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1.
Foods ; 12(19)2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37835258

RESUMO

Disgust associated with insect consumption is a significant challenge faced by the insect-based food industry. One cost-effective approach that managers can employ to increase consumer acceptance is by enhancing packaging design. The packaging represents a cheap and effective means of communication. It is also referred to as a silent seller. This study investigates the potential of packaging communication in reducing disgust towards insect-based products in Germany. In a survey, 422 participants were confronted with packaging designs representing different visual and informative elements. The results showed that images of familiar ingredients and transparent windows on the packaging are particularly effective in reducing disgust. The presence of the organic and specific Ento seals significantly increased the assumed food safety. Claims about protein content and sustainability were less effective. Cricket images had a significant impact on increasing disgust. Practical implications for managers who are seeking to address consumer resistance towards insect-based food products are discussed.

2.
Biomed Res Int ; 2021: 3108749, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33928146

RESUMO

AIM: To develop a population pharmacokinetic model for Uruguayan patients under treatment with cyclosporine (CsA) that can be applied to TDM. Patients and Methods. A total of 53 patients under treatment with CsA were included. 37 patients with at least one pharmacokinetic profile described with four samples were considered for model building, while the remaining 16 were considered for the assessments of predictive performances. Pharmacokinetic parameter estimation was performed using a nonlinear mixed effect modelling implemented in the Monolix® software (version 2019R1, Lixoft, France); meanwhile, simulations were performed in R v.3.6.0 with the mlxR package. RESULTS: A two-compartment model with a first-order disposition model including lag time was used as a structural model. The final model was internally validated using prediction corrected visual predictive check (pcVPC) and other graphical diagnostics. A total of 621 CsA steady-state concentrations were analyzed for model development. Population estimates for the absorption constant (ka) and lag time were 0.523 h-1 and 0.512 h, respectively; apparent clearance (CL/F) was 30.3 L/h (relative standard error [RSE] ± 8.25%) with an interindividual variability of 39.8% and interoccasion variability of 38.0%; meanwhile, apparent clearance of distribution (Q/F) was 17.0 L/h (RSE ± 12.1%) with and interindividual variability of 53.2%. The covariate analysis identified creatinine clearance (ClCrea) as an individual factor influencing the Cl of CsA. The predictive capacity of the population model was demonstrated to be effective since predictions made for new patients were accurate for C1 and C2 (MPPEs below 50%). Bayesian forecasting improved significantly in the second and third occasions. CONCLUSION: A population pharmacokinetic model was developed to reasonably estimate the individual cyclosporine clearance for patients. Hence, it can be utilized to individualize CsA doses for prompt and adequate achievement of target blood concentrations of CsA.


Assuntos
Ciclosporina/farmacocinética , Monitoramento de Medicamentos , Modelos Biológicos , Adulto , Ciclosporina/sangue , Feminino , Humanos , Masculino
3.
Food Sci Nutr ; 9(1): 414-428, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33473303

RESUMO

Due to the environmental and nutritional benefits of insects, their consumption would be one of the solutions to feed the growing human population. Despite the increasing interest in the use of insects as food and feed, consumer acceptance is the major obstacle to successful implementation in Western countries and we studied the factors that influence consumer acceptance in a group of university students from Germany and the Netherlands. In this exploratory research, a survey was conducted (n = 222). Socio-demographic and psychological factors were established from a theoretical review. In addition, we elaborated on questions regarding information on the health and environmental benefits of consuming insects. Initially, the data obtained are presented through descriptive statistics. The influence of the socio-demographic and psychological factors, and the information on the willingness to accept insects as animal feed and human food was analyzed using correlations and multiple linear regressions. Results showed more willingness to accept insects as animal feed than in human food. The acceptance among German and Dutch students seems to be driven by issues similar to those in other European countries, such as visual aspects and knowledge about the benefits. The effect of the information on willingness constitutes an important finding of this study, especially for the use of insects in animal feed, since most of the previous studies have focused on the use of insects as human food. Our data support the need to inform and educate consumers about the environmental and health benefits of entomophagy. We conclude that effective efforts to implement entomophagy could increase the level of familiarity with the insect food and inform (or educate) consumers about its benefits. Insights from this study are useful to address studies focusing on specific segments of possible early adopters and consequently addressing communication strategies in this market segmentation.

4.
Biomed Res Int ; 2020: 3902740, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32855964

RESUMO

Choosing an appropriate treatment for chronic pain remains problematic, and despite the available medication for its treatment, still, many patients complain about pain and appeal to the use of cannabis derivatives for pain control. However, few data have been provided to clinicians about the pharmacokinetic drug-drug interactions of cannabinoids with other concomitant administered medications. Therefore, the aim of this brief review is to assess the interactions between cannabinoids and pain medication through drug transporters (ATP-binding cassette superfamily members) and/or metabolizing enzymes (cytochromes P450 and glucuronyl transferases).


Assuntos
Canabinoides/farmacocinética , Dor Crônica/tratamento farmacológico , Interações Medicamentosas , Acetaminofen/farmacocinética , Acetaminofen/uso terapêutico , Analgésicos não Narcóticos/farmacocinética , Analgésicos não Narcóticos/uso terapêutico , Analgésicos Opioides/farmacocinética , Analgésicos Opioides/uso terapêutico , Animais , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapêutico , Antidepressivos/farmacocinética , Antidepressivos/uso terapêutico , Canabinoides/uso terapêutico , Sistema Enzimático do Citocromo P-450/metabolismo , Glucuronosiltransferase/metabolismo , Humanos , Inativação Metabólica/efeitos dos fármacos
5.
Insects ; 11(5)2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32365691

RESUMO

Plant-associated microbes may induce plant defenses against herbivores. Plants, in turn, can attract natural enemies, such as predators, using herbivore-induced plant volatiles. Intricate communication occurs between microorganisms, plants, and insects. Given that many aspects related to mechanisms involved in this symbiotic system remain unknown, we evaluated how beneficial soil-borne microorganisms can affect the interactions between plants, herbivores, and natural enemies. For this study, we established a multitrophic system composed of the predatory earwig Doru luteipes (Dermaptera: Forficulidae), arugula (Eruca sativa, Brassicaceae) as the host plant, Plutella xylostella (Lepidoptera: Plutellidae) larvae as a specialist herbivore, Spodoptera frugiperda (Lepidoptera: Noctuidae) larvae as a generalist herbivore, and Bacillus amyloliquefaciens as the plant growth-promoting rhizobacteria (PGPR), in a series of nocturnal olfactometry experiments. By assessing earwig preference towards herbivore-induced and PGPR-inoculated plants in different combinations, we showed that the interaction between rhizobacteria, plants, and herbivores can affect the predatory earwig's behavior. Furthermore, we observed a synergistic effect in which earwigs were attracted by plants that presented as PGPR inoculated and herbivore damaged, for both specialist and generalist herbivores. Our findings help fill the important knowledge gap regarding multitrophic interactions and should provide useful guidelines for their application to agricultural fields.

6.
Protein J ; 37(6): 548-571, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30259240

RESUMO

LDL, VLDL and other members of the low-density lipoparticles (LLPs) enter cells through a large family of receptors. The actual receptor ligand(s) in apolipoprotein B100, one of the main proteins of LLP, remain(s) unknown. The objective of this study was to identify true receptor ligand(s) in apo B100, a molecule of 4563 residues. Apo B100 contains 33 analogues of Cardin-Weintraub arginine/lysine-based receptor ligand motifs and shares key lysine motifs and sequence similarity with the LDL receptor-associated protein, MESD, and heat shock proteins. Eleven FITC-labeled synthetic peptides of 21-42 residues, with at least one ligand, were tested for binding and internalization using HeLa cells. All peptides bind but display different binding capacities and patterns. Peptides B0013, B0582, B2366, and B2932 mediate endocytosis and appear in distinct sites in the cytoplasm. B0708 and B3181 bind and remain on the cell surface as aggregates/clusters. Peptides B3119 (Site A) and B3347 (Site B), the putative ligands, showed low binding and no cell entry capacity. Apo B100 regions in this study share similarities with related proteins of known function including chaperone proteins and Apo BEC stimulating protein, and not directly related proteins, e.g., the DNA-binding domain of interferon regulatory factors, MSX2-interacting protein, and snake venom Zinc metalloproteinase-disintegrin-like proteins.


Assuntos
Apolipoproteína B-100 , Endocitose/efeitos dos fármacos , Peptídeos , Receptores de LDL , Motivos de Aminoácidos , Apolipoproteína B-100/química , Apolipoproteína B-100/farmacologia , Células HeLa , Humanos , Peptídeos/química , Peptídeos/farmacologia , Domínios Proteicos , Receptores de LDL/agonistas , Receptores de LDL/metabolismo
7.
Case Rep Med ; 2018: 5371854, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30228819

RESUMO

Lamotrigine (LTG) is currently indicated as adjunctive therapy for focal and generalized tonic-clonic seizures and for treatment of bipolar disorder and neuropathic pain. A common concern with LTG in children is the frequency of appearance of skin rash. The intensity of this adverse effect can vary from transient mild rash to Stevens-Johnson syndrome (SJS), which can be fatal mainly when LTG is coadministered with valproic acid (VPA). Hereby, we present the case of an 8-year-old boy who suffered from SJS and other complications two weeks after LTG was added to his VPA treatment in order to control his seizures. VPA is known to decrease LTG clearance via reduced glucuronidation. In this case, the minor elimination pathway of LTG would play a more important role, and the formation of an arene oxide metabolite would be enhanced. As this reactive metabolite is detoxified mainly by enzymatic reactions, involving microsomal epoxide hydrolase and/or GSH-S-transferases and these enzymes are polymorphically expressed in humans, arene oxide toxicity is increased when epoxide hydrolase or GSH-S-transferases is either defective or inhibited or a depletion of intracellular glutathione levels is taking place. VPA can cause inhibition of epoxide hydrolase enzymes and/or depletion of glutathione levels leading to adverse cutaneous reactions.

8.
Naturwissenschaften ; 104(9-10): 77, 2017 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-28871442

RESUMO

Numerous studies have demonstrated that entomophagous arthropods use herbivore-induced plant volatile (HIPV) blends to search for their prey or host. However, no study has yet focused on the response of nocturnal predators to volatile blends emitted by prey damaged plants. We investigated the olfactory behavioral responses of the night-active generalist predatory earwig Doru luteipes Scudder (Dermaptera: Forficulidae) to diurnal and nocturnal volatile blends emitted by maize plants (Zea mays) attacked by either a stem borer (Diatraea saccharalis) or a leaf-chewing caterpillar (Spodoptera frugiperda), both suitable lepidopteran prey. Additionally, we examined whether the earwig preferred odors emitted from short- or long-term damaged maize. We first determined the earwig diel foraging rhythm and confirmed that D. luteipes is a nocturnal predator. Olfactometer assays showed that during the day, although the earwigs were walking actively, they did not discriminate the volatiles of undamaged maize plants from those of herbivore damaged maize plants. In contrast, at night, earwigs preferred volatiles emitted by maize plants attacked by D. saccharalis or S. frugiperda over undamaged plants and short- over long-term damaged maize. Our GC-MS analysis revealed that short-term damaged nocturnal plant volatile blends were comprised mainly of fatty acid derivatives (i.e., green leaf volatiles), while the long-term damaged plant volatile blend contained mostly terpenoids. We also observed distinct volatile blend composition emitted by maize damaged by the different caterpillars. Our results showed that D. luteipes innately uses nocturnal herbivore-induced plant volatiles to search for prey. Moreover, the attraction of the earwig to short-term damaged plants is likely mediated by fatty acid derivatives.


Assuntos
Herbivoria , Animais , Cromatografia Gasosa-Espectrometria de Massas , Folhas de Planta , Spodoptera , Zea mays
9.
Pharmaceuticals (Basel) ; 10(3)2017 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-28820457

RESUMO

Phenytoin (PHT) oxidative route leads to its main metabolite p-hydroxyphenytoin (p-HPPH), by means of CYP2C9 and CYP2C19. Formation of p-HPPH proceeds via a reactive arene-oxide intermediate. This intermediate can also be converted into PHT dihydrodiol by microsomal epoxide hydrolase (EPHX). The three enzymes are polymorphically expressed and the genetic variants are responsible for changes in the enzyme activity. In order to evaluate the effect that these polymorphisms have on PHT metabolism, PHT and p-HPPH plasma concentrations were measured and the genotype for the three enzymes was assessed in 50 Uruguayan epileptic patients. 30% of the patients were intermediate and 2% were poor metabolizers for CYP2C9, while 20% were intermediate metabolizers for CYP2C19. 44%, 10%, and 46% of subjects had intermediate, increased and decreased activities of EPHX respectively. CYP2C9 was confirmed to be the main responsible enzyme for PHT biotransformation. CYP2C19 seemed to be preponderant in p-HPPH oxidative metabolism. Apart from being responsible for the production of the dihydrodiol metabolite, EPHX also seemed to contribute to pHPPH formation when its activity is low. PHT might be recovered with a decreased activity of EPHX regardless the activity of CYP2C9.

10.
J Int Med Res ; 45(3): 1268-1272, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28425821

RESUMO

Valproic acid is a broad-spectrum anticonvulsant that has also gained attention in the psychiatric setting. With respect to safety, valproic acid may induce a seemingly rare condition, hyperammonemia, which can induce a wide variety of symptoms ranging from irritability to coma. The proposed mechanism of hyperammonemia involves depletion of carnitine and overproduction of a toxic metabolite, 4-en-valproic acid, both of which impair the urea cycle and thus ammonia elimination. Carnitine is a commonly used antidote for acute intoxication of valproic acid, but is not a therapeutic option for management of chronic adults with adverse effects related to valproic acid. We herein report a case involving a woman with epilepsy who developed hyperammonemia after a change in her anticonvulsant therapy. She reported increased seizures and gastrointestinal disturbances. Her ammonia, valproic acid, 4-en-valproic acid, and carnitine levels were monitored. Her ammonia level was elevated and her carnitine level was at the inferior limit of the population range. She was supplemented with carnitine at 1 g/day. After 1 month, her ammonia level decreased, her carnitine level increased, and her seizures were better controlled. Carnitine supplementation was useful for reversal of her hyperammonemia, allowing her to continue valproic acid for seizure control.


Assuntos
Anticonvulsivantes/uso terapêutico , Carnitina/administração & dosagem , Hiperamonemia/tratamento farmacológico , Convulsões/tratamento farmacológico , Ácido Valproico/uso terapêutico , Adulto , Feminino , Humanos
11.
P R Health Sci J ; 35(4): 197-202, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27898165

RESUMO

OBJECTIVE: 1) To describe implant success in the posterior maxillary when a sinus augmentation procedure was performed simultaneously with implant placement and then compare differences in success when sinus augmentation was delayed in patients attending the maxillofacial surgery clinic of the University of Puerto Rico, 2008 through 2011. 2) To determine sociodemographic characteristics, ASA classification, graft material, and final restoration and, using a questionnaire, determine as well patient satisfaction. METHODS: A retrospective cohort study was conducted (approved by IRB) with 172 patients, using medical records. A total of 102 implants were placed in grafted maxillary areas, 55 placed simultaneously and 47 delayed. Patients were contacted, invited to participate, and, upon agreement, instructed to sign an informed consent. RESULTS: A total of 45 implants were evaluated clinically (22 immediate and 23 delayed), all with 100% success (according to Buser and Weber criteria). In the sample group, 72.5% of the participants were women and 26.8% were men; their ages ranged from 42 to 87 years, with a mean age of 57 years. Patient participation was low (44%). The categories of appearance and esthetics and function were both rated at 86.2%; cost of restoration came in at 86.1%, and maintenance was rated at 71.2%. CONCLUSION: Implant placement with simultaneous sinus augmentation was successful, and no differences were found between implants that were placed immediately and those that were delayed, which is similar to what has been found by previous studies. Patients reported being satisfied with the final cost of the implant restoration.


Assuntos
Implantação Dentária Endóssea , Levantamento do Assoalho do Seio Maxilar , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Retrospectivos , Fatores de Tempo
12.
Clin Pharmacol Drug Dev ; 5(3): 196-200, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27163498

RESUMO

Sixteen healthy volunteers (8 women and 8 men) participated in a 2-period, 2-treatment crossover study. A delayed-release gastroresistant formulation of ketoprofen was administered under fasting and fed conditions. Cmax , AUC, Cmax /AUC, and kel obtained after food coadministration did not differ from those calculated under fasting administration. Ninety-five percent confidence intervals for fed/fasting geometric mean ratio of Cmax /AUC and AUC were 0.80-1.14 and 0.80-1.23, respectively. A significant difference (P < .01) was found between lag-time medians (T0 ), with a longer T0 after food intake (5.5 vs 2.5 hours). Also, a significant difference between the medians of Tmax was found (P < .01), being 7.0 hours after food coadministration and 4.0 hours under fasting administration, but this difference disappeared once T0 was subtracted from Tmax . Cmax /AUC, which is related to drug absorption rate, showed significant differences between sexes. Men showed higher (P =.006) Cmax /AUC means (0.468 ± 0.094 vs 0.361 ± 0.087 h(-1) . Tmax was also significantly different (P < .05), being 4.0 (3.0-5.0) hours for men and 8.0 (5.0-10.0) hours for women. In conclusion, men showed a faster intestinal absorption rate with earlier time-to-peak plasma concentration of ketoprofen. Food coadministration extended the gastric residence time of formulation but exerted no effect on its intestinal absorption pattern.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Interações Alimento-Droga , Absorção Intestinal , Cetoprofeno/administração & dosagem , Adulto , Anti-Inflamatórios não Esteroides/farmacocinética , Área Sob a Curva , Estudos Cross-Over , Preparações de Ação Retardada , Feminino , Humanos , Cetoprofeno/farmacocinética , Masculino , Fatores Sexuais , Adulto Jovem
13.
Biomed Res Int ; 2016: 2920108, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26998483

RESUMO

Blood carnitine and/or acetylcarnitine deficiencies are postulated in the literature as possible causes of higher ammonia levels. The aim of this study was to investigate if the use of valproic acid, the age of the patients, or certain central nervous system pathologies can cause carnitine and/or acetylcarnitine deficiency leading to increased ammonia levels. Three groups of patients were studied: (A) epileptic under phenytoin monotherapy (n = 31); (B) with bipolar disorder under valproic acid treatment (n = 28); (C) elderly (n = 41). Plasma valproic acid and blood carnitine and acyl carnitine profiles were determined using a validated HPLC and LC-MS/MS method, respectively. Blood ammonia concentration was determined using an enzymatic automated assay. Higher ammonia levels were encountered in patients under valproic acid treatment and in the elderly. This may be due to the lower carnitine and/or acetylcarnitine found in these patients. Patients with controlled seizures had normal carnitine and acetylcarnitine levels. Further studies are necessary in order to conclude if the uncontrolled bipolar disorder could be the cause of higher carnitine and/or acetylcarnitine levels.


Assuntos
Acetilcarnitina , Amônia/sangue , Transtorno Bipolar , Carnitina , Epilepsia , Fenitoína/administração & dosagem , Ácido Valproico/administração & dosagem , Acetilcarnitina/sangue , Acetilcarnitina/deficiência , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtorno Bipolar/sangue , Transtorno Bipolar/tratamento farmacológico , Carnitina/sangue , Carnitina/deficiência , Epilepsia/sangue , Epilepsia/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Eur J Drug Metab Pharmacokinet ; 41(6): 787-793, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26590950

RESUMO

BACKGROUND AND OBJECTIVES: Ketoprofen, a potent nonsteroidal anti-inflammatory drug, is clinically administered as a racemic mixture. One of the possible metabolism routes of ketoprofen is the inversion of the R- to S-enantiomer in the gastrointestinal tract. Ketoprofen, as a weak acid drug, might undergo recirculation through pancreatic/intestinal juices. The aim of the work was to investigate if a plasma-gastrointestinal tract recirculation of ketoprofen could explain its R-to-S chiral inversion after the oral administration of two modified-release formulations: a gastro-resistant delayed-release tablet (Reference) and an extended-release-plus-immediate-release bilayer tablet (Test). METHODS: Sixteen healthy Caucasian volunteers (eight women and eight men) participated in a ketoprofen bioequivalence study. Both formulations were administered with and without food. In both cases, standard meals were given throughout the experiment. R- and S-enantiomers were measured separately using a validated HPLC-UV chiral method. Mean concentration-time profiles of ketoprofen enantiomers in plasma were obtained for men and women. Area under the plasma concentration-time curve, maximum ketoprofen plasma concentration, and time-to-peak were also computed for both isomers, both modes of administration, and both sexes. S/R concentration ratio was assessed as an indicator of enantiomer chiral inversion rate. RESULTS: Differences in the pharmacokinetics of S- and R-ketoprofen enantiomers were found after the Test administration. S-Ketoprofen presented a lower plasma exposure compared to R-enantiomer. However, the S/R concentration ratio increased 1 h (in men) and 2 h (in women) after meal intakes. This was related to pancreatic and/or intestinal and/or biliary secretions of the drug, followed by reabsorption and conversion of the R- to the S-isomer. The lower intestinal pH reported for men would lead to a higher oral bioavailability of the Test formulation and a higher reabsorption of both ketoprofen isomers in this sex. Hence, a higher rise of the S/R concentration ratio could be observed in men. No significant differences between isomers exposure were detected in both sexes after the Reference administration. Different lag times were observed after fed and fasting administration of this formulation; however, drug absorption coincided with food ingestion. Then, drug recirculation affected the S/R ratio from the beginning of drug exposure, minimizing the difference between isomers disposition. CONCLUSIONS: R-to-S conversion rate could be mainly associated with several passages of the drug through the intestinal mucosa. The concentration-time profiles of ketoprofen in plasma after the administration of both formulations evidenced R-to-S conversion of recirculating drug following meal intakes.


Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Inibidores de Ciclo-Oxigenase/farmacocinética , Composição de Medicamentos , Cetoprofeno/farmacocinética , Administração Oral , Adulto , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/sangue , Anti-Inflamatórios não Esteroides/química , Área Sob a Curva , Disponibilidade Biológica , Biotransformação , Estudos Cross-Over , Inibidores de Ciclo-Oxigenase/administração & dosagem , Inibidores de Ciclo-Oxigenase/sangue , Inibidores de Ciclo-Oxigenase/química , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/análise , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Feminino , Interações Alimento-Droga , Humanos , Absorção Intestinal , Cetoprofeno/administração & dosagem , Cetoprofeno/sangue , Cetoprofeno/química , Masculino , Taxa de Depuração Metabólica , Estrutura Molecular , Caracteres Sexuais , Estereoisomerismo , Comprimidos com Revestimento Entérico , Adulto Jovem
15.
J Viruses ; 20152015.
Artigo em Inglês | MEDLINE | ID: mdl-27123468

RESUMO

It is established that cell entry of low density lipoprotein particles (LLPs) containing Apo B100 and Apo E is mediated by receptors and GAGs. Receptor ligand motifs, XBBBXXBX, XBBXBX, and ΨBΨXB, and mono- and bipartite NLS sequences are abundant in Apo E and Apo B100 as well as in envelope and capsid proteins of Dengue viruses 1-4 (DENV1-4). Synthetic, fluorescence-labeled peptides of sequences in DENV2 envelope protein, and DENV3 capsid that include these motifs were used to conduct a qualitative assessment of cell binding and entry capacity using HeLa cells. DENV2 envelope peptide, Dsp2EP, 0564Gly-Gly0595, was shown to bind and remain at the cell surface. In contrast, DENV3 capsid protein peptide, Dsp3CP, 0002Asn-Gln0028, readily enters HeLa cells and accumulates at discrete loci in the nucleus. FITC-labeled dengue synthetic peptides colocalize with Low Density Lipoprotein-CM-DiI and Apo E-CM-DiI to a degree that suggests that Dengue viruses may utilize cell entry pathways used by LLPs.

16.
Eur J Pharm Sci ; 63: 140-6, 2014 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-25051348

RESUMO

The aim of this work was to study the effect of the sex and the smoking status on the pharmacokinetics and the bioequivalence assessment of a branded and a generic cyclosporine A microemulsion formulation in soft-gelatin capsule. Sixteen healthy volunteers (eight women and eight men) participated in a CyA bioequivalence study, with nine of the volunteers being smokers. Sandimmun Neoral® (brand formulation; Reference) and Sigmasporin Microral® (generic formulation; Test) were administered under fasting conditions. Pharmacokinetic parameters were calculated through non compartmental analysis. Bioequivalence was declared based on the 90% confidence intervals (90% CI) for the T/R ratio of the geometric means for each parameter. In vitro determination of the capsules opening time was performed in simulated gastric fluid without enzyme with USP Apparatus 2. The extent of absorption was similar between both products for all subjects or each sex-group. The absorption rate was similar for both products when considering all subjects, whereas a significant difference in the TMAX between the two products was observed for the male subjects only, which relates to its slower capsule opening time observed in vitro (12.4 versus 6.0 min). No differences were observed in women that could relate to their slower gastric emptying. Differences in drug exposure were observed between smokers and non-smokers. Sex- and smoke-related differences in the gastrointestinal transit should be considered when the on-set time would be determinant for the treatment success of a drug.


Assuntos
Ciclosporina/farmacocinética , Trânsito Gastrointestinal , Caracteres Sexuais , Fumar/metabolismo , Absorção Fisiológica , Adolescente , Adulto , Cápsulas , Ciclosporina/administração & dosagem , Ciclosporina/química , Emulsões , Feminino , Esvaziamento Gástrico , Voluntários Saudáveis , Humanos , Masculino , Fatores Sexuais , Fumaça/efeitos adversos , Equivalência Terapêutica , Fatores de Tempo , Adulto Jovem
17.
Biomed Res Int ; 2014: 217269, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24868521

RESUMO

Valproic acid, a branched short-chain fatty acid, has numerous action mechanisms which turn it into a broad spectrum anticonvulsant drug and make its use possible in some other pathologies such as bipolar disorder. It is extensively metabolized in liver, representing ß -oxidation in the mitochondria one of its main metabolic route (40%). Carnitine is responsible for its entry into the mitochondria as any other fatty acid. Long-term high-dose VPA therapy or acute VPA overdose induces carnitine depletion, resulting in high levels of ammonia in blood. As a high correlation between salivary valproic acid levels and plasma ultrafiltrate levels was found in humans, saliva becomes a promising monitoring fluid in order to study valproic acid pharmacokinetics and its toxic effect. Extended-release (twice daily) formulations of valproic acid or carnitine supplementation are the proposed two therapeutic strategies in order to reverse hyperammonemia.


Assuntos
Hiperamonemia/induzido quimicamente , Ácido Valproico/sangue , Adolescente , Adulto , Amônia/sangue , Transtorno Bipolar/tratamento farmacológico , Carnitina/administração & dosagem , Carnitina/química , Criança , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Epilepsia/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitocôndrias/efeitos dos fármacos , Saliva/efeitos dos fármacos , Ácido Valproico/administração & dosagem , Ácido Valproico/farmacocinética , Adulto Jovem
18.
Acta méd. colomb ; 39(2): 137-147, abr.-jun. 2014. ilus, tab
Artigo em Espanhol | LILACS, COLNAL | ID: lil-720226

RESUMO

Objetivo: describir los factores pronósticos demográficos, clínicos, hematológicos, inmunohistoquímicos y bioquímicos al diagnóstico de pacientes con linfoma B difuso de células grandes y su asociacióncon la severidad según el Índice Pronóstico Internacional en un Hospital Universitario, 2009-2012. Métodos: se realizó un estudio descriptivo en 40 pacientes con dicho linfoma. Se comparó laconcentración de β2 microglobulina con los factores pronósticos que componen el IPI y otros que nohacen parte; se determinó la asociación entre el IPI e IPI revisado y la concentración de β2 microglobulina,infiltración medular, masa voluminosa y expresión de BCL-2 y Ki-67. La información se analizó en SPSS. Resultados: 40% de los pacientes pertenecían al grupo de riesgo alto según el IPI y 55% al grupocon pronóstico pobre según el IPI revisado; 82.5% expresaron BCL-2 y 61.5% tenían un Ki-67>70%.Se observó asociación entre la β2 microglobulina y el Ann Arbor (p=0.036), la β2 microglobulina y lainfiltración medular (p=0.003), y la β2 microglobulina y el IPI revisado (p=0.037). Conclusiones: es probable que el tiempo transcurrido entre la aparición de los síntomas y eldiagnóstico haya favorecido que los pacientes se presentaran en estados avanzados de la enfermedady como consecuencia, con un pronóstico pobre. Así mismo, el estudio de la infiltración medular, elporcentaje de expresión de Ki-67 y la concentración de β2 microglobulina favorece a la identificaciónde pacientes con un pronóstico adverso. (Acta Med Colomb 2014: 39: 137-147).


Objective: to describe demographic, clinical, hematological, and immunohistochemical and biochemical prognostic factors to the diagnosis of patients with diffuse large B cell lymphoma and itsassociation with the severity according to the International Prognostic Index in a University Hospital,2009-2012. Methods: a descriptive study was conducted in 40 patients with this lymphoma. β2 microglobulinconcentration was compared with prognostic factors that compose the IPI and others which are not part of it; the association between IPI and revised IPI and β2 microglobulin concentration, bone marrow infiltration, bulky mass and expression of BCL -2 and Ki p-67 was determined. Data was analyzed in SPSS. Results: 40% of the patients were in the high risk group according to IPI and 55% to the group with poor prognosis according to the revised IPI; 82.5% expressed BCL-2 and 61.5% had a Ki-67 > 70%. Association between β2 microglobulin and Ann Arbor (p = 0.036), the β2 microglobulin and bone marrow infiltration (p = 0.003), and β2 microglobulin and revised IPI (p = 0.037) was observed. Conclusions: it is likely that the time between onset of symptoms and diagnosis has favored tha patients presented in advanced stages of the disease and as a result, with a poor prognosis. Likewise, the study of bone marrow infiltration, the percentage of Ki-67 expression and the concentration of β2 microglobulin favors the identification of patients with an adverse prognosis. (Acta Med Colomb 2014: 39: 137-147).


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Linfoma Difuso de Grandes Células B , Prognóstico , Medula Óssea , Microglobulina beta-2 , Antígeno Ki-67 , Rituximab
19.
Rev. cuba. farm ; 48(1)ene.-mar. 2014.
Artigo em Espanhol | LILACS, CUMED | ID: lil-721285

RESUMO

Objetivo: realizar una actividad de difusión a la población sobre el uso racional de medicamentos, mediante la inserción de los estudiantes en el equipo de salud y analizar los datos farmacoterapéuticos obtenidos de esta actividad educativa. Métodos: en la vía pública se instaló una carpa de Atención Farmacéutica durante tres días donde participaron químicos farmacéuticos y médicos, quienes impartieron charlas sobre diferentes temas de salud preponderantes en la población uruguaya. Asimismo, los alumnos de Atención Farmacéutica, como parte de su formación práctica, participaron de esta actividad mediante la realización de entrevistas a los transeúntes, llenado de fichas de perfiles farmacoterapéuticos y de consumo de plantas medicinales, elaboradas para este fin, y la entrega de folletos informativos. A partir de las fichas farmacoterapéuticas se desarrolló un trabajo de investigación. Resultados: los alumnos del curso participaron de forma activa en el llenado de las fichas farmacoterapéuticas y mantuvieron una comunicación fluida con los asistentes a la carpa y con los profesionales de la salud. Se completaron 117 fichas farmacoterapéuticas (90 mujeres y 27 hombres). El 60 por ciento de los entrevistados consumía plantas medicinales. Sesenta personas recibían cuatro o más especialidades farmacéuticas. Las drogas antihipertensivas resultaron las más utilizadas. Veintitrés personas presentaban hipotiroidismo y dos personas de este grupo recibían litio para trastorno bipolar. Entre el grupo de mujeres: 18 tomaban ansiolíticos, 12 antidepresivos, 7 hipnóticos y 2 antisicóticos. Diecinueve personas manifestaron tener colesterol alto y 14 recibían medicación. Catorce presentaban artrosis y 10 estaban en tratamiento con analgésicos. Nueve personas presentaban gastritis, grupo este con un alto consumo de café y mate. Seis mujeres mayores de 50 años, declararon tener osteoporosis y solo tres recibían medicación a base de calcio y vitamina D. Conclusiones: la experiencia tuvo aceptación por el público y muestra una vez más la necesidad de la población de una educación sanitaria responsable(AU)


Objective: to conduct a health promotion activity for the population on the rational use of drugs, in which students participate with the rest of the health team and to analyze pharmacotherapeutic data collected in this educational activity. Methods: a pharmaceutical care tent was put up on a public area for three days where physicians and pharmacists participated, giving talks on various prevailing health issues that affect the Uruguayan population. Also, a number of pharmaceutical care students, as part of their practical training, participated in this activity by interviewing passers-by, filling out forms of pharmacotherapeutic profiles and of consumption of herbal medicines and giving people some information leaflets. A research study was carried out from the data collected in these pharmacotherapeutic forms. Results: the students actively participated in filling out the pharmacotherapeutic profiles and keeping fluent communication with the audience and with health professionals. One hundred and seventeen pharmacotherapeutic forms were completed (90 women and 27 men). Sixty percent of the interviewed people consumed herbal medicines. Sixty people received four or more medicines. Antihypertensive drugs were the most commonly used. Twenty three people had hypothyroidism and two people in this group were treated with lithium for bipolar disorder. In the female group 18 took anxiolytics, 12 antidepressants, 7 hypnotic drugs and 2 antipsychotic drugs. Nineteen people reported high cholesterol condition and 14 of them took medication. Fourteen had osteoarthritis and 10 were under painkiller treatment. Nine people had gastritis and this group showed high consumption rates of coffee and mate. Six women over 50 years old reported having osteoporosis and only 3 of them took calcium-based medication and vitamin D. Conclusions: the experience was well-accepted by the public and once again, the need for responsible health education of the population was demonstrated(AU)


Assuntos
Humanos , Assistência Farmacêutica/normas , Preparações Farmacêuticas , Educação em Farmácia , Uruguai
20.
Acta méd. colomb ; 38(4): 268-272, oct.-dic. 2013. ilus, tab
Artigo em Espanhol | LILACS, COLNAL | ID: lil-700461

RESUMO

Resumen El mieloma de células plasmáticas secretor de IgD es una neoplasia de células plasmáticas poco frecuente, generalmente afecta individuos más jóvenes que los demás mielomas. Es de difícil diagnóstico, ya que no se observa el pico de proteína monoclonal característico de los mielomas; no obstante, la inmunofijación, la cuantificación de IgD y el estudio de orina son pruebas de gran utilidad para su diagnóstico. Con respecto a las manifestaciones clínicas, es frecuente anemia, falla renal y múltiples lesiones óseas; además, la enfermedad tiene un curso agresivo, con poca respuesta a la quimioterapia convencional. A continuación, se describe un caso de una mujer de 57 años con antecedentes de dolor óseo y múltiples lesiones líticas óseas, quien fue diagnosticada con mieloma secretor de IgD a partir de la electroforesis de proteínas en suero, la inmunofijación en suero y orina, la cuantificación de IgD y el estudio medular. (Acta Med Colomb 2013; 38: 268-272).


Abstract IgD secretory plasma cell myeloma is a rare and aggressive plasma cell neoplasm which usually affects younger individuals than other myelomas. Diagnosis is difficult since there is no monoclonal protein spike, characteristic of myelomas; however, immunofixation, IgD quantification and urine tests are useful for its diagnosis. With regard to clinical manifestations, anemia, renal failure and multiple bone lesions are frequent. In addition, the disease has an aggressive course with poor response to conventional chemotherapy. Here is reported a case of a 57 year old woman with a history of bone pain and multiple lytic bone lesions who was diagnosed with IgD secretory myeloma through serum protein electrophoresis, immunofixation in serum and urine, IgD quantification and medullary study. (Acta Med Colomb 2013; 38: 268-272).


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Mieloma Múltiplo , Imunoglobulina D , Insuficiência Renal
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