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.

CD40 and dendritic cell function

CD40 has emerged as a key signaling pathway for the function of B cells, monocytes, and dendritic cells (DC) in the immune system, and plays a major role in inflammatory pathways of nonhemopoletic cells. CD40 is expressed by monocytes and DC and is up-regulated when DC migrate from the periphery to draining lymph nodes (DLN) in response to microbial challenge. CD154 signaling by MHC-restricted, activated CD4* T cells induces differentiation of DC, as defined by an increased surface expression of MHC, costimulatory, and adhesion molecules. Thus, CD40 functions in the adaptive immune response as a trigger for the expression of costimulatory molecules for efficient T-cell activation. CD40 ligation of DC also has the capacity to induce high levels of the cytokine IL-12, which polarizes CD4(+) T cells toward a T helper 1 (Th1) type, enhances proliferation of CD8(+) T cells, and activates NK cells. CD40 may also play an important role in the decision between tolerance and immunity and the generation of regulatory CD4(+) T cells that are thought to maintain peripheral self-tolerance in vivo.

The ultrastructure and function of the silk-producing basitarsus in the Hilarini (Diptera : Ernpididae)

The tribe Hilarini (Diptera: Empididae), commonly known as dance flies, can be recognised by their swollen silk-producing prothoracic basitarsus, a male secondary sexual characteristic. The ultrastructure and function of the silk-producing basitarsus from one undescribed morphospecies of Hilarini, 'Hilarempis 20', is presented. Male H. 20 collect small parcels of diatomaceous algae from the surface of freshwater creeks that they bind with silk produced by the gland in the basitarsus. The gift is then presented to females in a nearby swarm, composed predominately of females. The basitarsus houses approximately 12 pairs of class III dermal glandular units that congregate on the ventral side of the cavity. Each gland cell has a large extracellular lumen where secretion accumulates. The lumen drains to the outside via a conducting canal encompassed by a canal cell and a duct extending through the shaft of a specialised secretory spine. The secretory spines lie in pairs in a ventral groove that runs the length of the basitarsus. A comparison of the basitarsal secretory spines with sensilla on the basitarsi of non gland-bearing legs of males, and with non gland-bearing prothoracic. basitarsi of females, suggests that the glandular units are derived from contact chemosensory sensilla. (C) 2003 Elsevier Ltd. All rights reserved.

Transdermal penetration of vasoconstrictors - Present understanding and assessment of the human epidermal flux and retention of free bases and ion-pairs

Purpose. As reductions in dermal clearance increase the residence time of solutes in the skin and underlying tissues we compared the topical penetration of potentially useful vasoconstrictors (VCs) through human epidermis as both free bases and ion-pairs with salicylic acid (SA). Methods. We determined the in vitro epidermal flux of ephedrine, naphazoline, oxymetazoline, phenylephrine, and xylometazoline applied as saturated solutions in propylene glycol: water (1: 1) and of ephedrine, naphazoline and tetrahydrozoline as 10% solutions of 1: 1 molar ratio ion-pairs with SA in liquid paraffin. Results. As free bases, ephedrine had the highest maximal flux, Jmax = 77.4 +/- 11.7 mug/cm(2)/h, being 4-fold higher than tetrahydrozoline and xylometazoline, 6-fold higher than phenylephrine, 10-fold higher than naphazoline and 100-fold higher than oxymetazoline. Stepwise regression of solute physicochemical properties identified melting point as the most significant predictor of flux. As ion-pairs with SA, ephedrine and naphazoline had similar fluxes (11.5 +/- 2.3 and 12.0 +/- 1.6 mug/cm(2)/h respectively), whereas tetrahydrozoline was approximately 3-fold slower. Corresponding fluxes of SA from the ion-pairs were 18.6 +/- 0.6, 7.8 +/- 0.8 and 1.1 +/- 0.1 respectively. Transdermal transport of VC's is discussed. Conclusions. Epidermal retention of VCs and SA did not correspond to their molar ratio on application and confirmed that following partitioning into the stratum corneum, ion-pairs separate and further penetration is governed by individual solute characteristics.

Indoor air quality in primary schools

Clean air is a basic requirement of life. The Indoor Air Quality (IAQ) has been the object of several studies due to an increasing concern within the scientific community on the effects of indoor air quality upon health, especially as people tend to spend more time indoors than outdoors. The quality of air inside homes, offices, schools or other private and public buildings is an essential determinant of healthy life and people’s well-being. People can be exposed to contaminants by inhalation, ingestion and dermal contact. In the past, scientists have paid much attention to the study of exposure to outdoor air contaminants, because they have realised the seriousness of outdoor air pollution problems. However, each indoor microenvironment has unique characteristics, determined by the local outdoor air, specific building characteristics and indoor activities. Indeed, hazardous substances are emitted from buildings, construction materials and indoor equipment or due to human activities indoors.

Surfaces contamination with 5-Fluorouracil in two Portuguese hospitals

During the last years there has been an increasing concern about occupational exposure to cytostatic drugs in hospitals. The first findings on occupational exposures among hospital personnel administering chemotherapy were reported only in 1979. Since then, a great number of studies have been publishing describing possible exposure-related health effects. Consequently, rigorous guidelines for the safe handling of cancer chemotherapeutic agents were devised and the handling facilities in hospitals were extensively improved. However, recent studies developed in European countries revealed detectable amounts of several drugs in surface wipe samples. Dermal absorption after contact with contaminated surfaces can play an important role in exposure to antineoplastic drugs. Therefore, the existence of contamination in workplace surfaces implies an increased risk of exposure for health care workers. Since there is no recent report in Portugal, regarding the occupational exposure to antineoplastic drugs, a study was developed aiming to determine the 5-fluorouracil (5-FU) contamination on work surfaces of two Portuguese hospitals.

Dermic diffusion and stratum corneum: a state of the art review of mathematical models

Transdermal biotechnologies are an ever increasing field of interest, due to the medical and pharmaceutical applications that they underlie. There are several mathematical models at use that permit a more inclusive vision of pure experimental data and even allow practical extrapolation for new dermal diffusion methodologies. However, they grasp a complex variety of theories and assumptions that allocate their use for specific situations. Models based on Fick's First Law found better use in contexts where scaled particle theory Models would be extensive in time-span but the reciprocal is also true, as context of transdermal diffusion of particular active compounds changes. This article reviews extensively the various theoretical methodologies for studying dermic diffusion in the rate limiting dermic barrier, the stratum corneum, and systematizes its characteristics, their proper context of application, advantages and limitations, as well as future perspectives.

Tratamento da cisticercose subcutânea co praziquantel: um novo agente cestoidicida

Twenty adult patients presenting dermal cysticercosis without cerebral or ocular involvement were treated with praziquantel. The first eleven cases received 60 mg/kg/day and the last nine cases 30 mg/kg/day. In both groups the daily dose was split into three oral intakes 4 to 6 hours apart and the drug administration lasted for 6 consecutive days. The latter group of patients also got dexamethasone, 3 mg daily, from one day before until four days after the treatment period with praziquantel. The drug proved to be 100% efficacious as demonstrated histopathologically by the death of the cysticerci of Taenia solium (Cysticercus cellulosae) in serial biopsies taken from the 2nd week on after the end of treatment, as well as clinically by the steady disappearence of the dermal nodules during the 6 months following the therapy. Tolerance of praziquantel was good as the incidence and severity of side-effects were not relevant. The drug safety was confirmed through laboratory tests which failed to detect any abnormal findings related to the hematopoietic, liver and kidney functions.

Tuberculosis in renal transplant patients

Tuberculosis (TB) was diagnosed in 25 of 466 patients who underwent renal transplant over a period of 15 years. TB developed from 1 month to 9 years post-transplant. In 56% of the cases the onset was within the first post-transplant year. TB affected several isolated or combined organs. Pulmonary involvement was present in 76% of cases, either as isolated pleuro-pulmonary (56%) or associated with other sites (20%). The non-pulmonary sites were: skin, joints, tests, urinary tract, central nervous system and lymphonodules. The diagnosis was confirmed by biopsy in 64% of the cases, by identification of tubercle bacilli in 24% and only at necropsy in 12% Biopsy specimens could be classified in three histological forms: exudative, that occurred in early onset and more severe cases granulomatous in late onset and benign cases; and mixed in intermediate cases. Azathioprine dosages were similar along post-transplant time periods in TB patients and in the control groups; and in TB patients who were cured and who died. The number of steroid treated rejection crises was greater in TB than in the control group. Prednisone doses were higher and the number of rejection crises was greater in TB patients who died than in those who were cured. Fifteen patients were cured and ten died, two of them of causes unrelated to TB. Six of the eight TB-related deaths occurred in the first 6 post-transplant months. The outcome was poor in patients in whom TB arose early in post-transplant period and where the exudative or mixed forms were present; whereas the prognosis was good in patients with late onset and granulomatous form of TB. In one patient TB was transmitted by the allograft.

Intestinal cryptosporidiosis. association with Pneumocystis carinii, cytomegalovirus and Candida sp. Infections

This is a case report of intestinal cryptosporidiosis diagnosed in histological specimen collected from autopsy. The patient was a child of 5 months admitted to the hospital with severe acute diarrhea associated with Pneumocystis carinii pneumonia, cytomegalic sialadenitis, oral and dermal candidiasis. The presence of multiple opportunistic infections in this case indicated immunodeficiency state. Cryptosporidium sp is a possible etiology of acute diarrhea in both immunodeficient and immunocompetent patients and has to be searched for at autopsy when diagnosis was not possible "in vivo".

Is Demodex really non-pathogenic?

Although usually considered a non-pathogenic parasite in parasitological textbooks, Demodex folliculorum has been implicated as a causative agent for some dermatological conditions, such as rosacea-like eruptions and some types of blepharitis. Several anecdotal reports have demonstrated unequivocal tissue damage directly related to the presence of the parasite. However, this seems to be exceedingly rare, in contrast with the marked prevalence of this infestation. We have had the opportunity to observe one of such cases. A 38-year-old woman presented with rosacea-like papular lesions in her right cheek. Histopathological examination revealed granulomatous dermal inflammation with a well-preserved mite phagocytized by a multinucleated giant cell. This finding may be taken as an evidence for the pathogenicity of the parasite, inasmuch as it does not explain how such a common parasite is able to produce such a rare disease.

Queimadura com Exposição Óssea dos Membros Inferiores: Reconstrução com Matriz de Regeneração Dérmica

Introdução: As soluções reconstrutivas das queimaduras dos membros inferiores com exposição óssea (transferência de tecidos vascularizados) e dos defeitos do escalpe, não susceptíveis de encerramento com retalhos locais (expansão tecidual), são complexas, morosas e, por vezes, inviáveis. O recurso a substitutos cutâneos biológicos, como a matriz de regeneração dérmica, constitui uma importante alternativa às soluções reconstrutivas tradicionais. Relato dos casos: Estudo retrospectivo de 246 doentes com queimaduras dos membros inferiores, admitidos na Unidade de Queimados/Serviço de Cirurgia Plástica do nosso Centro Hospitalar, entre Janeiro de 2007 e Dezembro de 2008. Os autores apresentam 2 casos clínicos com queimaduras bilaterais das pernas e com exposição óssea. Nos dois casos, realizou-se desbridamento tangencial e encerramento das áreas cruentas com um substituto cutâneo, a matriz de regeneração dérmica. Na 4ª semana após a aplicação da matriz, o componente externo da membrana bilaminar foi substituído por enxerto de pele parcial. Obteve-se cobertura estável das áreas cruentas, sem necessidade de procedimentos cirúrgicos adicionais. Conclusões: A utilização de substitutos dérmicos expande as opções reconstrutivas nos casos de queimaduras com exposição óssea dos membros inferiores. A utilização da matriz biológica permitiu a preservação dos membros nos dois pacientes. A matriz de regeneração dérmica possibilitou uma cobertura estável de estruturas vitais, sem necessidade de transferência ou expansão tecidual e com morbilidade mínima.

Treatment of Hepatitis C Virus Infection in Kidney Transplant Recipients: Case Report

Chronic hepatitis C virus (HCV) infection exists in a large proportion of patients undergoing renal transplantation. Nowadays it is not considered to be an absolute contraindication to transplantation; however, it is associated with an increased risk for the patient and accounts for a shorter half-life of the renal allograft. We present three transplant recipients who displayed serious hepatic dysfunction after renal transplantation due to an HCV infection. In two of these cases, the liver biopsies established the diagnosis of FCH. In the third case, the liver biopsy was compatible with the early stages of FCH. All patients were started on peg-interferon alfa 2-b and ribavirin with subsequent normalization of hepatic function and early complete viral responses.

L. (L.) chagasi in aids and visceral leishmaniasis (kala-azar) co-infection

Concomitant skin lesions in visceral leishmaniasis (VL) or kala-azar are rare, being more common the description of post-kala-azar dermal leishmaniasis occurring post treatment of kala-azar. Skin lesions caused by Leishmania donovani are frequently seen in the aids-VL co-infection. In Brazil cutaneous or mucosal forms of tegumentary leishmaniasis concomitant with aids are more commonly registered. Here we present a case of aids-VL co-infection, with unusual cutaneous and digestive compromising attributed to L. (L.) chagasi, with special attention to ecthymatous aspect of the lesion, allied to the absence of parasite on the histological skin biopsy.