Wilson disease: the diagnostic challenge and treatment outcomes in a series of 262 cases / Doença de Wilson: o desafio diagnóstico e resultados do tratamento em uma série de 262 casos

Abstract Background Wilson disease (WD) is an autosomal recessive disorder that leads to organ toxicity due to copper overload. Early diagnosis is complicated by the rarity and diversity of manifestations. Objective To describe the diagnostic features and response to treatment in our cohort of WD patients. Methods This was a retrospective analysis of 262 WD patients stratified by clinical presentation, complementary exams, ATP7B genotyping, and response to treatment. Results Symptoms occurred at an average age of 17.4 (7-49) years, and patients were followed up for an average of 9.6 (0-45) years. Patients presented mainly with hepatic (36.3%), neurologic (34.7%), and neuropsychiatric (8.3%) forms. Other presentations were hematologic, renal, or musculoskeletal, and 16.8% of the patients were asymptomatic. Kayser-Fleischer rings occurred in 78.3% of the patients, hypoceruloplasminemia in 98.3%, and elevated cupruria/24h in 73.0%, with an increase after D-penicillamine in 54.0%. Mutations of the ATP7B gene were detected in 84.4% of alleles. Brain magnetic resonance imaging showed abnormalities in the basal ganglia in 77.7% of patients. D-penicillamine was the first choice in 93.6% of the 245 patients, and 21.1% of these patients were switched due to adverse effects. The second-line therapies were zinc and trientine. The therapeutic response did not differ significantly between the drugs (p= 0.2). Nine patients underwent liver transplantation and 82 died. Conclusion Wilson disease is diagnosed at a late stage, and therapeutic options are limited. In people under 40 years of age with compatible manifestations, WD could be considered earlier in the differential diagnosis. There is a need to include ATP7B genotyping and therapeutic alternatives in clinical practice.

Resumo Antecedentes A doença de Wilson (DW) é um distúrbio autossômico recessivo caracterizado por acúmulo de cobre lesivo aos órgãos. O diagnóstico precoce é dificultado pela raridade e diversidade de apresentações. Objetivo Descrever características ao diagnóstico e resposta ao tratamento em uma coorte de DW. Métodos Análise retrospectiva de 262 casos de DW quanto à apresentação clínica, exames complementares, genotipagem e resposta ao tratamento. Resultados Os sintomas surgiram em uma média aos 17,4 (7-49) anos, e os pacientes foram acompanhados por uma média de 9,6 (0-45) anos. Os pacientes apresentaram principalmente formas hepáticas (36,3%), neurológicas (34,7%) e neuropsiquiátricas (8,3%). Outras apresentações foram hematológicas, renais e musculoesqueléticas. Apenas 16,8% eram assintomáticos. Anéis de Kayser-Fleischer ocorreram em 78,3% dos pacientes, hipoceruloplasminemia em 98,3%, e cuprúria elevada/24h em 73,0%, com aumento após D-penicilamina em 54,0%. Mutações do gene ATP7B foram detectadas em 84,4% dos alelos pesquisados. A ressonância magnética cerebral mostrou alterações em gânglios da base em 77,7% dos pacientes. O tratamento com D-penicilamina foi a escolha inicial em 93,6% dos 245 casos e foi trocado em 21,1% devido a efeitos adversos. Terapias de segunda linha foram zinco e trientina. A resposta terapêutica não diferiu significativamente entre os medicamentos (p= 0,2). Nove pacientes receberam transplante hepático e 82 faleceram. Conclusão O diagnóstico da DW ainda ocorre em estágios tardios, e as opções terapêuticas são limitadas. A DW deve ser considerada precocemente no diagnóstico diferencial de pessoas com menos de 40 anos com manifestações compatíveis. É necessário incorporar na prática clínica a genotipagem do ATP7B e alternativas terapêuticas à penicilamina.

Urbanization increases the risk of phosphorus loss in sandy soils of tropical ecosystems.

Phosphorus (P) is naturally present in soils. However, urbanization can promote additional inputs of P into the soil that lead to saturation of the binding sites exceeding the maximum sorption capacity. Soils saturated with P act as important diffuse sources of pollution of water resources. The flow of P from the soil to aquatic ecosystems is an aggravating factor for water scarcity, especially in the semiarid region. Knowing phosphorus dynamics in the soil is essential to protect water quality and ensure its multiple uses. In this paper, a total of fifty soil samples, twenty-five from natural soils and twenty-five from urban soils, were evaluated for the effect of urbanization on P sorption characteristics and their relationship with the physical and chemical attributes of the soil. The soil samples were characterized physically and chemically, and the P sorption characteristics were obtained from the adjustment of Langmuir and Freundlich equations by nonlinear regression. Urbanization results in increased soil P saturation and reduced P sorption capacity. Our results show that the sandy texture of the soils studied had a standardizing effect on the soil's physical properties, maintaining, even after urbanization, the physical quality similar to natural soil. In contrast, pH (in water and KCl), base saturation, sodium saturation, potential acidity, exchangeable Al3+, exchangeable Mg2+, available P, and P-rem are valuable indicators in the segregation between natural and urban soils. The reduction of P sorption capacity in urban soils increases the risks related to P loads in aquatic ecosystems that experience urban expansion worldwide. These data serve as a basis for decision-making regarding the appropriate soil monitoring and management of urban expansion areas in watersheds to control P flow to aquatic systems.

Effect of the addition of different concentrations of Solanum glaucophyllum desf. extract on chondrocyte cultures from the growth cartilage of newborn rats.

Solanum glaucophyllum Desf. is a calcinogenic plant responsible for enzootic calcinosis that affects ruminants and causes alterations in bone and cartilaginous tissues, among others. It is believed that changes in cartilage tissue, with reduced bone growth, are due to hypercalcitoninism, caused by excess vitamin D. However, we hypothesized that S. glaucophyllum Desf. can act directly on chondrocytes and therefore, chondrocyte cultures from the epiphysis of the long bones of newborn rats were used as a model to elucidate the direct effects of S. glaucophyllum Desf. on bone growth. Plant samples were collected from Cañuelas, Argentina. An aliquot of the plant extract was used to quantify vitamin D (1,25(OH)2D3). The effects of the three concentrations of the plant extract were tested in cultures of chondrocytes extracted from the epiphyses of the long bones of 32 three-day-old Wistar rats. A control group (without extract), and three groups treated with different concentrations of plant extract were formed: group 1 (100 µL/L); group 2 (1 mL/L), and group 3 (5 mL/L), containing respectively 1 × 10-9 M, 1 × 10-8 M, and 5 × 10-8 M of 1,25(OH)2D3. After 7, 14, and 21 days of culture, MTT assay for cell viability, alkaline phosphatase activity, and quantification of the percentage of areas with glycosaminoglycans (GAG) stained with periodic acid-Schiff (PAS) were performed. On day 7, all chondrocytes in group 3, that is, those with the highest concentration of plant extract, died. On days 14 and 21, groups 1 and 2 showed a significant reduction in chondrocyte viability compared to the control. At 7, 14, and 21 days, groups 1 and 2 showed significantly lower alkaline phosphatase activity than the control. On day 21, group 2 showed a significant reduction in areas with PAS + GAGs. There were no significant differences between the groups in the expression of gene transcripts for Sox9, Col2, ColX, and aggrecan. The S. glaucophyllum Desf. extract directly affected growing rat chondrocytes by reducing viability, alkaline phosphatase activity, and GAG synthesis without altering the expression of gene transcripts for Sox9, Col2, ColX, and aggrecan, which may be one of the mechanisms by which there is a reduction in bone growth in animals intoxicated by the plant.

Carcass characteristics and meat evaluation of cattle finished in temperate pasture and supplemented with natural additive containing clove, cashew oil, castor oils, and a microencapsulated blend of eugenol, thymol, and vanillin.

BACKGROUND: Forty crossbred steers were supplemented with different doses (from 0 control to 6000 mg/animal/day) of natural additive blend containing clove essential oil, cashew oil, castor oil, and a microencapsulated blend of eugenol, thymol, and vanillin for 80 days. Carcass characteristics, drip loss, and antioxidant activity were evaluated 24 h post mortem on longissimus thoracis, and the effects of aging (until 14 days) were evaluated for water losses (thawing/aging and cooking), texture, color, and lipid oxidation. RESULTS: The use of the natural additive blend did not modify (P > 0.05) carcass characteristics but did, however, modify body composition (P < 0.05). Drip losses were unaffected by the treatments tested (P > 0.05). There was an observed quadratic effect (P < 0.05) on losses from thawing/aging on the first day of storage. Regarding the effects of natural additives on cooking losses, there was a quadratic effect (P < 0.05) among the treatments on day 7 of aging. Differences between days of aging were only observed with control treatment. Shear force was similar among treatments on days 1 and 7 of aging. On day 14 a linear effect (P < 0.05) was observed. Also, a linear effect (P < 0.05) appeared on meat lightness, meat from the control group being clearer on day 1. No changes were observed in redness among treatments or days of storage (P > 0.05). Yellowness was not modified by the treatments (P > 0.05)but only by the days of storage in control and the lowest dosage used. CONCLUSION: The blend of natural additives has potential use in pasture feeding and could improve meat quality. However, doses should be adjusted. © 2021 Society of Chemical Industry.

Animal performance, ingestive behavior, and carcass characteristics of grazing-finished steers supplemented with castor bean (Ricinus communis L.) meal protein.

This study was carried out to evaluate the effects of replacing soybean meal by castor bean meal on nutrient intake, digestibility, animal performance, ingestive behavior activities, carcass characteristics, and fatty acid profile from steers finished in pasture. Crossbred steers were weighed to determine the initial body weight (331.6 ± 37.4 kg), which were kept in 4 paddocks (8 animals/paddock), on pastures of Brachiaria decumbens during the finishing phase. Dietary treatments included CC00-without castor bean meal; CC33-153 g/kg of castor bean meal; CC66-308 g/kg of castor bean meal; and CC100-434 g/kg of castor bean meal. No treatment effects were detected (P > 0.05) for final body weight, average daily gain, feed efficiency, and hot carcass weight. The DM, CP, NDF, and NFC total intake were lowest (P < 0.01) for steers fed CC100 diet than others. No treatment effects were detected (P > 0.05) for digestibility. For ingestive behavior activities, data on DM and NDF from feeding rate were greater (P < 0.01) in CC00 v. castor bean meal steers. DM and NDF from rumination rate were greater (P < 0.01) in CC33 v. CC100 steers that was the lowest. Carcass measures, carcass composition, chemical composition of Longissimus thoracis muscle, and profile and the sum of fatty acids were not affected (P > 0.05) by castor bean meal replacement on the diets. Results from this experiment suggest that castor bean meal may replace soybean meal in pasture supplementation without altered digestibility, carcass characteristics, and fatty acid profile.

Effects of polyaluminum chloride and lanthanum-modified bentonite on the growth rates of three Cylindrospermopsis raciborskii strains.

In tropical and subtropical lakes, eutrophication often leads to nuisance blooms of Cylindrospermopsis raciborskii. In laboratory experiments, we tested the combined effects of flocculant polyaluminum chloride (PAC) and lanthanum-modified bentonite (LMB) on the sinking and growth rates of three C. raciborskii strains. We tested the hypothesis that the combination of PAC and LMB would (1) effectively sink C. raciborskii in a test tube experiment and (2) impair C. raciborskii growth, irrespective of the biomass of the inoculum (bloom) and the strain in the growth experiment. We tested the recommended (LMB1) and a three-times higher dose of LMB (LMB3). The combined addition of PAC and LMB enhanced the sedimentation of all C. raciborskii strains. Moreover, both the PAC and LMB doses decreased the phosphate concentration. PAC and LMB1 decreased the growth rate of all strains, but the efficacy depended on the biomass and strain. The combined addition of PAC and LMB3 inhibited the growth of all strains independently of the biomass and strain. We conclude that a low dose of PAC in combination with the recommended dose of LMB decreases C. raciborskii blooms and that the efficiency of the technique depends on the biomass of the bloom. A higher dose of LMB is needed to obtain a more efficient control of C. raciborskii blooms.

Café (Coffea arabica, L. ) submetido a diferentes condições de torrefação: caracterização química e avaliação da atividade antioxidante e sensorial / Coffee (Coffea arabica, L. ) submitted to different roasting conditions: chemical characterization and evaluation of sensorial and antioxidant activity

A avaliação da atividade antioxidante de compostos fenólicos em vegetais tem sido estudada como alternativa ao uso de antioxidantes sintéticos como butil hidroxi tolueno (BHT). No presente trabalho foi avaliada a capacidade antioxidante in vitro dos extratos (etéreo, etanólico e aquoso) e frações de ácidos fenólicos (livres, ésteres de ácidos fenólicos solúveis e ácidos fenólicos insolúveis ligados) do café in natura e torrado em diferentes condições de tempo (10 e 20 min) e temperatura (140’graus’C, 160’graus’C e 180’graus’C). As análises in vitro foram realizadas através do sistema ‘beta’-caroteno e ácido linoléico (que indica a inibição da oxidação em meio emulsionado) e pelo método do Rancimat (que indica a inibição da oxidação em meio lipídico). Em ambos os métodos alguns extratos e todas as frações de ácidos fenólicos apresentaram atividade antioxidante igual ou superior ao BHT nas mesmas concentrações. Independente das condições de torrefação aplicadas, o extrato aquoso apresentou a maior atividade antioxidante em função do maior conteúdo de fenólicos. Os fatores cinéticos obtidos demonstraram também resultados maiores que o BHT. O perfil de ácidos fenólicos das frações foi caracterizado por cromatografia gasosa sendo identificados os seguintes ácidos fenólicos: salicílico, ferúlico, caféico, sinápico, clorogênico, quínico, p-cumárico, gentísico e protocatequínico. Foi realizada a avaliação sensorial da infusão de café não havendo diferença estatística entre as amostras mais torradas cujas torras estão próximas das amostras comerciais (p< 0,05). Com base nesses dados a amostra torrada a 180’graus’C/10 min foi utilizada na avaliação do potencial antioxidante in vivo. Para tanto, ratos Wistar foram suplementados por 30 dias com diferentes doses do extrato aquoso de café torrado (180ºC/10 min)...

Compostos bioativos do café e seus benefícios à saúde / Bioactive compounds of the coffee and its benefits to the health

O café é uma importante fonte de divisas para o Brasil e é bastante apreciado em todo mundo por seu aroma e sabor. Além disto, este produto tem sido foco de diversos trabalhos nos quais se pesquisa a ação de seus compostos sobre a saúde humana, entre elas, a atividade antioxidante. Em estudos “in vitro”, “in vivo” e epidemiológicos foi estabelecida uma correlação entre a atividade antioxidante do café e a redução do risco de doenças crônicas não transmissíveis.