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1.
J Chem Inf Model ; 64(7): 2467-2487, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-37774492

RESUMO

Carpophilus dimidiatus (Fabricius) (Nitidulidae) and Oryzaephilus mercator (L.) (Silvanidae) are insect pests that cause severe damage in important walnut growing regions in the northwest of Argentina. The current management approaches for these pests involve the use of unsafe phosphorus pesticides whose overuse have led to farmworker poisoning, pest resistance issues, and environmental contamination. Plant extracts, particularly essential oils, are an alternative source of insect control agents. Excito-repellent essential oils can be used to develop ecofriendly tools for managing the pest population without affecting quality and visual appearance of the stored walnuts. Laboratory studies were conducted to assess the excito-repellent effects of C. dimidiatus and O. mercator of 12 essential oils derived from aromatic plants used as food additives and traditional medicine in Argentina: Aloysia citrodora (AC), Aloysia gratissima (AG), Aloysia gratissima var. Gratissima (AGG), Blepharocalyx salicipholius (BS), Hyptis mutabilis (HM), Lippia junelliana (LJ), Lippia turbinata (LT), Mentha x piperita (MP), Minthostachys mollis (MM), Minthostachys verticillata (MV), Origanum vulgare(OV), and Rosmarinus officinalis (RO). The most bioactive EOs (ERijk ≥ 70%) were Aloysia gratissima var. Gratissima (AGG), Minthostachys verticillata, and Lippia junelliana. Their bioactivity profile and chemical space, characterized from GC-MS measures, Generalized Estimating Equations, and Hierarchical Cluster Analysis, revealed that they are mixtures of very functionalized molecules with physicochemical properties similar to those of insecticides with low residual property that enter the insect body through the respiratory system by inhalation. The AGG, MV, and LJ oils are promising as protective agents of walnut products. In our laboratory, studies of their formulations for use in integrated pest management programs are still ongoing.


Assuntos
Repelentes de Insetos , Inseticidas , Óleos Voláteis , Praguicidas , Verbenaceae , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Verbenaceae/química , Inseticidas/toxicidade , Repelentes de Insetos/farmacologia
2.
Drug Alcohol Depend ; 252: 110961, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37748425

RESUMO

BACKGROUND: Despite guidelines and recommendations, Wernicke's encephalopathy (WE) treatment lacks evidence, leading to clinical practice variability. AIMS: Given the overall lack of information on thiamine use for WE treatment, we analyzed data from a large, well-characterized multicenter sample of patients with WE, examining thiamine dosages; factors associated with the use of different doses, frequencies, and routes; and the influence of differences in thiamine treatment on the outcome. METHODS: This retrospective study was conducted with data from 443 patients from 21 centers obtained from a nationwide registry of the Spanish Society of Internal Medicine (from 2000 to 2012). Discharge codes and Caine criteria were applied for WE diagnosis, and treatment-related (thiamine dosage, frequency, and route of administration) demographic, clinical, and outcome variables were analyzed. RESULTS: We found marked variability in WE treatment and a low rate of high-dose intravenous thiamine administration. Seventy-eight patients out of 373 (20.9%) received > 300mg/day of thiamine as initial dose. Patients fulfilling the Caine criteria or presenting with the classic WE triad more frequently received parenteral treatment. Delayed diagnosis (after 24h hospitalization), the fulfillment of more than two Caine criteria at diagnosis, mental status alterations, and folic acid deficiency were associated significantly with the lack of complete recovery. Malnutrition, reduced consciousness, folic acid deficiency, and the lack of timely thiamine treatment were risk factors for mortality. CONCLUSIONS: Our results clearly show extreme variability in thiamine dosages and routes used in the management of WE. Measures should be implemented to ensure adherence to current guidelines and to correct potential nutritional deficits in patients with alcohol use disorders or other risk factors for WE.


Assuntos
Alcoolismo , Deficiência de Ácido Fólico , Deficiência de Tiamina , Encefalopatia de Wernicke , Humanos , Encefalopatia de Wernicke/diagnóstico , Encefalopatia de Wernicke/tratamento farmacológico , Alcoolismo/tratamento farmacológico , Estudos Retrospectivos , Deficiência de Ácido Fólico/complicações , Deficiência de Ácido Fólico/tratamento farmacológico , Tiamina/uso terapêutico , Deficiência de Tiamina/complicações , Deficiência de Tiamina/tratamento farmacológico
3.
Nat Prod Res ; 37(23): 4058-4062, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36622895

RESUMO

Essential oils from aerial parts of six aromatic plants were analysed by GC-MS. The major compounds identified were γ-terpinene (11.5%), cuminaldehyde (26.6%) and γ-terpinen-7-al (40.6%) in Cuminum cyminum, trans-anethol (95.2%) in Pimpinella anisum, α-pinene (11.6%), limonene (21.0%), ß-caryophyllene (22.3%) and α-humulene (16.7%) in Lippia integrifolia, limonene (40.8%) and artemisia ketone (19.3%) in Lippia junelliana, trans-ß-ocimene (15.6%), 4-ethyl-4-methyl-1-hexene (24.5%), trans-tagetone (20.5%) and verbenone (27.2%) in Tagetes minuta, 1,8-cineole (17.9%),elixene (10.3%) and spathulenol (13.8%) in Aloysia gratissima. Oils with strong insecticidal activity on Carpophilus dimidiatus and Oryzaephilus mercator were from P. anisum (LC50 = 4 µl/L; LC100 = 10 µl/L) and T. minuta (LC50=10.19-12.57 µl/L; LC100=20 µl/L). Scents of C. cyminum and L. junelliana were strong insecticides on O. mercator (LC50=7.02-7.17 µl/L; LC100=10.00-20.00 µl/L). The insecticidal activity was associated to the whole content of C10 molecules and oxygenated constituents. The P. anisum oil is promising as protective agent of nut products.


Assuntos
Besouros , Inseticidas , Óleos Voláteis , Animais , Óleos Voláteis/farmacologia , Limoneno , Inseticidas/farmacologia , Argentina
4.
Drug Alcohol Depend ; 230: 109186, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34864357

RESUMO

BACKGROUND: data regarding the association between Wernicke encephalopathy (WE) and alcoholic liver disease (ALD) are scarce in spite of alcohol consumption being the main risk factor for WE. AIMS: to describe the frequency of ALD in a cohort of patients diagnosed with WE and alcohol use disorders (AUDs) and to compare the characteristics of WE patients with and without ALD. METHODS: we conducted an observational study in 21 centers through a nationwide registry of the Spanish Society of Internal Medicine. WE Caine criteria were applied and demographic, clinical, and outcome variables were analyzed. RESULTS: 434 patients were included in the study, of which 372 were men (85.7%), and the mean age was 55 ± 11.8 years. ALD was present in 162 (37.3%) patients and we found a higher percentage of cases with tremor, flapping and hallucinations in the ALD group. A total of 22 patients (5.0%) died during admission (7.4% with ALD vs 3.7% without ALD; P = 0.087). Among the ALD patients, a relationship between mortality and the presence of anemia (Odds ratio [OR]=4.6 Confidence interval [CI]95% 1.1-18.8; P = 0.034), low level of consciousness (OR=4.9 CI95% 1.1-21.2; P = 0.031) and previous diagnosis of cancer (OR=10.3 CI95% 1.8-59.5; P = 0.009) was detected. Complete recovery was achieved by 27 patients with ALD (17.8%) and 71 (27.8%) without ALD (P = 0.030). CONCLUSION: the association of WE and ALD in patients with AUDs is frequent and potentially linked to differences in clinical presentation and to poorer prognosis, as compared to alcoholic patients with WE without ALD.


Assuntos
Alcoolismo , Hepatopatias Alcoólicas , Encefalopatia de Wernicke , Adulto , Idoso , Consumo de Bebidas Alcoólicas , Alcoolismo/complicações , Alcoolismo/epidemiologia , Estudos de Coortes , Humanos , Hepatopatias Alcoólicas/complicações , Hepatopatias Alcoólicas/epidemiologia , Masculino , Pessoa de Meia-Idade , Encefalopatia de Wernicke/complicações , Encefalopatia de Wernicke/diagnóstico , Encefalopatia de Wernicke/epidemiologia
5.
J Mol Graph Model ; 101: 107751, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32961479

RESUMO

The Quantitative Structure-Activity Relationships (QSAR) theory, which allows predicting the insecticidal activity of chemical compounds through calculations from the molecular structure, is applied on 23 essential oils composed of 402 structurally diverse compounds at different chemical compositions. A large number of 114,871 conformation-independent molecular descriptors are computed through different types of freely available open-source programs. Mixture descriptors are calculated based on molecular descriptors of the essential oil components and their composition. The best resulting three-descriptor linear regression models are established through the Replacement Method variable subset selection approach. The results obtained in the present work are interesting for predicting the fumigant activity of these essential oil complex mixtures, by means of simple non-conformational QSAR models.


Assuntos
Inseticidas , Óleos Voláteis , Conformação Molecular , Estrutura Molecular , Relação Quantitativa Estrutura-Atividade
6.
Neurología (Barc., Ed. impr.) ; 35(2): 75-81, mar. 2020. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-196781

RESUMO

INTRODUCCIÓN: Aunque la asociación de arteritis de la temporal e ictus isquémico no es frecuente, su diagnóstico y su manejo posterior plantean serias dificultades, requiriendo un alto índice de sospecha. MÉTODOS: Analizamos una serie de 6 pacientes con arteritis de la temporal confirmada por biopsia con ictus isquémico como forma de presentación. Discutimos las características clínicas y las dificultades en su valoración, su evolución a corto y largo plazo, el tratamiento realizado y la utilidad de las nuevas pruebas diagnósticas. RESULTADOS: Nuestra serie de 6 pacientes tenía una edad media de 68,3 años y el 50% eran mujeres. La mayoría de los pacientes asociaba síntomas sistémicos. No hubo diferencias en la afectación de territorio anterior y posterior. La RM y angio, el Doppler y la PET-TAC fueron muy útiles en el diagnóstico y la orientación terapéutica de los pacientes. El seguimiento medio fue de 26 meses y la evolución distó de ser benigna: el 33% quedó con Rankin ≥ 3, falleciendo un paciente. Además, 2 pacientes, tratados con corticoides a dosis plena, tuvieron nuevos ictus. Dos pacientes fueron tratados con angioplastia. CONCLUSIONES: El ictus provocado por la arteritis de células gigantes es una enfermedad potencialmente grave, que requiere una alta sospecha diagnóstica y un tratamiento corticoideo temprano. Los nuevos métodos diagnósticos ayudan a refinar la correcta evaluación de los pacientes y a determinar el tratamiento óptimo. El tratamiento endovascular puede ser una opción terapéutica válida en casos seleccionados


INTRODUCTION: Though uncommon, ischaemic stroke due to temporal arteritis carries serious difficulties for diagnosis and subsequent management and requires a high level of suspicion. METHODS: We analysed a series of 6 patients with biopsy-proven temporal arteritis presenting with ischaemic stroke. We discuss clinical characteristics, difficulties of assessment, short- and long-term progression, treatment, and the usefulness of new diagnostic techniques. RESULTS: Our sample of 6 patients had a mean age of 68.3 years; 50% were women. The majority of patients showed systemic symptoms. Anterior and posterior circulation were affected similarly. MRI angiography, Doppler sonography, and PET-CT proved to be very useful for diagnosis and treatment. Mean follow-up time was 26 months. Clinical outcomes were far from good: 33% scored ≥ 3 on the modified Rankin scale, including one death. Two patients had recurrent stroke despite treatment with full doses of corticosteroids, and 2 underwent angioplasty. CONCLUSIONS: Stroke caused by giant cell arteritis is a serious and potentially severe condition which requires a high level of suspicion and early treatment with corticosteroids. New diagnostic techniques contribute to refining patient assessment and identifying the optimal treatment. Endovascular treatment may be a valid therapeutic option in selected patients


Assuntos
Humanos , Masculino , Feminino , Idoso , Corticosteroides/uso terapêutico , Arterite de Células Gigantes , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Artérias Temporais/diagnóstico por imagem , Angioplastia , Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Acidente Vascular Cerebral/etiologia
7.
Neurologia (Engl Ed) ; 35(2): 75-81, 2020 Mar.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28869044

RESUMO

INTRODUCTION: Though uncommon, ischaemic stroke due to temporal arteritis carries serious difficulties for diagnosis and subsequent management and requires a high level of suspicion. METHODS: We analysed a series of 6 patients with biopsy-proven temporal arteritis presenting with ischaemic stroke. We discuss clinical characteristics, difficulties of assessment, short- and long-term progression, treatment, and the usefulness of new diagnostic techniques. RESULTS: Our sample of 6 patients had a mean age of 68.3 years; 50% were women. The majority of patients showed systemic symptoms. Anterior and posterior circulation were affected similarly. MRI angiography, Doppler sonography, and PET-CT proved to be very useful for diagnosis and treatment. Mean follow-up time was 26 months. Clinical outcomes were far from good: 33% scored≥3 on the modified Rankin scale, including one death. Two patients had recurrent stroke despite treatment with full doses of corticosteroids, and 2 underwent angioplasty. CONCLUSIONS: Stroke caused by giant cell arteritis is a serious and potentially severe condition which requires a high level of suspicion and early treatment with corticosteroids. New diagnostic techniques contribute to refining patient assessment and identifying the optimal treatment. Endovascular treatment may be a valid therapeutic option in selected patients.


Assuntos
Corticosteroides/uso terapêutico , Arterite de Células Gigantes , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Artérias Temporais/diagnóstico por imagem , Idoso , Angioplastia , Feminino , Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/diagnóstico por imagem , Humanos , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Espanha , Acidente Vascular Cerebral/etiologia
8.
Benef Microbes ; 10(5): 497-509, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31090458

RESUMO

Microbial metabolism in the gut may alter human bile acid metabolism in a way that beneficially affects lipid homeostasis and therefore cardiovascular disease risk. Deconjugation of bile acids by microbes is thought to be key to this mechanism but has yet to be characterised in blood and stool while observing lipid markers. The aim of this study was to determine the effect of 3 different probiotic strains on plasma and stool bile acids in the context of lipid and glucose metabolism. In this 18-week, randomised, double-blind crossover study, healthy adults (53±8 years) with a high waist circumference underwent a 1-week pre-baseline period and were then randomised to receive 1 capsule/day of Bacillus subtilis R0179 (2.5×109 cfu/capsule; n=39), Lactobacillus plantarum HA-119 (5×109 cfu/capsule; n=38), Bifidobacterium animalis subsp. lactis B94 (5×109 cfu/capsule; n=37) or placebo for 6 weeks. Following a 3-week washout and second pre-baseline week, participants were crossed to the other intervention for 6 weeks followed by a 1-week post-intervention period. Blood and stool samples were collected at the beginning and end of each intervention to measure bile acids, serum lipid profiles, and glucose and insulin levels. Data from the placebo intervention were combined for all participants for analyses. In obese participants, the difference (final-baseline) in the sum of deconjugated plasma bile acids was greater with consumption of B. subtilis (691±378 nmol/l, P=0.01) and B. lactis (380±165 nmol/l, P=0.04) than with placebo (98±176 nmol/l, n=57). No significant differences were observed for any probiotics for stool bile acids, serum lipids, blood glucose or insulin. These data suggest that B. subtilis and B. lactis had no effect on glucose metabolism or serum cholesterol but increased deconjugated plasma bile acids in obese individuals. Additional studies should be conducted to confirm these findings and explore potential mechanisms. This trial was registered at clinicaltrials.gov as NCT01879098.


Assuntos
Ácidos e Sais Biliares/sangue , Fármacos Gastrointestinais/administração & dosagem , Obesidade/terapia , Plasma/química , Probióticos/administração & dosagem , Adulto , Bacillus subtilis/crescimento & desenvolvimento , Bifidobacterium animalis/crescimento & desenvolvimento , Estudos Cross-Over , Método Duplo-Cego , Fezes/química , Feminino , Humanos , Lactobacillus plantarum/crescimento & desenvolvimento , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Resultado do Tratamento
9.
J Agric Food Chem ; 66(48): 12855-12865, 2018 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-30418029

RESUMO

Essential oils from six species of aromatic plants collected in the Catamarca Province of Argentina were evaluated for their chemical composition and repellent and insecticidal activities against beetles of the genus Carpophilus (Coleoptera: Nitidulidae) and Oryzaephilus (Coleoptera: Silvanidae) that infest the local walnut production. Experimental data were analyzed using generalized estimating equations, with normal distribution and the identity link function. From the spectral information from the tested essential oils, we worked their molecular modeling as mixtures by developing mixture descriptors ( Dmix) that combined the molecular descriptor of each component in the mixture ( d i) and its relative concentration ( x i), i.e., Dmix = f( d i, x i). The application of chemoinformatic approaches determined that a combination of mixture descriptors related to molecular size, branchedness, charge distribution, and electronegativity were useful to explain the bioactivity profile against Carpophilus spp. and Oryzaephilus spp. The reported models were rigorously validated using stringent statistical parameters and essential oils reported with repellent activity against other beetle species from the Nitidulidae and Silvanidae families. This model confirmed each essential oil as a repellent with a comparable performance to the experimental reports.


Assuntos
Besouros/efeitos dos fármacos , Repelentes de Insetos/química , Repelentes de Insetos/farmacologia , Juglans/parasitologia , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Doenças das Plantas/parasitologia , Animais , Argentina , Besouros/fisiologia , Nozes/parasitologia , Doenças das Plantas/prevenção & controle , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Relação Quantitativa Estrutura-Atividade
10.
Mayo Clin Proc ; 92(6): 899-907, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28578781

RESUMO

OBJECTIVE: To analyze the differences in characteristics and prognosis between alcoholic and nonalcoholic patients with Wernicke encephalopathy (WE). PATIENTS AND METHODS: A retrospective observational cohort of 468 patients diagnosed with WE with at least 2 Caine criteria was selected from all patients discharged with a diagnosis of WE from 21 medical centers in Spain from January 1, 2000, through December 31, 2012. Demographic, clinical, and outcome variables were described. RESULTS: Among the 468 patients, the most common risk factor was alcoholism (n=434 [92.7%]). More than one-third of patients (n=181 [38.7%]) had the classic WE triad of symptoms (ocular signs, cerebellar dysfunction, and confusion). Among 252 patients for whom magnetic resonance imaging data were available, 135 (53.6%) had WE-related lesions and 42 (16.7%) had cerebellar lesions. Of the 468 patients, 25 (5.3%) died during hospitalization. Alcoholic patients presented more frequently than nonalcoholic patients with cerebellar signs (P=.01) but less frequently with ocular signs (P=.02). Alcoholic patients had a significantly higher frequency of hyponatremia (P=.04) and decreased platelet count (P=.005) compared with nonalcoholics. Alcoholic patients were diagnosed earlier than nonalcoholics (median time to diagnosis, 1 vs 4 days; P=.001) and had shorter hospitalizations (13 vs 23 days; P=.002). CONCLUSION: Compared with nonalcoholic patients, alcoholic patients with WE are more likely to present with cerebellar signs and less likely to have ocular signs. Diagnosis may be delayed in nonalcoholic patients. Mortality in the present series was lower than described previously.


Assuntos
Alcoolismo/patologia , Encéfalo/patologia , Encefalopatia de Wernicke/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Espanha
11.
Benef Microbes ; 7(3): 327-36, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26839075

RESUMO

Psychological stress is associated with gastrointestinal (GI) distress. This secondary analysis from a randomised, double-blind, placebo-controlled study examined whether three different probiotics could normalise self-reported stress-associated GI discomfort and reduce overall self-reported stress. Undergraduate students (n=581) received Lactobacillus helveticus R0052, Bifidobacterium longum ssp. infantis R0033, Bifidobacterium bifidum R0071, or placebo. Participants self-reported 2 outcomes for a 6-week period, which included final academic exams: daily level of stress (0=no stress to 10=extremely stressed) and weekly three diarrhoea-related symptoms (DS, 1=no discomfort to 7=severe discomfort) using the GI Symptom Rating Scale. Self-reported stress was positively related to DS (P=0.0068). Mean DS scores were lower with B. bifidum versus placebo at week 2 at the average level of stress and the average body mass index (BMI). DS scores were lower with B. bifidum at week 5 versus week 0 and 1 and with B. infantis R0033 at week 6 versus week 0. DS scores were higher when antibiotics were used in the prior week with placebo (P=0.0092). DS were not different with or without antibiotic use with the probiotics. Only B. bifidum had an effect on self-reported stress scores (P=0.0086). The self-reported stress score was also dependent on hours of sleep per day where it decreased by 0.13 for each additional hour of sleep. During a stressful period, B. bifidum R0071 decreases DS and self-reported stress scores. This trial was registered at clinicaltrials.gov as NCT01709825.


Assuntos
Bifidobacterium bifidum/imunologia , Diarreia/patologia , Diarreia/terapia , Probióticos/administração & dosagem , Estresse Fisiológico , Bifidobacterium longum/imunologia , Método Duplo-Cego , Feminino , Humanos , Lactobacillus helveticus/imunologia , Masculino , Placebos/administração & dosagem , Estudantes , Inquéritos e Questionários , Resultado do Tratamento , Estados Unidos
12.
Transl Psychiatry ; 5: e537, 2015 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-25826112

RESUMO

Stress inoculation entails intermittent exposure to mildly stressful situations that present opportunities to learn, practice and improve coping in the context of exposure psychotherapies and resiliency training. Here we investigate behavioral and hormonal aspects of stress inoculation modeled in mice. Mice randomized to stress inoculation or a control treatment condition were assessed for corticosterone stress hormone responses and behavior during open-field, object-exploration and tail-suspension tests. Stress inoculation training sessions that acutely increased plasma levels of corticosterone diminished subsequent immobility as a measure of behavioral despair on tail-suspension tests. Stress inoculation also decreased subsequent freezing in the open field despite comparable levels of thigmotaxis in mice from both treatment conditions. Stress inoculation subsequently decreased novel-object exploration latencies and reduced corticosterone responses to repeated restraint. These results demonstrate that stress inoculation acutely stimulates glucocorticoid signaling and then enhances subsequent indications of active coping behavior in mice. Unlike mouse models that screen for the absence of vulnerability to stress or presence of traits that occur in resilient individuals, stress inoculation training reflects an experience-dependent learning-like process that resembles interventions designed to build resilience in humans. Mouse models of stress inoculation may provide novel insights for new preventive strategies or therapeutic treatments of human psychiatric disorders that are triggered and exacerbated by stressful life events.


Assuntos
Adaptação Psicológica/fisiologia , Comportamento Animal/fisiologia , Corticosterona/sangue , Estresse Psicológico/sangue , Estresse Psicológico/fisiopatologia , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Psicológico/psicologia
13.
Eur J Pharm Sci ; 62: 171-9, 2014 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-24909730

RESUMO

The inhibitory activity of 103 thiophene and 33 imidazopyridine derivatives against Polo-Like Kinase 1 (PLK1) expressed as pIC50 (-logIC50) was predicted by QSAR modeling. Multivariate linear regression (MLR) was employed to model the relationship between 0D and 3D molecular descriptors and biological activities of molecules using the replacement method (MR) as variable selection tool. The 136 compounds were separated into several training and test sets. Two splitting approaches, distribution of biological data and structural diversity, and the statistical experimental design procedure D-optimal distance were applied to the dataset. The significance of the training set models was confirmed by statistically higher values of the internal leave one out cross-validated coefficient of determination (Q2) and external predictive coefficient of determination for the test set (Rtest2). The model developed from a training set, obtained with the D-optimal distance protocol and using 3D descriptor space along with activity values, separated chemical features that allowed to distinguish high and low pIC50 values reasonably well. Then, we verified that such model was sufficient to reliably and accurately predict the activity of external diverse structures. The model robustness was properly characterized by means of standard procedures and their applicability domain (AD) was analyzed by leverage method.


Assuntos
Proteínas de Ciclo Celular/antagonistas & inibidores , Imidazóis/química , Modelos Moleculares , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Piridinas/química , Relação Quantitativa Estrutura-Atividade , Tiofenos/química , Inibidores de Proteínas Quinases/química , Reprodutibilidade dos Testes , Quinase 1 Polo-Like
14.
Acta Med Centro ; 7(3)2013.
Artigo em Espanhol | CUMED | ID: cum-54475

RESUMO

Se presenta un paciente con fiebre de origen desconocido, dolor abdominal, eosinofilia e imágenes nodulares hepáticas observadas en ultrasonido y tomografía axial computadorizada abdominal sugestivas, en un inicio, de hígado polimetastásico; hallazgos laparoscópicos en la glándula hepática mostraron una larva migrans visceral y, posteriormente, por la técnica de copa cónica, en las heces fecales aparecieron huevos de Fasciola hepática. Se decidió tratamiento con triclabendazol en dos dosis; la respuesta terapéutica fue buena(AU)


Assuntos
Humanos , Fasciola hepatica , Fasciolíase
15.
Curr Drug Saf ; 7(4): 282-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23062240

RESUMO

In our continuing efforts to find out acceptable Absorption, Distribution, Metabolization, Elimination and Toxicity (ADMET) properties of organic compounds, we establish linear QSAR models for the carcinogenic potential prediction of 1464 compounds taken from the "Galvez data set", that include many marketed drugs. More than a thousand of geometry-independent molecular descriptors are simultaneously analyzed, obtained with the softwares E-Dragon and Recon. The variable subset selection method employed is the Replacement Method, and also the improved version Enhanced Replacement Method. The established models are properly validated through an external test set of compounds, and by means of the Leave-Group-Out Cross Validation method. In addition, we apply the Y-Randomization strategy and analyze the Applicability Domain of the developed model. Finally, we compare the results obtained in present study with the previous ones from the literature. The novelty of present work relies on the development of an alternative predictive structure-carcinogenicity relationship in a large heterogeneous set of organic compounds, by only using a reduced number of geometry independent molecular descriptors.


Assuntos
Carcinógenos/toxicidade , Modelos Moleculares , Compostos Orgânicos/efeitos adversos , Testes de Carcinogenicidade , Carcinógenos/química , Humanos , Modelos Lineares , Compostos Orgânicos/química , Relação Quantitativa Estrutura-Atividade , Software
16.
Mol Inform ; 31(2): 181-8, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27476963

RESUMO

This work establishes a Quantitative Structure-Property Relationships (QSPR) based analysis with the aim of interpreting both the structural and electronic properties of the polar region of valproic acid and its derivatives, in terms of stabilizing intramolecular interactions related to the involved substituents. We consider ten different calculated properties as dependent variables for the QSPR models: the bond lengths C8 O9 , C8 X10 , and the percentage of s-character of the natural hybrids forming the bonding σ orbitals of the O9 C8 X10 region. The representative descriptors are the charges transferred during donor/acceptor interactions around this function calculated at the B3LYP/6-311++G**(6d,10f) level of theory, and/or hybrid descriptors derived therefrom. The models so established result simple, predictive, and have a quite direct physical meaning.

17.
J Phys Chem A ; 115(9): 1686-700, 2011 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-21309610

RESUMO

The conformational and electronic characteristics of the polar O(9)═C(8)-X(10) moiety in the anticonvulsant valproic acid (Vpa) drug and some of their amides and ester derivatives are analyzed at the B3LYP level using the 6-31+G(d,p) and 6-311++G(d,p) 6d,10f basis sets. Exploring the delocalization of the electron density of the O(9)═C(8)-X(10) moiety by means of ELF, NBO, and AIM calculations, we found that the bending away from coplanarity of the atoms in O(9)═C(8)-X(10) is accompanied by a three-dimensional arrangement of donor and acceptor proton units closing nearly planar pseudorings of four, five, and six members arising from stabilizing interactions around the O(9)═C(8)-X(10) backbone. From the structure-property relationship analysis, we explain the origin of the change in the structural parameters and atomic charges in the polar moiety.


Assuntos
Anticonvulsivantes/química , Elétrons , Ácido Valproico/química , Anticonvulsivantes/farmacologia , Eletrochoque , Modelos Moleculares , Conformação Molecular , Relação Estrutura-Atividade , Ácido Valproico/análogos & derivados , Ácido Valproico/farmacologia
18.
J Mol Model ; 16(2): 343-59, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19609575

RESUMO

The equilibrium structures, the planarity of the C(=O)X linkage and the nature of the chemical bond in the Y-C(=O)-XR(1)R(2) [where: Y= -CH-(CH(2)-CH(2)-CH(3))(2), X=N,O and R(1), R(2)= H; alkyl and aryl groups and lone pair electrons (lp)] molecular fragment of derivates of Valproic acid (Vpa) with antiepileptic activity were studied systematically by means of B3LYP calculations and topological analysis of the electron localization function (ELF). The covariance parameter cov[Omega(i), Omega(j)] reveals a dominating delocalization effect between the lone pair V(O(1)), V(X) and the electron density of the H-C and H-X(1) bonds resulting from the existence of not only non-conventional intramolecular hydrogen bonding patterns as C-H...O/N but also a weak closed-shell stabilizing interaction type arising from a dihydrogen bonding as C-H...H-N, where H...H contacts at a significantly shorter distance than twice the hydrogen atom van der Waals radius. The analyzed data derived from ELF domains were found to be in agreement with the known features and properties of the hydrogen bonding interactions discussed in this work.


Assuntos
Ácido Valproico/química , Amidas/química , Anticonvulsivantes , Inibidores Enzimáticos , Ésteres/química , Ligação de Hidrogênio , Modelos Teóricos
19.
Int J Nurs Stud ; 46(2): 189-96, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18990392

RESUMO

BACKGROUND: The information generated by nurses through standardised nursing languages is insufficiently evaluated and exploited, mainly in home care services, as is its potential impact on outcomes. OBJECTIVES: To find out how often nursing diagnoses are made during nursing home care visits, and to explore their relation with use of resources, mortality, institutionalisation and satisfaction. DESIGN: Observational, longitudinal follow-up study. SETTINGS: Home care services delivered by Primary Healthcare Districts in Málaga, Costa del Sol, Almería and Granada, in Spain. PARTICIPANTS: Patients and caregivers who initiated the Home Care Programme. METHODS: The accumulated incidence of nursing diagnosis was analysed over 34 months of follow-up. Diagnoses were made by nurse case managers in their daily practice. Several regression models were devised to analyse their linkage with the use of resources, mortality, institutionalisation and satisfaction. RESULTS: Two hundred and forty-seven subjects were included (129 patients and 118 caregivers). 93.8 had been diagnosed (2.8 diagnoses per subject). Risk of caregiver strain and mobility impairment accounted for 40% of total home visits (p=0.033). Significant differences were observed in the use of physiotherapy and rehabilitation services. The home visits for caregivers were, in 78% of cases, due to the recipient's baseline functional status. No relation was detected for institutionalisation or for patient satisfaction. There was a higher rate of anxiety diagnosed in the caregiver when the recipient was at greater risk for mortality (RR: 2.08 CI 95%: 1.26-3.42) (p=0.012). CONCLUSIONS: These data confirm results from other studies which find nursing diagnoses to be sound predictors of resources use. Their synergy with other case-mix systems in home care should be investigated.


Assuntos
Cuidadores , Alocação de Recursos para a Atenção à Saúde , Diagnóstico de Enfermagem , Avaliação de Resultados em Cuidados de Saúde , Idoso , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Espanha
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