Stratum corneum lipids liposomes for the topical delivery of 5-aminolevulinic acid in photodynamic therapy of skin cancer: preparation and in vitro permeation study

Abstract Background Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) is a skin cancer therapy that still has limitations due to the low penetration of this drug into the skin. We have proposed in this work a delivery system for 5-ALA based on liposomes having lipid composition similar to the mammalian stratum corneum (SCLLs) in order to optimize its skin delivery in Photodynamic Therapy (PDT) of skin cancers. Methods SCLLs were obtained by reverse phase evaporation technique and size distribution of the vesicles was determinated by photon correlation spectroscopy. In vitro permeation profile was characterized using hairless mouse skin mounted in modified Franz diffusion cell. Results Size exclusion chromatography on gel filtration confirmed vesicle formation. SCLLs obtained by presented a degree of encapsulation of 5-ALA around 5.7%. A distribution of vesicle size centering at around 500 nm and 400 nm respectively for SCLLs and SCLLs containing 5-ALA was found. In vitro 5-ALA permeation study showed that SCLLs preparations presented higher skin retention significantly (p < 0.05) on the epidermis without SC + dermis, with a decreasing of skin permeation compared to aqueous solution. Conclusions The in vitro delivery performance provided by SCLLs lead to consider this systems adequate for the 5-ALA-PDT of skin cancer, since SCLLs have delivered 5-ALA to the target skin layers (viable epidermis + dermis) to be treated by topical PDT of skin cancer.

Histological composition and progression of carotid plaque

Abstract Background To analyse histological composition and progression of carotid plaque. Methods Thirty-one patients (22 males, mean age 68.03 ± 7.3 years) admitted for carotid endarterectomy for extracranial high-grade internal carotid artery stenosis (≥ 70% luminal narrowing) were enrolled. The patients were divided into 2 groups according to symptomatology (group I, 17 symptomatic patients; and group II, 14 asymptomatic patients). A histological analysis and inflammatory cell quantification of each excised carotid plaque was made. Nine carotid arteries were removed from human cadavers that were not preselected for carotid artery disease. These specimens were used as a control tissue without any macroscopic signs of atherosclerotic plaques. Results Fifty eight percent of all carotid plaques were classified as complex plaque with possible surface defect, hemorrhage or thrombus. The inflammatory cells concentration did not differ between the two groups. All specimens from human cadavers were classified as preatheroma with extracellular lipid pools. Conclusion Asymptomatic and symptomatic patients could have the same histological components on their carotid plaques. Fibrotic and calcific plaques could become vulnerable as complex plaques with surface defect, hemorrhage and thrombus could remain silent. Asymptomatic carotid stenosis should be followed close with no invasive diagnostic methods and clinical evaluation.

Diagnosis and biomarkers of predementia in Alzheimer's disease

In view of the growing prevalence of Alzheimer's disease (AD) worldwide, there is an urgent need for the development of better diagnostic tools and more effective therapeutic interventions. At the earliest stages of AD, no significant cognitive or functional impairment is detected by conventional clinical methods. However, new technologies based on structural and functional neuroimaging, and on the biochemical analysis of cerebrospinal fluid (CSF) may reveal correlates of intracerebral pathology in individuals with mild, predementia symptoms. These putative correlates are commonly referred to as AD-related biomarkers. The relevance of the early diagnosis of AD relies on the hypothesis that pharmacological interventions with disease-modifying compounds are likely to produce clinically relevant benefits if started early enough in the continuum towards dementia. Here we review the clinical characteristics of the prodromal and transitional states from normal cognitive ageing to dementia in AD. We further address recent developments in biomarker research to support the early diagnosis and prediction of dementia, and point out the challenges and perspectives for the translation of research data into clinical practice.

Electroconvulsive therapy use in adolescents: a systematic review

Abstract Background Considered as a moment of psychological vulnerability, adolescence is remarkably a risky period for the development of psychopathologies, when the choice of the correct therapeutic approach is crucial for achieving remission. One of the researched therapies in this case is electroconvulsive therapy (ECT). The present study reviews the recent and classical aspects regarding ECT use in adolescents. Methods Systematic review, performed in November 2012, conformed to the PRISMA statement. Results From the 212 retrieved articles, only 39 were included in the final sample. The reviewed studies bring indications of ECT use in adolescents, evaluate the efficiency of this therapy regarding remission, and explore the potential risks and complications of the procedure. Conclusions ECT use in adolescents is considered a highly efficient option for treating several psychiatric disorders, achieving high remission rates, and presenting few and relatively benign adverse effects. Risks can be mitigated by the correct use of the technique and are considered minimal when compared to the efficiency of ECT in treating psychopathologies.

Isolation of Microsporum gypseum in soil samples from different geographical regions of Brazil, evaluation of the extracellular proteolytic enzymes activities (keratinase and elastase) and molecular sequencing of selected strains

A survey of Microsporum gypseum was conducted in soil samples in different geographical regions of Brazil. The isolation of dermatophyte from soil samples was performed by hair baiting technique and the species were identified by morphology studies. We analyzed 692 soil samples and the recuperating rate was 19.2%. The activities of keratinase and elastase were quantitatively performed in 138 samples. The sequencing of the ITS region of rDNA was performed in representatives samples. M. gypseum isolates showed significant quantitative differences in the expression of both keratinase and elastase, but no significant correlation was observed between these enzymes. The sequencing of the representative samples revealed the presence of two teleomorphic species of M. gypseum (Arthroderma gypseum and A. incurvatum). The enzymatic activities may play an important role in the pathogenicity and a probable adaptation of this fungus to the animal parasitism. Using the phenotypical and molecular analysis, the Microsporum identification and their teleomorphic states will provide a useful and reliable identification system.

The impact of psychiatric diagnosis on treatment adherence and duration among victimized children and adolescents in São Paulo, Brazil

OBJECTIVE: Despite the high prevalence of substance abuse and mood disorders among victimized children and adolescents, few studies have investigated the association of these disorders with treatment adherence, represented by numbers of visits per month and treatment duration. We aimed to investigate the effects of substance abuse and mood disorders on treatment adherence and duration in a special program for victimized children in São Paulo, Brazil. METHODS: A total of 351 participants were evaluated for psychiatric disorders and classified into one of five groups: mood disorders alone; substance abuse disorders alone; mood and substance abuse disorders; other psychiatric disorders; no psychiatric disorders. The associations between diagnostic classification and adherence to treatment and the duration of program participation were tested with logistic regression and survival analysis, respectively. RESULTS: Children with mood disorders alone had the highest rate of adherence (79.5%); those with substance abuse disorders alone had the lowest (40%); and those with both disorders had an intermediate rate of adherence (50%). Those with other psychiatric disorders and no psychiatric disorders also had high rates of adherence (75.6% and 72.9%, respectively). Living with family significantly increased adherence for children with substance abuse disorders but decreased adherence for those with no psychiatric disorders. The diagnostic correlates of duration of participation were similar to those for adherence. CONCLUSIONS: Mood and substance abuse disorders were strong predictive factors for treatment adherence and duration, albeit in opposite directions. Living with family seems to have a positive effect on treatment adherence for patients with substance abuse disorders. More effective treatment is needed for victimized substance-abusing youth

Suppressive effect of low-level laser therapy on tracheal hyperresponsiveness and lung inflammation in rat subjected to intestinal ischemia and reperfusion

Intestinal ischemia and reperfusion (i-I/R) is an insult associated with acute respiratory distress syndrome (ARDS). It is not known if pro- and anti-inflammatory mediators in ARDS induced by i-I/R can be controlled by low-level laser therapy (LLLT). This study was designed to evaluate the effect of LLLT on tracheal cholinergic reactivity dysfunction and the release of inflammatory mediators from the lung after i-I/R. Anesthetized rats were subjected to superior mesenteric artery occlusion (45 min) and killed after clamp release and preestablished periods of intestinal reperfusion (30 min, 2 or 4 h). The LLLT (660 nm, 7.5 J/cm(2)) was carried out by irradiating the rats on the skin over the right upper bronchus for 15 and 30 min after initiating reperfusion and then euthanizing them 30 min, 2, or 4 h later. Lung edema was measured by the Evans blue extravasation technique, and pulmonary neutrophils were determined by myeloperoxidase (MPO) activity. Pulmonary tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), intercellular adhesion molecule-1 (ICAM-1), and isoform of NO synthase (iNOS) mRNA expression were analyzed by real-time PCR. TNF-α, IL-10, and iNOS proteins in the lung were measured by the enzyme-linked immunoassay technique. LLLT (660 nm, 7.5 J/cm(2)) restored the tracheal hyperresponsiveness and hyporesponsiveness in all the periods after intestinal reperfusion. Although LLLT reduced edema and MPO activity, it did not do so in all the postreperfusion periods. It was also observed with the ICAM-1 expression. In addition to reducing both TNF-α and iNOS, LLLT increased IL-10 in the lungs of animals subjected to i-I/R. The results indicate that LLLT can control the lung's inflammatory response and the airway reactivity dysfunction by simultaneously reducing both TNF-α and iNOS.

Phenotypic and genotypic features of Aggregatibacter actinomycetemcomitans isolated from patients with periodontal disease

Aggregatibacter actinomycetemcomitans is strongly implicated in the pathogenesis of periodontitis. In this study, the phenotypic and genotypic features of A. actinomycetemcomitans and the presence of genes involved in toxicity were determined. Sixty-five patients with periodontal pocket and 48 healthy subjects were evaluated. Biotyping, adherence and invasion, neuraminidase and biofilm production, presence of capsule and fimbria, as well as the presence of flp-1, apaH, ltx, and cdt genes were determined. Biotype II was the most prevalent. Sixty-six strains were adherent and 33 of them were able to invade KB cells. Sixty strains produced neuraminidase, and 55 strains biofilms. Strains showed capsule but not fimbriae. Forty-six strains were cytotoxic, and most strains harbored the apaH and flp-1 genes. LTX promoter and the ltxA gene were observed in all strains from periodontal patients. The cdtA gene was observed in 50 (71.4%) strains, cdtB in 48 (68.6%) strains, cdtC in 60 (85.7%), and cdtABC in 40 (57.1%) strains. The presence of A. actinomycetemcomitans harboring the cdtC gene from healthy subjects may represent a transitory microorganism in the oral microbiota. More studies are necessary to understand the real role of this microorganism in the pathogenesis of periodontal disease

Canine heartworm disease in Porto Velho: first record, distribution map and occurrence of positive mosquitoes

The aim of this study was to make the first report on canine heartworm disease in the state of Rondônia and confirm its transmission in this state. Blood samples were randomly collected from 727 dogs in the city of Porto Velho. The samples were analyzed to search for microfilariae and circulating antigens, using three different techniques: optical microscopy on thick blood smears stained with Giemsa; immunochromatography; and PCR. Mosquitoes were collected inside and outside the homes of all the cases of positive dogs and were tested using PCR to search for DNA of Dirofilaria immitis. Ninety-three blood samples out of 727 (12.8%) were positive according to the immunoassay technique and none according to the thick smear method. Among the 93 positive dogs, 89 (95.7%) were born in Porto Velho. No difference in the frequency of infection was observed between dogs raised indoors and in the yard. PCR on the mosquitoes resulted in only one positive pool. This result shows that the transmission of canine heartworm disease is occurring in the city of Porto Velho and that there is moderate prevalence among the dogs. The techniques of immunochromatography and PCR were more effective for detecting canine heartworm than thick blood smears. The confirmation of canine heartworm disease transmission in Porto Velho places this disease in the ranking for differential diagnosis of pulmonary nodules in humans in Rondônia.