How epidemiology has challenged 3 prevailing concepts about atopic dermatitis

We challenge 3 prevailing concepts in understanding atopic dermatitis using data from epidemiologic studies. First, we show that although atopy is associated with atopic dermatitis to some degree, its importance is not likely to be a simple causeand- effect relationship, especially at a population level. Our epidemiologic data do not exclude a contributory role for IgEmediated immunologic processes, especially in those with existing and severe disease. Second, evidence is presented that does not support a straightforward inverse relationship between infections and atopic dermatitis risk. A link, if present, is likely to be more complex, depending critically on the timing and type of infectious exposure. Third, recent evidence suggests that the risk of subsequent childhood asthma is not increased in children with early atopic dermatitis who are not also early wheezers, suggesting a comanifestation of phenotypes rather than a progressive atopic march. Collectively, these observations underline the importance of epidemiologic studies conducted at a population level to gain a more balanced understanding of the enigma of atopic dermatitis.

New treatments for atopic dermatitis

Atopic dermatitis now affects 15% to 20% of chil­ dren in developed countries, and prevalence in cities in developing countries undergoing rapid demographic changes is quickly following suit.1 Most cases of atopic dermatitis in a given community are mild, but children with moderate to severe disease can have continuous itching and associated loss of sleep. The social stigma of a visible skin disease can also be soul destroying for both patient and family. A few studies have suggested that some degree of prevention of the disease is possible,2 although these measures have not been taken up widely. In the absence of any treatment that is known to alter the clinical course of the disease, most treatment is aimed at reducing symp­ toms and signs. After a relative lull of almost 40 years, new drugs—tacrolimus and pimecrolimus—have appeared that offer different approaches to managing this miserable disease. Do they work? Are they safe? And how do they compare with existing treatments?

Established corticosteroid creams should be applied only once daily in patients with atopic eczema

Atopic eczema affects many adults and up to 20% of children,1 with health costs comparable to diabetes2 and asthma.3 One community survey of 1760 young children in the United Kingdom found that 84% had mild eczema, 14% moderate, and 2% severe eczema.4 Topical corticosteroids are a mainstay of treatment for inflammatory episodes.5 Most long established topical corticosteroids such as betamethasone valerate or hydrocortisone are applied at least twice daily, but three newer preparations (mometasone, fluticasone, and methylprednisolone) have been developed for once daily application. Here, I propose that established preparations need be applied only once daily.

Randomised controlled trial of short bursts of a potent topical corticosteroid versus prolonged use of a mild preparation for children with mild or moderate atopic eczema

Objective To determine whether a three day burst of a potent corticosteroid is more effective than a mild preparation used for seven days in children with mild or moderate atopic eczema. Design Randomised, double blind, parallel group study of 18 weeks' duration. Setting 13 general practices and a teaching hospital in the Nottingham area. Participants 174 children with mild or moderate atopic eczema recruited from general practices and 33 from a hospital outpatient clinic. Interventions 0.1% betamethasone valerate applied for three days followed by the base ointment for four days versus 1% hydrocortisone applied for seven days. Main outcome measures Primary outcomes were total number of scratch­free days and number of relapses. Secondary outcomes were median duration of relapses, number of undisturbed nights, disease severity (six area, six sign atopic dermatitis severity scale), scores on two quality of life measures (children's life quality index and dermatitis family impact questionnaire), and number of patients in whom treatment failed in each arm. Results No differences were found between the two groups. This was consistent for all outcomes. The median number of scratch­free days was 118.0 for the mild group and 117.5 for the potent group (difference 0.5, 95% confidence interval - 2.0 to 4.0, P = 0.53). The median number of relapses for both groups was 1.0. Both groups showed clinically important improvements in disease severity and quality of life compared with baseline. Conclusion A short burst of a potent topical corticosteroid is just as effective as prolonged use of a milder preparation for controlling mild or moderate atopic eczema in children.

Atopic Manifestations: Dermatitis, Allergic Rhinitis and Asthma in Patients With Hypogammaglobulinemia

Background: Most of the hypogammaglobulinemic patients have a clinical history in favor of allergic respiratory disease. Nevertheless, in these patients the importance and prevalence of atopic disorders have not been completely explained. Objectives: This study was aimed to evaluate atopic manifestations (dermatitis, allergic rhinitis and asthma) and pulmonary function in patients with hypogammaglobulinemia. Patients and Methods: We used the international study of asthma and allergies in childhood (ISAAC) questionnaire in forty-five patients diagnosed with hypogammaglobulinemia and spirometry was done in 41 patients older than 5 years. Results: Spirometry results were normal in 21 (51%), and showed obstructive in 15 (37%) and restrictive pattern in 5 (12%) of the 41 patients who were evaluated. By the end of the study, asthma was diagnosed in nine (20%) patients and other atopies (rhinitis and dermatitis) identified in 10 (22%), and four (9%), respectively. Conclusions: Atopic conditions should be investigated in the hypogammaglobulinemic patients and the prevalence in these patients may be higher than in normal population. Also, it is recommended to perform a pulmonary function test as a routine procedure in patients with hypogammaglobulinemia and atopy should be assessed in these patients.

Skin microbiome before development of atopic dermatitis: Early colonization with commensal staphylococci at 2 months is associated with a lower risk of atopic dermatitis at 1 year

Background: Disease flares of established atopic dermatitis (AD) are generally associated with a low-diversity skin microbiota and Staphylococcus aureus dominance. The temporal transition of the skin microbiome between early infancy and the dysbiosis of established AD is unknown. Methods: We randomly selected 50 children from the Cork Babies After SCOPE: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints (BASELINE) longitudinal birth cohort for microbiome sampling at 3 points in the first 6 months of life at 4 skin sites relevant to AD: the antecubital and popliteal fossae, nasal tip, and cheek. We identified 10 infants with AD and compared them with 10 randomly selected control infants with no AD. We performed bacterial 16S ribosomal RNA sequencing and analysis directly from clinical samples. Results: Bacterial community structures and diversity shifted over time, suggesting that age strongly affects the skin microbiome in infants. Unlike established AD, these patients with infantile AD did not have noticeably dysbiotic communities before or with disease and were not colonized by S aureus. In comparing patients and control subjects, infants who had affected skin at month 12 had statistically significant differences in bacterial communities on the antecubital fossa at month 2 compared with infants who were unaffected at month 12. In particular, commensal staphylococci were significantly less abundant in infants affected at month 12, suggesting that this genus might protect against the later development of AD. Conclusions: This study suggests that 12-month-old infants with AD were not colonized with S aureus before having AD. Additional studies are needed to confirm whether colonization with commensal staphylococci modulates skin immunity and attenuates development of AD.

Veterinary allergy diagnosis: past, present and future perspectives

Fleas, several aeroallergens as well as many food allergens are the most common allergenic sources for animals and frequent cause of allergic reactions with different target organs such as skin, eyes, and respiratory or digestive systems. Allergy diagnosis needs to follow well-established guidelines under clinical and laboratory approaches. Since 1980 with the Hanifin & Rajka’s criteria for the diagnosis of atopic dermatitis (AD) in humans, successive proposals have been developed to identify atopic dermatitis in dogs. A consensual plan was first proposed by Willemse in 1986 undergoing several modifications in 1994. Prélaud and colleagues made important changes to the plan in 1998 and it was further adjusted by Favrot in 2009. In 2010, this plan was approved by the International Task Force on Canine Atopic Dermatitis (CAD). It was subjected in 2015 to minor updates with regard to therapeutic options. To improve diagnostic accuracy by integrating the basic knowledge on sensitization development and allergen nature and diversity, allergen sources and implicated molecular allergens for animals should be clearly identified. As well as in human medicine, this molecular epidemiology concept is essential for the veterinary allergy diagnosis in the near future, standing as the basis of a component-resolved diagnosis (CRD). Besides current pharma- cotherapy, it will be highly relevant to increase the efficiency of the avoidance measures and specific immunotherapy. Clinical guidelines will lead to at least 80 % of positive diagnosis of atopy, but newer laboratory methods in veterinary medicine aiming to a more precise diagnosis and a better integration of the clinical/laboratory diagnostic course are needed. Allergoms identification for animals, from different allergen sources proteoms should become a priority in veterinary allergology, in order to allow the intended CRD, which is essential to understand the cross-reaction phenomena, allowing a more precise and possibly effective component-resolved immunotherapy (CRIT). Further research has been carried out for a better understanding of the interaction between allergic clinical condition and immune pathophysiology. As well as in human medicine, a deeper knowledge of the molecular immunological mechanisms in veterinary allergy — with their specific allergen triggers — will also provide the veterinary allergist with the necessary information to act more efficiently in the future.

Allergological evaluation of a dog population in a veterinary immuno-allergology consultation: What correlates in a canine model

Introduction: Allergic dermatitis (AD) is the most common canine pruritic condition in veterinary dermatology. Allergic dermatitis to flea bites presents the highest prevalence, followed by atopic dermatitis and food AD. This study aimed to identify possible correlation between data from clinical signs, intradermal tests (IDT) and specific IgE levels, which are used in dog AD assessment. Methods: Fifty five dogs from the Veterinary Hospital of the University of Évora (Portugal) and Rof Codina University Hospital (Lugo, Spain) outpatient consultations were studied by means of clinical inquiry, IDT and specific IgE determination. Thirty five of the patients belonged to predisposed breeds, 30 were females and 25 males. Forty one (74%) were indoor. Results: In 82% of cases first clinical signs appeared before the age of 3 years and 24% even before 1 year old. In 70% of the individuals clinical signs included itching, which was generalized in 66%, with 78% of paw licking and chewing. Clinical profile showed seasonal worsening in 64% of cases. From the 69.1% of dogs already presenting with dermatitis, 50% also presented external otitis and 28.9% self-inflicted alopecia. "Intense itching" was found in 10.5%, "medium itching" in 81.6% and “mild itching” in 5.26% of the patients. Prevalence of positive IDT was 37.3 % to Lep d, 29.41% to Der f, 27.5% to Der p, 25.5% to Dac g and 21.6% to Malassezia sp. From the 37 dogs submitted to food IDT, 40.5% revealed positive to beef, 27% to chicken, 27% to porc and 5.4% to lamb. Specific IgE > 150 EAU was found in 84% of dogs to indoor allergen sources and in 68% to pollens. A negative correlation was found between an outdoor life and the intensity (p = 0.033) and precocity (p = 0.026) of clinical signs. Sensitization to pollens was found positively correlated with the seasonality of clinical signs (p = 0.001) and the positivity for Dac g (p = 0.007). The prevalence of chronic otitis correlated positively with alopecia and reactivity to Lep d (p = 0.008), Plantago lanceolata (p = 0.026) and Platanus acerifolia (p = 0.017). There was no correlation between the results of ITD and specific IgE. Conclusion: We can conclude that correlation between different clinical signs and positive testing for some allergenic sources may occur, as well as between sensitization to pollens and the beginning, the intensity and the seasonality of dog patient clinical signs.

Sensitization and Disposition to Change Facing the Challenges of the New Educational Circumstances

This article is about the necessity of an up to date vision in teachers’ training. It starts with the latest studies and advances surrounding learning-along-life term. It presents a set of topics inspired in the contributions of new fields of study connected to learning. Such contributions, as neuroscience, should be considered in the decisions related to future teachers’ training, thus favoring the transformation of the pedagogical practice. Awareness and disposition to change are essential requirements for teacher trainers who will drive investigative processes and pedagogical proposals generation; all of this according to the new and dynamic knowledge society.

Reduction Of Blood Nitric Oxide Levels Is Associated With Clinical Improvement Of The Chronic Pelvic Pain Related To Endometriosis.

The objective of this prospective study was to determine the plasma levels of nitric oxide (NO) in women with chronic pelvic pain secondary to endometriosis (n=24) and abdominal myofascial pain syndrome (n=16). NO levels were measured in plasma collected before and 1 month after treatment. Pretreatment NO levels (μM) were lower in healthy volunteers (47.0±12.7) than in women with myofascial pain (64.2±5.0, P=0.01) or endometriosis (99.5±12.9, P<0.0001). After treatment, plasma NO levels were reduced only in the endometriosis group (99.5±12.9 vs 61.6±5.9, P=0.002). A correlation between reduction of pain intensity and reduction of NO level was observed in the endometriosis group [correlation = 0.67 (95%CI = 0.35 to 0.85), P<0.0001]. Reduction of NO levels was associated with an increase of pain threshold in this group [correlation = -0.53 (-0.78 to -0.14), P<0.0001]. NO levels appeared elevated in women with chronic pelvic pain diagnosed as secondary to endometriosis, and were directly associated with reduction in pain intensity and increase in pain threshold after treatment. Further studies are needed to investigate the role of NO in the pathophysiology of pain in women with endometriosis and its eventual association with central sensitization.

Effect Of Pain Chronification And Chronic Pain On An Endogenous Pain Modulation Circuit In Rats.

We tested the hypothesis that chronic pain development (pain chronification) and ongoing chronic pain (chronic pain) reduce the activity and induce plastic changes in an endogenous analgesia circuit, the ascending nociceptive control. An important mechanism mediating this form of endogenous analgesia, referred to as capsaicin-induced analgesia, is its dependence on nucleus accumbens μ-opioid receptor mechanisms. Therefore, we also investigated whether pain chronification and chronic pain alter the requirement for nucleus accumbens μ-opioid receptor mechanisms in capsaicin-induced analgesia. We used an animal model of pain chronification in which daily subcutaneous prostaglandin E2 (PGE2) injections into the rat's hind paw for 14 days, referred to as the induction period of persistent hyperalgesia, induce a long-lasting state of nociceptor sensitization referred to as the maintenance period of persistent hyperalgesia, that lasts for at least 30 days following the cessation of the PGE2 treatment. The nociceptor hypersensitivity was measured by the shortening of the time interval for the animal to respond to a mechanical stimulation of the hind paw. We found a significant reduction in the duration of capsaicin-induced analgesia during the induction and maintenance period of persistent mechanical hyperalgesia. Intra-accumbens injection of the μ-opioid receptor selective antagonist Cys(2),Tyr(3),Orn(5),Pen(7)amide (CTOP) 10 min before the subcutaneous injection of capsaicin into the rat's fore paw blocked capsaicin-induced analgesia. Taken together, these findings indicate that pain chronification and chronic pain reduce the duration of capsaicin-induced analgesia, without affecting its dependence on nucleus accumbens μ-opioid receptor mechanisms. The attenuation of endogenous analgesia during pain chronification and chronic pain suggests that endogenous pain circuits play an important role in the development and maintenance of chronic pain.

Participation of neuronal nitric oxide synthase in experimental neuropathic pain induced by sciatic nerve transection

Nerve injury leads to a neuropathic pain state that results from central sensitization. This phenomenom is mediated by NMDA receptors and may involve the production of nitric oxide (NO). In this study, we investigated the expression of the neuronal isoform of NO synthase (nNOS) in the spinal cord of 3-month-old male, Wistar rats after sciatic nerve transection (SNT). Our attention was focused on the dorsal part of L3-L5 segments receiving sensory inputs from the sciatic nerve. SNT resulted in the development of neuropathic pain symptoms confirmed by evaluating mechanical hyperalgesia (Randall and Selitto test) and allodynia (von Frey hair test). Control animals did not present any alteration (sham-animals). The selective inhibitor of nNOS, 7-nitroindazole (0.2 and 2 µg in 50 µL), blocked hyperalgesia and allodynia induced by SNT. Immunohistochemical analysis showed that nNOS was increased (48% by day 30) in the lumbar spinal cord after SNT. This increase was observed near the central canal (Rexed’s lamina X) and also in lamina I-IV of the dorsal horn. Real-time PCR results indicated an increase of nNOS mRNA detected from 1 to 30 days after SNT, with the highest increase observed 1 day after injury (1469%). Immunoblotting confirmed the increase of nNOS in the spinal cord between 1 and 15 days post-lesion (20%), reaching the greatest increase (60%) 30 days after surgery. The present findings demonstrate an increase of nNOS after peripheral nerve injury that may contribute to the increase of NO production observed after peripheral neuropathy.

Exposição repetida à cafeína aumenta a atividade locomotora induzida pelo femproporex em ratos adolescentes e adultos

A cafeína e o femproporex são substâncias psicoestimulantes. O femproporex é muito utilizado no Brasil como anorexígeno enquanto a cafeína é amplamente consumida como constituinte regular da dieta. A administração repetida de psicoestimulantes induz sensibilização comportamental que se caracteriza pelo aumento progressivo dos seus efeitos locomotores. Pode ocorrer ainda sensibilização cruzada entre essas substâncias. Investigamos se a administração repetida de cafeína aumenta a locomoção induzida pelo femproporex em ratos adolescentes e adultos. Quarenta e oito ratos adolescentes (dia pós-natal 27) e 32 adultos (dia pós-natal 60) foram distribuídos em dois grupos que receberam injeção intra-peritoneal de 10,0 mg/kg de cafeína (CAF) (adolescentes N = 24; adultos N = 16) ou salina (SAL) (adolescentes N = 24; adultos N = 16) diariamente durante 10 dias. Três dias após a última injeção, cada grupo CAF ou SAL foi subdividido em dois subgrupos que receberam injeção i.p. de salina (SAL) (1 mL/kg) ou femproporex (FEM) (2,0 mg/kg). Após as injeções, a atividade locomotora foi avaliada automaticamente em intervalos de 5 minutos durante 1 hora. Nossos resultados demonstraram que em ratos adolescentes e adultos o pré-tratamento com CAF aumenta a atividade locomotora induzida pela administração aguda de FEM, sugerindo que a cafeína causa sensibilização aos efeitos locomotores desse derivado anfetamínico.

Estudo do mecanismo de corrosão por pites em água do mar de aços inoxidáveis supermartensíticos microligados com Nb e Ti

Os aços inoxidáveis supermartensíticos (SMSS) são usados em ambientes agressivos devido à sua boa soldabilidade, boas propriedades mecânicas em temperaturas elevadas e superior resistência à corrosão sob tensão. Aplicações na exploração de petróleo demandam superior combinação de propriedades e os aços inoxidáveis duplex e superduplex têm sido aplicados nessa área, a despeito de seus custos elevados. Os SMSS consistem numa alternativa técnica e econômica ao uso daqueles aços. Nesse trabalho, adições de Nb e Ti foram realizadas com o intuito de minimizar o efeito de sensitização, promover o refino de grãos e foram estudados os aspectos microestruturais e a resistência à corrosão por pites em água do mar. A formação e a evolução dos pites foram acompanhadas por ensaios de corrosão, microscopia óptica e eletrônica, focalizando suas morfologias. O aço com Ti apresentou o melhor desempenho quanto à corrosão, com o maior potencial de corrosão e menor potencial de pite entre os aços em estudo. O aço com Nb, apesar de apresentar potencial de corrosão superior ao do aço sem adição, teve um potencial de pite inferior ao do mesmo.