Yarrowia lipolytica produces lipid-rich biomass in medium mimicking lignocellulosic biomass hydrolysate.

In recent years, lignocellulosic biomass has become an attractive low-cost raw material for microbial bioprocesses aiming the production of biofuels and other valuable chemicals. However, these feedstocks require preliminary pretreatments to increase their utilization by microorganisms, which may lead to the formation of various compounds (acetic acid, formic acid, furfural, 5-hydroxymethylfurfural, p-coumaric acid, vanillin, or benzoic acid) with antimicrobial activity. Batch cultures in microplate wells demonstrated the ability of Yarrowia strains (three of Y. lipolytica and one of Y. divulgata) to grow in media containing each one of these compounds. Cellular growth of Yarrowia lipolytica W29 and NCYC 2904 (chosen strains) was proven in Erlenmeyer flasks and bioreactor experiments where an accumulation of intracellular lipids was also observed in culture medium mimicking lignocellulosic biomass hydrolysate containing glucose, xylose, acetic acid, formic acid, furfural, and 5-HMF. Lipid contents of 35% (w/w) and 42% (w/w) were obtained in bioreactor batch cultures with Y. lipolytica W29 and NCYC 2904, respectively, showing the potential of this oleaginous yeast to use lignocellulosic biomass hydrolysates as feedstock for obtaining valuable compounds, such as microbial lipids that have many industrial applications. KEY POINTS: • Yarrowia strains tolerate compounds found in lignocellulosic biomass hydrolysate • Y. lipolytica consumed compounds found in lignocellulosic biomass hydrolysate • 42% (w/w) of microbial lipids was attained in bioreactor batch cultures.

Shelf-Life Performance of Fish Feed Supplemented with Bioactive Extracts from Fermented Olive Mill and Winery By-Products.

Fortifying fish feeds with bioactive compounds, such as enzymes and antioxidants, has been an adopted strategy to improve feed nutritional quality and sustainability. However, feed additives can lose activity/effectiveness during pelleting and storage processes. This work aimed to monitor functional activity stability in feeds supplemented with a bioactive extract, including cellulases, xylanases, and antioxidants. This bioactive extract (FBE) was produced by Aspergillus ibericus under solid-state fermentation of olive mill and winery by-products. Two isoproteic and isolipidic diets were formulated and unsupplemented or supplemented with lyophilized FBE (0.26% w/w). Both diets were stored at room temperature (RT) or 4 °C for 4 months. Results showed that feed storage at 4 °C enhanced the stability of the enzymes and cellulase was more stable than xylanase. Compared to RT, storage at 4 °C increased cellulase and xylanase half-life by circa 60 and 14%. Dietary FBE supplementation increased antioxidant activity and storage at 4 °C reduced antioxidant activity loss, while in the unsupplemented diet, antioxidant activity decreased to the same level in both storage temperatures. Dietary supplementation with FBE reduced lipid peroxidation by 17 and 19.5% when stored at 4 °C or RT, respectively. The present study is a step toward improving the storage conditions of diets formulated with bioactive compounds.

Potential of Red, Green and Brown Seaweeds as Substrates for Solid State Fermentation to Increase Their Nutritional Value and to Produce Enzymes.

Seaweeds are valuable feedstocks with the potential to be used as ingredients in aquafeeds. However, their use are still limited, given their recalcitrant polysaccharide structure. To break this structure, a biotechnological approach such as solid-state fermentation (SSF) by filamentous fungi can be used, which simultaneously increases the nutritional value of the biomass. However, SSF has hardly been studied in seaweeds; thus, in this study, five different seaweeds (Gracilaria sp., Porphyra dioica, Codium tomentosum, Ulva rigida, and Alaria esculenta) were used as substrates in SSF with Aspergillus ibericus MUM 03.49 and A. niger CECT 2915. Firstly, the seaweeds were fully characterized, and, then, changes in the crude protein and carbohydrate contents were assessed in the fermented biomass, as well as any carbohydrases production. The SSF of U. rigida with both fungi resulted in the maximum xylanase and ß-glucosidase activities. The maximum cellulase activity was achieved using Gracilaria sp. and U. rigida in the SSF with A. niger. The protein content increased in C. tomentosum after SSF with A. ibericus and in U. rigida after SSF with both fungi. Moreover, U. rigida's carbohydrate content decreased by 54% and 62% after SSF with A. ibericus and A. niger, respectively. Seaweed bioprocessing using SSF is a sustainable and cost-effective strategy that simultaneously produces high-value enzymes and nutritionally enhanced seaweeds to be included in aquafeeds.

Pulsed Light Application for Campylobacter Control on Poultry Meat and Its Effect on Colour and Volatile Profile.

Campylobacter on poultry meat needs to be controlled to reduce the risk of infection caused by the consumption of chicken meat. Pulsed light (PL) application on poultry meat was studied to control Campylobacter spp. The effect of this technology was evaluated regarding poultry meat colour and volatile compound changes. Two breast sample groups were prepared: inoculated with Campylobacter (107 bacteria of Campylobacter jejuni strains) and not inoculated. Samples were submitted to PL, five pulses/s of 300 ms, 1 Hz, and 1 J/cm2 in the apparatus, PL Tecum unit (Claranor). A response surface experimental design was applied regarding the factors of voltage (1828 to 3000 W) and distance to the source UV lamp (2.6 to 5.4 cm). The binomial factorial treatment (voltage and distance) with PL induced different energy doses (fluence J/cm2) received by samples, 2.82 to 9.67 J/cm2. Poultry meat pulsed light treated had a significant decrease of Enterobacteriaceae counts. The treatments applied were unable to reduce 1 log Campylobacter cfu/g of poultry meat. The poultry meat PL treated became slightly light, redder, and yellower than those not treated. PL can decrease the proportion of aldehydes on total volatiles in meat, particularly on those associated with chicken-like, chicken skin-like, and sweet odour notes in fresh poultry meat. Further studies of PL with higher energy doses will be necessary to confirm if there are Campylobacter reductions and about poultry meat treated under storage to evaluate if volatile compounds can affect the flavour of PL-treated meat samples.

Valorization of Brewer's Spent Grain Using Biological Treatments and its Application in Feeds for European Seabass (Dicentrarchus labrax).

Brewer's spent grain (BSG) is the main brewery industry by-product, with potential applications in the feed and food industries due to its carbohydrate composition. In addition, the lignocellulosic nature of BSG makes it an adequate substrate for carbohydrases production. In this work, solid-state fermentation (SSF) of BSG was performed with Aspergillus ibericus, a non-mycotoxin producer fungus with a high capacity to hydrolyze the lignocellulosic matrix of the agro-industrial by-products. SSF was performed at different scales to produce a crude extract rich in cellulase and xylanase. The potential of the crude extract was tested in two different applications: -(1) - the enzymatic hydrolysis of the fermented BSG and (2) - as a supplement in aquafeeds. SSF of BSG increased the protein content from 25% to 29% (w/w), while the fiber content was reduced to 43%, and cellulose and hemicellulose contents were markedly reduced to around 15%. The scale-up of SSF from 10 g of dry BSG in flasks to 50 g or 400 g in tray-type bioreactors increased 55% and 25% production of cellulase and xylanase, up to 323 and 1073 U g-1 BSG, respectively. The optimum temperature and pH of maximal activities were found to be 55°C and pH 4.4 for xylanase and 50°C and pH 3.9 for cellulase, cellulase being more thermostable than xylanase when exposed at temperatures from 45°C to 60°C. A Box-Behnken factorial design was applied to optimize the hydrolysis of the fermented BSG by crude extract. The crude extract load was a significant factor in sugars release, highlighting the role of hydrolytic enzymes, while the load of fermented BSG, and addition of a commercial ß-glucosidase were responsible for the highest phenolic compounds and antioxidant activity release. The lyophilized crude extract (12,400 and 1050 U g-1 lyophilized extract of xylanase and cellulase, respectively) was also tested as an enzyme supplement in aquafeed for European seabass (Dicentrarchus labrax) juveniles. The dietary supplementation with the crude extract significantly improved feed and protein utilization. The processing of BSG using biological treatments, such as SSF with A. ibericus, led to the production of a nutritionally enriched BSG and a crude extract with highly efficient carbohydrases capable of hydrolyzing lignocellulosic substrates, such as BSG, and with the potential to be used as feed enzymes with remarkable results in improving feed utilization of an important aquaculture fish species.

Solid-state fermented brewer's spent grain enzymatic extract increases in vitro and in vivo feed digestibility in European seabass.

Brewer's spent grain (BSG) is the largest by-product originated from the brewery industry with a high potential for producing carbohydrases by solid-state fermentation. This work aimed to test the efficacy of a carbohydrases-rich extract produced from solid-state fermentation of BSG, to enhance the digestibility of a plant-based diet for European seabass (Dicentrarchus labrax). First, BSG was fermented with A. ibericus to obtain an aqueous lyophilized extract (SSF-BSG extract) and incorporated in a plant-based diet at increasing levels (0-control; 0.1%, 0.2%, and 0.4%). Another diet incorporating a commercial carbohydrases-complex (0.04%; Natugrain; BASF) was formulated. Then, all diets were tested in in vitro and in vivo digestibility assays. In vitro assays, simulating stomach and intestine digestion in European seabass, assessed dietary phosphorus, phytate phosphorus, carbohydrates, and protein hydrolysis, as well as interactive effects between fish enzymes and dietary SSF-BSG extract. After, an in vivo assay was carried out with European seabass juveniles fed selected diets (0-control; 0.1%, and 0.4%). In vitro digestibility assays showed that pentoses release increased 45% with 0.4% SSF-BSG extract and 25% with Natugrain supplemented diets, while amino acids release was not affected. A negative interaction between endogenous fish enzymes and SSF-BSG extract was observed in both diets. The in vivo digestibility assay corroborated in vitro data. Accordingly, the dietary supplementation with 0.4% SSF-BSG increased the digestibility of dry matter, starch, cellulose, glucans, and energy and did not affect protein digestibility. The present work showed the high potential of BSG to produce an added-value functional supplement with high carbohydrases activity and its potential contribution to the circular economy by improving the nutritional value of low-cost and sustainable ingredients that can be included in aquafeeds.

Polyunsaturated fatty acids production by solid-state fermentation on polyurethane foam by Mortierella alpina.

Polyunsaturated fatty acids (PUFAs) are essential in healthy diets and their production is extremely important. Natural sources of PUFAs includes animal and aquatic products such as marine fish oil, however there are several limitations such as the decrease of fish stocks throughout the world. Thus, microbial oils are a preferable source of PUFAs. Herein, it was studied the production of PUFAs by Mortierella alpina under solid-state fermentation (SSF) using polyurethane foam as inert substrate and synthetic medium or lignocellulosic hydrolysate as source of C, N, and other nutrients. Several parameters of fermentation conditions were evaluated as carbon source, inductors addition, ratio C/N and temperature. The highest amount of total PUFAs per mass of solid (535.41 ± 24.12 mg/g), linoleic acid (129.66 ± 5.84 mg/g), and α-linoleic acid (401.93 ± 18.10 mg/g) were produced when the culture medium contained 20 g/L glucose, 10% (w/v) linseed oil, the C/N ratio was adjusted to 25 and the incubation temperature was 25°C for 3 days decreasing to 16°C on the remaining 4 days of fermentation. In addition, a hemicellulosic hydrolysate can be used as low-cost substrate to produce PUFAs, although the production was lower than the achieved with synthetic medium. SSF showed an interesting technology for microbial PUFAs production.

Congenital Disorders of Glycosylation in Portugal-Two Decades of Experience.

OBJECTIVE: To describe the clinical, biochemical, and genetic features of both new and previously reported patients with congenital disorders of glycosylation (CDGs) diagnosed in Portugal over the last 20 years. STUDY DESIGN: The cohort includes patients with an unexplained multisystem or single organ involvement, with or without psychomotor disability. Serum sialotransferrin isoforms and, whenever necessary, apolipoprotein CIII isoforms and glycan structures were analyzed. Additional studies included measurement of phosphomannomutase (PMM) activity and analysis of lipid-linked oligosaccharides in fibroblasts. Sanger sequencing and massive parallel sequencing were used to identify causal variants or the affected gene, respectively. RESULTS: Sixty-three individuals were diagnosed covering 14 distinct CDGs; 43 patients diagnosed postnatally revealed a type 1, 14 a type 2, and 2 a normal pattern on serum transferrin isoelectrofocusing. The latter patients were identified by whole exome sequencing. Nine of them presented also a hypoglycosylation pattern on apolipoprotein CIII isoelectrofocusing, pointing to an associated O-glycosylation defect. Most of the patients (62%) are PMM2-CDG and the remaining carry pathogenic variants in ALG1, ATP6AP1, ATP6AP2, ATP6V0A2, CCDC115, COG1, COG4, DPAGT1, MAN1B1, SLC35A2, SRD5A3, RFT1, or PGM1. CONCLUSIONS: Portuguese patients with CDGs are presented in this report, some of them showing unique clinical phenotypes. Among the 14 genes mutated in Portuguese individuals, 8 are shared with a previously reported Spanish cohort. However, regarding the mutational spectrum of PMM2-CDG, the most frequent CDG, a striking similarity between the 2 populations was found, as only 1 mutated allele found in the Portuguese group has not been reported in Spain.

Defatted microalgae (Nannochloropsis sp.) from biorefinery as a potential feed protein source to replace fishmeal in European sea bass diets.

The present work focuses on the use of defatted biomass of the microalga Nannochloropsis sp. from the biodiesel industry, as a partial substitute of fish meal (FM) in diets for European sea bass. The effects of increasing inclusion levels of microalgal meal on growth performance, body composition, nutrient utilization, gut morphology, and innate immunity were evaluated after 93 days. A reference alga-free diet was the control (CTRL) diet, and the three experimental diets contained 5 (MA5), 10 (MA10), and 15% (MA15) of the microalgal meal. The microalga-rich diets were supplemented with DL-methionine to assure sea bass dietary requirement. Overall, nutrient apparent digestibilities (ADCs) of the diets were not altered by the microalgal inclusion, but energy ADC was highest in fish fed the CTRL diet (90% vs 88%). At the end of the trial, fish growth performance was similar among dietary treatments (DGI of 1.0), but fish fed MA10 had a significantly higher feed conversion ratio than those fed CTRL and MA5. Final whole body composition and nutrient gain of fish fed the different diets were similar. No significant differences were detected in gut morphology among treatments. Innate immune parameters (lysozyme, alternative complement pathway-ACH50, and peroxidase) were examined, and ACH50 of the fish fed MA15 was significantly lower than those fed MA10, suggesting a dose-dependent stimulation of the innate immune response. The present results indicate that defatted microalgal meal can replace fishmeal in European sea bass diets-at inclusion levels of up to 15%-contributing to a circular economy approach.

Sequential bioprocessing of Ulva rigida to produce lignocellulolytic enzymes and to improve its nutritional value as aquaculture feed.

The macroalgae aquaculture industry has grown up in the last years, and new applications for macroalgae should be considered. In this work, sequential biological treatments as solid-state fermentation (SSF) by Aspergillus ibericus and enzymatic hydrolysis (EH) were applied to washed and unwashed Ulva rigida. SSF of unwashed macroalgae showed higher xylanase (359.8 U/g), cellulase (73.07 U/g) and ß-glucosidase (14.9 U/g) activities per dry mass of macroalgae. After SSF, two strategies to carry out EH were assayed. The best process was SSF followed by EH by simply adding a buffer. The non-starch polysaccharides content was reduced by 93.2%, achieving a glucan conversion of 98%. In addition, the antioxidant activity was improved 2.8-fold and the protein concentration of macroalgae extracts increased from 16.9% to 29.8% (w/w). These biological treatments allowed to increase macroalgae value as feedstuff with potential for use in aquafeeds.

LED Optrode with Integrated Temperature Sensing for Optogenetics.

In optogenetic studies, the brain is exposed to high-power light sources and inadequate power density or exposure time can cause cell damage from overheating (typically temperature increasing of 2 ∘ C). In order to overcome overheating issues in optogenetics, this paper presents a neural tool capable of assessing tissue temperature over time, combined with the capability of electrical recording and optical stimulation. A silicon-based 8 mm long probe was manufactured to reach deep neural structures. The final proof-of-concept device comprises a double-sided function: on one side, an optrode with LED-based stimulation and platinum (Pt) recording points; and, on the opposite side, a Pt-based thin-film thermoresistance (RTD) for temperature assessing in the photostimulation site surroundings. Pt thin-films for tissue interface were chosen due to its biocompatibility and thermal linearity. A single-shaft probe is demonstrated for integration in a 3D probe array. A 3D probe array will reduce the distance between the thermal sensor and the heating source. Results show good recording and optical features, with average impedance magnitude of 371 k Ω , at 1 kHz, and optical power of 1.2 mW·mm - 2 (at 470 nm), respectively. The manufactured RTD showed resolution of 0.2 ∘ C at 37 ∘ C (normal body temperature). Overall, the results show a device capable of meeting the requirements of a neural interface for recording/stimulating of neural activity and monitoring temperature profile of the photostimulation site surroundings, which suggests a promising tool for neuroscience research filed.

Hiperuricemia assintomática - tratar ou não tratar? - Uma revisão baseada na evidência / Hiperuricemia asintomática - ¿tratar o no tratar? - Una revisión basada en la evidencia / Asymptomatic hyperuricemia - to treat or not to treat? - An evidence based review

Introduction: Assessment of serum uric acid is frequently done in Primary Health Care, although not scientifically recommended. The subsequent therapeutic approach is often a clinical challenge, particularly in the case of asymptomatic hyperuricemia (AH). The aim of this study was to review the evidence on AH treatment. Methods: A research was conducted on Medline and evidence-based medical sites for articles published between April 2012 and April 2016 in English, Spanish or Portuguese using the keywords "hyperuricemia" and "asymptomatic conditions". Results: Five articles met the inclusion criteria: one meta-analysis (MA), three systematic reviews (SR) and one original study (OS). MA and OS recommend treatment of AH, for the prevention of renal dysfunction and for the prevention of cardiovascular events (CV), respectively. Two SR do not recommend treatment of AH and one says that pharmacological treatment should be considered after an individual assessment of risk/benefit ratio, particularly in the prevention of gout in subjects with serum uric acid above 9 mg/dL. Conclusion: Very limited scientific data are available on the pharmacologic treatment of AH, with limitations and controversial results. The clinical significance of AH and its causal relationship with occurrence of acute attacks of gout, renal dysfunction and cardiovascular disease are still uncertain. There is no scientific evidence to support the pharmacological treatment of HA in asymptomatic patients (SOR B). Further studies, that are methodologically robust and oriented to the patient are needed.

Introducción: La evaluación de los niveles de ácido úrico es una práctica frecuente en los Cuidados de Salud Primarios, pero no hay evidencia científica. El enfoque terapéutico posterior es frecuentemente un desafío clínico, particularmente en el caso de la hiperuricemia asintomática (HA). Objetivo: Revisar la evidencia sobre la relevancia del tratamiento de la HA. Métodos: Búsqueda de normas de orientación clínica, revisiones sistemáticas (RS), meta-análisis (MA) y estudios originales (EO) en la MEDLINE y otros lugares de Medicina Basada en la Evidencia, publicados desde abril/2012 hasta abril/2016, en inglés, español y portugués. Términos MeSH: "hyperuricemia" e "asymptomatic conditions". Resultados: Cinco estudios cumplían los criterios de inclusión: una MA, tres RS y un EO. La MA y el EO recomiendan el tratamiento de la HA, para la prevención de la disfunción renal y de problemas cardiovasculares (CV), respectivamente. Dos RS no recomiendan el tratamiento de la HA y una recomienda una decisión individualizada para valores de uricemia superiores a 9mg/dL, particularmente para la prevención de la gota. Conclusiones: La evidencia científica disponible es escasa, con limitaciones, y controversia, en lo que se refiere a la institución del tratamiento farmacológico. La importancia clínica de la HA y su relación causal con la ocurrencia de ataques agudos de gota, disfunción renal y las enfermedades cardiovasculares siguen siendo inciertas. No hay evidencia científica que justifique el tratamiento farmacológico de la HA en pacientes asintomáticos (SOR B). Son necesarios más estudios, metodológicamente robustos y orientados al paciente.

Introdução: A avaliação dos níveis séricos de ácido úrico é realizada com frequência nos Cuidados de Saúde Primários, porém sem evidência científica que a justifique. A abordagem terapêutica subsequente constitui frequentemente um desafio clínico, particularmente no caso da hiperuricemia assintomática (HA). O objetivo desta revisão foi rever a evidência sobre a pertinência do tratamento da HA. Métodos: Pesquisa de normas de orientação clínica (NOC), revisões sistemáticas (RS), meta-análises (MA) e estudos originais (EO) no Medline e outros sítios de Medicina Baseada na Evidência, publicados desde abril de 2012 até abril de 2016, em inglês, espanhol e português. Termos MeSH: "hyperuricemia" e "asymptomatic conditions". Resultados: Cinco estudos cumpriam os critérios de inclusão: uma MA, três RS e um EO. A MA e o EO recomendam o tratamento da HA, para a prevenção da disfunção renal e para prevenção de eventos cardiovasculares (CV), respetivamente. Duas RS não recomendam o tratamento da HA e uma recomenda uma decisão individualizada para valores de uricemia acima de 9mg/dL, particularmente para a prevenção da gota. Conclusões: A evidência científica disponível é escassa, com limitações, e controversa no que diz respeito à instituição de tratamento farmacológico. O significado clínico da HA e sua relação causal com ocorrência de crises agudas de gota, disfunção renal e doença cardiovascular ainda são incertos. Não existe evidência científica que justifique o tratamento farmacológico da HA em doentes assintomáticos (SOR B). São, por isso, necessários mais estudos, metodologicamente robustos e orientados para o paciente.

Dietary Protein Requirement During Juvenile Growth of Zebrafish (Danio rerio).

A standard diet for zebrafish, based on their specific nutritional requirements, is of primary importance to improve experimental outcomes with this model organism and optimize its large-scale production. However, the main basic nutritional requirements of zebrafish are yet to be determined. This study aimed at contributing to fill this gap by evaluating the dietary protein requirement of zebrafish juvenile. Ten isoenergetic fishmeal-based diets with increasing protein levels (15%-60%) were formulated, and each diet was assigned to duplicated groups of zebrafish (53.6 mg/17.8 mm initial mean body weight/fork length), fed to apparent satiation during 8 weeks. Weight gain, protein retention, and feed efficiency significantly increased in fish fed diets with increasing protein levels up to 35%-40% and then stabilized. Based on dose-response models, the dietary protein requirement of zebrafish juvenile was estimated at 37.6% and 44.8% for maximum weight gain and maximum protein retention, respectively (with a crude protein-to-energy ratio of about 22.5 g/MJ), corresponding to a protein intake of 14 mg/g average body weight/day. Feed intake increased linearly when fish were fed diets with decreasing protein levels below the estimated requirement, suggesting that zebrafish would regulate feed intake primarily to meet protein needs. On the other hand, the efficiency of protein utilization and retention linearly decreased when fish were fed diets with increasing protein levels above the estimated requirement, indicating that the excess of dietary protein would be deaminated, contributing to increased ammonia excretion. The whole-body composition of fish was affected by the dietary protein level, with fish fed diets with higher protein levels having higher water and protein contents and lower energy content. Considering that zebrafish juveniles are often reared with diets containing excessive amounts of protein, we suggest that the estimated protein requirement should be taken into account to formulate a more suitable, cost-effective, and less pollutant diet for this species.

Juvenile Systemic Lupus Erythematosus: neuropsychiatric manifestations.

Juvenile Systemic Lupus Erythematosus (jSLE) is a chronic and multisystemmic autoimmune disease, which appears before 16 years old with an incidence of 10 to 20 cases per 100,000 children. The clinical spectrum of jSLE can be quite variable. The most common symptoms are constitutional, followed by the cutaneous, musculoskeletal, renal, and neuropsychiatric involvement. Neuropsychiatric involvement in jSLE has a prevalence ranging from 20 to 50.9% and results in significant morbidity and mortality. The most common clinical manifestations of juvenile neuropsychiatric SLE (NPSLE) are headache, cognitive dysfunction, mood disturbances and seizures. The pathophysiology of juvenile NPSLE is not yet fully known, but immunological and inflammatory factors, such as autoantibodies, cytokines and prothrombotic states are widely described. The role of autoantibodies in the onset of specific clinical manifestations has also been recognized. Juvenile NPSLE manifestations are often difficult to diagnose. In addition to semiological aspects, the study and validation of neuropsychological testing and neurocognitive assessment for the juvenile SLE population are essential. The role of advanced imaging techniques should be explored. The treatment of juvenile NPSLE must be individualized according to the type and severity of clinical manifestations, relying on symptomatic therapy, anticoagulants or steroids. New therapeutic approaches, including biotherapies need controlled randomized trials for further validation. This article aims to review the pathogenesis, clinical manifestations, diagnosis and treatment of juvenile NPSLE.

Doença de Crohn metastática sem manifestação clínica intestinal / Metastatic Crohn's disease without intestinal clinical manifestation

Os autores relatam caso de paciente feminina de 47 anos, com lesões cutâneas ulceradas, disseminadas, iniciadas sete anos antes do acompanhamento. Os achados histopatológicos de tais lesões, somados aos endoscópicos, permitiram o diagnóstico de uma entidade rara: a doença de Crohn metastática. O valor deste diagnóstico é ainda maior, por não se encontrar na literatura, relato de caso com atividade da doença de Crohn restrita às lesões cutâneas, sem a observação de queixas digestivas expressivas.

The authors report the case of a 47-year-old female patient with dispersed ulcerated skin lesions that appeared 7 years before medical follow-up. Histopathological and endoscopic findings of such lesions led to the diagnosis of a rare disorder: metastatic Crohn’s disease. This diagnosis is even more relevant because there is no case report in the literature of Crohn’s disease restricted to cutaneous lesions, without major gastro-intestinal complaints.

[Metastatic Crohn's disease without intestinal clinical manifestation]. / Doença de Crohn metastática sem manifestação clínica intestinal.

The authors report the case of a 47-year-old female patient with dispersed ulcerated skin lesions that appeared 7 years before medical follow-up. Histopathological and endoscopic findings of such lesions led to the diagnosis of a rare disorder: metastatic Crohn's disease. This diagnosis is even more relevant because there is no case report in the literature of Crohn's disease restricted to cutaneous lesions, without major gastro-intestinal complaints.

Clinical hypochondroplasia in a family caused by a heterozygous double mutation in FGFR3 encoding GLY380LYS.

In classical achondroplasia (Ach), a glycine residue is replaced by an arginine at codon 380 in exon 10 of the fibroblast growth factor receptor 3 gene (FGFR3). Here we report on a mother and daughter with hypochondroplasia (Hch) caused by a new heterozygous double mutation (1138_1139GG > AA) at the same codon 380, but encoding a lysine instead of the usual arginine. Previous functional assays of these codon 380 amino acid substitutions demonstrated a lesser activation of receptor signaling by lysine compared to arginine [Webster and Donoghue, 1996; EMBO J 15:520-527]. This could explain the milder phenotype observed in our patients. Several other rare double mutations were previously described in both FGFR2 and FGFR3 and interpreted as resulting from positive selection of spermatogonial cells owing to gain-of-function in the encoded protein [Goriely et al., 2005; Proc Natl Acad Sci USA 102:6051-6056]. The present case contributes additional support for this hypothesis.

Clinical significance of elevated alanine aminotransferase in blood donors: a follow-up study.

UNLABELLED: Alanine aminotransferase (ALT) elevation in blood donors can be related to many variables such as viral hepatitis, overweight and ethanol consumption. BACKGROUND/AIMS: This study aims to define factors associated with ALT elevation in candidates for blood donation, to evaluate ALT levels during follow-up, and to establish a histological diagnosis of hepatic disease. METHODS: Alcoholism, obesity, drug-induced liver disease, diabetes, hemochromatosis and alpha 1-anti-trypsin deficiency were investigated in 119 subjects (113 males, six females, aged 33.4+/-8.4 years) who were hepatitis B surface antigen/anti-hepatitis C virus negative and had been rejected as blood donors as a result of elevated ALT (>1.5 times the upper normal limit (UNL) in two determinations). During follow-up, ALT was determined every 8 weeks and liver biopsy recommended in cases with persistently elevated ALT levels. RESULTS: Obesity (30.2%) and alcoholism (28.6%) were most frequently associated with ALT elevation and in 9.2% of cases no association was found. ALT levels decreased significantly, regardless of the associated factor. Liver histology in 40 patients showed steatosis (35%), steatohepatitis (30%), non-specific reactive hepatitis (12.5% of cases), normal liver (15% of cases) and alcoholic cirrhosis, hemochromatosis and non-specific portal fibrosis in three cases. CONCLUSION: ALT levels usually dropped during follow-up and although severe hepatic lesions can be found in asymptomatic blood donors, mild hepatic damage is the rule.