Determination of the effect of lipophilicity on the in vitro permeability and tissue reservoir characteristics of topically applied solutes in human skin layers

In order to establish the relationship between solute lipophilicity and skin penetration (including flux and concentration behavior), we examined the in vitro penetration and membrane concentration of a series of homologous alcohols (C2-C10) applied topically in aqueous solutions to human epidermal, full-thickness, and dermal membranes. The partitioning/distribution of each alcohol between the donor solution, stratum corneum, viable epidermis, dermis, and receptor phase compartments was determined during the penetration process and separately to isolated samples of each tissue type. Maximum flux and permeability coefficients are compared for each membrane and estimates of alcohol diffusivity are made based on flux/concentration data and also the related tissue resistance (the reciprocal of permeability coefficient) for each membrane type. The permeability coefficient increased with increasing lipophilicity to alcohol C8 (octanol) with no further increase for C10 (decanol). Log vehicle:stratum corneum partition coefficients were related to logP , and the concentration of alcohols in each of the tissue layers appeared to increase with lipophilicity. No difference was measured in the diffusivity of smaller more polar alcohols in the three membranes; however, the larger more lipophilic solutes showed slower diffusivity values. The study showed that the dermis may be a much more lipophilic environment than originally believed and that distribution of smaller nonionized solutes into local tissues below a site of topical application may be estimated based on knowledge of their lipophilicity alone.

Effect of solute lipophilicity on penetration through canine skin

Objective To investigate the effect of lipophilicity on the percutaneous penetration of a homologous series of alcohols through canine skin Design Skin harvested from Greyhound thorax was placed in Franz-type diffusion cells and the in vitro passage of radio-labelled (C-14) alcohols (ethanol, butanol, hexanol and octanol (Log P 0.19 - 3.0)) through separate skin sections was measured in replicates of five. Permeability coefficient (k(P), cm/h), maximum flux (J(max), mol/cm(2)/h) and residue remaining within the skin were determined. Results The k(P) increased with increasing lipophilicity (6.2 x 10(-4) +/- 1.6 x 10(-4) cm/h for ethanol to 1.8 x 10(-2) 3.6 x 10(-3) cm/h for octanol). Alcohol residues remaining within each skin sample followed a similar pattern. An exponential decrease in Jmax with increasing lipophilicity was observed. Conclusion Changes in canine skin permeability occur with increasing alcohol lipophilicity. This finding has practical consequences for the design of topical formulations and optimisation of drug delivery through animal skin.

Thermal skin reference values in healthy late pregnancy

Digital thermal imaging has been employed in medicine for over 50 years. However, its use has been focused on vascular, musculoskeletal and neurological conditions, while other potential applications,such as obstetrics, have been much less explored. This paper presents a study conducted during 2011 at the Hospital of Braga on a group of healthy pregnant women in the last third of gestation. The analysis focused on characterizing typical pregnant women steady temperature profiles in specific defined regions of interest (ROI), and determining if the thermal symmetry values for late pregnant healthy women are in line with the values for non-pregnant healthy women. A temperature distribution pattern was found in the defined ROI. The obtained thermal symmetry value had a maximum of 0.370.2 1C, and there was no evidence for the influence of age (p40.05) in the observed group. The influence of the BMI requires further investigation since one ROI (P2 right) presented a p¼0.059, close to the threshold of statistical evidence in the influence of BMI. The study group presented symmetry values in line with non-pregnant reference values, but the profiles in temperature distribution are different. Assumptions can therefore now be used with higher confidence when assessing abnormalities in specific pathologic states during pregnancy using the defined ROI. This work represents a first contribution towards establishing guidelines for future research in this specific field of study.

Fractional order inductive phenomena based on the skin effect

The Maxwell equations play a fundamental role in the electromagnetic theory and lead to models useful in physics and engineering. This formalism involves integer-order differential calculus, but the electromagnetic diffusion points towards the adoption of a fractional calculus approach. This study addresses the skin effect and develops a new method for implementing fractional-order inductive elements. Two genetic algorithms are adopted, one for the system numerical evaluation and another for the parameter identification, both with good results.

Multiple skin neoplasms in subjects under 40 years of age in Goiania, Brazil

OBJECTIVE To describe the trend for malignant skin neoplasms in subjects under 40 years of age in a region with high ultraviolet radiation indices.METHODS A descriptive epidemiological study on melanoma and nonmelanoma skin cancers that was conducted in Goiania, Midwest Brazil, with 1,688 people under 40 years of age, between 1988 and 2009. Cases were obtained fromRegistro de Câncer de Base Populacional de Goiânia(Goiania’s Population-Based Cancer File). Frequency, trends, and incidence of cases with single and multiple lesions were analyzed; transplants and genetic skin diseases were found in cases with multiple lesions.RESULTS Over the period, 1,995 skin cancer cases were observed to found, of which 1,524 (90.3%) cases had single lesions and 164 (9.7%) had multiple lesions. Regarding single lesions, incidence on men was observed to have risen from 2.4 to 3.1/100,000 inhabitants; it differed significantly for women, shifting from 2.3 to 5.3/100,000 (Annual percentage change – [APC] 3.0%, p = 0.006). Regarding multiple lesions, incidence on men was observed to have risen from 0.30 to 0.98/100,000 inhabitants; for women, it rose from 0.43 to 1.16/100,000 (APC 8.6%, p = 0.003). Genetic skin diseases or transplants were found to have been correlated with 10.0% of cases with multiple lesions – an average of 5.1 lesions per patient. The average was 2.5 in cases without that correlation.CONCLUSIONS Skin cancer on women under 40 years of age has been observed to be increasing for both cases with single and multiple lesions. It is not unusual to find multiple tumors in young people – in most cases, they are not associated with genetic skin diseases or transplants. It is necessary to avoid excessive exposure to ultraviolet radiation from childhood.

Electrical skin phenomena: a fractional calculus analysis

The internal impedance of a wire is the function of the frequency. In a conductor, where the conductivity is sufficiently high, the displacement current density can be neglected. In this case, the conduction current density is given by the product of the electric field and the conductance. One of the aspects of the high-frequency effects is the skin effect (SE). The fundamental problem with SE is it attenuates the higher frequency components of a signal.

Schistosoma mansoni: importance of skin and pulmonary phases to concomitant immunity in albino mice

Fourteen-day-old schistosomula obtained from mice previously infected were surgically transferred to the portal vein of receptor mice. Another group of mice was infected with cercariae by transcutaneous route. After 90 days, those groups were challenged with 100 cercariae, transcutaneously, as well as a control group. Two weeks later the animals were perfused and mature and immature worms counted separately. Statistically significant differences were observed in the recovery of immature worms, when the control group was compared with those twice infected. No statistical difference was detected between the group infected transcutaneously, and that infected by worm inoculation in portal vein. Results demonstrated that suppression of skin and lung migration of the parasite does not interfere with the development of the so called concomitant immunity.

Schistosoma mansoni: acquired immunity in mice after the use of oxamniquine at the evolutive skin and pulmonary phases

Mice infected with 350 cercariae of Schistosoma mansoni (LE strain) were treated with oxamniquine, at the dose of 400 mg/kg, 24, 48, 72, and 96 h after infection. Forty days after the treatment, the animals were submitted to a challenge infection with 80 cercariae, through the abdominal and ear skins. The number of immature worms in the animal groups treated 24 and 96 h after the first infection was found to be lower than that in the control group, thus showing that the death of schisto-somes by chemotherapy, at the skin and pulmonary phases, causes an acquired resistance state.

Effect of skin colour and selected physical characteristics on Schistosoma mansoni dependent morbidity

The effect of the colour group on the morbidity due to Schistosoma mansoni was examined in two endemic areas situated in the State of Minas Gerais, Brazil. Of the 2773 eligible inhabitants, 1971 (71.1%) participated in the study: 545 (27.6%) were classified as white, 719 (36.5%) as intermediate and 707 (35.9%) as black. For each colour group, signs and symptoms of individuals who eliminated S.mansoni eggs (cases) were compared to those who did not present eggs in the faeces (controls). The odds ratios were adjusted by age, gender, previous treatment for schistosomiasis, endemic area and quality of the household. There was no evidence of a modifier effect of colour on diarrhea, bloody faeces or abdominal pain. A modifier effect of colour on hepatomegaly was evident among those heaviest infected (> 400 epg): the adjusted odds ratios for palpable liver at the middle clavicular and the middle sternal lines were smaller among blacks (5.4 and 6.5, respectively) and higher among whites (10.6 and 12.9) and intermediates (10.4 and 10.1, respectively). These results point out the existence of some degree of protection against hepatomegaly among blacks heaviest infected in the studied areas.

Histoplasmin and paracoccidioidin skin reactivity in infantile population of Northern Argentina

In order to estimate ages at which etiological agents of systemic mycoses initiate infection, histoplasmin and paracoccidioidin skin tests were performed in 344 children of both sexes, between 2 and 15 years old. They were selected from a statistically significant population sample Gral. San Martín city (Northeast Argentina). Tests were read 48h after injection and considered positive if a 5 mm on larger induration was present. Circulating antibodies were also evaluated by agar gel immunodiffusion. The overall infection rate for H. capsulatum was 9.2%, belonging to children from 4 to 14 years old, without significant differences among sexes. Five children from 2 to 14 years old were positive to paracoccidioidin (1.6%). None of the children had specific antibodies neither signs of active mycosis. Results show H. capsulatum infection can be found from age 4, while for P. brasiliensis the lower limit was two years old. These findings may contribute to better knowledge on infantile fungal infection in a geographical region where no previous references can be found.

EPIDEMIOLOGICAL SURVEY ON CANINE POPULATION WITH THE USE OF IMMUNOLEISH SKIN TEST IN ENDEMIC AREAS OF HUMAN AMERICAN CUTANEOUS LEISHMANIASIS IN THE STATE OF RIO DE JANEIRO, BRAZIL

A survey for canine tegumentary leishmaniasis (CTL) has been carried out between 1986 and 1993 in seven endemic localities for American cutaneous leishmaniasis in the State of Rio de Janeiro. 270 dogs have been examined for their clinical aspects, the development of delayed hypersensitivity (DHS) with Immunoleish antigen and with immunofluorescent antibody research of IgG (IF). 28.2% of them had ulcer lesions and 3.3% had scars. The lesions consisted of single (39.5%) and mucocutaneous lesions (31.6%), multiple cutaneous (25.0%) and mucocutaneous lesions associated with cutaneous ulcers (4.0%). Twelve (15.8%) isolates from biopsies were analyzed by zimodeme and schizodeme and identified as L. (V.) braziliensis. The overall prevalence of canine infection that was evaluated with the skin test was of 40.5% and with IF it was of 25.5%. Both tests showed a high positive rate with relation to the animals with mucosal lesions, as in the case of human mucocutaneous leishmaniasis. The comparison of the two tests showed the skin test to have a better performance although there was no statistical difference (p>0.05) between them. The proportional sensitivity and specificity was of 84.0% and 74.0%, respectively. The Immunoleish skin test and IF are useful tools to be employed in CTL field epidemiological surveys.

MICROCIRCULATION AND CHAGAS' DISEASE: HYPOTHESIS AND RECENT RESULTS

This review focuses on studies that support the microvascular hypothesis, as well as on immunological and neurogenic mechanisms, and the role of the parasite itself, to explain further the pathology and clinical course of myocardial involvement in chagasic cardiomyopathy. The salient features of coronary microcirculation and Chagas' disease are discussed.

Proposal of abolition of the skin sensitivity test before equine rabies immune globulin application

An epizootic outbreak of rabies occurred in 1995 in Ribeirão Preto, SP, with 58 cases of animal rabies (54 dogs, 3 cats and 1 bat) confirmed by the Pasteur Institute of São Paulo, and one human death. The need to provide care to a large number of people for the application of equine rabies immune globulin (ERIG) prevented the execution of the skin sensitivity test (SST) and often also the execution of desensitization, procedures routinely used up to that time at the Emergency Unit of the University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo (EU-UHFMRP-USP), a reference hospital for the application of heterologous sera. In view of our positive experience of several years with the abolition of SST and of the use of premedication before the application of antivenom sera, we used a similar schedule for ERIG application. Of the 1489 victims of animal bites, 1054 (71%) received ERIG; no patient was submitted to SST and all received intravenously anti-histamines (anti-H1 + anti-H2) and corticosteroids before the procedure. The patients were kept under observation for 60 to 180 minutes and no adverse reaction was observed. On the basis of these results, since December 1995 ERIG application has been decentralized in Ribeirão Preto and has become the responsibility of the Emergency Unit of the University Hospital and the Central Basic Health Unit, where the same routine is used. Since then, 4216 patients have received ERIG (1818 at the Basic Health Unit and 2398 at the EU-UHFMRP), with no problems. The ideal would be the routine use of human rabies immune globulin (HRIG) in public health programs, but this is problematic, because of their high cost. However, while this does not occur, the use of SST is no longer justified at the time of application of ERIG, in view of the clinical evidence of low predictive value and low sensitivity of SST involving the application of heterologous sera. It is very important to point out that a negative SST result may lead the health team to a feeling of false safety that no adverse reaction will occur, but this is not true for the anaphylactoid reactions. The decision to use premedication, which is based on knowledge about anaphylaxis and on the pharmacology of the medication used, is left to the judgment of health professionals, who should always be prepared for eventual untoward events.

Skin Prick Tests and Allergy Diagnosis

Skin testing remains an essential diagnostic tool in modern allergy practice. A signifi cant variability has been reported regarding technical procedures, interpretation of results and documentation. This review has the aim of consolidating methodological recommendations through a critical analysis on past and recent data. This will allow a better understanding on skin prick test (SPT) history; technique; (contra-) indications; interpretation of results; diagnostic pitfalls; adverse reactions; and variability factors.