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1.
Analyst ; 144(15): 4647-4652, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31257384

RESUMO

The challenging diagnosis and differentiation between multiple sclerosis and amyotrophic lateral sclerosis relies on the clinical assessment of the symptoms along with magnetic resonance imaging and sampling cerebrospinal fluid for the search of biomarkers for either disease. Despite the progress made in imaging techniques and biomarker identification, misdiagnosis still occurs. Here we used 2.5 µL of serum samples to obtain the infrared spectroscopic signatures of sera of multiple sclerosis and amyotrophic lateral sclerosis patients and compared them to those of healthy controls. The spectra are then classified with the help of a two-fold Random Forest cross-validation algorithm. This approach shows that infrared spectroscopy is powerful in discriminating between the two diseases and healthy controls by offering high specificity for multiple sclerosis (100%) and amyotrophic lateral sclerosis (98%). In addition, data after six and twelve months of treatment of the multiple sclerosis patients with biotin are discussed.


Assuntos
Esclerose Amiotrófica Lateral/diagnóstico , Biomarcadores/sangue , Esclerose Múltipla/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Esclerose Amiotrófica Lateral/tratamento farmacológico , Biotina/uso terapêutico , Árvores de Decisões , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/tratamento farmacológico , Projetos Piloto , Espectroscopia de Infravermelho com Transformada de Fourier/métodos
2.
J Pept Sci ; 25(8): e3197, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31264321

RESUMO

Platelet-activating factor (PAF) is known as an important mediator of anaphylaxis and, therefore, may possibly serve as a direct target for anti-anaphylactic drugs. We recently reported that a synthetic N-terminally biotinylated peptide, BP21, alleviates hypothermia and vascular hyperpermeability during anaphylactic reactions in a mouse model of anaphylaxis via the direct binding of a Tyr-Lys-Asp-Gly sequence in the peptide to PAF. In this study, we investigated the effect of BP21 on in vivo anaphylactic hypotension. Results showed that BP21 significantly inhibited anaphylactic hypotension in a dose-dependent manner, with peak severity being reached within 20 minutes. Adrenaline, which is the recommended first line treatment for anaphylactic patients, did not inhibit anaphylactic hypothermia. The combined administration of BP21 with adrenaline inhibited both hypotension and hypothermia, even at both low doses, more effectively compared with solo administration of BP21 or adrenaline. These results suggested that BP21 could potentially be a novel anti-anaphylactic agent for targeting PAF in vivo.


Assuntos
Anafilaxia/tratamento farmacológico , Biotina/análogos & derivados , Proteínas Hemolisinas/uso terapêutico , Hipotensão/tratamento farmacológico , Fragmentos de Peptídeos/uso terapêutico , Animais , Biotina/química , Biotina/metabolismo , Biotina/uso terapêutico , Biotinilação , Proteínas Hemolisinas/química , Proteínas Hemolisinas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Estrutura Molecular , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo
4.
Biotechnol Adv ; 37(5): 634-641, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30872068

RESUMO

Biotinylated antibodies/antigens are currently used in many immunoassay formats in clinical settings for diversified analytes and biomarkers to offer high detection selectivity and sensitivity. Biotin cannot be synthesized by mammals and must be taken as an essential supplement. Normal intake of biotin from various foods and milk causes no effect on the streptavidin/biotin-based immunoassays. However, overconsumption of biotin (daily doses 100-300 mg) poses a significant problem for immunoassays using the biotin-strept(avidin) pair. Biotin interferences are noted in immunoassays of thyroid markers, drugs, hormones, cancer markers, the biomarker for cardiac function (ß-human chorionic gonadotropin), etc. The biotin level required for serious interference in test results varies significantly from test to test and cannot easily be predicted. Immunoassay manufacturers with technologies based on strept(avidin)-biotin binding must investigate the interference from biotin (up to at least 1200 ng/mL or 4.9 µM of biotin) in various formats. There is no concrete solution to circumvent the biotin interference encountered in blood samples, short of biotin removal. Considering the short half-life of biotin in the human body, patients must stop taking biotin supplements for >48 h before the test. However, this scenario is not considered for patients in emergency situations or those with biotinidase deficiency, mitochondrial metabolic disorders or multiple sclerosis. Apparently, a rapid analytical procedure for biotin is urgently needed to quantify for its interference in immunoassays using strep(avidin)-biotin chemistry. To date, there is no quick and reliable procedure for the detection of biotin at below nanomolar levels in blood and biological samples. Traditional lab-based techniques including HPLC/MS-MS cannot process an enormous number of public samples. Biosensors with high detection sensitivity, miniaturization, low cost, and multiplexing have the potential to address this issue.


Assuntos
Biotina/química , Imunoensaio/métodos , Estreptavidina/química , Animais , Artefatos , Biomarcadores/análise , Biomarcadores/sangue , Técnicas Biossensoriais/métodos , Biotina/análise , Biotina/isolamento & purificação , Biotina/uso terapêutico , Humanos , Sensibilidade e Especificidade
5.
Cochrane Database Syst Rev ; 3: CD011380, 2019 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-30828791

RESUMO

BACKGROUND: Infantile seborrhoeic dermatitis (ISD) is a chronic, inflammatory, scaling skin condition, which causes redness and a greasy scaling rash in infants and young children. It can last from weeks to months, but rarely years. When it occurs on the scalp, it is referred to as 'cradle cap'. While benign and self-limiting, irrelevant of its location on the body, it can distress parents. The effectiveness of commonly promoted treatments is unclear. OBJECTIVES: To assess the effects of interventions for infantile seborrhoeic dermatitis in children from birth to 24 months of age. SEARCH METHODS: We searched the following databases up to 22 May 2018: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched trials registers and checked reference lists of included studies for further references to randomised controlled trials (RCTs). We searched for unpublished RCTs and grey literature via web search engines, and wrote to authors and pharmaceutical companies. SELECTION CRITERIA: We included RCTs of interventions for ISD in children from birth up to 24 months who were clinically diagnosed by a healthcare practitioner with ISD or cradle cap. We allowed comparison of any treatment to no treatment or placebo, and the comparison of two or more treatments or a combination of treatments. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The primary outcome measures were 'Change in severity score from baseline to end of study' and 'Percentage of infants treated who develop adverse effects or intolerance to treatment'. The secondary outcome was 'Improvement in quality of life (QoL) as reported by parents'. MAIN RESULTS: We included six RCTs (one with a cross-over design) randomising 310 children and reporting outcomes for 297 children. Most participants were aged under seven months with only two participants aged over one year (seven and 12 years old); where specified, 60% were boys. In two studies, condition severity was mild to moderate; one study included two participants with severe ISD; the other studies did not describe baseline severity or described it as body surface area affected.The study setting was not always clear but likely a paediatric outpatient clinic in the following countries: Thailand, Israel, USA, France, and Australia.Two studies compared oral biotin (a B group vitamin) against placebo, two studies compared proprietary products against placebo cream or a control shampoo, and two studies compared topical corticosteroids against other products. The studies were generally short-term, between 10 and 42 days' duration; only one study followed the participants until resolution of the rash or eight months of age.We assessed the risk of bias as unclear for most aspects due to lack of reporting, but two of the studies were at high risk of performance and detection bias due to the appearance of the intervention, the trial design (open-label), or use of overlabelled tubes. Two trials had a high risk of attrition bias.All the results given below were based on very low-quality evidence. Treatment duration ranged from one week to three weeks.For the two trials comparing biotin versus placebo (n = 35), one did not report a measure of change in severity (only change in duration of rash) while the other did not report raw data (only 'no statistically significant difference'), measured at three weeks. Neither trial reported on adverse events.Two trials compared proprietary products against placebo (n = 160). One trial assessed change in severity via percentage success (96% of participants in non-steroidal cream Promiseb versus 92% in placebo), and reported no adverse events (both assessed at day 14). The other trial assessed change in severity via reduction in lesional score (surface area covered), finding better results for lactamide MEA gel (a moisturising agent) plus shampoo (81.4%) compared with shampoo only (70.2%; P = 0.0092). No adverse events were described, but signs of discomfort were similar in both groups (both assessed at day 21).In the comparison of topical steroids versus another product, change in severity was measured through evaluation of cure and body surface (n = 102).In one trial comparing hydrocortisone 1% lotion with licochalcone 0.025% lotion, there was no significant difference in participants cured (95.8% with hydrocortisone compared to 97.1% with licochalcone). One person in the licochalcone group developed more erythema, but there were no other adverse events (both outcomes assessed at day 14). In the trial comparing flumethasone pivalate 0.02% ointment versus eosin 2% aqueous solution, a reduction in body surface area affected was seen in both groups at day 10 (9% with corticosteroid versus 7% with aqueous solution), with all infants showing less than 10% involvement. There were no adverse events (both outcomes assessed at day 10).No studies measured QoL.We found no trials testing commonly used treatments such as mineral oils, salicylic acid, or antifungals. AUTHORS' CONCLUSIONS: Our review identified only a limited number of studies investigating the effects of interventions for ISD in infants and young children. Unlike the reviews investigating the effects of treatments in adults, our results showed that there is uncertainty regarding the effectiveness and safety of studied treatments due to the very low-certainty evidence for all comparisons and outcomes.We assessed most bias domains as at unclear risk, but there was a high risk of bias for (mainly) performance, attrition, and detection bias. Evidence was limited further by imprecision (small studies, low number of events), indirectness (mainly with the outcomes assessed), and poor trial reporting. In most studies, the prognosis for the condition was favourable regardless of intervention but interpretation is limited by the very low-certainty evidence.Further research is needed with large, well-conducted, and well-reported intervention trials, particularly of interventions commonly recommended or used, such as emollients or shampoos and brushing, antifungals, or steroids. All studies should report standardised and validated relevant outcome measures, including adverse events, severity, and QoL, and they should be conducted in primary care settings where the majority of ISD is managed. Future trials should compare against placebo, no treatment, or standard care.


Assuntos
Biotina/uso terapêutico , Dermatite Seborreica/terapia , Emolientes/uso terapêutico , Preparações para Cabelo/uso terapêutico , Dermatoses do Couro Cabeludo/terapia , Complexo Vitamínico B/uso terapêutico , Amidas/uso terapêutico , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Bioorg Med Chem Lett ; 28(20): 3312-3314, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30243588

RESUMO

Oxidized form of avidin, named AvidinOX, provides stable fixation of biotinylated molecules in tissues thus representing a breakthrough in topical treatment of cancer. AvidinOX proved to be a stable receptor for radiolabeled biotin, biotinylated antibodies and cells. In order to expand applicability of the AvidinOX-based delivery platform, in the present study we investigated the possibility to hold biotinylated chemotherapeutics in AvidinOX-treated sites. A novel biotinylated gimatecan-derived camptothecin, coded ST8161AA1, was injected at suboptimal doses into human tumors xenografted in mice alone or pre-complexed to AvidinOX. Significantly higher growth inhibition was observed when the drug was anchored to AvidinOX suggesting the potential utility of this delivery modality for the local treatment of inoperable tumors.


Assuntos
Antineoplásicos/uso terapêutico , Biotina/análogos & derivados , Biotina/uso terapêutico , Camptotecina/análogos & derivados , Carcinoma/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Animais , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Avidina/metabolismo , Biotina/síntese química , Biotina/metabolismo , Camptotecina/síntese química , Camptotecina/metabolismo , Camptotecina/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Camundongos , Ligação Proteica
10.
Nutr Res ; 57: 86-96, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30122199

RESUMO

Several reports have demonstrated that pharmacological concentrations of biotin reduce hyperglycemia, hypertriglyceridemia, and hypertension. We hypothesized that biotin could exert a protective effect on some illness-associated metabolic syndrome. To test this hypothesis, male Wistar rats were fed a diet containing 30% fructose in drinking water and classified into four groups: C, the control group; B, the group receiving biotin (intraperitoneal injection, 2 mg/kg); F, the group receiving fructose (30% w/v); and FB, the group receiving fructose-biotin. The administration of biotin began after the rats had been on a high-fructose diet for 12 weeks and continued for 4 weeks. Our results showed that food and fluid intake were diminished in the F and FB groups. However, the final body weights were similar between the groups. A significant increase in hepatic triglyceride and cholesterol content, plasma cholesterol, triglycerides, transaminases, low-density lipoprotein cholesterol (LDL-c), systolic blood pressure, and vasocontraction, as well as a decrease in high-density lipoprotein cholesterol (HDL-c) were observed in the F group. Glucose tolerance and insulin tolerance were also impaired in the F group. The administration of biotin ameliorated all these changes. Hepatic oxidative stress as well as macrovesicular fatty changes in hepatocytes caused by a high-fructose diet were also improved by biotin. Our findings demonstrate that biotin has a protective role against metabolic syndrome by improving insulin resistance associated with normal hepatic and serum levels of triglyceride and cholesterol, blood pressure, and the prevention of steatosis and hepatic oxidative damage. Therefore, biotin could be used as a therapeutic strategy in the pharmacological treatment of metabolic syndrome.


Assuntos
Biotina/uso terapêutico , Glicemia/metabolismo , Suplementos Nutricionais , Frutose/efeitos adversos , Metabolismo dos Lipídeos/efeitos dos fármacos , Síndrome Metabólica/prevenção & controle , Substâncias Protetoras/farmacologia , Animais , Biotina/farmacologia , Fígado Gorduroso/sangue , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/prevenção & controle , Resistência à Insulina , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Complexo Vitamínico B/farmacologia , Complexo Vitamínico B/uso terapêutico
12.
J Dairy Sci ; 101(9): 7851-7856, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30007814

RESUMO

The current study was conducted to investigate the effects of dietary supplementation of biotin, intramuscular injections of vitamin B12 (VB12), or both beginning at the prepartum period on feed intake and lactation performance in postpartum dairy cows. Forty-eight dairy cows were allocated into 12 blocks, based on parity and milk yield of the previous lactation cycle, and randomly assigned to 1 of 4 treatments. Supplementation of VB12 (weekly intramuscular injections of 0 or 10 mg) and biotin (dietary supplements of 0 or 30 mg/d) were used in a 2 × 2 factorial arrangement in a randomized complete block design of 12 blocks with repeated measures. The study started at 3 wk before the expected calving date and ended at 8 wk after calving. Feed intake and lactation performance (milk yield and composition) were recorded weekly after calving. Blood variables were measured on d -10, 0, 8, 15, 29, 43, and 57 relative to calving. When VB12 was given, the cows had greater feed intake, better lactation performance and lower body weight loss in the postpartum period compared with animals without injection of VB12. The VB12-injected cows had lower plasma nonesterified fatty acids and ß-hydroxybutyrate concentrations but higher plasma superoxide dismutase activity compared with cows without VB12. Cows fed a biotin supplement had higher milk protein yield (6 and 8 wk) and lactose yield (6-8 wk), compared with animals without biotin. However, under the present experimental conditions, we found no additive effect of a combined supplement of biotin and vitamin B12 on lactation performance of dairy cows.


Assuntos
Biotina/uso terapêutico , Bovinos , Lactação/efeitos dos fármacos , Vitamina B 12/uso terapêutico , Animais , Dieta , Suplementos Nutricionais , Feminino , Injeções Intramusculares/veterinária , Lactação/fisiologia , Período Pós-Parto , Gravidez
13.
Clin Chim Acta ; 484: 320-322, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29856977

RESUMO

We report on a 47 year old male patient with multiple sclerosis (MS) presenting in our outpatient neurology clinic in Frankfurt/Main for therapy evaluation. Before change of treatment laboratory investigations were performed. Thyroid function tests (TFTs) with a streptavidin/biotin based immunoassay revealed severe hyperthyroidism with positive thyroid autoantibodies suggestive for Graves' disease. Clinical presentation and thyroid sonography were unremarkable. Due to the discordance between clinical presentation and TFTs, we repeated medical history, in which the patient reported taking high-doses of biotin (300 mg/day) for MS. Recent studies with patients suffering from primary and secondary progressive MS, indicated promising effects of high-dose biotin on MS-related disability. In immunoassays relaying on streptavidin-biotin interaction, biotin intake can cause falsely high or low results. Two weeks after withdrawing biotin, biotin/streptavidin dependant assays showed no longer the biochemical picture of severe hyperthyroidism. Biotin intake should be paused for at least two to five days prior to the use of biotin/streptavidin dependant assays. Alternatively, non-biotin/streptavidin dependant assays (radioimmunoassay, gas chromatography-mass spectrometry/liquid chromatography-mass spectrometry) may be used.


Assuntos
Artefatos , Biotina/análise , Imunoensaio , Esclerose Múltipla/diagnóstico , Testes de Função Tireóidea , Glândula Tireoide/metabolismo , Biotina/administração & dosagem , Biotina/uso terapêutico , Relação Dose-Resposta a Droga , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/tratamento farmacológico , Estreptavidina/análise , Glândula Tireoide/efeitos dos fármacos
14.
J Vis Exp ; (134)2018 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-29708526

RESUMO

High molecular weight biotinylated dextran amine (BDA) has been used as a highly sensitive neuroanatomical tracer for many decades. Since the quality of its labeling was affected by various factors, here, we provide a refined protocol for the application of high molecular weight BDA for studying optimal neural labeling in the central nervous system. After stereotactic injection of BDA into the ventral posteromedial nucleus (VPM) of the thalamus in the rat through a delicate glass pipette, BDA was stained with fluorescent streptavidin-Alexa (AF) 594 and counterstained with fluorescent Nissl stain AF500/525. On the background of green Nissl staining, the red BDA labeling, including neuronal cell bodies and axonal terminals, was more distinctly demonstrated in the somatosensory cortex. Furthermore, double fluorescent staining for BDA and the calcium-binding protein parvalbumin (PV) was carried out to observe the correlation of BDA labeling and PV-positive interneurons in the cortical target, providing the opportunity to study the local neural circuits and their chemical characteristics. Thus, this refined method is not only suitable for visualizing high quality neural labeling with the high molecular weight BDA through reciprocal neural pathways between the thalamus and cerebral cortex, but also will permit the simultaneous demonstration of other neural markers with fluorescent histochemistry or immunochemistry.


Assuntos
Biotina/análogos & derivados , Córtex Cerebral/diagnóstico por imagem , Dextranos/uso terapêutico , Corantes Fluorescentes/uso terapêutico , Tálamo/diagnóstico por imagem , Animais , Biotina/farmacologia , Biotina/uso terapêutico , Dextranos/farmacologia , Corantes Fluorescentes/farmacologia , Masculino , Peso Molecular , Ratos
15.
JAMA Neurol ; 75(8): 1013-1021, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29710293

RESUMO

Importance: Surveys of patients with multiple sclerosis report that most are interested in modifying their diet and using supplements to potentially reduce the severity and symptoms of the disease. This review provides an updated overview of the current state of evidence for the role that vitamins and dietary supplements play in multiple sclerosis and its animal models, with an emphasis on recent studies, and addresses biological plausibility and safety issues. Observations: Several vitamins and dietary supplements have been recently explored both in animal models and by patients with multiple sclerosis. Most human trials have been small or nonblinded, limiting their generalizability. Biotin and vitamin D are currently being tested in large randomized clinical trials. Smaller trials are ongoing or planned for other supplements such as lipoic acid and probiotics. The results of these studies may help guide clinical recommendations. Conclusions and Relevance: At the present time, the only vitamin with sufficient evidence to support routine supplementation for patients with multiple sclerosis is vitamin D. Vitamin deficiencies should be avoided. It is important for clinicians to know which supplements their patients are taking and to educate patients on any known efficacy data, along with any potential medication interactions and adverse effects of individual supplements. Given that dietary supplements and vitamins are not subject to the same regulatory oversight as prescription pharmaceuticals in the United States, it is recommended that vitamins and supplements be purchased from reputable manufacturers with the United States Pharmacopeia designation.


Assuntos
Suplementos Nutricionais , Encefalomielite Autoimune Experimental/dietoterapia , Esclerose Múltipla/dietoterapia , Vitaminas/uso terapêutico , Acetilcarnitina/uso terapêutico , Animais , Ácido Ascórbico/uso terapêutico , Biotina/uso terapêutico , Cafeína/uso terapêutico , Creatina/uso terapêutico , Curcumina/uso terapêutico , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/tratamento farmacológico , Ácidos Graxos Insaturados/uso terapêutico , Ácido Fólico/uso terapêutico , Ginkgo biloba , Humanos , Esclerose Múltipla/tratamento farmacológico , Niacina/uso terapêutico , Ácido Pantotênico/uso terapêutico , Preparações de Plantas/uso terapêutico , Probióticos/uso terapêutico , Piridoxina/uso terapêutico , Resveratrol/uso terapêutico , Riboflavina/uso terapêutico , Chá , Tiamina/uso terapêutico , Ácido Tióctico/uso terapêutico , Ubiquinona , Vitamina A/uso terapêutico , Vitamina B 12/uso terapêutico , Vitamina D/uso terapêutico , Vitamina E/uso terapêutico
16.
CNS Drugs ; 32(7): 661-672, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29808469

RESUMO

BACKGROUND: Chronic visual loss is a disabling feature in patients with multiple sclerosis (MS). It was recently shown that MD1003 (high-dose pharmaceutical-grade biotin or hdPB) may improve disability in patients with progressive MS. OBJECTIVE: The aim of this study was to evaluate whether MD1003 improves vision compared with placebo in MS patients with chronic visual loss. METHODS: The MS-ON was a 6-month, randomized, double-blind, placebo-controlled study with a 6-month open-label extension phase. Adult patients with MS-related chronic visual loss of at least one eye [visual acuity (VA) below 0.5 decimal chart] were randomized 2:1 to oral MD1003 300 mg/day or placebo. The selected eye had to show worsening of VA within the past 3 years following either acute optic neuritis (AON) or slowly progressive optic neuropathy (PON). The primary endpoint was the mean change from baseline to month 6 in VA measured in logarithm of the minimum angle of resolution (logMAR) at 100% contrast of the selected eye. Visually evoked potentials, visual field, retinal nerve fiber layer (RNFL) thickness, and health outcomes were also assessed. RESULTS: Ninety-three patients received MD1003 (n = 65) or placebo (n = 28). The study did not meet its primary endpoint, as the mean change in the primary endpoint was nonsignificantly larger (p = 0.66) with MD1003 (- 0.061 logMAR, + 3.1 letters) than with placebo (- 0.036 logMAR, + 1.8 letters). Pre-planned subgroup analyses showed that 100% contrast VA improved by a mean of + 2.8 letters (- 0.058 logMAR) with MD1003 and worsened by - 1.5 letters (+ 0.029 logMAR) with placebo (p = 0.45) in the subgroup of patients with PON. MD1003-treated patients also had nonsignificant improvement in logMAR at 5% contrast and in RNFL thickness and health outcome scores when compared with placebo-treated patients. There was no superiority of MD1003 vs placebo in patients with AON. The safety profile of MD1003 was similar to that of placebo. CONCLUSIONS: MD1003 did not significantly improve VA compared with placebo in patients with MS experiencing chronic visual loss. An interesting trend favoring MD1003 was observed in the subgroup of patients with PON. Treatment was overall well tolerated. TRIAL REGISTRATION: EudraCT identifier 2013-002112-27. ClinicalTrials.gov Identifier: NCT02220244 FUNDING: MedDay Pharmaceuticals.


Assuntos
Biotina/uso terapêutico , Esclerose Múltipla/complicações , Neurite Óptica/complicações , Neurite Óptica/etiologia , Transtornos da Visão/tratamento farmacológico , Transtornos da Visão/etiologia , Complexo Vitamínico B/uso terapêutico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Resultado do Tratamento , Acuidade Visual/efeitos dos fármacos
18.
Pediatr Neurol ; 79: 61-64, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29413639

RESUMO

BACKGROUND: Patients with autism spectrum disorder and developmental delay or encephalopathy rarely demonstrate no or negligible hair and nail growth, suggesting a biotin-responsive clinical disorder. METHODS: A ten-year-old girl presented with features of autism spectrum disorder, isolated headaches, and episodes of headaches and limb shaking. Her medical history revealed that her hair and nails did not grow. Administration of biotin restored her nail and hair growth and improved intellectual ability and school performance. Her episodes of headaches, single limb shaking, and loss of consciousness responded to administration of acetazolamide, and her school performance and social skills further improved. RESULTS: A de novo c.1091 C > T, p.T364M pathogenic variant was found in the ATP1A2 gene by whole-exome sequencing, but a genetic etiology in the biotin-responsive metabolic pathways was not identified. CONCLUSIONS: The combination of biotin and acetazolamide treatment was successful in restoring normal mental function and school performance. Poor or no clinical nail and hair growth in any child with a developmental delay-autism spectrum disorder presentation should be considered as evidence for a biotin-responsive genetic disorder even when exome testing is negative.


Assuntos
Acetazolamida/uso terapêutico , Anticonvulsivantes/uso terapêutico , Transtorno do Espectro Autista/tratamento farmacológico , Biotina/uso terapêutico , Complexo Vitamínico B/uso terapêutico , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/genética , Criança , Feminino , Doenças do Cabelo/diagnóstico , Doenças do Cabelo/tratamento farmacológico , Doenças do Cabelo/genética , Humanos , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/genética , Doenças da Unha/diagnóstico , Doenças da Unha/tratamento farmacológico , Doenças da Unha/genética , ATPase Trocadora de Sódio-Potássio/genética
19.
J Med Food ; 21(3): 274-281, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29068758

RESUMO

During maturation, pancreatic islets achieve their full capacity to secrete insulin in response to glucose, undergo morphological changes in which alpha-cells decrease and beta-cell mass increases, and they acquire the normal alpha- and beta-cell proportion changes that are important for islet functions later in life. In rodents, the first week of postweaning is critical for islet maturation. Multiple studies have documented the detrimental effects of several conditions on pancreatic maturation; however, few studies have addressed the use of pharmacological agents to enhance islet maturation. Biotin might have a potential action on islet maturation. Pharmacological concentrations of biotin have been found to modify islet morphology and function. In a previous study, we found that mice fed a biotin-supplemented diet for 8 weeks after weaning showed an increase in basal and glucose stimulated insulin secretion, enlarged islet size, and modified islet structure. In the present study, we investigated the effect of biotin on maturation features during the first week postweaning. Female BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet for 1 week after weaning. Compared with the control, biotin-supplemented mice showed an increase in pancreatic islet number and area in addition to an augmented proportion of beta-cells in the islet. These effects were related to an increase in beta-cell proliferation. No differences were found in insulin secretion, blood glucose concentrations, or serum insulin levels. These results indicate that biotin supplementation is capable of affecting beta-cell proliferation and might be a therapeutic agent for establishing strategies for regenerative medicine.


Assuntos
Biotina/administração & dosagem , Diferenciação Celular , Proliferação de Células , Suplementos Nutricionais , Células Secretoras de Insulina/citologia , Ilhotas Pancreáticas/crescimento & desenvolvimento , Complexo Vitamínico B/administração & dosagem , Animais , Apoptose , Biotina/efeitos adversos , Biotina/metabolismo , Biotina/uso terapêutico , Glicemia/análise , Contagem de Células , Suplementos Nutricionais/efeitos adversos , Feminino , Insulina/sangue , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/metabolismo , Camundongos Endogâmicos BALB C , Tamanho do Órgão , Concentração Osmolar , Estado Pré-Diabético/prevenção & controle , Distribuição Aleatória , Técnicas de Cultura de Tecidos , Complexo Vitamínico B/efeitos adversos , Complexo Vitamínico B/metabolismo , Complexo Vitamínico B/uso terapêutico , Desmame
20.
Ann Clin Biochem ; 55(2): 216-226, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28406314

RESUMO

Background Biotin interference in streptavidin-based immunoassays causes widespread analytical distortions that may lead to clinical confusion, inappropriate patient management and, ultimately, adverse events. Its prevalence has increased recently due to the increased use of high-dose biotin therapy in specific patient groups (notably multiple sclerosis) and possibly the general community. Methods We have developed a method to deplete biotin from samples using the streptavidin-coated magnetic microparticles that are a component of most susceptible assays. Results We show that high concentrations of spiked biotin can be adequately depleted from serum using this approach, and that gross biochemical derangements can be restored to normality. We also show that biotin in samples derived from multiple sclerosis patients receiving 300 mg biotin daily can be adequately depleted to remove associated analytical interference and restore normal results. The method is applicable to competitive and sandwich immunoassays and importantly, because it does not change the volume of the sample, suitable for the measurement of free thyroid hormone assays. Application of the method does not significantly change the precision of measurement, and for the majority of analytes, the accuracy is not substantially altered. Conclusions Adopting this method enables laboratories to confirm biotin interference in the appropriate clinical setting. Moreover, it enables laboratories to remove the interference and report accurate and reliable results, without the need for patients to withhold beneficial therapy prior to blood tests. Until the biotin tolerance of susceptible assays is improved, our method gives laboratories a safe alternative for reporting results using streptavidin-based methods.


Assuntos
Biotina/isolamento & purificação , Materiais Revestidos Biocompatíveis/química , Imunoensaio/métodos , Estreptavidina/química , Artefatos , Biotina/sangue , Biotina/química , Biotina/uso terapêutico , Técnicas de Laboratório Clínico/métodos , Técnicas de Laboratório Clínico/normas , Humanos , Imunoensaio/normas , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/fisiopatologia , Testes de Função Tireóidea
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