, with worse adjusted postseason performance among applicators versus controls (P = 0.001). This study found no clear evidence of clinically significant decrements in neuropsychological performance following one 6-month season of pesticide exposure in a cohort of applicators who were felt to have generally low, intermittent, and well-controlled organophosphate exposures.

Adult↗

Tolerance to analgesia and dependence liability by topical application of dihydroetorphine to hairless rats.

The tolerance to analgesia and dependence liability of dihydroetorphine following topical application were investigated in hairless rats with and without formalin-induced inflammation. The analgesic effect of dihydroetorphine (s.c.) was 4600- to 7200-fold more potent than that of morphine. In non-inflamed rats, the analgesic effect of 24-h topical application of dihydroetorphine tape (35 microg) and 4-day repeated tape applications (20 microg/5 h/day) decreased with time after the start of application, even though the plasma dihydroetorphine concentrations did not decrease. In formalin-inflamed rats, however, the tolerance to analgesia diminished. Naloxone-precipitated weight loss was observed after 24-h infusion of dihydroetorphine but not after the tape application in non-inflamed rats. A significant rewarding effect was found in the non-inflamed rats conditioned by s.c. injection and tape application but not in the formalin-inflamed rats. These results indicate that topical application of dihydroetorphine has a tolerance and dependence liability when there is no pain, and therefore, it should be used only for pain relief.

Administration, Cutaneous↗

Effect of the type carrier used on the results of dichlorodifluoromethane application to teeth.

Thermal testing, especially cold, is an important part of diagnosing pulpal vitality. It was the purpose of this study to determine (i) if a difference exists in temperature when Endo ice is used with four different applicators, and (ii) if there is one applicator device that provides the greatest thermal change for a tooth. Endo ice was used with the following applicators: a #2 standard size large cotton pellet, a #4 standard size small cotton pellet, a wood stick cotton tip applicator, and a cotton roll. The temperature of a mandibular incisor pulp chamber was measured in degree C 10 s after the application of the dichlorodifluoromethane (DDM) to the midfacial surface of the crown. Also, the DDM was applied to each applicator either by direct spray or by submergence in DDM liquid. This study found that the greatest temperature change was recorded by Endo Ice (DDM) sprayed directly onto a large cotton pellet. There was no significant difference between directly spraying or submerging the applicator in DDM liquid.

Aerosols↗

Nutrient losses by surface run-off following the application of organic manures to arable land. 2. Phosphorus.

Phosphorus (P) surface run-off losses were studied following organic manure applications to land, utilising a purpose-built facility on a sloping site in Herefordshire under arable tillage. Different rates and timing of cattle slurry, farm yard manure (FYM) and inorganic nitrogen (N) and P fertiliser were compared, over a 4-year period (1993-97). N losses from the same studies are reported in a separate paper. The application of cattle FYM and, especially slurry, to the silty clay loam soil increased both particulate and soluble P loss in surface water flow. Losses via subsurface flow (30 cm interflow) were consistently much lower than via surface water movement and were generally unaffected by treatment. Increased application of slurry solids increased all forms of P loss via surface run-off; the results suggested that a threshold for greatly increased risk of P losses via this route, as for N, occurred at ca. 2.5-3.0 t/ha solids loading. This approximates to the 50 m3/ha application rate limit suggested for slurry within UK 'good agricultural practice'. The studies also provided circumstantial evidence of the sealing of the soil surface by slurry solids as the major mechanism by which polluting surface run-off may occur following slurry application on susceptible soils. Losses of total and soluble P, recorded for each of the 4 years of experiments, reached a maximum of only up to 2 kg/ha total P (TP), even after slurry applications initiating run-off. Whilst these losses are insignificant in agronomic terms, peak concentrations of P (up to 30,000 micrograms/l TP) in surface water during a run-off event, could be of considerable concern in sensitive catchments. Losses of slurry P via surface run-off could make a significant contribution to accelerated eutrophication on entry to enclosed waters, particularly when combined with high concentrations of NO3(-)-N. Restricting slurry application rates to those consistent with good agronomic practice, and within the limits specified in existing guidelines on good agricultural practice, offers the simplest and most effective control measure against this potentially important source of diffuse pollution.

Agriculture↗

Applicator-guided intensity-modulated radiation therapy.

PURPOSE: We are introducing a novel method for delivering highly conformal dose distributions to cervical cancer tumors using external beam intensity-modulated radiation therapy. The method, termed applicator-guided intensity-modulated radiation therapy (AGIMRT), will use an applicator substitute placed in the vagina and uterus to provide spatial registration and immobilization of the gynecologic organs. The main reason for the applicator substitute will be to localize the fornices, cervix, and uterus with the expectation that the other nearby organs will also be reproducibly positioned with respect to the applicator substitute. Intensity-modulated radiation therapy (IMRT) dose distributions will be used as a substitute for high-dose-rate intracavitary brachytherapy procedures. The flexibility of IMRT will enable customized dose distributions that have the potential to reduce complications and improve local control, especially for locally advanced disease. METHODS AND MATERIALS: To test the advantages of IMRT over intracavitary brachytherapy, volumetric scans of three cervical cancer patients were obtained with implanted CT-compatible applicators. IMRT dose distribution simulations using tomotherapy, were compared against intracavitary brachytherapy using cesium tubes to investigate the dosimetric differences of the two modalities. Because these tumor volumes do not image well on CT, the target volumes were defined as the isodose surface containing the traditional point A, defined as 2 cm superior to the vaginal fornices and 2 cm lateral to the intrauterine canal. One patient had a uterus that wrapped superior and anterior to the bladder. For this case, the cervix and uterus were selected as the target volume. To determine the potential for using an applicator substitute to localize internal organs, the posterior bladder and anterior rectal surfaces were localized relative to the colpostats. Comparisons of the colpostat-localized surfaces were conducted for two scan studies for 3 patients. RESULTS: The IMRT distributions covered the point-A isodose surfaces while reducing doses to the bladder and rectum. Brachytherapy showed extensive underdose regions in the target volume for the wrapped-around target. Spatial positioning was better than 0.7 and 1.3 cm in the rectum and bladder, respectively, indicating the potential that an applicator substitute may be able to localize these structures. CONCLUSIONS: AGIMRT has the potential for improving critical structure avoidance while maintaining highly reproducible and accurate internal organ registration found with brachytherapy.

Female↗

Hair cell regeneration after local application of gentamicin at the round window of the cochlea in the pigeon.

Hair cells in the basilar papilla of birds have the capacity to regenerate after injury. Methods commonly used to induce cochlear damage are systemic application of ototoxic substances such as aminoglycoside antibiotics or loud sound. Both methods have disadvantages. The systemic application of antibiotics results in damage restricted to the basal 50% of the papilla and has severe side effects on the kidneys. Loud sound damages only small parts of the papilla and is restricted to the short hair cells. The present study was undertaken to determine the effect of local aminoglycoside application on the physiology and morphology of the avian basilar papilla. Collagen sponges loaded with gentamicin were placed at the round window of the cochlea in adult pigeons. The time course of hearing thresholds was determined from auditory brain stem responses elicited with pure tone bursts within a frequency range of 0.35-5.565 kHz. The condition of the basilar papilla was determined from scanning electron micrographs. Five days after application of the collagen sponges loaded with gentamicin severe hearing loss, except for the lowest frequency tested, was observed. Only at the apical 20% of the basilar papilla hair cells were left intact, all other hair cells were missing or damaged. At all frequencies there was little functional recovery until day 13 after implantation. At frequencies above 1 kHz functional recovery occurred at a rate of up to 4 dB/day until day 21, beyond that day recovery continued at a rate below 1 dB/day until day 48 at the 5.6 kHz. Below 1 kHz recovery occurred up to day 22, the recovery rate was below 2 dB/day. A residual hearing loss of about 15-25 dB remained at all frequencies, except for the lowest frequency tested. At day 20 new hair cells were seen on the basilar papilla. At day 48 the hair cells appeared to have recovered fully, except for the orientation of the hair cell bundles. The advantage of the local application of the aminoglycoside drug over systemic application is that it damages almost all hair cells in the basilar papilla and it has no toxic side effects. The damage is more extensive than with systemic application.

Acoustic Stimulation↗

Application of enzymes in the pulp and paper industry

The pulp and paper industry processes huge quantities of lignocellulosic biomass every year. The technology for pulp manufacture is highly diverse, and numerous opportunities exist for the application of microbial enzymes. Historically, enzymes have found some uses in the paper industry, but these have been mainly confined to areas such as modifications of raw starch. However, a wide range of applications in the pulp and paper industry have now been identified. The use of enzymes in the pulp and paper industry has grown rapidly since the mid 1980s. While many applications of enzymes in the pulp and paper industry are still in the research and development stage, several applications have found their way into the mills in an unprecedented short period of time. Currently the most important application of enzymes is in the prebleaching of kraft pulp. Xylanase enzymes have been found to be most effective for that purpose. Xylanase prebleaching technology is now in use at several mills worldwide. This technology has been successfully transferred to full industrial scale in just a few years. The enzymatic pitch control method using lipase was put into practice in a large-scale paper-making process as a routine operation in the early 1990s and was the first case in the world in which an enzyme was successfully applied in the actual paper-making process. Improvement of pulp drainage with enzymes is practiced routinely at mill scale. Enzymatic deinking has also been successfully applied during mill trials and can be expected to expand in application as increasing amounts of newsprint must be deinked and recycled. The University of Georgia has recently opened a pilot plant for deinking of recycled paper. Pulp bleaching with a laccase mediator system has reached pilot plant stage and is expected to be commercialized soon. Enzymatic debarking, enzymatic beating, and reduction of vessel picking with enzymes are still in the R&D stage but hold great promise for reducing energy. Other enzymatic applications, i.e., removal of shives and slime, retting of flax fibers, and selective removal of xylan, are also expected to have a profound impact on the future technology of the pulp and paper-making process.

Journal Article↗

Do UK Medical School Applicants Prefer Interviewing to Non-Interviewing Schools?

Medical schools select applicants; applicants who hold two or more offers also select medical schools. In this study we examine a large cohort of applicants applying for admission to UK medical schools in October 1991, and show that when presented with a choice, applicants are more likely to select an interviewing school over a non-interviewing school. Preferences for individual schools are examined in detail using the Bradley-Terry method for paired comparisons. The analysis shows that the preference for interviewing schools cannot be explained in terms of a preference for Oxford and Cambridge (which both interview), nor is it due to confounding by more non-interviewing schools being in the north of the UK. Nevertheless, interviewing status does not account for all the preferences expressed by applicants. The preference for interviewing schools is perhaps explained by applicants feeling closer and more involved with schools which they have visited, which have talked to them personally, and which have selected them individually, rather than on the basis of an impersonal application form.

Journal Article↗

Sunscreen application technique in photosensitive patients: a quantitative assessment of the effect of education.

Photosensitive patients are known to apply insufficient sunscreen and to neglect several prominently exposed skin sites. The aim of this study was to use fluorescence spectroscopy to assess the effect of education on sunscreen application technique in the short and longer term. Six patients with longstanding photosensitivity conditions were asked to apply an intrinsically fluorescent sunscreen to exposed skin, as they normally would on a sunny day. Detailed fluorescence measurements were taken from 70 sites on the head, neck and arms. Using the previously established dose-response relationship for cream fluorescence, measurements were converted to equivalent thicknesses of cream. Patients were told the results of their sunscreen application assessment and deficiencies in technique were highlighted. Following education, application technique was reassessed twice, after intervals of 2 weeks and 6 months. Before education, sunscreen application was poor with inadequate amounts applied, and prominently exposed sites including ears, temples and neck often missed. At 2 weeks following education, improved application was seen at all sites, and the improvement was sustained at 6 months. Overall, education improved sunscreen application from a baseline median sunscreen thickness of 0.11 mg/cm2 to 0.82 mg/cm2 at 2 weeks and 1.13 mg/cm2 at 6 months (P<0.0001). Notably, median sunscreen thickness on the face improved from a baseline of 0.33 mg/cm2 to 1.51 mg/cm2 at 6 months. These findings demonstrate the importance of careful instruction to patients concerning sunscreen application technique; failure to do this may result in overconfidence in the ability of a sunscreen to protect. The next step is to assess a larger number of photosensitive patients with different diagnoses and to see whether improved technique correlates with improvement in clinical features.

Administration, Cutaneous↗

Adenosine antagonist theophylline prevents the reduction of glomerular filtration rate after contrast media application.

Radiographic contrast media (CM) can induce renal failure and this may serve as an experimental model of acute renal failure (ARF). One vasoactive factor likely to be involved in ARF is adenosine. In a double-blind, placebo-controlled study we investigated the effect of theophylline (TP), an adenosine receptor antagonist, regarding changes in renal hemodynamics induced by CM. Thirty-nine patients who received 100 ml of a non-ionic low osmolar CM (iopromide) were studied for changes in GFR and RPF by continuous inulin and PAH clearance before and until four hours after CM application. Forty-five minutes before the application of CM, patients were randomized and received either theophylline (5 mg/kg body wt) or the vehicle and placebo (saline) intravenously in a blinded manner. We additionally measured the creatinine clearance on the day before and two days after CM application. Sodium excretion, N-acetyl-beta-glucosaminidase (NAG) excretion, plasma renin activity (PRA) and aldosterone levels were also measured before and after CM application. Theophylline levels were within the therapeutic range in patients of the theophylline group during and four hours after CM application (59.0 +/- 10.6 mumol/liter and 40.1 +/- 10.9 mumol/liter). GFR, measured by inulin clearance significantly declined under CM application in patients without TP application (N = 19; 88 +/- 40 to 75 +/- 32 ml/min/1.72 m2; P < 0.01). In the group of patients receiving theophylline (N = 18) the GFR remained constant (75 +/- 26 vs. 78 +/- 33 ml/min/1.72 m2).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Ethnic and gender variations in university applicants to United Kingdom medical and dental schools.

AIM: To explore ethnic and gender variations amongst applicants to undergraduate United Kingdom medical and dental schools. METHOD: Retrospective analyses of University and College Admissions Services (UCAS) data on all students applying to study pre-clinical medicine and dentistry, during the academic years 1994/5, 1995/6 and 1996/7. Information for each medical and dental applicant included age, gender, social class and ethnic group. RESULTS: Of all applicants, just over half (50.2%) were male, though a greater proportion of applicants to dentistry were male (54.1%) than for medicine (49.3%) (OR = 1.21, 95% CI = 1.15, 1.28). Over one third (36.4%) of all students were from minority ethnic groups, a larger proportion of which were dental students (48.3%) than were medical students (33.8%) (OR = 1.83, 95% CI = 1.73, 1.94). There were also marked differences between medicine and dentistry when the ethnic groups were examined separately. The largest number of applicants from minority ethnic groups came from the Indian community, and this group increased in size annually by 4.1% (P < 0.05) for medicine, and 29% (P < 0.05) for dentistry. CONCLUSIONS: Significant inter-ethnic and gender differences are observed amongst applicants to medicine and dentistry. Dentistry appears to be relatively more attractive to minority ethnic applicants.

Black or African American↗

Phthalate and alkyl phenol concentrations in soil following applications of inorganic fertiliser or sewage sludge to pasture and potential rates of ingestion by grazing ruminants.

Soil concentrations of dioctyl phthalate (DOP) and the alkyl phenols, octyl phenol (OP) and nonyl phenol (NP), after repeated surface applications of sewage sludge to pastures, were investigated. Liquid sludge was applied at a rate of 2.25 tonnes dry matter (DM) per hectare to each of three treated (T) plots on three occasions during the summer and two occasions in the early spring over a period of 2.5 years. Control (C) plots were treated with inorganic fertiliser containing amounts of nitrogen equivalent to those applied to the treated plots. At between 69 and 81 days after the application of sludge, 15 separate soil samples were collected from one half of each of the plots (Experiment 1). Concentrations (microg g(-1)) of DOP were higher (P < 0.001) than those of NP, while those of OP were generally below detectable levels. Mean soil concentrations of DOP were not significantly different in T and C plots [0.233 vs. 0.155 microg g(-1); standard error of the difference (SED) = 0.046; not significant (NS)], partly because there was already a relatively large amount of DOP present. NP concentrations were, however, significantly higher in T than in C plots (0.021 vs. 0.013 microg g(-1) SED = 0.002; P < 0.05). There was no consistent change over time in the mean soil concentrations of these compounds when sampled at intervals of 3-6 months. Concentrations in soil samples collected at monthly intervals following sludge application indicated that the variation in concentrations of these endocrine-disrupting compounds (EDC) was unrelated to time since sludge application. Rates of soil ingestion, expressed as the percentage of DM intake represented by soil, were higher during the winter than the summer (5.40 vs. 1.17; SED = 0.360; P < 0.001) and estimated daily intakes of DOP and NP were up to 150 microg and 8 microg, respectively. It is concluded that the application of sewage sludge to pasture does not increase soil concentrations of phthalate (as DOP) or alkyl phenols. Thus, the risk of increased exposure to these EDC as a result of sludge application is small. However, the small effect of sludge application on soil concentrations may be largely a reflection of the relatively high concentrations of DOP already present in the soil, which may be biologically significant.

Agriculture↗

Effect of elevating the skin temperature during topical ALA application on in vitro ALA penetration through mouse skin and in vivo PpIX production in human skin.

An approach to induce increased protoporphyrin IX (PpIX) production in aminolevulinic acid (ALA)-based photodynamic therapy (PDT) of skin lesions is to elevate the skin temperature during topical ALA application. Increased skin temperature may increase the (depth of) penetration of ALA into the skin, which may in turn increase PpIX production (in deeper layers). The effect of skin temperature on in vitro ALA penetration into mouse skin was determined in an in vitro percutaneous penetration model at two different temperatures. The effect of skin temperature on PpIX production in human skin during ALA application was measured with in vivo fluorescence spectroscopy in temperature-controlled areas (5 different temperatures). The data from the experiment with the in vitro percutaneous penetration model clearly show that the penetration of ALA into skin is temperature dependent. The penetration of ALA through the mouse skin was higher when its temperature was maintained at 37 [degree]C than through skin that was kept at 32 [degree]C. The fluorescence data from the in vivo experiment show that the PpIX fluorescence increases with increasing temperature of the skin during the application period. The overall activation energy (E(a)) for PpIX production was obtained for each hour of the ALA application period from the fluorescence data using the Arrhenius equation. The E(a) value in the first hour of ALA application was not significant, indicating that the PpIX production in that period is dominated by processes that are not temperature dependent, like the passive diffusion of ALA across the stratum corneum. In the second, third and fourth hours of ALA application, the E(a) for PpIX production proved to be significant, which indicates that the PpIX production in these time intervals is dominated by temperature-dependent processes. In conclusion, the data from the present study indicate that improving ALA-based PDT of skin lesions might be achieved by elevating the skin temperature during the ALA application.

Administration, Topical↗