Oral tryptophan activates duodenal aryl hydrocarbon receptor in healthy subjects: a crossover randomized controlled trial.

Background and Aims: Tryptophan is an essential amino acid transformed by host and gut microbial enzymes into metabolites that regulate mucosal homeostasis through Aryl hydrocarbon receptor (AhR) activation. Alteration of tryptophan metabolism has been associated with chronic inflammation, however whether tryptophan supplementation affects the metabolite repertoire and AhR activation under physiologic conditions in humans, is unknown. Methods: We performed a randomized, double blind, placebo-controlled, crossover study in 20 healthy volunteers. Subjects on a low tryptophan background diet were randomly assigned to a 3-week L-tryptophan supplementation (3 g/day) or placebo, and after a 2-week washout switched to opposite interventions. We assessed gastrointestinal and psychological symptoms by validated questionnaires, AhR activation by cell reporter assay, tryptophan metabolites by liquid chromatography and high-resolution mass spectrometry, cytokine production in isolated monocytes by ELISA and microbiota profile by 16S rRNA Illumina technique. Results: Oral tryptophan supplementation was well tolerated, with no changes in gastrointestinal or psychological scores. Compared with placebo, tryptophan increased AhR activation capacity by duodenal contents, but not by feces. This was paralleled by higher urinary and plasma kynurenine metabolites and indoles. Tryptophan had a modest impact on fecal microbiome profiles, and no significant effect on cytokine production. Conclusions: At the doses used in this study, oral tryptophan supplementation in humans induces microbial indole and host kynurenine metabolic pathways in the small intestine, known to be immunomodulatory. The results should prompt tryptophan intervention strategies in inflammatory conditions of the small intestine where the AhR pathway is impaired.

Gluten-Free Diet Reduces Symptoms, Particularly Diarrhea, in Patients With Irritable Bowel Syndrome and Antigliadin IgG.

BACKGROUND & AIMS: Many patients with irritable bowel syndrome (IBS) perceive that their symptoms are triggered by wheat-containing foods. We assessed symptoms and gastrointestinal transit before and after a gluten-free diet (GFD) in unselected patients with IBS and investigated biomarkers associated with symptoms. METHODS: We performed a prospective study of 50 patients with IBS (ROME III, all subtypes), with and without serologic reactivity to gluten (antigliadin IgG and IgA), and 25 healthy subjects (controls) at a university hospital in Hamilton, Ontario, Canada, between 2012 and 2016. Gastrointestinal transit, gut symptoms, anxiety, depression, somatization, dietary habits, and microbiota composition were studied before and after 4 weeks of a GFD. HLA-DQ2/DQ8 status was determined. GFD compliance was assessed by a dietitian and by measuring gluten peptides in stool. RESULTS: There was no difference in symptoms among patients at baseline, but after the GFD, patients with antigliadin IgG and IgA reported less diarrhea than patients without these antibodies (P = .03). Compared with baseline, IBS symptoms improved in 18 of 24 patients (75%) with antigliadin IgG and IgA and in 8 of 21 patients (38%) without the antibodies. Although constipation, diarrhea, and abdominal pain were reduced in patients with antigliadin IgG and IgA, only pain decreased in patients without these antibodies. Gastrointestinal transit normalized in a higher proportion of patients with antigliadin IgG and IgA. Anxiety, depression, somatization, and well-being increased in both groups. The presence of antigliadin IgG was associated with overall reductions in symptoms (adjusted odds ratio compared with patients without this antibody, 128.9; 95% CI, 1.16-1427.8; P = .04). Symptoms were reduced even in patients with antigliadin IgG and IgA who reduced gluten intake but were not strictly compliant with the GFD. In controls, a GFD had no effect on gastrointestinal symptoms or gut function. CONCLUSIONS: Antigliadin IgG can be used as a biomarker to identify patients with IBS who might have reductions in symptoms, particularly diarrhea, on a GFD. Larger studies are needed to validate these findings. ClinicalTrials.gov: NCT03492333.

The Evolutionary History and Functional Divergence of Trehalase (treh) Genes in Insects.

Trehalases (treh) have been found in different organisms, such as bacteria, fungi, yeast, nematodes, insects, vertebrates, and plants. Their biochemical properties are extremely variable and not yet fully understood. Gene expression patterns have shown differences among insect species suggesting a potential functional diversification of trehalase enzymes during their evolution. A second gene family encoding for enzymes with hypothetical trehalase activity has been repeatedly annotated in insect genome as acid trehalases/acid trehalase-like (ath), but its functional role is still not clear. The currently available large amount of genomic data from many insect species may enable a better understanding of the evolutionary history, phylogenetic relationships and possible roles of trehalase encoding genes in this taxon. The aim of the present study is to infer the evolutionary history of trehalases and acid trehalase genes in insects and analyze the trehalase functional divergence during their evolution, combining phylogenetic and genomic synteny/colinearity analyses.

Alergias a tatuajes y otras reacciones adversas

La realización de tatuajes es una práctica popular y creciente dentro de la población hoy en día, principalmente en los jóvenes. Sus complicaciones constituyen un motivo frecuente de consulta en la práctica médica, éstas se producen principalmente por los pigmentos utilizados, sobre todo los rojos con alto contenido de derivados mercuriales. Existen diferentes complicaciones producidas por los tatuajes, entre las cuales se pueden mencionar las siguientes: traumáticas, infecciosas, granulomatosas, alérgicas, dermatosis asociadas al área del tatuaje, tumorales y otras en las que podríamos incluir los queloides, colagenopatías perforantes reactivas entre otras. Las complicaciones relacionadas con las tintas rojas pueden ser: dermatitis de contacto alérgica y fotodermatitis, reacciones liquenoides, los granulomas de tipo cuerpo extraño con características sarcoidales y los pseudolinfomas. La prueba del parche parece inadecuada para identificar los tintes del tatuaje correspondientes como alergenos. Las reacciones alérgicas contra los tatuajes se desarrollan lentamente y es improbable que sean causadas por un alergeno directamente presente en la tinta del tatuaje. Las opciones de tratamiento médico incluyen corticoides tópicos, oclusivos o intralesionales, también se puede utilizar tacrolimus y factor de protección solar. Las opciones terapéuticas para la eliminación de tatuajes son: salabrasión, dermoabrasión, eliminación química. Otros métodos empleados son la electrocoagulación, la criocirugía, extirpación quirúrgica y los láseres. Cabe destacar la necesidad e importancia de una adecuada regulación nacional para que puedan realizarse medidas de protección sanitaria eficientes y controladas, en todos los aspectos relacionados con ésta práctica, pero principalmente prestando especial atención a las tintas utilizadas.

Tattooing is a popular and growing practice within the population today, especially in the young. Its complications are a frequent reason for consultation in medical practice, these are mainly produced by the pigments used, especially red with a high content of mercury derivatives. There are different complications produced by tattoos, among which we can mention the following: traumatic, infectious, granulomatous, allergic, dermatosis associated with the area of the tattoo, tumoral and others in which we could include keloids, reactive perforating collagenosis among others.Complications related to red inks may include: allergic contact dermatitis and photodermatitis, lichenoid reactions, granulomas of foreign body type with sarcoid characteristics and pseudolymphomas. The patch test seems inadequate to identify the corresponding tattoo dyes as allergens. Allergic reactions to tattoos develop slowly and are unlikely to be caused by an allergen directly present in the tattoo ink. Medical treatment options include topical, occlusive or intralesional steroids; tacrolimus and sun protection factor can also be used. The therapeutic options for the removal of tattoos are: salabrasión, dermabrasion, chemical elimination. Other methods used are electrocoagulation, cryosurgery, surgical removal and lasers. It is important to emphasize the need and importance of an adequate national regulation so that efficient and controlled sanitary protection measures can be carried out in all aspects related to this practice, but mainly paying particular attention to the inks used.

Probiotic Bifidobacterium longum NCC3001 Reduces Depression Scores and Alters Brain Activity: A Pilot Study in Patients With Irritable Bowel Syndrome.

BACKGROUND & AIMS: Probiotics can reduce symptoms of irritable bowel syndrome (IBS), but little is known about their effects on psychiatric comorbidities. We performed a prospective study to evaluate the effects of Bifidobacterium longum NCC3001 (BL) on anxiety and depression in patients with IBS. METHODS: We performed a randomized, double-blind, placebo-controlled study of 44 adults with IBS and diarrhea or a mixed-stool pattern (based on Rome III criteria) and mild to moderate anxiety and/or depression (based on the Hospital Anxiety and Depression scale) at McMaster University in Canada, from March 2011 to May 2014. At the screening visit, clinical history and symptoms were assessed and blood samples were collected. Patients were then randomly assigned to groups and given daily BL (n = 22) or placebo (n = 22) for 6 weeks. At weeks 0, 6, and 10, we determined patients' levels of anxiety and depression, IBS symptoms, quality of life, and somatization using validated questionnaires. At weeks 0 and 6, stool, urine and blood samples were collected, and functional magnetic resonance imaging (fMRI) test was performed. We assessed brain activation patterns, fecal microbiota, urine metabolome profiles, serum markers of inflammation, neurotransmitters, and neurotrophin levels. RESULTS: At week 6, 14 of 22 patients in the BL group had reduction in depression scores of 2 points or more on the Hospital Anxiety and Depression scale, vs 7 of 22 patients in the placebo group (P = .04). BL had no significant effect on anxiety or IBS symptoms. Patients in the BL group had a mean increase in quality of life score compared with the placebo group. The fMRI analysis showed that BL reduced responses to negative emotional stimuli in multiple brain areas, including amygdala and fronto-limbic regions, compared with placebo. The groups had similar fecal microbiota profiles, serum markers of inflammation, and levels of neurotrophins and neurotransmitters, but the BL group had reduced urine levels of methylamines and aromatic amino acids metabolites. At week 10, depression scores were reduced in patients given BL vs placebo. CONCLUSION: In a placebo-controlled trial, we found that the probiotic BL reduces depression but not anxiety scores and increases quality of life in patients with IBS. These improvements were associated with changes in brain activation patterns that indicate that this probiotic reduces limbic reactivity. ClinicalTrials.gov no. NCT01276626.

Genomic and Cytogenetic Localization of the Carotenoid Genes in the Aphid Genome.

Data published in the scientific literature suggests a possible link between chromosomal rearrangements involving autosomes 1 and 3 and the presence of red morphs in the peach-potato aphid Myzus persicae (Sulzer). In order to begin a study of this relationship, we analysed the genomic and chromosomal location of genes involved in carotenoid biosynthesis in M. persicae and the pea aphid, Acyrthosiphon pisum (Harris), since carotenoids are the basis of the colour in many aphid species. Genomic analysis identified a DNA sequence containing carotenoid genes in synteny between the 2 species. According to the results obtained using in situ PCR, carotenoid genes were located in a subterminal portion of autosome 1 in both species. The same localization has also been observed in the onion aphid Neotoxoptera formosana Takahashi that, as M. persicae and A. pisum, belongs to the tribe Macrosiphini, thereby suggesting a synteny of this chromosomal region in aphids. In situ PCR experiments performed on 2 M. persicae asexual lineages bearing heterozygous translocations involving autosomes 1 and 3 revealed that carotenoid genes were located within chromosomal portions involved in recurrent rearrangements. We also verified by bioinformatics analyses the presence of fragile sites that could explain these recurrent rearrangements in M. persicae.

Dermatitis alérgica por contacto a Lyral / Allergic contact dermatitis to Lyral®

La alergia de contacto a fragancias constituye un problema clínico importante. Su frecuencia se estima de 1 a 2% en la población general y alrededor del 8% en los pacientes con eccema de contacto. La sensibilización a fragancias se encuentra entre las causas más comunes de dermatitis alérgica por contacto, después del níquel y de los conservantes. Han surgido nuevas sustancias de detección con el finde aumentar la capacidad de diagnóstico de alergia a los perfumes. Desde el año 2005, una novedosa mezcla de fragancia compuesta por seis sustanciasse ha comercializado para su introducción en la batería estándar de alérgenos.El alérgeno más frecuente en esta mezcla es el Carboxaldehído hidroxilo isohexylcyclohexene (HICC) (Lyral ®).Se comunican cuatro pacientes con reacción positiva a Lyral® que han sido relevantes en relación al cuadro clínico.Este estudio ilustra que la alergia de contacto a fragancias es común en los pacientes que sufren de dermatitis de contacto...

Results of patch testing with fragrance mix 1, fragrance mix 2, and their ingredients, and Myroxylon pereirae and colophonium, over a 21-year period.

BACKGROUND: The frequency of fragrance contact allergy has shown a fluctuating trend over the years. OBJECTIVES: To describe the frequency of positive reactions to the baseline screening agents and fragrance mix (FM) 1 and 2 components, to determine trends of the latter over the years, and to evaluate simultaneous reactions. PATIENTS AND METHODS: This was a cross-sectional study on patch test results of 13 332 patients from January 1990 to December 2011. RESULTS: Of the total population, 9.6% reacted positively to FM 1, and 6% of 3416 tested with FM 2 reacted positively. Of those tested with both, 30.4% of 349 FM 1-positive patients reacted to FM 2, and 51.7% of 205 FM 2-positive patients reacted to FM 1. Hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) and FM 2 were tested simultaneously in 3401 patients: 6 reacted to HICC alone. Nine hundred and forty patients were tested with FM 1 ingredients and 205 with FM 2 ingredients; Evernia prunastri was the most frequent FM 1 allergen, and HICC was the most frequent FM 2 allergen. Simultaneous reactions were frequently observed. CONCLUSIONS: Fragrance-allergic subjects often show multiple positive reactions, some of which are highly significantly associated. Recently, there has been a decreasing trend in positivity for both Evernia prunastri and HICC, whereas a slight increase for cinnamyl alcohol has been observed.

Fragrance allergens in 'specific' cosmetic products.

BACKGROUND: Together with preservative agents, fragrance components are the most important sensitizing culprits in cosmetic products. OBJECTIVES: To identify the nature of the fragrance ingredients responsible for allergic contact dermatitis (ACD) from specific cosmetic products. METHODS: Between 2000 and 2009, positive patch test reactions or positive usage tests with the patients' own cosmetic products, were recorded using a standardised form. RESULTS: Of the 806 cosmetic records, corresponding to 485 patient files, 344 concerned reactions to fragrance ingredients that according to the label were present ('Presence Confirmed' [PC n = 301]) or suspected to be present ('Presence Not Confirmed' [PNC n = 376]) in the causal cosmetic products used, which belonged to 15 different categories, toilet waters/fine perfumes being the most frequent. Geraniol in fragrance mix I (FM I) and hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) in FM II were the most frequent PC, and together with hydroxycitronellal and Evernia prunastri (oak moss) the most frequent PNC ingredients in the causal cosmetic products. Limonene was the most frequent PC confirmed fragrance allergen. CONCLUSIONS: This study not only underlines the usefulness of fragrance-ingredient labelling in order to identify the causal allergen(s) present in specific cosmetic products, but may also provide information on trends in the actual use of sensitizing fragrance ingredients in them.

Allergic contact dermatitis from fragrance components in specific topical pharmaceutical products in Belgium.

OBJECTIVES: To determine which topical pharmaceutical products marketed in Belgium contain fragrances and to examine the nature of the fragrance allergens in specific pharmaceutical products having caused iatrogenic contact dermatitis. METHODS: All topical pharmaceutical products marketed in Belgium, that is 3820 products, were examined as to their fragrance content as labelled. Data of 18, 960 patients investigated for contact allergy between 1978 and 2008 were retrieved from our database, including information on the nature of the topical pharmaceutical products used, the results of patch tests, and the sensitization sources. RESULTS: Three hundred and seventy (10%) of 3280 of the topical pharmaceutical products were found to contain a total of 66 fragrance substances. Among 3378 patients suffering from iatrogenic allergic contact dermatitis, 127 were found to react to 48 specific products, for which 38 different fragrance substances gave relevant positive reactions. Women were more affected than men, and legs, hands, and face were the most commonly affected body sites. CONCLUSIONS: Fragrances, the presence of which is in most cases unnecessary, do contribute to iatrogenic allergic contact dermatitis. Moreover, sensitized patients have difficulties in avoiding their specific allergens because standardized labelling of the ingredients in pharmaceutical products is lacking.

Is a low content in atranol/chloroatranol safe in oak moss-sensitized individuals?

BACKGROUND: Chloroatranol and atranol are degradation products of chloroatranorin and atranorin, respectively, and have been identified as important contact allergens in oak moss absolute (Evernia prunastri). OBJECTIVES: To investigate whether chemically modified extracts of oak moss produce positive patch test reactions in previously sensitized subjects. METHODS: A sample of oak moss was treated by a polymer-based method to reduce the content of the two main allergens, namely atranol and chloroatranol, from 3.4% to less than 75 p.p.m. and from 1.8% to less than 25 p.p.m., respectively. Fourteen subjects with positive reactions to oak moss from Trolab and/or Chemotechnique were patch tested to this sample, diluted 1% in petrolatum. RESULTS: The chemically modified sample reacted negatively in six but gave still positive reactions in eight subjects, with the same intensity as the commercially available oak moss patch test materials. CONCLUSIONS: Polymer-based treatment of oak moss extract reduces the allergenic elicitation potential in previously sensitized individuals only to a minor extent. The residual concentrations of atranol and chloroatranol being less than 75 p.p.m. and 25 p.p.m., respectively, are unsafe for the consumer.

Frequency of and trends in fragrance allergy over a 15-year period.

BACKGROUND: The widespread use of fragrance-containing products is probably the most important reason for its high impact in allergic contact dermatitis. OBJECTIVES: To describe the frequency of contact allergy to fragrance allergens as tested in the standard series, in relation to age, sex and lesion locations. To determine trends in frequency over the years and to study the association between positive tests observed with the different fragrance-allergy markers as well as between specific fragrance allergens and locations of the lesions. PATIENTS/METHODS: 10 128 patients underwent patch testing between January 1990 and December 2005 at the Dermatology department in Leuven. RESULTS: 1463 (14.5%), that is, 380 (26%) males and 1083 (74%) females, reacted positively to at least 1 fragrance-allergy marker in the standard series: 9% to fragrance mix I, 6% to Myroxylon pereirae, and 4.8% to colophonium (often in association), 2.1% to hydroxyisohexyl 3-cyclohexene carboxaldehyde and 2.1% to fragrance mix II, the latter 2 allergens having been introduced more recently. Over the years, fragrance contact allergy has shown a fluctuating trend. Hands and face were the most commonly affected body sites. Moreover, a significant association was found between specific fragrance allergens and certain locations. CONCLUSIONS: This study illustrates that fragrance contact allergy is common in patients suffering from contact dermatitis.

Nuestra experiencia en el uso de la citología exfoliativa para el diagnóstico del cáncer cutáneo no melanoma / Our experience with exfoliative cytology for the diagnosis of non-melanoma skin cancer

El propósito de nuestro trabajo fue valorar la utilidad de la citología exfoliativa para confirmar la sospecha clínica del cáncer cutáneo no melanoma, determinando la sensibilidad y especificidad de ésta en el diagnóstico, corroborando los resultados con histopatología. La población la constituyeron los pacientes mayores de 16 años, ambos sexos, que concurrieron a nuestra sección Oncológica Cutánea en el curso del año 2000. Se utilizó la técnica de raspado con hoja de bisturí estéril, directamente sobre la superficie tumoral. Las lesiones intervenidas quirúrgicamente se analizaron histológicamente, con procedimiento de rutina, y ambos se observaron con microscopía óptica. Se utilizó para el tratamiento de los datos obtenidos el test de Discriminancia, que mide la sensibilidad y especificidad del método. Se realizaron 92 citologías, 70 fueron comparadas con el diagnóstico clínico y 22 con clínica e histopatología, obteniendo una tasa de sensibilidad del 88 por ciento y de especificidad del 50 por ciento. En coincidencia con la experiencia previa sobre el tema, concluimos que la citología exfoliativa es un método fácil, rápido y de bajo costo para el diagnóstico del cáncer cutáneo no melanoma

Nuestra experiencia en el uso de la citología exfoliativa para el diagnóstico del cáncer cutáneo no melanoma / Our experience with exfoliative cytology for the diagnosis of non-melanoma skin cancer

El propósito de nuestro trabajo fue valorar la utilidad de la citología exfoliativa para confirmar la sospecha clínica del cáncer cutáneo no melanoma, determinando la sensibilidad y especificidad de ésta en el diagnóstico, corroborando los resultados con histopatología. La población la constituyeron los pacientes mayores de 16 años, ambos sexos, que concurrieron a nuestra sección Oncológica Cutánea en el curso del año 2000. Se utilizó la técnica de raspado con hoja de bisturí estéril, directamente sobre la superficie tumoral. Las lesiones intervenidas quirúrgicamente se analizaron histológicamente, con procedimiento de rutina, y ambos se observaron con microscopía óptica. Se utilizó para el tratamiento de los datos obtenidos el test de Discriminancia, que mide la sensibilidad y especificidad del método. Se realizaron 92 citologías, 70 fueron comparadas con el diagnóstico clínico y 22 con clínica e histopatología, obteniendo una tasa de sensibilidad del 88 por ciento y de especificidad del 50 por ciento. En coincidencia con la experiencia previa sobre el tema, concluimos que la citología exfoliativa es un método fácil, rápido y de bajo costo para el diagnóstico del cáncer cutáneo no melanoma (AU)

Contact allergic reactions of the vulva: a 14-year review.

BACKGROUND: In women with vulval complaints, irritant contact dermatitis is more common than allergic contact dermatitis, but secondary sensitization has to be taken into consideration since these patients often use several topical medications. OBJECTIVE: The aims of this retrospective study were to establish the prevalence of allergic contact dermatitis in patients with vulval complaints and to verify how many patients with allergic contact dermatitis suffered from a previous pathology. METHODS: We reviewed patch- and prick-test results from 92 women. The women had all been administered the European Standard series, and most had also been tested for other allergens such as the ingredients of topical pharmaceutical products and cosmetics. RESULTS: Thirty-five patients (38%) presented with one or more positive allergic reactions. For 15 of the patients, these reactions were considered to be relevant to their clinical condition and were most often due to contact dermatitis from topical pharmaceutical products. Three patients presented with positive and relevant contact urticaria syndrome from latex, and two patients presented with protein contact dermatitis from human seminal plasma. CONCLUSION: Patients with vulval dermatitis are at risk of developing contact sensitivities, particularly to topical pharmaceutical products; therefore, attention should be paid to this problem when such products are prescribed.