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1.
Food Funct ; 9(12): 6599-6607, 2018 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-30489585

RESUMO

Nutritional compounds could be a safe and less expensive treatment for complications associated with obesity and metabolic syndrome (MetS). The aim of this study was to investigate the mechanism of action and the target tissues of a pepsin egg white hydrolysate (EWH) which had previously been demonstrated to improve some obesity-related disorders on a high-fat/high-glucose rat model. Wistar rats were used and divided into 3 groups: Control group (C), High-fat/high-glucose diet (MS) and high-fat/high-glucose diet + EWH (MSH). The rats were fed for 20 weeks and the EWH was administered from the 9th week. At the end of the study, white adipose tissue (WAT), brown adipose tissue (BAT) and muscle samples were collected for RT-qPCR analyses and immunohistochemistry. Our results showed a gene expression enhancement (2-fold basal level) in BAT of genes related to thermogenesis and mitochondrial dynamics. Mitochondrial DNA quantification and immunohistochemistry results also showed an increase of the mitochondrial content in this tissue. In conclusion, our results show the potential metabolic effect of this pepsin EWH by enhancing mitochondrial proliferation and gene expression related to thermogenesis in BAT. The EWH could be used as a functional food ingredient which is able to increase energy expenditure and counteract obesity-related MetS in a chronically obese society.


Assuntos
Tecido Adiposo Marrom/metabolismo , Proteínas do Ovo/metabolismo , Clara de Ovo/química , Síndrome Metabólica/dietoterapia , Síndrome Metabólica/genética , Dinâmica Mitocondrial , Pepsina A/química , Termogênese , Tecido Adiposo Branco , Animais , Biocatálise , Proteínas do Ovo/química , Metabolismo Energético , Humanos , Masculino , Síndrome Metabólica/metabolismo , Síndrome Metabólica/fisiopatologia , Hidrolisados de Proteína/química , Hidrolisados de Proteína/metabolismo , Ratos , Ratos Wistar
2.
Biochem Pharmacol ; 157: 134-147, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30076849

RESUMO

Cannabis sp. and their products (marijuana, hashish…), in addition to their recreational, industrial and other uses, have a long history for their use as a remedy for symptoms related with gastrointestinal diseases. After many reports suggesting these beneficial effects, it was not surprising to discover that the gastrointestinal tract expresses endogenous cannabinoids, their receptors, and enzymes for their synthesis and degradation, comprising the so-called endocannabinoid system. This system participates in the control of tissue homeostasis and important intestinal functions like motor and sensory activity, nausea, emesis, the maintenance of the epithelial barrier integrity, and the correct cellular microenvironment. Thus, different cannabinoid-related pharmacological agents may be useful to treat the main digestive pathologies. To name a few examples, in irritable bowel syndrome they may normalize dysmotility and reduce pain, in inflammatory bowel disease they may decrease inflammation, and in colorectal cancer, apart from alleviating some symptoms, they may play a role in the regulation of the cell niche. This review summarizes the main recent findings on the role of cannabinoid receptors, their synthetic or natural ligands and their metabolizing enzymes in normal gastrointestinal function and in disorders including irritable bowel syndrome, inflammatory bowel disease, colon cancer and gastrointestinal chemotherapy-induced adverse effects (nausea/vomiting, constipation, diarrhea).


Assuntos
Canabinoides/uso terapêutico , Gastroenteropatias/tratamento farmacológico , Animais , Canabinoides/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Endocanabinoides/metabolismo , Motilidade Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/fisiologia , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Dor Visceral/tratamento farmacológico , Dor Visceral/etiologia
3.
Neurogastroenterol Motil ; 30(11): e13399, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29971865

RESUMO

BACKGROUND: Vincristine is a commonly used chemotherapeutic agent. It is associated with undesirable digestive side effects. However, the impact of vincristine on gastrointestinal structure and motility or its long-term effects have not been deeply studied in animal models. This could be useful in order to develop therapeutic or preventive strategies for cancer patients. The aim of this study was to analyze such effects. METHODS: Rats received saline or vincristine (0.1 mg kg-1 , ip) daily for 10 days. Evaluations were performed during treatment and 2-6 weeks after. Somatic mechano-sensitivity was assessed using von Frey hairs. Gastrointestinal motor function was studied by means of radiographic still images and colonic propulsion of fecal pellets using fluoroscopy videos. Histological assessment of the gut morphology and immunohistochemistry for HuC/D and nNOS were performed in whole-mount myenteric plexus preparations. KEY RESULTS: Peripheral sensitivity was increased in animals treated with vincristine and did not subside 2 weeks after treatment finalization. Vincristine treatment inhibited gastrointestinal motility although this was recovered to normal values with time. Damage in the digestive wall after vincristine treatment was greater in the ileum than in the colon. Villi shortening (in ileum) and large inflammatory nodules still remained 2 weeks after treatment finalization. Finally, the proportion of nNOS-immunoreactive neurons was increased with vincristine and continued to be increased 2 weeks after treatment finalization. CONCLUSIONS AND INFERENCES: Vincristine alters gastrointestinal motility, peripheral sensitivity and mucosal architecture. Vincristine-induced neuropathy (somatic and enteric), intestinal mucosa damage and inflammatory infiltrations are relatively long-lasting.


Assuntos
Antineoplásicos Fitogênicos/toxicidade , Motilidade Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Vincristina/toxicidade , Animais , Masculino , Ratos , Ratos Wistar
4.
Food Funct ; 9(1): 78-86, 2018 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-29114652

RESUMO

The aim of this study was to examine the effect of a pepsin egg white hydrolysate (EWH) on metabolic complications using a high-fat/high-dextrose diet-induced Metabolic Syndrome (MetS) experimental model. Male Wistar rats were divided into 4 groups which received: standard diet and water (C), standard diet and a solution with 1 g kg-1 day-1 of EWH (CH), high-fat/high-dextrose diet and water (MS), and high-fat/high-dextrose diet and a solution with 1 g kg-1 day-1 of EWH (MSH). EWH consumption normalized body weight gain; abdominal obesity and peripheral neuropathy developed in MetS animals, and adipose tissue and liver weight, as well as plasma glucose were reduced. Oxidative stress and inflammation biomarkers were normalized in MSH animals. In conclusion, the oral administration of EWH could be used as a functional food ingredient to improve some complications associated with MetS induced by unhealthy diets.


Assuntos
Proteínas do Ovo/metabolismo , Clara de Ovo/química , Síndrome Metabólica/dietoterapia , Hidrolisados de Proteína/metabolismo , Tecido Adiposo/metabolismo , Animais , Biocatálise , Dieta Hiperlipídica/efeitos adversos , Proteínas do Ovo/química , Glucose/efeitos adversos , Glucose/metabolismo , Humanos , Fígado/metabolismo , Masculino , Síndrome Metabólica/metabolismo , Estresse Oxidativo , Pepsina A/química , Ratos , Ratos Wistar
5.
Neurologia (Engl Ed) ; 33(5): 290-300, 2018 Jun.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27349151

RESUMO

INTRODUCTION: The objective of the EPICON Project is to develop a set of recommendations on how to adequately switch from carbamazepine (CBZ) and oxcarbazepine (OXC) to eslicarbazepine acetate (ESL) in some patients with epilepsy. METHODS: A steering committee drafted a questionnaire of 56 questions regarding the transition from CBZ or OXC to ESL in clinical practice (methodology and change situation). The questionnaire was then distributed to 54 epilepsy experts in 2 rounds using the Delphi method. An agreement/disagreement consensus was defined when a median ≥ 7 points or ≤ 3 was achieved, respectively, and a relative interquartile range ≤ 0.40. We analysed the results obtained to reach our conclusions. RESULTS: Our main recommendations were the following: switching from CBZ to ESL must be carried out over a period of 1 to 3 weeks with a CBZ:ESL dose ratio of 1:1.3 and is recommended for patients who frequently forget to take their medication, those who work rotating shifts, polymedicated patients, subjects with cognitive problems, severe osteoporosis-osteopaenia, dyslipidaemia, or liver disease other than acute liver failure, as well as for men with erectile dysfunction caused by CBZ. The transition from OXC to ESL can take place overnight with an OXC:ESL dose ratio of 1:1 and it is recommended for patients who frequently forget to take their medication, those who work rotating shifts, polymedicated patients, or those with cognitive problems. The transition was not recommended for patients with prior rash due to CBZ or OXC use. CONCLUSION: The EPICON Project offers a set of recommendations about the clinical management of switching from CBZ or OXC to ESL, using the Delphi method.


Assuntos
Consenso , Dibenzazepinas/uso terapêutico , Substituição de Medicamentos/métodos , Epilepsia/tratamento farmacológico , Guias como Assunto , Bloqueadores do Canal de Sódio Disparado por Voltagem/uso terapêutico , Anticonvulsivantes/uso terapêutico , Carbamazepina/análogos & derivados , Carbamazepina/uso terapêutico , Técnica Delfos , Humanos , Neurologistas , Oxcarbazepina , Inquéritos e Questionários
6.
Int J Biol Macromol ; 105(Pt 2): 1358-1368, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28735006

RESUMO

Chitin is one of the most abundant natural polysaccharides in the world and it is mainly used for the production of chitosan by a deacetylation process. Chitosan is a bioactive polymer with a wide variety of applications due to its functional properties such as antibacterial activity, non-toxicity, ease of modification, and biodegradability. This review summarizes the most common chitosan processing methods and highlights some applications of chitosan in various industrial and biomedical fields. Finally, environmental concerns of chitosan-based films, considering the stages from raw materials extraction up to the end of life after disposal, are also discussed with the aim of finding more eco-friendly alternatives.


Assuntos
Quitosana , Animais , Materiais Biocompatíveis , Quitosana/química , Quitosana/farmacologia , Meio Ambiente , Humanos
7.
Seizure ; 48: 53-56, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28419947

RESUMO

PURPOSE: Eslicarbazepine-acetate (ESL) is a third generation antiepileptic drug licensed as adjunctive therapy in adults with focal seizures. Efficacy and safety of ESL have been established in real-life setting. However, data about outcomes in elderly patients are scarce. Primary endpoint was to evaluate outcomes of ESL in elderly patients. METHOD: This was a retrospective survey that included patients >65years with focal seizures who started ESL between January 2010 and July 2012 at 12 Spanish Hospitals. ESL was prescribed individually according to real-life practice. Efficacy and safety were evaluated over 1year. These patients were included within the bigger study ESLIBASE. RESULTS: We included 29 patients, most of them males (18). Mean age was 71.2 year-old and epilepsy evolution was 20 years. Eighteen were pharmacorresistant at baseline. At 12 months, the mean dose was 850mg/day, the retention rate 69%, the responder rate 62% and 24.1% were seizure-free. At 12 months, 16 patients (55.2%) had ≥1 adverse effect (AE), that led to discontinuation in 7 patients. Dizziness, nausea and ataxia were the most common AEs. The tolerability profile improved in 4/5 patients who switched from carbamazepine (CBZ) or oxcarbazepine (OXC) to ESL due to AEs. CONCLUSIONS: ESL was well-tolerated and effective in elderly patients in a real-life setting over 1year, with a dose around 800mg/day. AE effects improved in most of who switched from CBZ or OXC to ESL.


Assuntos
Anticonvulsivantes/uso terapêutico , Dibenzazepinas/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/efeitos adversos , Dibenzazepinas/efeitos adversos , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
8.
Artigo em Inglês | MEDLINE | ID: mdl-28261911

RESUMO

BACKGROUND: Gastrointestinal adverse effects occurring during cancer chemotherapy are well known and feared; those persisting once treatment has finished are relatively unknown. We characterized the alterations occurring in the rat small intestine, after repeated treatment with cisplatin. METHODS: Male Wistar rats received saline or cisplatin (2 mg kg-1  week-1 , for 5 weeks, ip). Gastric motor function was studied non-invasively throughout treatment (W1-W5) and 1 week after treatment finalization (W6). During W6, upper gastrointestinal motility was also invasively studied and small intestinal samples were collected for histopathological and molecular studies. Structural alterations in the small intestinal wall, mucosa, submucosa, muscle layers, and lymphocytic nodules were histologically studied. Periodic acid-Schiff staining and immunohistochemistry for Ki-67, chromogranin A, and neuronal-specific enolase were used to detect secretory, proliferating, endocrine and neural cells, respectively. The expression of different markers in the tunica muscularis was analyzed by RT/qPCR. KEY RESULTS: Repeated cisplatin induced motility alterations during and after treatment. After treatment (W6), the small intestinal wall showed histopathological alterations in most parameters measured, including a reduction in the thickness of circular and longitudinal muscle layers. Expression of c-KIT (for interstitial cells of Cajal), nNOS (for inhibitory motor neurons), pChAT, and cChAT (for excitatory motor neurons) increased significantly (although both ChATs to a lesser extent). CONCLUSIONS & INFERENCES: Repeated cisplatin induces relatively long-lasting gut dysmotility in rat associated with important histopathological and molecular alterations in the small intestinal wall. In cancer survivors, the possible chemotherapy-induced histopathological, molecular, and functional intestinal sequelae should be evaluated.


Assuntos
Cisplatino/toxicidade , Motilidade Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/toxicidade , Cisplatino/administração & dosagem , Motilidade Gastrointestinal/fisiologia , Mucosa Intestinal/fisiopatologia , Intestino Delgado/fisiopatologia , Masculino , Ratos , Ratos Wistar
10.
Artigo em Inglês | MEDLINE | ID: mdl-27686064

RESUMO

BACKGROUND: The antineoplastic drug 5-fluoruracil (5-FU) is a pirimidine analog, which frequently induces potentially fatal diarrhea and mucositis. Cannabinoids reduce gastrointestinal motility and secretion and might prevent 5-FU-induced gut adverse effects. Here, we asked whether cannabinoids may prevent diarrhea and mucositis induced by 5-FU in the rat. METHODS: Male Wistar rats received vehicle or the non-selective cannabinoid agonist WIN 55,212-2 (WIN; 0.5 mg kg-1 injection-1 , 1 injection day-1 , 4 consecutive days) by intraperitoneal (ip) route; on the first 2 days, animals received also saline or 5-FU (150 mg kg-1 injection-1 , cumulative dose of 300 mg kg-1 ). Gastrointestinal motor function was radiographically studied after barium contrast intragastric administration on experimental days 1 and 4. Structural alterations of the stomach, small intestine and colon were histologically studied on day 4. PAS staining and immunohistochemistry for Ki67, chromogranin A and CD163 were used to detect secretory, proliferating, and endocrine cells, and activated macrophages respectively. KEY RESULTS: As shown radiographically, 5-FU induced significant gastric emptying delay (on days 1 and 4) and diarrhea (on day 4). WIN did not significantly alter the motility curves obtained for either control or 5-FU-treated animals but tended to reduce the severity of 5-FU-induced diarrhea and increased permanence of barium from day 1 to the beginning of day 4 in 5-FU-treated animals. 5-FU-induced mucositis was severe and not counteracted by WIN. CONCLUSIONS AND INFERENCES: 5-FU-induced diarrhea, but not mucositis, was partly prevented by WIN at a low dose. Cannabinoids might be useful to prevent chemotherapy-induced diarrhea.


Assuntos
Antineoplásicos/toxicidade , Canabinoides/uso terapêutico , Diarreia/prevenção & controle , Fluoruracila/toxicidade , Mucosa Intestinal/efeitos dos fármacos , Mucosite/prevenção & controle , Animais , Canabinoides/farmacologia , Diarreia/induzido quimicamente , Diarreia/patologia , Motilidade Gastrointestinal/efeitos dos fármacos , Motilidade Gastrointestinal/fisiologia , Mucosa Intestinal/patologia , Masculino , Mucosite/induzido quimicamente , Mucosite/diagnóstico por imagem , Ratos , Ratos Wistar
11.
Acta Neurol Scand ; 136(3): 254-264, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27935017

RESUMO

PURPOSE: Evaluate real-life experience with eslicarbazepine acetate (ESL) after first monotherapy failure in a large series of patients with focal epilepsy. METHOD: Multicentre, retrospective, 1-year, observational study in patients older than 18 years, with focal epilepsy, who had failed first antiepileptic drug monotherapy and who received ESL. Data from clinical records were analysed at baseline, 3, 6 and 12 months to assess effectiveness and tolerability. RESULTS: Eslicarbazepine acetate was initiated in 253 patients. The 1-year retention rate was 92.9%, and the final median dose of ESL was 800 mg. At 12 months, 62.3% of patients had been seizure free for 6 months; 37.3% had been seizure free for 1 year. During follow-up, 31.6% of the patients reported ESL-related adverse events (AEs), most commonly somnolence (8.7%) and dizziness (5.1%), and 3.6% discontinued due to AEs. Hyponatraemia was observed in seven patients (2.8%). After starting ESL, 137 patients (54.2%) withdrew the prior monotherapy and converted to ESL monotherapy; 75.9% were seizure free, 87.6% were responders, 4.4% worsened, and 23.4% reported ESL-related AEs. CONCLUSION: Use of ESL after first monotherapy failure was associated with an optimal seizure control and tolerability profile. Over half of patients were converted to ESL monotherapy during follow-up.


Assuntos
Anticonvulsivantes/efeitos adversos , Dibenzazepinas/efeitos adversos , Tontura/etiologia , Epilepsias Parciais/tratamento farmacológico , Hiponatremia/etiologia , Vertigem/etiologia , Adulto , Idoso , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/uso terapêutico , Dibenzazepinas/administração & dosagem , Dibenzazepinas/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
Epilepsy Res ; 126: 201-10, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27521586

RESUMO

BACKGROUND: Real-world data of current antiepileptic drugs (AEDs) used to treat focal seizures is of importance to understand the efficacy and safety outside of the clinical trial setting. Here we report real-world data from a large series of patients treated with perampanel for 1year. METHODS: FYDATA was a multicentre, retrospective, 1-year observational study assessing the efficacy and safety of adjuvant perampanel in patients ≥12 years of age with focal epilepsy in a real-world setting. At 12 months, the proportion of patients who were seizure free, median percentage seizure reduction, proportion of responders, retention rate and proportion of patients with adverse events (AEs) were assessed. Analyses were also performed to identify any patient-, medication- and disease-related factors associated with a large clinical response or carry a risk for AEs. RESULTS: A total of 464 patients were included in the study with a retention rate of 60.6% at 1year. The mean number of prior AEDs was 7.8. The median percentage reduction in overall seizures was 33.3% (75% for secondary generalised seizures) after 1year, with 7.2% of patients achieving seizure freedom. Furthermore, patients on non-enzyme-inducing AEDs were more likely to achieve seizure freedom, and logistic regression revealed that patients aged ≥65 years, those with epilepsy due to a vascular aetiology and those who had received fewer prior AEDs showed a better clinical response to perampanel. A total of 62.9% of the patients experienced AEs at 12 months; dizziness, somnolence and irritability were the most frequent AEs. Patients with prior psychiatric comorbidities (hyperactivity and personality disorder) were more likely to experience psychiatric AEs with perampanel, and slower titration schedules were associated with less AEs overall. CONCLUSION: Perampanel, for the treatment of focal epilepsy in a real-world setting in a refractory population, over 1year, demonstrates a similar efficacy and safety profile to that observed in clinical trials. Our results have implications for the optimisation of perampanel use in a clinical setting.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Piridonas/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/efeitos adversos , Criança , Comorbidade , Epilepsias Parciais/complicações , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Transtornos Mentais/complicações , Pessoa de Meia-Idade , Nitrilas , Piridonas/efeitos adversos , Estudos Retrospectivos , Convulsões/complicações , Convulsões/tratamento farmacológico , Resultado do Tratamento , Adulto Jovem
13.
PLoS One ; 11(3): e0151193, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26985993

RESUMO

The aim of this work was to evaluate the effect of the administration of egg white hydrolysates on obesity-related disorders, with a focus on lipid metabolism, inflammation and oxidative stress, in Zucker fatty rats. Obese Zucker rats received water, pepsin egg white hydrolysate (750 mg/kg/day) or Rhizopus aminopeptidase egg white hydrolysate (750 mg/kg/day) for 12 weeks. Lean Zucker rats received water. Body weight, solid and liquid intakes were weekly measured. At the end of the study, urine, faeces, different organs and blood samples were collected. The consumption of egg white hydrolysed with pepsin significantly decreased the epididymal adipose tissue, improved hepatic steatosis, and lowered plasmatic concentration of free fatty acids in the obese animals. It also decreased plasma levels of tumor necrosis factor-alpha and reduced oxidative stress. Pepsin egg white hydrolysate could be used as a tool to improve obesity-related complications.


Assuntos
Clara de Ovo , Fígado Gorduroso/tratamento farmacológico , Inflamação/tratamento farmacológico , Obesidade/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/patologia , Animais , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Clara de Ovo/química , Fígado Gorduroso/complicações , Fígado Gorduroso/patologia , Hidrólise , Inflamação/complicações , Inflamação/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Obesidade/complicações , Obesidade/patologia , Pepsina A/química , Ratos Zucker
14.
Epilepsy Res ; 108(7): 1243-52, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24908564

RESUMO

BACKGROUND: Eslicarbazepine acetate (ESL) is a new antiepileptic drug (AED) licensed as adjunctive therapy in adults with partial-onset or focal seizures. OBJECTIVE: To evaluate in a clinical practice setting the long-term efficacy and safety of ESL in patients with focal seizures. METHODS: ESLIBASE was a retrospective study that included all patients with focal seizures who started ESL between January 2010 and July 2012 at 12 hospitals. ESL was prescribed individually according to real-life practice. Efficacy and safety were evaluated over 1 year. Switching from carbamazepine (CBZ) and oxcarbazepine (OXC) was assessed. RESULTS: Three hundred and twenty-seven patients were included; 78% of patients were taking ≥2 other AEDs at baseline. Most (87%) began ESL because of poor seizure control and 13% because of adverse events (AEs) with CBZ or OXC. After 1 year, 237 patients (72.4%) remained on ESL. At 3, 6 and 12 months, the responder rate was 46.3%, 57.9%, and 52.5%, and 21.0%, 28.0%, and 25.3% of patients were seizure free. The responder rate significantly increased when ESL was combined with a non-sodium channel-targeting drug (non-SC drug) (66.7%) versus an SC drug (47.7%; p<0.001). At 12 months, 40.7% of patients had ≥1 AE; AEs led to treatment discontinuation in 16.2%. Dizziness, nausea, and somnolence were the most common AEs. The tolerability profile improved in >50% of the patients who switched from CBZ or OXC to ESL because of AEs. CONCLUSIONS: ESL was well tolerated and effective in a real-world setting over 1 year. Side-effect profile improved when OXC and CBZ recipients were switched to ESL.


Assuntos
Dibenzazepinas/uso terapêutico , Convulsões/tratamento farmacológico , Bloqueadores do Canal de Sódio Disparado por Voltagem/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estatísticas não Paramétricas , Fatores de Tempo , Adulto Jovem
15.
Chemistry ; 19(21): 6862-73, 2013 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-23536477

RESUMO

The attack of hydroxyl radicals on aromatic amino acid side chains, namely phenylalanine, tyrosine, and tryptophan, have been studied by using density functional theory. Two reaction mechanisms were considered: 1) Addition reactions onto the aromatic ring atoms and 2) hydrogen abstraction from all of the possible atoms on the side chains. The thermodynamics and kinetics of the attack of a maximum of two hydroxyl radicals were studied, considering the effect of different protein environments at two different dielectric values (4 and 80). The obtained theoretical results explain how the radical attacks take place and provide new insight into the reasons for the experimentally observed preferential mechanism. These results indicate that, even though the attack of the first (·)OH radical on an aliphatic C atom is energetically favored, the larger delocalization and concomitant stabilization that are obtained by attack on the aromatic side chain prevail. Thus, the obtained theoretical results are in agreement with the experimental evidence that the aromatic side chain is the main target for radical attack and show that the first (·)OH radical is added onto the aromatic ring, whereas a second radical abstracts a hydrogen atom from the same position to obtain the oxidized product. Moreover, the results indicate that the reaction can be favored in the buried region of the protein.


Assuntos
Aminoácidos Aromáticos/química , Radical Hidroxila/química , Modelos Químicos , Estrutura Molecular , Oxirredução , Fenilalanina/química , Proteínas/química , Estereoisomerismo , Termodinâmica , Triptofano/química , Tirosina/química
17.
Neurologia ; 23(3): 152-6, 2008 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-18370334

RESUMO

INTRODUCTION: There is a strong association between the e4 allele of apolipoprotein E (APOE) and Alzheimer's disease (AD). This converts this allele into a risk factor for the development of AD. The association between APOE4 and dementia with Lewy bodies (DLB) is under discussion. In DLB, the presence of APOE4 has been related with a greater amount of senile plaques and neurofibrillary tangles. METHOD: This is a case-control study in which the APOE genotype was determined using the modified PCR technique of Wenham in 306 patients with diagnosis of probably AD, NINCDS-ADRDA criteria, 58 cases of probably DLB, McKeith et al. consensus criteria (1996), all of them with SPECT with pathological 123I-FP-CIT and 80 normal controls (NC) having similar age and gender distribution. RESULTS: The frequency of alleles was: DLB group epsilon4: 16%; epsilon3: 75%; epsilon2: 9%; AD: epsilon4: 32%; epsilon3: 67%; epsilon2: 1%; and in the normal control group: epsilon4: 12%; epsilon3: 83%; epsilon2: 5%. The percentage of alleles in both genders was similar in the three groups. CONCLUSIONS: APOE4 percentage in DLB group (16%) was lower than in AD group (32%), and similar to the control group (12%). Considering that the presence of morphopathological Alzheimer type alterations in DBL, essentially neurofibrillary tangles, is inversely correlated with the presence of Parkinsonian signs, this group may represent pure forms of the disease, although the lack of neuropathological demonstration does not make it possible to confirm this hypothesis.


Assuntos
Apolipoproteína E4 , Doença por Corpos de Lewy/genética , Doença por Corpos de Lewy/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Apolipoproteína E4/genética , Apolipoproteína E4/metabolismo , Radioisótopos de Carbono/metabolismo , Feminino , Frequência do Gene , Genótipo , Humanos , Radioisótopos do Iodo/metabolismo , Doença por Corpos de Lewy/diagnóstico , Doença por Corpos de Lewy/patologia , Masculino , Tomografia Computadorizada de Emissão de Fóton Único , Tropanos/metabolismo
18.
Radiologia ; 48(2): 79-86, 2006.
Artigo em Espanhol | MEDLINE | ID: mdl-17058373

RESUMO

OBJECTIVES: Cerebral venous thrombosis (CVT) is an uncommon condition. Its variable, unspecific clinical presentation causes delays in diagnosis. We analyze the validity of different neuroimaging techniques, including CT, MRI, MR angiography, and conventional angiography in the diagnosis of CVT. MATERIAL AND METHODS: We review the imaging findings of 12 patients with the final diagnosis of CVT. All 12 patients underwent CT as the initial imaging test; all 12 underwent MRI; 11 underwent MR angiography; and 4 underwent conventional angiography. Visualization of the thrombus or filling defects in the affected vessel were considered direct signs of CVT, whereas findings compatible with venous infarction were considered indirect signs. RESULTS: Of the 12 CT examinations, 4 showed direct signs, 2 indirect signs, and 6 only normal findings. Indirect signs of CVT were seen on follow-up CT in three of the patients with normal initial CT examination. CT failed to show the real extent of the process except in one case in which a cortical vein was affected. MRI detected thrombi in the affected territory in 6 cases; the empty delta sign was seen in 2 and signs of venous infarction in 8. MRI failed to diagnose CVT in one case. MR angiography showed direct signs of CVT in all cases, even without intravenous contrast, and the results were similar to those seen at conventional angiography. More than two locations were affected in 11 patients. CONCLUSIONS: At CT, indirect signs of CVT are seen, although sometimes not immediately. Direct signs can be so subtle that they can only be interpreted with experience. Furthermore, CT does not show the real extent of the process. Nevertheless, given its availability, contrast-enhanced CT should be the primary imaging test, both to rule out other possibilities and to indicate other neuroimaging studies, in this case MRI and MR angiography. The results obtained when these two techniques are performed simultaneously, even without contrast administration, are sufficient for diagnosis and are comparable to those at conventional angiography, but without the risks entailed and without exposing the patient to ionizing radiation.


Assuntos
Trombose Intracraniana/diagnóstico , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Trombose Venosa/diagnóstico , Adulto , Feminino , Humanos , Masculino
19.
Radiología (Madr., Ed. impr.) ; 48(2): 79-86, mar. 2006. ilus, tab
Artigo em Es | IBECS | ID: ibc-044146

RESUMO

Objetivos. La trombosis venosa cerebral (TVC) es una patología poco frecuente. Su presentación clínica es inespecífica y variable, lo que ocasiona retrasos en el diagnóstico. Analizamos la validez de las diferentes pruebas de neuroimagen, tomografía computarizada (TC), resonancia magnética (RM), angio-resonancia magnética (RMV) y angiografía, en el diagnóstico de TVC. Material y métodos. Estudio retrospectivo sobre 12 pacientes con diagnóstico final de TVC. Se realizó TC, que fue la prueba inicial, y RM a todos los pacientes, a 11 RMV y en 4 ocasiones se hizo angiografía. Se valoraron como signos directos la visualización del trombo o defectos de repleción en el vaso afecto y como signo indirecto la identificación de hallazgos compatibles con infarto venoso. Resultados. De las 12 TC, 4 mostraron signos directos, 2 indirectos y 6 fueron normales; de éstas, en 3 pacientes se objetivaron signos indirectos en TC evolutivos. No mostró la extensión real del proceso salvo en un caso de afectación localizada de una vena cortical. En la RM se objetivó ocupación de los vasos del territorio venosos afecto en 6 casos, en 2 se apreció el signo del delta vacío y en 8 signos de infarto venoso. En una ocasión no fue diagnóstica. En todas las RMV se visualizaron signos directos de TVC, incluso sin contraste intravenoso. Los resultados fueron similares a los de las angiografías. Once pacientes presentaban afectación de más de 2 localizaciones. Conclusiones. La TC pone de manifiesto signos indirectos, a veces de modo tardío, y signos directos tan sutiles que requieren experiencia para ser interpretados. Además no valora la extensión real del proceso. De todos modos debe utilizarse como técnica de primer nivel, con contraste intravenoso, dada su disponibilidad en la mayoría de los centros, para excluir otras causas y servir para la indicación de otras pruebas de neuroimagen, en este caso RM y RMV. Los resultados obtenidos con la realización simultánea de ambas son equiparables a los de la angiografía, evita los riesgos de esta técnica, no expone al paciente a radiaciones ionizantes y es diagnóstica incluso sin la administración de contraste


Objectives. Cerebral venous thrombosis (CVT) is an uncommon condition. Its variable, unspecific clinical presentation causes delays in diagnosis. We analyze the validity of different neuroimaging techniques, including CT, MRI, MR angiography, and conventional angiography in the diagnosis of CVT. Material and methods. We review the imaging findings of 12 patients with the final diagnosis of CVT. All 12 patients underwent CT as the initial imaging test; all 12 underwent MRI; 11 underwent MR angiography; and 4 underwent conventional angiography. Visualization of the thrombus or filling defects in the affected vessel were considered direct signs of CVT, whereas findings compatible with venous infarction were considered indirect signs. Results. Of the 12 CT examinations, 4 showed direct signs, 2 indirect signs, and 6 only normal findings. Indirect signs of CVT were seen on follow-up CT in three of the patients with normal initial CT examination. CT failed to show the real extent of the process except in one case in which a cortical vein was affected. MRI detected thrombi in the affected territory in 6 cases; the empty delta sign was seen in 2 and signs of venous infarction in 8. MRI failed to diagnose CVT in one case. MR angiography showed direct signs of CVT in all cases, even without intravenous contrast, and the results were similar to those seen at conventional angiography. More than two locations were affected in 11 patients. Conclusions. At CT, indirect signs of CVT are seen, although sometimes not immediately. Direct signs can be so subtle that they can only be interpreted with experience. Furthermore, CT does not show the real extent of the process. Nevertheless, given its availability, contrast-enhanced CT should be the primary imaging test, both to rule out other possibilities and to indicate other neuroimaging studies, in this case MRI and MR angiography. The results obtained when these two techniques are performed simultaneously, even without contrast administration, are sufficient for diagnosis and are comparable to those at conventional angiography, but without the risks entailed and without exposing the patient to ionizing radiation


Assuntos
Masculino , Feminino , Humanos , Trombose Intracraniana/diagnóstico , Tomografia Computadorizada por Raios X , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Angiografia Cerebral , Estudos Retrospectivos
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