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1.
N Engl J Med ; 390(10): 889-899, 2024 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-38407394

RESUMO

BACKGROUND: Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy. METHODS: In this trial, we assessed whether omalizumab, a monoclonal anti-IgE antibody, would be effective and safe as monotherapy in patients with multiple food allergies. Persons 1 to 55 years of age who were allergic to peanuts and at least two other trial-specified foods (cashew, milk, egg, walnut, wheat, and hazelnut) were screened. Inclusion required a reaction to a food challenge of 100 mg or less of peanut protein and 300 mg or less of the two other foods. Participants were randomly assigned, in a 2:1 ratio, to receive omalizumab or placebo administered subcutaneously (with the dose based on weight and IgE levels) every 2 to 4 weeks for 16 to 20 weeks, after which the challenges were repeated. The primary end point was ingestion of peanut protein in a single dose of 600 mg or more without dose-limiting symptoms. The three key secondary end points were the consumption of cashew, of milk, and of egg in single doses of at least 1000 mg each without dose-limiting symptoms. The first 60 participants (59 of whom were children or adolescents) who completed this first stage were enrolled in a 24-week open-label extension. RESULTS: Of the 462 persons who were screened, 180 underwent randomization. The analysis population consisted of the 177 children and adolescents (1 to 17 years of age). A total of 79 of the 118 participants (67%) receiving omalizumab met the primary end-point criteria, as compared with 4 of the 59 participants (7%) receiving placebo (P<0.001). Results for the key secondary end points were consistent with those of the primary end point (cashew, 41% vs. 3%; milk, 66% vs. 10%; egg, 67% vs. 0%; P<0.001 for all comparisons). Safety end points did not differ between the groups, aside from more injection-site reactions in the omalizumab group. CONCLUSIONS: In persons as young as 1 year of age with multiple food allergies, omalizumab treatment for 16 weeks was superior to placebo in increasing the reaction threshold for peanut and other common food allergens. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT03881696.).


Assuntos
Antialérgicos , Dessensibilização Imunológica , Hipersensibilidade Alimentar , Omalizumab , Adolescente , Criança , Humanos , Lactente , Alérgenos/efeitos adversos , Arachis/efeitos adversos , Dessensibilização Imunológica/métodos , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/tratamento farmacológico , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/terapia , Omalizumab/efeitos adversos , Omalizumab/uso terapêutico , Hipersensibilidade a Amendoim/tratamento farmacológico , Hipersensibilidade a Amendoim/imunologia , Hipersensibilidade a Amendoim/terapia , Antialérgicos/administração & dosagem , Antialérgicos/uso terapêutico , Pré-Escolar , Adulto Jovem , Adulto , Pessoa de Meia-Idade
2.
N Engl J Med ; 388(19): 1755-1766, 2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37163622

RESUMO

BACKGROUND: No approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown. METHODS: We conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months. The primary end point was a treatment response as measured by the eliciting dose of peanut protein at 12 months. Safety was assessed according to the occurrence of adverse events during the use of the peanut patch or placebo. RESULTS: Of the 362 patients who underwent randomization, 84.8% completed the trial. The primary efficacy end point result was observed in 67.0% of children in the intervention group as compared with 33.5% of those in the placebo group (risk difference, 33.4 percentage points; 95% confidence interval, 22.4 to 44.5; P<0.001). Adverse events that occurred during the use of the intervention or placebo, irrespective of relatedness, were observed in 100% of the patients in the intervention group and 99.2% in the placebo group. Serious adverse events occurred in 8.6% of the patients in the intervention group and 2.5% of those in the placebo group; anaphylaxis occurred in 7.8% and 3.4%, respectively. Serious treatment-related adverse events occurred in 0.4% of patients in the intervention group and none in the placebo group. Treatment-related anaphylaxis occurred in 1.6% in the intervention group and none in the placebo group. CONCLUSIONS: In this trial involving children 1 to 3 years of age with peanut allergy, epicutaneous immunotherapy for 12 months was superior to placebo in desensitizing children to peanuts and increasing the peanut dose that triggered allergic symptoms. (Funded by DBV Technologies; EPITOPE ClinicalTrials.gov number, NCT03211247.).


Assuntos
Anafilaxia , Dessensibilização Imunológica , Hipersensibilidade a Amendoim , Pré-Escolar , Humanos , Lactente , Alérgenos/efeitos adversos , Anafilaxia/etiologia , Arachis/efeitos adversos , Dessensibilização Imunológica/efeitos adversos , Dessensibilização Imunológica/métodos , Hipersensibilidade a Amendoim/complicações , Hipersensibilidade a Amendoim/terapia , Administração Cutânea
3.
Glob Chang Biol ; 30(1): e17090, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38273483

RESUMO

Microalgae are the main source of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), essential for the healthy development of most marine and terrestrial fauna including humans. Inverse correlations of algal EPA and DHA proportions (% of total fatty acids) with temperature have led to suggestions of a warming-induced decline in the global production of these biomolecules and an enhanced importance of high latitude organisms for their provision. The cold Arctic Ocean is a potential hotspot of EPA and DHA production, but consequences of global warming are unknown. Here, we combine a full-seasonal EPA and DHA dataset from the Central Arctic Ocean (CAO), with results from 13 previous field studies and 32 cultured algal strains to examine five potential climate change effects; ice algae loss, community shifts, increase in light, nutrients, and temperature. The algal EPA and DHA proportions were lower in the ice-covered CAO than in warmer peripheral shelf seas, which indicates that the paradigm of an inverse correlation of EPA and DHA proportions with temperature may not hold in the Arctic. We found no systematic differences in the summed EPA and DHA proportions of sea ice versus pelagic algae, and in diatoms versus non-diatoms. Overall, the algal EPA and DHA proportions varied up to four-fold seasonally and 10-fold regionally, pointing to strong light and nutrient limitations in the CAO. Where these limitations ease in a warming Arctic, EPA and DHA proportions are likely to increase alongside increasing primary production, with nutritional benefits for a non-ice-associated food web.


Assuntos
Diatomáceas , Ácidos Graxos Ômega-3 , Humanos , Camada de Gelo , Oceanos e Mares , Regiões Árticas , Ácidos Graxos
4.
Br J Haematol ; 201(4): 682-689, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36822820

RESUMO

Daratumumab, bortezomib and dexamethasone (DVd) is approved for patients with relapsed multiple myeloma following the CASTOR phase 3 clinical trial. This retrospective multicentre analysis assesses the overall response rate (ORR) and progression-free survival (PFS) in routine clinical practice for patients at first relapse treated with DVd incorporating weekly bortezomib. Data were collected from 296 sequential patients treated across 15 UK centres. After a median follow-up of 21 months, the ORR was 82% (26% partial response, 56% very good partial response or better) and the median PFS was 16 months [95% confidence interval (CI) 12-20 months]. Results were similar regardless of prior lenalidomide exposure. The median time to next treatment was 20 months (95% CI 15-25 months) and the estimated overall survival at two years was 74%. Patients with high-risk features (by cytogenetics, International Staging System or extramedullary disease) and those treated within 18 months of initiation of progression-free treatment, or within 12 months of autologous stem cell transplant, had significantly inferior outcomes. The grade 2 and 3 peripheral neuropathy rate was 7%. DVd with weekly bortezomib was effective in a heterogenous real-world population at first relapse with a low rate of peripheral neuropathy. However, high-risk patients had inferior outcomes and should be considered for alternative treatments.


Assuntos
Mieloma Múltiplo , Humanos , Bortezomib/uso terapêutico , Estudos Retrospectivos , Dexametasona/efeitos adversos , Doença Crônica , Recidiva , Reino Unido/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
5.
Ann Allergy Asthma Immunol ; 131(4): 421-426, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37098403

RESUMO

Serum immunoglobulin E (IgE) assays to food specific IgE (s-IgE) are useful tools for the confirmation of clinical suspicion of food allergy. However, the specificity of these assays is poor given that sensitization is much more common than clinical food allergy. Therefore, the use of broad panels to assess sensitization to multiple foods often leads to overdiagnosis and unnecessary food avoidance. Unintended consequences that may occur as a result include physical harm, psychological harm, financial cost, opportunity cost, and even worsening of existing health care disparities. Although current guidelines recommend against the use of s-IgE food panel testing, these tests are widely available and frequently used. To limit the negative impacts of s-IgE food panel testing, further work is needed to effectively spread the message that these food panels may cause unintended harm to patients and families.


Assuntos
Hipersensibilidade Alimentar , Humanos , Testes Cutâneos , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/epidemiologia , Alérgenos , Alimentos , Imunoglobulina E
6.
Mar Drugs ; 22(1)2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38276649

RESUMO

The continuous growth of aquaculture places a growing demand on alternative sources of fish oil (FO). Certain microorganisms provide a sustainable replacement for FO due to their content of EPA and DHA, which are essential for fish health. Appreciable evidence shows that changes in feeding sources may alter the nutritional components of salmon; however, the influence of diets on lipid species remains unclear. In this study, the identification and semi-quantification of lipid molecular species in salmon muscle during feeding with a microbial oil (MO) were carried out by focusing on triacylglycerol (TAG) and diacyl-phospholipid using shotgun-based mass spectrometry analysis. DHA in the MO diet was efficiently incorporated into phospholipid structures on feeding, followed by accumulation in salmon muscle. The MO diet elevated the level of certain EPA-containing TAGs, such as TAG C52:5 (16:0_16:0_20:5) and TAG C54:6 (16:0_18:1_20:5), indicating that the MO diet may be an excellent source for enhancement of the abundance of ω3 lipids. Further, prostaglandins (PGs) PGE2 and PGF3α were identified and quantified for the first time in salmonid tissue.


Assuntos
Fosfolipídeos , Salmo salar , Animais , Fosfolipídeos/química , Triglicerídeos , Salmão , Óleos de Plantas/química , Eicosanoides , Óleos de Peixe/farmacologia , Músculos , Ácidos Graxos/química
7.
Br J Haematol ; 197(1): 82-96, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35166376

RESUMO

Multiple myeloma (MM) accounts for 10% of haematological malignancies. Overall survival (OS) has improved in recent years due to increased use of autologous stem cell transplantation (ASCT) in the treatment of newly diagnosed MM and the advent of novel agents, including proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies. To assess trends in ASCT including patient selection, choice of induction regimen, depth of response and survival, we performed a retrospective analysis of all patients undergoing first ASCT for MM in European Society for Blood and Marrow Transplantation centres between 1995 and 2019. A total of 117 711 patients across 575 centres were included. The number of transplants performed increased sevenfold across the study period. The median age increased from 55 to 61 years, and the percentage of patients aged >65 years rose from 7% to 30%. Use of chemotherapy-based induction fell significantly, being largely replaced by bortezomib-based regimens. The two-year complete response rate increased from 22% to 42%. The five-year progression-free survival and OS rates increased from 28% to 31% and from 52% to 69%, respectively. Transplant mortality fell from 5.9% to 1.5%. Ongoing advances in MM treatment may challenge the future role of ASCT. However, at the current time, ASCT remains central to the MM treatment paradigm.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/patologia , Bortezomib/uso terapêutico , Dexametasona/uso terapêutico , Humanos , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/terapia , Estudos Retrospectivos , Transplante de Células-Tronco , Taxa de Sobrevida , Transplante Autólogo , Resultado do Tratamento
8.
J Pediatr Gastroenterol Nutr ; 75(2): 192-195, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35666881

RESUMO

The incidence and prevalence of eosinophilic esophagitis (EoE), eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC) are increasing ( 1 ). These conditions will inevitably become more widely recognized and better understood. There is currently no Food and Drug Administration (FDA)-approved treatment for EoE, but there are standard-of-care treatments that are well established and widely used. In contrast, there is a paucity of data regarding standard-of-care treatment for non-EoE eosinophilic gastrointestinal disorders (EGID). We identified 3 patients that all achieved clinical and histopathologic remission on dupilumab, a monoclonal antibody that blocks the downstream signaling of interleukin (IL)-4 and IL-13. These patients had extra-esophageal forms of EGID with two patients failing to achieve remission on standard-of-care therapies and one patient experiencing significant side effects on swallowed budesonide therapy. The reduction in mucosal eosinophilia in several GI tract segments in these 3 patients highlights a new potential clinical indication for dupilumab in the treatment of pediatric EGID patients.


Assuntos
Enterite , Esofagite Eosinofílica , Gastrite , Anticorpos Monoclonais Humanizados , Criança , Enterite/epidemiologia , Eosinofilia , Esofagite Eosinofílica/terapia , Gastrite/terapia , Humanos
9.
Aquac Nutr ; 2022: 6336060, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36860469

RESUMO

The salmon aquaculture industry must be proactive at developing mitigation tools/strategies to offset the potential negative impacts of climate change. Therefore, this study examined if additional dietary cholesterol could enhance salmon production at elevated temperatures. We hypothesized that supplemental cholesterol could aid in maintaining cell rigidity, reducing stress and the need to mobilize astaxanthin muscle stores, and improving salmon growth and survival at high rearing temperatures. Accordingly, postsmolt female triploid salmon were exposed to an incremental temperature challenge (+0.2°C day-1) to mimic conditions that they experience in sea cages in the summer, with temperature held at both 16 and 18°C for several weeks [i.e., 3 weeks at 16°C, followed by an increase at 0.2°C day-1 to 18°C (10 days), then 5 weeks at 18°C] to prolong their exposure to elevated temperatures. From 16°C onwards, the fish were fed either a control diet, or one of two nutritionally equivalent experimental diets containing supplemental cholesterol [+1.30%, experimental diet #1 (ED1); or +1.76%, experimental diet #2 (ED2)]. Adding cholesterol to the diet did not affect the salmon's incremental thermal maximum (ITMax), growth, plasma cortisol, or liver stress-related transcript expression. However, ED2 appeared to have a small negative impact on survival, and both ED1 and ED2 reduced fillet "bleaching" above 18°C as measured using SalmoFan™ scores. Although the current results suggest that supplementing salmon diets with cholesterol would have few/minimal benefits for the industry, ≤ 5% of the female triploid Atlantic salmon used in this study irrespective of diet died before temperature reached 22°C. These latter data suggest that it is possible to produce all female populations of reproductively sterile salmon that can withstand summer temperatures in Atlantic Canada.

10.
Geophys Res Lett ; 48(5): e2020GL090629, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33776162

RESUMO

Bathymetry retrievals from 2D, multispectral imagery, referred to as Satellite-Derived Bathymetry (SDB), afford the potential to obtain global, nearshore bathymetric data in optically clear waters. However, accurate SDB depth retrievals are limited in the absence of "seed depths." The Ice, Cloud, and land Elevation Satellite-2 (ICESat-2) space-based altimeter has proven capable of accurate bathymetry, but methods of employing ICESat-2 bathymetry for SDB retrievals over broad spatial extents are immature. This research aims to establish and test a baseline methodology for generating bathymetric surface models using SDB with ICESat-2. The workflow is operationally efficient (17-37 min processing time) and capable of producing bathymetry of sufficient vertical accuracy for many coastal science applications, with RMSEs of 0.96 and 1.54 m when using Sentinel-2 and Landsat 8, respectively. The highest priorities for further automation have also been identified, supporting the long-range goal of global coral reef habitat change analysis using ICESat-2-aided SDB.

11.
Int J Mol Sci ; 22(5)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33668816

RESUMO

Shotgun lipidomics was applied to identify and quantify phospholipids (PLs) in salmon muscle tissue by focusing on the distribution of ω-3 fatty acids (e.g., docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)) in the form of phospholipids, as well as to identify and quantify eicosanoids, which has not yet been attempted in Atlantic salmon muscle. Shotgun lipidomics enabled the identification of 43 PL species belonging to four different classes: phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), phosphatidylserines (PSs), and phosphatidylinositols (PIs). Among others, 16:0-22:6 PtdCho m/z [M + Na]+ at 828.4 was the predominant PL species in salmon muscle tissue. The present study provided the quantification of individual phospholipid species, which has not been performed for salmon muscle tissue so far. In addition, two eicosanoids-prostaglandin E2 (PGE2) and prostaglandin F3α (PGF3α)-were identified for the first time in salmon muscle. Thus, the rapid and high-throughput shotgun lipidomics approach should shed new light on phospholipids and eicosanoids in salmon muscle tissue.


Assuntos
Eicosanoides/metabolismo , Lipidômica , Músculos/metabolismo , Fosfolipídeos/metabolismo , Salmo salar/metabolismo , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Animais , Dinoprostona/química , Dinoprostona/metabolismo , Eicosanoides/química , Fosfolipídeos/química
12.
Mar Drugs ; 18(12)2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33260983

RESUMO

Triterpenoid biosynthesis is generally anaerobic in bacteria and aerobic in Eukarya. The major class of triterpenoids in bacteria, the hopanoids, is different to that in Eukarya, the lanostanoids, and their 4,4,14-demethylated derivatives, sterols. In the deep sea, the prokaryotic contribution to primary productivity has been suggested to be higher because local environmental conditions prevent classic photosynthetic processes from occurring. Sterols have been used as trophic biomarkers because primary producers have different compositions, and they are incorporated in primary consumer tissues. In the present study, we inferred food supply to deep sea, sponges, cnidarians, mollusks, crustaceans, and echinoderms from euphotic zone production which is driven by phytoplankton eukaryotic autotrophy. Sterol composition was obtained by gas chromatography and mass spectrometry. Moreover, we compared the sterol composition of three phyla (i.e., Porifera, Cnidaria, and Echinodermata) collected between a deep and cold-water region and a shallow tropical area. We hypothesized that the sterol composition of shallow tropical benthic organisms would better reflect their photoautotrophic sources independently of the taxonomy. Shallow tropical sponges and cnidarians from environments showed plant and zooxanthellae sterols in their tissues, while their deep-sea counterparts showed phytoplankton and zooplankton sterols. In contrast, echinoids, a class of echinoderms, the most complex phylum along with hemichordates and chordates (deuterostomes), did not show significant differences in their sterol profile, suggesting that cholesterol synthesis is present in deuterostomes other than chordates.


Assuntos
Artrópodes/metabolismo , Cnidários/metabolismo , Equinodermos/metabolismo , Moluscos/metabolismo , Poríferos/metabolismo , Esteróis/metabolismo , Animais , Oceano Atlântico , Dieta , Ecossistema , Cromatografia Gasosa-Espectrometria de Massas , Golfo do México , Especificidade da Espécie , Esteróis/isolamento & purificação
13.
Fish Physiol Biochem ; 46(6): 2331-2353, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33001367

RESUMO

Limited fish meal and fish oil supplies have necessitated research on alternatives for aquafeeds. Seven dietary treatments with different protein and lipid sources were formulated for farmed Atlantic salmon, and their effects on liver and head kidney lipid class, fatty acid, and elemental composition were studied. Fish meal, fish oil, and EPA + DHA content ranged from 5-35%, 0-12%, and 0.1-3%, respectively. Elemental analysis showed that the C to N ratio was higher in the head kidney than in the liver, which is consistent with higher content of total lipids in the head kidney compared with the liver. There was a greater susceptibility to dietary lipid alterations in the liver compared with the head kidney despite liver having a greater proportion of phospholipid and a much lower proportion of triacylglycerol. So long as fish oil levels were 5% or more of the diet, arachidonic acid (ARA) and docosahexaenoic acid (DHA) proportions were the same for each tissue as with feeding the marine diet with 12% fish oil; however, livers and head kidneys from fish fed the lowest amount of fish meal and fish oil had the lowest levels of eicosapentaenoic (EPA) and DHA and the highest ARA levels. Removal of fish oil and reduction of fish meal to 5% in diets of farmed Atlantic salmon affected elemental and lipid compositions of the liver and head kidney tissues potentially increasing susceptibility to inflammation. However, with 10% of the diet comprising fish meal and fish oil, lipid contents were comparable with fish fed marine-based diets.


Assuntos
Dieta/veterinária , Rim Cefálico/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Salmo salar/metabolismo , Ração Animal/análise , Animais , Aquicultura , Ácido Araquidônico/análise , Ácidos Docosa-Hexaenoicos/análise , Ácido Eicosapentaenoico/análise , Óleos de Peixe , Produtos Pesqueiros , Salmo salar/crescimento & desenvolvimento
14.
Br J Haematol ; 185(3): 450-467, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30729512

RESUMO

The Myeloma X trial (ISCRTN60123120) registered patients with relapsed multiple myeloma. Participants were randomised between salvage autologous stem cell transplantation (ASCT) or weekly cyclophosphamide following re-induction therapy. Cytogenetic analysis performed at trial registration defined t(4;14), t(14;16) and del(17p) as high-risk. The effect of cytogenetics on time to progression (TTP) and overall survival was investigated. At 76 months median follow-up, ASCT improved TTP compared to cyclophosphamide (19 months (95% confidence interval [95% CI] 16-26) vs. 11 months (9-12), hazard ratio [HR]: 0·40, 95% CI: 0·29-0·56, P < 0·001), on which the presence of any single high-risk lesion had a detrimental impact [likelihood ratio test (LRT): P = 0·011]. ASCT also improved OS [67 months (95% CI 59-not reached) vs. 55 months (44-67), HR: 0·64, 95% CI: 0·42-0·99, P = 0·0435], with evidence of a detrimental impact with MYC rearrangement (LRT: P = 0·021). Twenty-one (24·7%) cyclophosphamide patients received an ASCT post-trial, median OS was not reached (95% CI: 39-not reached) for these participants compared to 31 months (22-39), in those who did not receive a post-trial ASCT. The analysis further supports the benefit of salvage ASCT, which may still be beneficial after second relapse in surviving patients. There is evidence that this benefit reduces in cytogenetic high-risk patients, highlighting the need for targeted study in this patient group.


Assuntos
Mieloma Múltiplo/genética , Idoso , Antineoplásicos Alquilantes/uso terapêutico , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 14/ultraestrutura , Cromossomos Humanos Par 16/genética , Cromossomos Humanos Par 16/ultraestrutura , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 17/ultraestrutura , Cromossomos Humanos Par 4/genética , Cromossomos Humanos Par 4/ultraestrutura , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Terapia Combinada , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas , Humanos , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Terapia de Salvação , Deleção de Sequência , Translocação Genética , Transplante Autólogo
15.
J Exp Biol ; 222(Pt 22)2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31645375

RESUMO

In fishes, the effect of O2 limitation on cardiac mitochondrial function remains largely unexplored. The sablefish (Anoplopoma fimbria) encounters considerable variations in environmental oxygen availability, and is an interesting model for studying the effects of hypoxia on fish cardiorespiratory function. We investigated how in vivo hypoxia acclimation (6 months at 40% then 3 weeks at 20% air saturation) and in vitro anoxia-reoxygenation affected sablefish cardiac mitochondrial respiration and reactive oxygen species (ROS) release rates using high-resolution fluorespirometry. Further, we investigated how hypoxia acclimation affected the sensitivity of mitochondrial respiration to nitric oxide (NO), and compared mitochondrial lipid and fatty acid (FA) composition between groups. Hypoxia acclimation did not alter mitochondrial coupled or uncoupled respiration, or respiratory control ratio, ROS release rates, P50 or superoxide dismutase activity. However, it increased citrate synthase activity (by ∼20%), increased the sensitivity of mitochondrial respiration to NO inhibition (i.e., the NO IC50 was 25% lower), and enhanced the recovery of respiration (by 21%) and reduced ROS release rates (by 25-30%) post-anoxia. In addition, hypoxia acclimation altered mitochondrial FA composition [increasing arachidonic acid (20:4ω6) and eicosapentaenoic acid (20:5ω3) proportions by 11 and 14%, respectively], and SIMPER analysis revealed that the phospholipid:sterol ratio was the largest contributor (24%) to the dissimilarity between treatments. Overall, these results suggest that hypoxia acclimation may protect sablefish cardiac bioenergetic function during or after periods of O2 limitation, and that this may be related to alterations in mitochondrial sensitivity to NO and to adaptive changes in membrane composition (fluidity).


Assuntos
Hipóxia/fisiopatologia , Mitocôndrias/metabolismo , Óxido Nítrico/farmacologia , Perciformes/fisiologia , Aclimatação , Animais , Ácidos Graxos/análise , Ventrículos do Coração/fisiopatologia , Lipídeos/análise , Mitocôndrias/química , Oxigênio/metabolismo , Perciformes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
16.
Pract Neurol ; 19(6): 511-517, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31273077

RESUMO

Multiple myeloma is a haematological malignancy with clonal plasma cell proliferation and production of monoclonal immunoglobulins. Its neurological complications are relatively common, caused by both the disease and the treatment. Neurologists should therefore be familiar with its neurological manifestations and complications. We describe a 40-year-old woman who presented with lower cranial neuropathies mimicking variant Guillain-Barré syndrome, with normal brain and spinal cord imaging and cerebrospinal fluid (CSF) albuminocytological dissociation, and subsequently diagnosed with IgD myeloma. She relapsed repeatedly with differing neurological presentations: numb chin syndrome and twice with impaired vision, first from cerebral venous sinus thrombosis and later from leptomeningeal infiltration of the optic chiasm. We discuss the neurological complications of myeloma, emphasising the need to consider it in a wide variety of neurological presentations and repeatedly to reassess its associated neurological diagnoses. We also highlight the complexity of myeloma treatment.


Assuntos
Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Doenças do Sistema Nervoso/etiologia , Adulto , Feminino , Humanos
17.
BMC Genomics ; 19(1): 796, 2018 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-30390635

RESUMO

BACKGROUND: Dependence on marine natural resources threatens the sustainability of Atlantic salmon aquaculture. In the present study, Atlantic salmon fed for 14 weeks with an experimental diet based on animal by-products and vegetable oil (ABP) exhibited reduced growth performance compared with others fed a fish meal/fish oil based experimental diet (MAR) and a plant protein/vegetable oil-based experimental diet (VEG). To characterize the molecular changes underlying the differences in growth performance, we conducted a 44 K microarray study of the liver transcriptome of the three dietary groups. RESULTS: The microarray experiment identified 122 differentially expressed features (Rank Products, PFP < 10%). Based on their associated Gene Ontology terms, 46 probes were classified as metabolic and growth-relevant genes, 25 as immune-related, and 12 as related to oxidation-reduction processes. The microarray results were validated by qPCR analysis of 29 microarray-identified transcripts. Diets significantly modulated the transcription of genes involved in carbohydrate metabolism (gck and pfkfb4), cell growth and proliferation (sgk2 and htra1), apoptosis (gadd45b), lipid metabolism (fabp3, idi1, sqs), and immunity (igd, mx, ifit5, and mhcI). Hierarchical clustering and linear correlation analyses were performed to find gene expression patterns among the qPCR-analyzed transcripts, and connections between them and muscle and liver lipid composition. Overall, our results indicate that changes in the liver transcriptome and tissue lipid composition were driven by cholesterol synthesis up-regulation by ABP and VEG diets, and the lower carbohydrate intake in the ABP group. Two of the microarray-identified genes (sgk2 and htra1) might be key to explaining glucose metabolism regulation and the dietary-modulation of the immune system in fish. To evaluate the potential of these genes as predictive biomarkers, we subjected the qPCR data to a stepwise discriminant analysis. Three sets of no more than four genes were found to be able to predict, with high accuracy (67-94%), salmon growth and fatty acid composition. CONCLUSIONS: This study provides new findings on the impact of terrestrial animal and plant products on the nutrition and health of farmed Atlantic salmon, and a new method based on gene biomarkers for potentially predicting desired phenotypes, which could help formulate superior feeds for the Atlantic salmon aquaculture industry.


Assuntos
Ração Animal , Óleos de Peixe , Fígado/metabolismo , Salmo salar/genética , Transcriptoma , Ração Animal/análise , Animais , Biomarcadores , Biologia Computacional/métodos , Ácidos Graxos/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Óleos de Plantas , Salmo salar/crescimento & desenvolvimento , Salmo salar/metabolismo
18.
Curr Allergy Asthma Rep ; 18(8): 41, 2018 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-29904820

RESUMO

PURPOSE OF REVIEW: This review aims to provide an update of recent advances in the epidemiology, clinical features and diagnosis, and management of food-induced anaphylaxis (FIA). RECENT FINDINGS: Food allergy prevalence and FIA rates continue to rise, but FIA fatalities are stable. Basophil and mast cell activation tests promise more accurate identification of food triggers. Oral, sublingual, and epicutaneous immunotherapy can desensitize a significant portion of subjects. Epinephrine use for FIA remains sub-optimal. As the burden of food allergy continues to increase, it appears that the corresponding increase in research focused on this epidemic is beginning to bear fruit. The stable number of FIA fatalities in the face of an ongoing epidemic indicates lives have already been saved. The emergence of new diagnostic tests and interventional therapies may transform the management of FIA in the coming years.


Assuntos
Anafilaxia , Hipersensibilidade Alimentar , Anafilaxia/etiologia , Hipersensibilidade Alimentar/complicações , Humanos
19.
Curr Allergy Asthma Rep ; 18(3): 18, 2018 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-29470658

RESUMO

PURPOSE OF REVIEW: The goal of this review is to provide the reader with an updated summary of published trial data regarding the use of oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT) for treatment of IgE-mediated food allergies. RECENT FINDINGS: Data from phase 2 trials for treatment of peanut allergy with OIT and EPIT reveal an increase in the threshold of reactivity for peanut-allergic children. Compared to EPIT, OIT promotes a greater increase in the threshold of reactivity; however, adverse events are more common with OIT. OIT, EPIT, and SLIT appear to modulate the immune response for some food-allergic individuals. Data regarding utility for treatment of food allergies regardless of modality is limited to few foods, as is investigation into treatment of food-allergic infants, young children, and adults. Future trials are likely to focus on young children, food allergies other than peanut, and treatment of multifood-allergic individuals.


Assuntos
Arachis/efeitos adversos , Dessensibilização Imunológica/métodos , Hipersensibilidade Alimentar/terapia , Administração Oral , Administração Sublingual , Criança , Hipersensibilidade Alimentar/imunologia , Humanos
20.
Adv Mar Biol ; 81: 1-22, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30471654

RESUMO

Since 2012, the scallop fishery in Port au Port Bay, Newfoundland, Canada has experienced a drastic decline, while no decline was observed in adjacent St. George's Bay. Local fishermen have raised concerns about an abandoned oil exploration well in the Port au Port Bay. This study investigated the potential impact of petroleum hydrocarbons on sediments and blue mussels [Mytilus edulis] (a proxy organism for scallops) in the area. Sediments from both bays were characterized for their hydrocarbons and compared to potential petroleum hydrocarbon sources. Mussels were analysed for health indices and their 14C content. The results showed that the concentration of hydrocarbons found in the sediments of the fishing ground was within the range of unpolluted marine sediments and that the hydrocarbons present were likely from a mixture of sources. The health indices of the mussels in Port au Port Bay were similar to the health indices of mussels in St. George's Bay and the 14C content of the mussels from both bays was modern. These data suggest that the Port au Port fishing ground was not solely contaminated from crude oil leaking from an oil exploration well, that the mussels were not contaminated with petroleum hydrocarbons, and that Port au Port mussels were just as healthy as the mussels of St. George's Bay. Therefore, whatever caused the scallop decline was most likely scallop- and bay-specific. During this study a fast and efficient method for extracting petroleum hydrocarbons from sediment using accelerated solvent extraction with integrated silica gel was developed.


Assuntos
Bivalves/efeitos dos fármacos , Hidrocarbonetos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Baías , Pesqueiros , Hidrocarbonetos/química , Terra Nova e Labrador , Poluentes Químicos da Água/química
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