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Enterotoxigenic Escherichia coli (ETEC) is the primary etiologic agent of traveler's diarrhea and a major cause of diarrheal disease and death worldwide, especially in infants and young children. Despite significant efforts over the past several decades, an affordable vaccine that appreciably decreases mortality and morbidity associated with ETEC infection among children under the age of 5 years remains an unmet aspirational goal. Here, we describe robust, cost-effective biosynthetic routes that leverage glycoengineered strains of non-pathogenic E. coli or their cell-free extracts for producing conjugate vaccine candidates against two of the most prevalent O serogroups of ETEC, O148 and O78. Specifically, we demonstrate site-specific installation of O-antigen polysaccharides (O-PS) corresponding to these serogroups onto licensed carrier proteins using the oligosaccharyltransferase PglB from Campylobacter jejuni. The resulting conjugates stimulate strong O-PS-specific humoral responses in mice and elicit IgG antibodies that possess bactericidal activity against the cognate pathogens. We also show that one of the prototype conjugates decorated with serogroup O148 O-PS reduces ETEC colonization in mice, providing evidence of vaccine-induced mucosal protection. We anticipate that our bacterial cell-based and cell-free platforms will enable creation of multivalent formulations with the potential for broad ETEC serogroup protection and increased access through low-cost biomanufacturing.
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Background: Inappropriate antibiotic use among outpatients is recognized as the primary driver of antibiotic resistance. A proper understanding of appropriate antibiotic usage and associated factors helps to determine and limit inappropriateness. We aimed to identify the rate of appropriate use of antibiotics and identify factors associated with the inappropriate prescriptions. Methods: We conducted a cross-sectional descriptive study in outpatient antibiotic use at a hospital in Can Tho City, Vietnam, from August 1, 2019, to January 31, 2020. Data were extracted from all outpatient prescriptions at the Medical Examination Department and analyzed by SPSS 18 and Chi-squared tests, with 95% confidence intervals. The rationale for antibiotic use was evaluated through antibiotic selection, dose, dosing frequency, dosing time, interactions between antibiotics and other drugs, and general appropriate usage. Results: A total of 420 prescriptions were 51.7% for females, 61.7% with health insurance, and 44.0% for patients with one comorbid condition. The general appropriate antibiotic usage rate was 86.7%. Prescriptions showed that 11.0% and 9.5% had a higher dosing frequency and dose than recommended, respectively; 10.2% had an inappropriate dosing time; 3.1% had drug interactions; and only 1.7% had been prescribed inappropriate antibiotics. The risk of inappropriate antibiotic use increased in patients with comorbidities and antibiotic treatment lasting >7 days (p < 0.05). Conclusions: The study indicated a need for more consideration when prescribing antibiotics to patients with comorbidities or using more than 7 days of treatment.
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This study aimed to assess the knowledge of antiretroviral (ARV) treatment and the associated factors in HIV-infected patients in Vietnam. We conducted a cross-sectional descriptive study of 350 human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients being treated with ARV at outpatient clinics at Soc Trang, Vietnam, from June 2019 to December 2019. Using an interview questionnaire, patients who answered at least eight out of nine questions correctly, including some required questions, were considered to have a general knowledge of ARV treatment. Using multivariate logistic regression to identify factors associated with knowledge of ARV treatment, we found that 62% of HIV-infected patients had a general knowledge of ARV treatment, with a mean score of 8.2 (SD 1.4) out of 9 correct. A higher education level (p < 0.001); working away from home (p = 0.013); getting HIV transmitted by injecting drugs or from mother-to-child contact (p = 0.023); the presence of tension, anxiety, or stress (p = 0.005); self-reminding to take medication (p = 0.024); and a high self-evaluated adherence (p < 0.001) were found to be significantly associated with an adequate knowledge of ARV treatment. In conclusion, education programs for patients, as well as the quality of medical services and support, should be strengthened.
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BACKGROUND: Our study was conducted to determine the prevalence of drug-related problems (DRPs) in outpatient prescriptions, the impact of DRPs on treatment efficacy, safety, and cost, and the determinants of DRPs in prescribing for pediatric outpatients in Vietnam. METHODS: A retrospective cross-sectional study was conducted on pediatric outpatients at a pediatric hospital in Can Tho, Vietnam. DRPs were classified according to the Pharmaceutical Care Network Europe classification (PCNE) of 2020. The study determined prevalence of DRPs and their impacts on efficacy, safety, and cost. Multivariate regression was used to identify the determinants of DRPs. RESULTS: The study included 4339 patients (mean age 4.3, 55.8% male), with a total of 3994 DRPs, averaging 0.92 DRP/prescription. The proportion of prescriptions with at least one DRP was 65.7%. DRPs included inappropriate drug selection (35.6%), wrong time of dosing relative to meals (35.6%), inappropriate dosage form (9.3%), inappropriate indication (7.1%), and drug-drug interactions (0.3%). The consensus of experts was average when evaluating each aspect of efficiency reduction, safety reduction, and treatment cost increase, with Fleiss' coefficients of 0.558, 0.511, and 0.541, respectively (p < 0.001). Regarding prescriptions, 50.1% were assessed as reducing safety. The figures for increased costs and decreased treatment effectiveness were 29.0% and 23.9%, respectively. Patients who were ≤2 years old were more likely to have DRPs than patients aged 2 to 6 years old (OR = 0.696; 95% CI = 0.599-0.809) and patients aged over 6 years old (OR = 0.801; 95% CI = 0.672-0.955). Patients who had respiratory system disease were more likely to have DRPs than patients suffering from other diseases (OR = 0.715; 95% CI = 0.607-0.843). Patients with comorbidities were less likely to have DRPs than patients with no comorbidities (OR = 1.421; 95% CI = 1.219-1.655). Patients prescribed ≥5 drugs were more likely to have DRPs than patients who took fewer drugs (OR = 3.677; 95% CI = 2.907-4.650). CONCLUSION: The proportion of prescriptions in at least one DRP was quite high. Further studies should evaluate clinical significance and appropriate interventions, such as providing drug information and consulting doctors about DRPs.
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This study was conducted to determine the prevalence and determinants of medication adherence among patients with HIV/AIDS in southern Vietnam. METHODS: A cross-sectional study was conducted in a hospital in southern Vietnam from June to December 2019 on patients who began antiretroviral therapy (ART) for at least 6 months. Using a designed questionnaire, patients were considered adherent if they took correct medicines with right doses, on time and properly with food and beverage and had follow-up visits as scheduled. Multivariable logistic regression was used to identify determinants of adherence. KEY FINDINGS: A total of 350 patients (from 861 medical records) were eligible for the study. The majority of patients were male (62.9%), and the dominant age group (≥35 years old) accounted for 53.7% of patients. Sexual intercourse was the primary route of transmission of HIV (95.1%). The proportions of participants who took the correct medicine and at a proper dose were 98.3% and 86.3%, respectively. In total, 94.9% of participants took medicine appropriately in combination with food and beverage, and 75.7% of participants were strictly adherent to ART. The factors marital status (odds ratio (OR) = 2.54; 95%CI = 1.51-4.28), being away from home (OR = 1.7; 95%CI = 1.03-2.78), substance abuse (OR = 2.7; 95%CI = 1.44-5.05), general knowledge about ART (OR = 2.75; 95%CI = 1.67-4.53), stopping medication after improvement (OR = 4.16; 95%CI = 2.29-7.56) and self-assessment of therapy adherence (OR = 9.83; 95%CI = 5.44-17.77) were significantly associated with patients' adherence. CONCLUSIONS: Three-quarters of patients were adherent to ART. Researchers should consider these determinants of adherence in developing interventions in further studies.
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OBJECTIVES: To assess the effectiveness of a combined online and face-to-face continuing medical education (CME) programme, for improvement in clinical knowledge and skills of family doctors, in comparison with a control group; and to explore the self-reported satisfaction, competencies and confidence of those in the intervention group. METHODS: We used a cluster randomised controlled trial, with pre- and post-testing, and a feedback survey at the end of the 18-month CME programme. The measurements consisted of a multiple-choice test, an objective structured clinical examination test and an anonymously self-administered questionnaire. RESULTS: There were 58 family doctors from four provinces in the intervention group and 32 doctors from three provinces in control group, both in the Mekong Delta region in Vietnam. The mean age of participants was 47.8 years, and the female/male ratio was 1/2.9. After training, the intervention group had significantly higher scores on overall knowledge (mean difference = 1.4, 95% CI 1.0-1.86, P < 0.001; Cohen's d 1.36, Pearson's r 0.53), in four of the five education modules: peptic disorders, diabetes, hypertension and bone-muscle-joint diseases (Pearson's r 0.56, 0.56, 0.34 and 0.4, respectively), and in problem-solving skills (Pearson's r 0.27). Self-reports showed a positive learning attitude, strong interest and improved confidence and competency among doctors in the intervention group. CONCLUSIONS: A combined online and face-to-face CME programme proved applicable and effective for improving the clinical knowledge and problem-solving skills of family doctors in Vietnam.
OBJECTIFS: Evaluer l'efficacité d'une combinaison d'un programme de formation médicale continue (FMC), en ligne et en face-à-face pour l' amélioration des connaissances cliniques et les compétences des médecins de famille, par rapport à un groupe témoin et explorer la satisfaction, les compétences et la confiance autodéclarées des participants dans le groupe d'intervention. Méthodes Nous avons utilisé un essai contrôlé randomisé en grappes , avec pré et post-test, et une enquête de rétroaction à la fin du programme de FMC de 18 mois. Les mesures consistaient en un test à choix multiple, un test d'examen clinique objectif structuré et un questionnaire anonyme administré. Résultats Il y avait 58 médecins de famille de 4 provinces dans le groupe d'intervention et 32 médecins de 3 provinces dans le groupe témoin, tous deux dans la région du delta du Mékong au Vietnam. L'âge moyen des participants était de 47,8 ans, et le ratio femmes/hommes était de 1/2,9. Après la formation, le groupe d'intervention avaient des scores significativement plus élevés sur l' ensemble des connaissances (moyenne de différence = 1,4 ; IC95%: 1,0 à 1,86 ; p < 0,001 ; d de Cohen: 1,36 ; r de Pearson 0,53), dans 4 des 5 modules d'éducation: troubles gastro-duodénaux, diabète, hypertension et maladies des os-muscles- articulaires (r de Pearson 0,56 ; 0,56 ; 0,34 et 0,4, respectivement), et dans les compétences à résoudre des problèmes (r de Pearson: 0,2 7). Les auto-évaluations ont montré une attitude d'apprentissage positive, un vif intérêt et une amélioration de la confiance et des compétences chez les médecins du groupe d'intervention. CONCLUSIONS: Une FMC combiné basé sur Internet et en direct est applicable et efficace pour l'amélioration des connaissances cliniques et les compétences à résoudre les problèmes chez les médecins de famille au Vietnam.
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Competência Clínica/normas , Educação Médica Continuada , Médicos de Família/educação , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde , Treinamento por Simulação , Inquéritos e Questionários , VietnãRESUMO
OBJECTIVES: Well-designed studies on the impact of a family medicine rotation on medical students are rare, and very few studies include a qualitative component. This study aimed to determine the improvement of medical students' knowledge, communication skills and attitude towards primary care and explore their perceptions after rotations, in comparison with a control group. METHODS: We used a mixed-methods design, comprising a pre-test-post-test comparison between a sample of trained students who took family medicine rotations and a control group and a qualitative survey. The measurement of improvement included (i) multiple choice question testing, (ii) objective structured checklist examinations, (iii) self-reporting and (iv) interviews and focus group discussions. Data were collected from August 2017 to June 2018. RESULTS: There were 696 students in the trained group and 617 controls. The two groups' baseline scores in knowledge, communication skills and attitude were not significantly different. Knowledge covering five domains of family medicine (Pearson's r from 0.6 to 0.9) improved significantly, as did attitudes towards primary care in the trained group. There were no differences in communication and counselling skills between the two groups for four situations, but for two-health check-ups and mental health care-skills were significantly improved (Pearson's r from 0.28 to 0.43). The qualitative survey showed highly positive feedback from trained students. CONCLUSIONS: The family medicine rotation significantly improved students' knowledge and attitude towards primary care and some communication skills. Further studies should investigate students' interest in and career choice for this discipline.
OBJECTIFS: Des études bien conçues sur l'impact d'une rotation de la médecine familiale sur les étudiants en médecine sont rares et très peu d'études comprennent une composante qualitative. Cette étude visait à mesurer l'amélioration des connaissances, des compétences en communication et de l'attitude des étudiants en médecine à l'égard des soins primaires, et à explorer leurs perceptions après les rotations, en comparaison avec un groupe témoin. MÉTHODES: Nous avons utilisé un concept de méthodes mixtes, comprenant une comparaison pre-test et post-test entre un échantillon d'étudiants formés qui ont effectué des rotations de la médecine familiale et un groupe témoins, et une enquête qualitative. La mesure de l'amélioration comprenait (1) des tests de questions à choix multiples, (2) des examens objectifs structurés de listes, (3) des rapports personnels et (4) des entretiens et des discussions focalisées de groupes. Les données ont été collectées d'août 2017 à juin 2018. RÉSULTATS: Il y avait 696 élèves dans le groupe formé et 617 témoins. Les scores de référence des deux groupes en termes de connaissances, de communication et d'attitude n'étaient pas significativement différents. Les connaissances couvrant cinq domaines de la médecine familiale se sont considérablement améliorées (r de Pearson de 0,6 à 0,9), tout comme l'attitude à l'égard des soins primaires dans le groupe formé. Il n'y avait pas de différence dans les compétences de communication et de conseil entre les deux groupes pour quatre situations, mais pour deux (bilan de santé et soins de santé mentale) les compétences ont été significativement améliorées (r de Pearson de 0. 28 à 0. 43). L'enquête qualitative a montré une rétroaction très positive des étudiants formés. CONCLUSIONS: La rotation de la médecine familiale a amélioré de manière significative la connaissance et l'attitude des étudiants à l'égard des soins primaires et certaines compétences de communications. Des études ultérieures devraient examiner l'intérêt des étudiants et le choix de carrière pour cette discipline.
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Atitude do Pessoal de Saúde , Medicina de Família e Comunidade/educação , Conhecimentos, Atitudes e Prática em Saúde , Atenção Primária à Saúde , Estudantes de Medicina/psicologia , Feminino , Humanos , Masculino , Inquéritos e Questionários , Vietnã , Adulto JovemRESUMO
OBJECTIVES: To determine the prevalence, patterns and determinants of drug-related problems (DRPs) in prescribing for coronary artery diseases (CADs) in Vietnam. METHODS: Retrospective cross-sectional study on outpatients with CADs at a general hospital in Can Tho, Vietnam. DRPs were classified according to Pharmaceutical Care Network Europe definitions. We determined the prevalence and patterns of DRPs. Logistic regression was used to identify the determinants of DRPs. RESULTS: Among 683 patients (mean age 63.4; 64.3% female), the prevalence of DRPs was 61.1%. DRPs comprised inappropriate indication (3.5%), inappropriate dosage (22.2%), wrong frequency of use (24.2%), wrong time of taking medications (4.1%), taking medications at the wrong time around meals (19.2%) and drug interactions (19.3%). Patients who took ≥ 5 drugs were more likely to have DRPs (adjusted odds ratio = 1.96; 95% confidence interval = 1.31-2.93). Patients without health insurance were more likely to have inappropriate indication (ORa = 2.93; 95%CI = 1.28-6.70). Taking medications at inappropriate times around meals was common among men (ORa = 1.82; 95%CI = 1.23-2.69) and among those with health insurance (ORa = 1.66; 95%CI = 1.05-2.63). Patients < 65 years old were more likely to be prescribed inappropriate doses (ORa = 1.67; 95%CI = 1.15-2.45). Prescriptions with ≥ 5 drugs were more likely to be taken at inappropriate frequency (ORa = 1.87; 95%CI = 1.09-3.21) and to cause drug interactions (ORa = 6.48; 95%CI = 2.59-16.24). CONCLUSIONS: DRPs are common among patients with CADs in Vietnam. The number of DRPs increases with the number of drugs in prescriptions. Further studies should identify other potential determinants of DRPs and effective interventions to improve prescribing practice in Vietnam.
PROBLÈMES LIÉS AUX MÉDICAMENTS DANS LES PRESCRIPTIONS POUR LES MALADIES CORONARIENNES AU VIETNAM: ÉTUDE TRANSVERSALE: OBJECTIFS: Déterminer la prévalence, les caractéristiques et les déterminants des problèmes liés aux médicaments (PLM) lors des prescriptions pour des maladies coronariennes au Vietnam. MÉTHODES: Etude transversale rétrospective sur les patients ambulatoires atteints de coronaropathies dans un hôpital général à Can Tho, au Vietnam. Les PLM ont été classés selon les définitions du Pharmaceutical Care Network Europe. Nous avons déterminé la prévalence et les modèles de PLM. La régression logistique a été utilisée pour identifier les déterminants des PLM. RÉSULTATS: Parmi 683 patients (âge moyen 63,4 ans; femme 64,3%), la prévalence de PLM était de 61,1%. Les PLM comprenaient une indication inappropriée (3,5%), une posologie inappropriée (22,2%), une fréquence d'utilisation inappropriée (24,2%), prendre les médicaments à des mauvais moments (4,1%), prendre les médicaments au mauvais moment autour des repas (19,2%) et les interactions médicamenteuses (19,3%). Les patients ayant pris 5 médicaments ou plus étaient plus susceptibles d'avoir un PLM (odds ratio ajusté = 1,96; intervalle de confiance à 95%: 1,31-2,93). Les patients sans assurance santé étaient plus susceptibles d'avoir une indication inappropriée (ORa = 2,93; IC95%: 1,28-6,70). La prise de médicaments à des moments inappropriés autour des repas était courante chez les hommes (ORa = 1,82; IC 95% = 1,23-2,69) et chez ceux ayant une assurance santé (ORa = 1,66; IC95%: 1,05-2,63). Les patients de moins de 65 ans étaient plus susceptibles de prendre des doses inappropriées (ORa = 1,67; IC95% = 1,15-2,45). Les prescriptions de 5 médicaments ou plus étaient plus susceptibles d'être prises à une fréquence inappropriée (ORa = 1,87; IC95%: 1,09-3,21) et à provoquer des interactions médicamenteuses (ORa = 6,48; IC95%: 2,59-16,24). CONCLUSIONS: Les PLM sont fréquents chez les patients atteints de coronaropathies au Vietnam. Le nombre de PLM augmente avec le nombre de médicaments dans les prescriptions. Des études supplémentaires devraient identifier d'autres déterminants potentiels des PLM et des interventions efficaces pour améliorer les pratiques des prescriptions au Vietnam.
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Fármacos Cardiovasculares/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Uso Indevido de Medicamentos sob Prescrição/estatística & dados numéricos , Fatores Etários , Idoso , Fármacos Cardiovasculares/administração & dosagem , Fármacos Cardiovasculares/efeitos adversos , Estudos Transversais , Interações Medicamentosas , Feminino , Interações Alimento-Droga , Humanos , Prescrição Inadequada/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Polimedicação , Estudos Retrospectivos , Fatores Sexuais , Fatores de Tempo , VietnãRESUMO
Silicic acid and soluble Fe are among the most abundant components in acid mine drainage. During the oxidation of Fe(II), the interaction between silicic acid and freshly formed Fe oxides might change the colloidal dynamics, altering surface charge properties. However, the effects of silicic acid on colloidal Fe oxides formed from acid mine drainage are not fully understood. In this work, we examined the colloidal dynamics of freshly formed Fe oxides in synthetic acid mine drainage (prepared from FeSO solution) under the effect of silicic acid as a function of changes in pH and ionic strength. The results demonstrate that through adsorption, silicic acid progressively slows oxidation and enhances the dispersion of freshly formed Fe oxides by shifting the surface charge toward more negative values. This effect was most prominent between pH 5 and 9. The current results demonstrate that silicic acid enhances the dispersion and transport of freshly formed Fe oxides and suggest that aggregation-based techniques for the treatment of Fe-rich drainage may require further consideration of this effect.
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Ferro , Ácido Silícico , Compostos Férricos , Oxirredução , ÓxidosRESUMO
Intractable and untreatable pain from cancer remains a challenge for both patients and clinicians. The pain may be related to the disease itself or the consequences of treatment, such as surgery, chemotherapy or radiation therapy. Cancer pain is intense and has a major impact on patients' quality of life and survival. A significant number of patients receiving analgesic therapy with opioids report persisting pain of a higher intensity than the pain in those who were not on this class of drugs. The pathophysiology of pain in cancer patients is complex and remains poorly understood. Several research groups have studied and demonstrated that cancer and cancer-related symptoms may have an underlying problem of membrane hyper-excitability due to over-presentation of sodium channels and glutamate build-up or over-stimulation of glutamate/N-methyl-D-aspartate (NMDA)/α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) system in cancer cells and the body. Dimethyl sulfoxide (DMSO) is a naturally derived, inexpensive, non-toxic solvent and pharmaceutical agent that has been demonstrated to have numerous health enhancing and therapeutic benefits. In the present article, we provide the scientific evidence and substantiate possible application of DMSO as a well-tolerated excitatory modulator in the management of cancer pain.
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Dimetil Sulfóxido/farmacologia , Neoplasias/complicações , Dor Intratável/tratamento farmacológico , Analgésicos/farmacologia , Animais , Ácido Glutâmico/metabolismo , Humanos , N-Metilaspartato/metabolismo , Dor Intratável/etiologia , Dor Intratável/fisiopatologia , Qualidade de Vida , Canais de Sódio/metabolismo , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/metabolismoRESUMO
The hypothesis that prothrombin (FII) protects coagulation factor Va (FVa) from proteolytic inactivation by activated protein C (APC) was tested using purified proteins. FII dose-dependently protected FVa from APC proteolysis under conditions where competition of proteins for binding to negatively-charged phospholipid surface was not relevant (i.e. either at high phospholipid vesicle concentrations or using soluble dicaproylphosphatidylserine at levels below its critical micellar concentration). Cleavages in FVa at both Arg(506) and Arg(306) by APC were inhibited by FII. FII did not alter the amidolytic activity of APC towards chromogenic oligopeptide substrates or inhibit FVIIIa inactivation by APC, implying that the FII-mediated protection of FVa from APC proteolysis was due to the ability of FII to inhibit protein-protein interactions between FVa and APC. FII also protected FVa from inactivation by Gla-domainless APC, ruling out a role for the APC Gla domain for these observations. To identify domains of FII responsible for the observed phenomenon, various forms or fragments of FII were employed. Biotin-Phe-ProArg-CMK-inhibited meizothrombin and fII-fragment 1*2 protected FVa from proteolysis by APC. In contrast, no significant protection of FVa from APC cleavage was observed for Gladomainless-FII, prethrombin-1, prethrombin-2, FII fragment 1 or active site inhibited-thrombin (DEGR-thrombin). Overall, these data demonstrate that the Gla domain of FII linked to kringle 1 and 2 is necessary for the ability of FII to protect FVa from APC cleavage and support the general concept that assembly of the FII activation complex (FXa*FVa*FII*lipid surface) protects FVa from APC inactivation so that the procoagulant, thrombin generating pathway can act unhindered by APC. Only following FII activation and dissociation of the FII Gla domain fragments from the FII-ase complex, can APC inactivate FVa and down-regulate thrombin generation.
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Coagulação Sanguínea , Fator Va/metabolismo , Proteína C/metabolismo , Protrombina/metabolismo , Animais , Ligação Competitiva , Precursores Enzimáticos/metabolismo , Fator VIIIa/metabolismo , Fator Va/genética , Fator Xa/metabolismo , Humanos , Kringles , Mutação , Fragmentos de Peptídeos/metabolismo , Fosfolipídeos/metabolismo , Ligação Proteica , Estrutura Terciária de Proteína , Proteínas Recombinantes/metabolismo , Trombina/metabolismo , Fatores de TempoRESUMO
Many herbs and spices have been shown to contain high levels of polyphenolic compounds with potent antioxidant properties. In the present study, we explore how nutrient availability, specifically nitrogen fertilization, affects the production of polyphenolic compounds in three cultivars (Dark Opal, Genovese, and Sweet Thai) of the culinary herb, basil ( Ocimum basilicum L.). Nitrogen fertilization was found to have a significant effect on total phenolic levels in Dark Opal ( p < 0.001) and Genovese ( p < 0.001) basil with statistically higher phenolic contents observed when nutrient availability was limited at the lowest (0.1 mM) applied nitrogen treatment. Similarly, basil treated at the lowest nitrogen fertilization level generally contained significantly higher rosmarinic ( p = 0.001) and caffeic ( p = 0.001) acid concentrations than basil treated at other nitrogen levels. Nitrogen fertilization also affected antioxidant activity ( p = 0.002) with basil treated at the highest applied nitrogen level, 5.0 mM, exhibiting lower antioxidant activity than all other nitrogen treatments. The anthocyanin content of Dark Opal basil was not affected by applied nitrogen level, but anthocyanin concentrations were significantly impacted by growing season ( p = 0.001). Basil cultivar was also determined to have a statistically significant effect on total phenolic levels, rosmarinic and caffeic acid concentrations, and antioxidant activities.
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Antioxidantes/análise , Fertilizantes , Nitrogênio/administração & dosagem , Ocimum basilicum/química , Fenóis/análise , Antocianinas/análise , Ácidos Cafeicos/análise , Cinamatos/análise , Depsídeos/análise , Ocimum basilicum/crescimento & desenvolvimento , Ácido RosmarínicoRESUMO
Activated protein C (APC) inactivates factor Va (fVa) by proteolytically cleaving fVa heavy chain at Arg(506), Arg(306), and Arg(679). Factor Xa (fXa) protects fVa from inactivation by APC. To test the hypothesis that fXa and APC share overlapping fVa binding sites, 15 amino acid-overlapping peptides representing the heavy chain (residues 1-709) of fVa were screened for inhibition of fVa inactivation by APC. As reported, VP311-325, a peptide comprising residues 311-325 in fVa, dose-dependently and potently inhibited fVa-dependent prothrombin activation by fXa in the absence of APC. This peptide also inhibited the inactivation of fVa by APC, suggesting that this region of fVa interacts with APC. The peptide inhibited the APC-dependent cleavage of both Arg(506) and Arg(306) because inhibition was observed with plasma-derived fVa and recombinant R506Q and RR306/679QQ fVa. VP311-325 altered the fluorescence emission of dansyl-active site-labeled APC(i) but not a dansyl-active site-labeled thrombin control, showing that the peptide binds to APC(i). This peptide also inhibited the resonance energy transfer between membrane-bound fluorescein-labeled fVa (donor) and rhodamine-active site-labeled S360C-APC (acceptor). These data suggest that peptide VP311-325 represents both an APC and fXa binding region in fVa.
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Fator Va/química , Fator Xa/química , Peptídeos/química , Proteína C/química , Substituição de Aminoácidos , Sítios de Ligação/genética , Ativação Enzimática , Fator Va/genética , Fator Xa/genética , Humanos , Mutação de Sentido Incorreto , Peptídeos/genética , Proteína C/genética , Protrombina/química , Protrombina/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/genéticaRESUMO
A novel amphiphilic ABA dendritic-linear-dendritic block copolymer consisting of poly(amidoamine) and poly(propylene oxide) has been synthesized. The solution-phase behavior of the block copolymer was studied as a function of the generation of the dendritic block, ionic strength, and solution pH. The triblock self-assembles in aqueous media to form stable micelles with CMC values ranging from 10(-6) to 10(-5) M. Dynamic light scattering results indicate the formation of particles ranging from 9 to 18 nm in diameter, with smaller diameters exhibited at higher generations. Additional experiments were performed to assess the feasibility of the nanoparticles for drug delivery applications. Drug loading studies were performed with a model hydrophobic drug, triclosan, resulting in high loading efficiencies ranging from 79 to 86%w/w. The dendritic-linear-dendritic block copolymer synthesized was found to be a promising candidate for drug delivery due to its relative stability in aqueous solution and its drug encapsulation and release properties.